U.S. patent application number 17/458880 was filed with the patent office on 2021-12-16 for curable polymeric compositions.
The applicant listed for this patent is Poly-Med, Inc.. Invention is credited to HAFIZ BUSARI, PRABHJOT SAINI, MATHEW STANFORD, DEBRA TINDALL, MICHAEL AARON VAUGHN.
Application Number | 20210388232 17/458880 |
Document ID | / |
Family ID | 1000005865016 |
Filed Date | 2021-12-16 |
United States Patent
Application |
20210388232 |
Kind Code |
A1 |
VAUGHN; MICHAEL AARON ; et
al. |
December 16, 2021 |
Curable Polymeric Compositions
Abstract
Compounds and compositions are provided which are useful in
additive printing, particularly additive printing techniques such
as stereolithography (SLA), wherein a composition of one or more
photocurable compounds, such as a compound with multiple
ethylenically unsaturated groups and a compound with multiple thiol
groups, is photopolymerized, optionally in the presence of two or
more thermocurable compounds which are reactive with one another
and are subjected to thermopolymerization, to form a manufactured
article in solid form.
Inventors: |
VAUGHN; MICHAEL AARON;
(Anderson, SC) ; SAINI; PRABHJOT; (Anderson,
SC) ; TINDALL; DEBRA; (Easly, SC) ; BUSARI;
HAFIZ; (Greenville, SC) ; STANFORD; MATHEW;
(Greenville, SC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Poly-Med, Inc. |
Anderson |
SC |
US |
|
|
Family ID: |
1000005865016 |
Appl. No.: |
17/458880 |
Filed: |
August 27, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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PCT/US20/54839 |
Oct 8, 2020 |
|
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17458880 |
|
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62913063 |
Oct 9, 2019 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B29C 64/129 20170801;
B29K 2067/00 20130101; B29K 2995/006 20130101; B29K 2069/00
20130101; B29K 2081/04 20130101; B29C 64/30 20170801; C08G 81/00
20130101; B33Y 40/20 20200101; B29K 2033/08 20130101; C09D 187/005
20130101; B33Y 70/00 20141201; B33Y 10/00 20141201 |
International
Class: |
C09D 187/00 20060101
C09D187/00; C08G 81/00 20060101 C08G081/00; B33Y 70/00 20060101
B33Y070/00; B29C 64/129 20060101 B29C064/129; B29C 64/30 20060101
B29C064/30; B33Y 40/20 20060101 B33Y040/20 |
Claims
1-54. (canceled)
55. A composition comprising a first organic compound (polySH)
having multiple thiol groups (SH), a second organic compound
(polyEU) having multiple ethylenically unsaturated groups (EU), and
a photoinitiator; and optionally a stabilizer; wherein the
composition has an SH to EU equivalents ratio of X:Y, where X
ranges from 25-75 and Y ranges from 75-25 and the sum of X and Y is
100.
56. The composition of claim 55 wherein polySH is a water soluble,
bioabsorbable macromere having a molecular weight of greater than
1,000 g/mol.
57. The composition of claim 55 wherein polyEU is a water soluble,
bioabsorbable methacrylate.
58. The composition of claim 55 wherein EU of polyEU is
norbornenyl.
59. The composition of claim 55 wherein at least one polyEU and
polySH further has multiple ester groups and multiple carbonate
groups, where optionally polyEU has both multiple ester groups and
multiple carbonate groups, or where optionally both of polySH and
polyEU further have both multiple ester groups and multiple
carbonate groups.
60. The composition of claim 55 wherein at least one of polySH and
polyEU further has multiple carbonate groups and multiple urethane
groups, where optionally polyEU has both multiple carbonate groups
and multiple urethane groups, or where optionally both of polySH
and polyEU further have both multiple carbonate groups and multiple
urethane groups.
61. The composition of claim 55 which is free of volatile materials
having a boiling point of less than 110.degree. C.
62. A composition comprising a photochemically cured reaction
product of the composition of claim 55.
63. An additive manufacturing process comprising: (a) providing a
vat containing a composition of claim 55; (b) directing actinic
radiation from a light source into the first composition in the
vat, where the actinic radiation is effective to induce
polymerization of components of the composition so as to form a
second composition; and (c) forming a solid article.
64. A composition comprising a first organic compound (polyhv)
having multiple photopolymerizable groups (hv), a photoinitiator, a
second organic compound (poly.DELTA.1) having multiple reactive
groups .DELTA.1, and a third organic compound (poly.DELTA.2) having
multiple reactive groups .DELTA.2, where .DELTA.1 reacts with
.DELTA.2 upon contact and exposure to a temperature of greater than
50.degree. C., wherein the polyhv is a bioabsorbable macromere
having a molecular weight of greater than 1,000 g/mol.
65. The composition of claim 64 wherein polyhv is polyEU acrylate
or methyacrylate.
66. The composition of claim 64 wherein hv of polyhv is
norbornenyl.
67. The composition of claim 64 wherein at least one polyhv,
poly.DELTA.1 and poly.DELTA.2 further has multiple ester groups and
multiple carbonate groups, where optionally polyhv has both
multiple ester groups and multiple carbonate groups, or where
optionally polyhv and at least one of poly.DELTA.1 and poly.DELTA.2
has both multiple ester groups and multiple carbonate groups.
68. The composition of claim 64 wherein at least one of polyhv,
poly.DELTA.1 and poly.DELTA.2 further has multiple carbonate groups
and multiple urethane groups, where optionally polyhv has both
multiple carbonate groups and multiple urethane groups, or where
optionally polyhv and at least one of poly.DELTA.1 and poly.DELTA.2
has both multiple carbonate groups and multiple urethane
groups.
69. The composition of claim 64 wherein the multiple .DELTA.1 of
poly.DELTA.1 is 2, 3 or 4; or the multiple .DELTA.2 of poly.DELTA.2
is 2, 3 or 4, or both the multiple .DELTA.1 of poly.DELTA.1 is 2, 3
or 4 and the multiple .DELTA.2 of poly.DELTA.2 is 2, 3 or 4.
70. The composition of claim 64 which is free of volatile materials
having a boiling point of less than 110.degree. C.
71. The composition of claim 64 which is bioabsorbable.
72. An additive manufacturing process comprising: (a) providing a
vat containing a first composition of claim 64; (b) directing
actinic radiation from a light source into the first composition in
the vat, where the actinic radiation is effective to induce
polymerization of components of the first composition so as to form
a second composition comprising photochemically cured composition;
and (c) applying thermal energy to the second composition
comprising the photochemically cured composition so as to form a
third composition comprising photochemically cured and thermally
cured composition.
73. An article comprising a photochemically cured and thermally
cured reaction product of the method of claim 72.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of PCT/US2020/054839,
filed Oct. 8, 2020, which claims the benefit under 35 U.S.C. .sctn.
119(e) of U.S. Provisional Patent Application No. 62/913,063 filed
Oct. 9, 2019, each of which is incorporated herein by reference in
its entirety for all purposes.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates generally to the preparation
and use of curable compositions, such as photocurable and
thermocurable compositions to prepare bioabsorbable implants by an
additive manufacturing process.
BACKGROUND
[0003] Stereolithography (SLA) is a relatively well-developed
additive printing technique for preparing three-dimensional (3-D)
objects. In stereolithographic methods, light, such as ultraviolet
(UV) or visible light, is used to photopolymerize liquid material
into designed structures, such as three-dimensional articles, with
high accuracy and precision. Thin successive layers are
photopolymerized by UV or visible light, for example, under the
direction of a sliced CAD (computer aided design) model.
[0004] SLA generally uses a liquid photopolymerizable composition
that may be referred to as a resin or an ink formulation. The
macroscopic properties and degradation profiles of articles
produced by SLA depend in part on the polymer chemistry and the
processing techniques.
[0005] The present disclosure provides compounds and compositions
useful in a curing process such as stereolithography (SLA), which
have advantages over currently known compounds and compositions for
this purpose.
[0006] All of the subject matter discussed in the Background
section is not necessarily prior art and should not be assumed to
be prior art merely as a result of its discussion in the Background
section. Along these lines, any recognition of problems in the
prior art discussed in the Background section or associated with
such subject matter should not be treated as prior art unless
expressly stated to be prior art. Instead, the discussion of any
subject matter in the Background section should be treated as part
of the inventor's approach to the particular problem, which in and
of itself may also be inventive.
SUMMARY
[0007] In brief, in one aspect, the present disclosure provides
compounds and compositions useful in a curing process, such as a
photocuring process or such as a thermocuring process that is used
in conjunction with a photocuring process. The curing process is
useful in manufacturing articles, such as medical devices and
coatings. An exemplary curing process is stereolithography (SLA),
which is an additive manufacturing process wherein a curable
composition according to the present disclosure containing one or
more photoreactive compounds, including e.g., a photoreactive
macromer, is photopolymerized (photocured) during a process to form
a manufactured article. Another exemplary process is a coating
process whereby a compound and/or composition of the present
disclosure is placed on a surface and then cured by exposure to
heat (thermocuring) and/or by exposure to actinic radiation (i.e.,
photopolymerized or photocured) to provide a solid coating on the
surface. These cured products, i.e., products formed by curing a
composition as disclosed herein, may generally be referred to
herein as articles, coatings, films, materials and the like. Thus,
when the present disclosure is exemplified by preparing an article,
it should be understood that a coating or other material can
likewise be prepared. In one aspect, the articles, coatings etc.
are biodegradable.
[0008] In one aspect the present disclosure provides biodegradable
polymeric materials formed by a curing process. The materials may
be used to produce articles that have a limited lifetime, such that
after some period of time, the article formed from the
biodegradable material is no longer present. For example, the
material may be a coating on a device, such as a medical device,
where the coating degrades after some period of time. In another
example, the material may be a used to prepare a medical device,
for example, a mesh for tissue repair, so that after a time, some
or none of the article is present and tissue repair is
accomplished. As another example, the medical device may be a
tissue adhesive or sealant, where a polymerizable composition of
the present disclosure may be applied to a tissue in need of
adhesive or sealant, and then that composition is exposed to
actinic radiation sufficient to cause photopolymerization of the
composition on the tissue.
[0009] According to the present disclosure, in one aspect
stereolithography may be used to prepare such materials and
articles, using, e.g., compounds and compositions as disclosed
herein. The present disclosure addresses concerns about thermo- and
photo-cured materials, such as SLA-produced articles, that come
into contact with living entities, include concerns regarding the
safety and efficacy of the produced articles, particularly their
biocompatibility and cytotoxicity.
[0010] In one aspect, the present disclosure provides for the
preparation and use of polymeric compositions. The polymeric
composition may include or be made from a photopolymerizable
polymer comprising a homopolymer, copolymer, block copolymer,
random copolymer, random block copolymer, or combinations thereof.
The polymeric composition may include or be made from a thermally
curable polymer comprising a homopolymer, copolymer, block
copolymer, random copolymer, random block copolymer, or
combinations thereof. In one aspect, the polymeric composition is a
double network, in that two chemically distinct polymers are
present in admixture in the composition, where optionally the
double network polymeric composition may be characterized as being
a solid. In one aspect, the polymeric composition is a single
network, in that a single polymer is present in the composition,
where optionally the single network polymeric composition may be
characterized as being a solid. In one aspect, the single network
includes a crosslinked polymer. In one aspect, the double network
includes a crosslinked polymer. The polymeric compositions may be
used, e.g., to prepare bioabsorbable implants by an additive
manufacturing process.
[0011] In one aspect, the present disclosure provides a composition
comprising (1) a compound having multiple photopolymerizable
groups, referred to herein as a polyhv, and (2) a mixture of two
compounds that are thermally reactive with one another
(thermocurable) so as to form a polymer, where the two compounds
may be referred to herein as poly.DELTA.1 and poly.DELTA.2 or
collectively as poly.DELTA. (i.e., poly.DELTA. refers to a mixture
of poly.DELTA.1 and poly.DELTA.2). In one aspect, the composition
additionally comprises a photoinitiator. In one aspect, the
composition additionally comprises a stabilizer. In one aspect, the
present disclosure provides a cured, and optionally crosslinked,
composition resulting from the photopolymerization of a composition
comprising a photoinitiator, a polyhv and a poly.DELTA., where this
cured (e.g., crosslinked) composition may be said to have a single
network, which refers to the network formed from polyhv reacting
with itself. In one aspect, the present disclosure provides a
double network composition resulting from the photopolymerization
of polyhv, and the thermal polymerization of poly.DELTA.1 with
poly.DELTA.2, where each of polyhv and poly.DELTA. forms an
independent network, one or both optionally being a crosslinked
network. The two independent networks together form an
interpenetrating double network. The double network is thus formed
by thermocuring and photocuring a composition having both
thermoreactive components (poly.DELTA.1 and poly.DELTA.2) and at
least one photoreactive component (polyhv). In one aspect,
photocuring precedes thermocuring. In one aspect, thermocuring
precedes photocuring.
[0012] In one aspect, the present disclosure provides a composition
comprising 1) a compound having multiple photopolymerizable thiol
groups, referred to herein as a polySH, and 2) a compound having
multiple photopolymerizable ethylenically unsaturated groups,
referred to herein as a polyEU, where polySH and polyEU are
photoreactive with one another. In one aspect, the composition
additionally comprises a photoinitiator. In one aspect, the
composition additionally comprises a stabilizer. In one aspect, the
present disclosure provides a single network polymeric composition
resulting from the photocuring (photopolymerization) of a
composition comprising a photoinitiator, a polySH and a polyEU. In
one aspect, the present disclosure provides a single network
crosslinked composition resulting from the photocuring
(photopolymerization) of a composition comprising a photoinitiator,
a polySH and a polyEU. In another aspect, the present disclosure
provides a single network crosslinked composition resulting from
the photocuring (photopolymerization) of a composition comprising a
photoinitiator, a stabilizer, a polySH and a polyEU. Exemplary EU
groups are acrylate, methacrylate and norbornenyl, where polyEU
refers to a compound comprising multiple EU groups, optionally two
EU groups, or three EU groups, or four EU groups.
[0013] In one aspect, disclosed herein are methods and compositions
for curing processes, such as 3-D printing, and for making and
using the resulting cured articles. For example, the present
disclosure provides a method for photopolymerization printing an
article comprising, a) exposing for a time to light of suitable
wavelength, a photopolymerizable composition comprising a polyEU
macromer and a polySH as disclosed herein; optionally in
combination with one or more other components such as at least one
photoinitiator component and/or at least one light reflective
material component comprising a light reflective material suspended
in the composition, and/or at least one stabilizer; and forming a
printed article comprising a polymerization product of the
photopolymerizable composition. In another aspect, the present
disclosure provides a method for photopolymerization printing an
article comprising, a) exposing for a time to light of suitable
wavelength, a photopolymerizable composition comprising a polyhv,
poly.DELTA.1, and poly.DELTA.2; and b) thermally polymerizing the
poly.DELTA.1 with poly.DELTA.2; optionally in combination with one
or more other components such as at least one photoinitiator
component and/or at least one light reflective material component
comprising a light reflective material suspended in the
composition, and/or at least one stabilizer; and forming a printed
article comprising a polymerization product of the
photopolymerizable composition.
[0014] In one aspect, disclosed herein are methods and compositions
for photopolymerization processes, such as a film-forming process
including a coating process, and for making and using such
photopolymerized materials. For example, the present disclosure
provides a method for photopolymerization coating of an article
comprising, a) applying a photopolymerizable composition of the
present disclosure to a surface, b) exposing for a time to light of
suitable wavelength, the photopolymerizable composition comprising
polyEU and polySH as disclosed herein; optionally in combination
with one or more other components such as at least one
photoinitiator component and/or at least one light reflective
material component comprising a light reflective material suspended
in the composition, and/or at least one stabilizer; and forming a
solid coating comprising a polymerization product of the
photopolymerizable composition.
[0015] In other aspects, the present disclosure provides the
polymerization product of a macromer (which may also be referred to
as a prepolymer) where the macromer has been polymerized by, e.g.,
one or more methods disclosed herein. In addition, the present
disclosure provides an article, which may be referred to as a
polymeric article, produced from a photopolymerizable compound or
composition as disclosed herein, optionally by one or more methods
as disclosed herein. The photopolymerized macromer or article may
be a nontoxic article. In addition, the article may comprise
biodegradable photopolymerized macromer, optionally in admixture
with a nontoxic amount of photoinitiator. Optionally, the article
may comprise biodegradable photopolymerized macromer, optionally in
admixture with a nontoxic amount of stabilizer. Optionally, the
article may comprise biodegradable photopolymerized macromer,
optionally in admixture with a nontoxic amount of UV reflective
material. In one aspect, the polymeric article is biodegradable, in
whole or in part, under physiological conditions. However, in an
alternative aspect, the polymeric article is not biodegradable
under physiological conditions.
[0016] In addition, the present disclosure provides a
photopolymerizable compound, also referred to herein as a macromer,
comprising a polyaxial central core (CC) and 2-4 arms of the
formula (A)-(B) or (B)-(A) extending from the central core, where
at least one of the arms comprise a light-reactive functional group
(Q) and (A) is the polymerization product of monomers selected from
trimethylene carbonate (also referred to herein as T, or as TMC)
and .epsilon.-caprolactone (also referred to herein as
caprolactone, or C, or CAP), while (B) is the polymerization
product of monomers selected from glycolide, lactide and
p-dioxanone. The macromer may be a photopolymerizable macromer
component in compositions and methods as disclosed herein, and may
be photopolymerized to provide articles.
[0017] Optionally, any of the compositions of the present
disclosure, before they are cured, may contain an effective amount
of a photoinitiator, i.e., an amount of photoinitiator which is
effective to achieve polymerization of the photopolymerizable
compound when the composition is exposed to radiation emitted from
a light source that delivers light of a selected wavelength
suitable to activate the photoinitiator.
[0018] In one aspect, the present disclosure provides a method of
3D-printing, also known as additive printing, e.g.,
stereolithography, which comprises providing a polymerizable
composition as disclosed herein having a photopolymerizable
compound and a photoinitiator, and exposing that composition to
light which is effective to activate the photoinitiator, in order
to photopolymerize the photopolymerizable compound in the
polymerizable composition. In one aspect, the composition is
selectively exposed to the light, so that a selected portion of,
and not all of, the composition undergoes a photopolymerization. In
one aspect, the photopolymerizable compound is a mixture including
one or more polyhv compounds, e.g., two photopolymerizable
compounds denoted herein as polyEU and polySH. In one aspect, one
or more photopolymerizable compounds is admixed with one or more
thermally reactive compounds, e.g., two thermally reactive
compounds denoted herein as poly.DELTA.1 and poly.DELTA.2.
[0019] The above-mentioned and additional features of the present
disclosure and the manner of obtaining them will become apparent,
and the disclosure will be best understood by reference to the
following more detailed description. All references disclosed
herein are hereby incorporated by reference in their entirety as if
each was incorporated individually.
[0020] This Brief Summary has been provided to introduce certain
concepts in a simplified form that are further described in detail
below in the Detailed Description. Except where otherwise expressly
stated, this Brief Summary is not intended to identify key or
essential features of the claimed subject matter, nor is it
intended to limit the scope of the claimed subject matter.
[0021] The details of one or more embodiments are set forth in the
description below. The features illustrated or described in
connection with one exemplary embodiment may be combined with the
features of other embodiments. Thus, any of the various embodiments
described herein can be combined to provide further embodiments.
Aspects of the embodiments can be modified, if necessary to employ
concepts of the various patents, applications and publications as
identified herein to provide yet further embodiments. Other
features, objects and advantages will be apparent from the
description, the drawings, and the claims.
[0022] The above-mentioned and additional features of the present
disclosure and the manner of obtaining them will become apparent,
and the disclosure will be best understood by reference to the
following more detailed description. All references disclosed
herein are hereby incorporated by reference in their entirety as if
each was incorporated individually.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Exemplary features of the present disclosure, its nature and
various advantages will be apparent from the accompanying drawings
and the following detailed description of various embodiments.
Non-limiting and non-exhaustive embodiments are described with
reference to the accompanying drawings, wherein like labels or
reference numbers refer to like parts throughout the various views
unless otherwise specified. The sizes and relative positions of
elements in the drawings are not necessarily drawn to scale. For
example, the shapes of various elements are selected, enlarged, and
positioned to improve drawing legibility. The particular shapes of
the elements as drawn have been selected for ease of recognition in
the drawings. One or more embodiments are described hereinafter
with reference to the accompanying drawings in which:
[0024] FIG. 1 shows degradation profiles for selected cured
compositions of the present disclosure.
[0025] FIG. 2 shows water swelling profiles for selected cured
compositions of the present disclosure.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0026] The present disclosure may be understood more readily by
reference to the following detailed description of preferred
embodiments of the disclosure and the Examples included herein. In
reading this detailed description, and unless otherwise explained,
all technical and scientific terms used herein have the same
meaning as commonly understood by one of ordinary skill in the art
to which this disclosure belongs. The singular terms "a," "an," and
"the" include plural referents unless context clearly indicates
otherwise. Similarly, the word "or" is intended to include "and"
unless the context clearly indicates otherwise. The term
"comprises" means "includes." The abbreviation, "e.g." is derived
from the Latin exempli gratia, and is used herein to indicate a
non-limiting example. Thus, the abbreviation "e.g." is synonymous
with the term "for example."
[0027] In one aspect, the present disclosure provides compositions
which are liquid at a temperature of about room temperature, i.e.,
about 18.degree. C. to about 23.degree. C., and which can undergo
curing. The curing process will include photocuring, also referred
to herein as photopolymerization, and depending on the composition,
may also include thermocuring, also referred to herein as
thermopolymerization. Photocuring occurs when the composition is
exposed to actinic radiation of selected energy for a selected
period of time, to cause reaction between the photochemical (also
referred to herein as photoreactive or photopolymerizable or the
like) components of the composition, and an increase in the average
molecular weight of components in the composition. Thermocuring is
the corresponding process achieved when the composition is heated
above room temperature to a suitable temperature for a suitable
length of time, to cause reaction between the thermally reactive
(also referred to herein as thermoreactive or thermopolymerizable
or the like) components of the composition, and increase the
average molecular weight of components in the composition. When the
reactants include compounds having three or more photoreactive or
thermoreactive chemical groups, then the curing process will
provide for a composition having crosslinked components. As used
herein, curing refers to photocuring, optionally with thermocuring
if the composition has thermally reactive components.
[0028] Compositions of the present disclosure include photoreactive
components. Optionally, the compositions may also include thermally
reactive components. When a composition includes both thermally and
photochemically reactive components, the resulting cured
composition may be referred to herein as having a double network or
a dual network: a first network formed from the photochemically
reactive compounds and a second network formed from the thermally
reactive compounds. When a composition has photochemically reactive
components but not thermally reactive components, the resulting
cured composition may be referred to herein as having a single
network.
[0029] As explained in further detail below, compositions of the
present disclosure may comprise one or more compounds having at
least two photochemically reactive functional groups, denoted "hv"
groups, and may optionally include two or more compounds having at
least two thermally reactive functional groups, denoted as
".DELTA." groups. The reactive functional groups will be joined to
an organic backbone, i.e., a backbone made from atoms including
carbon and hydrogen. As a simple example, if the .DELTA. group is
hydroxyl, a thermally reactive compound may be ethylene glycol,
i.e., HO--CH.sub.2--CH.sub.2--OH, where the backbone is
--CH.sub.2--CH.sub.2--.
[0030] When the backbone of a compound includes repeating chemical
units, the compound may be referred to herein as a macromer. For
example, a reaction between a minor amount of ethylene glycol
(referred to as an initiator) and a major amount of a hydroxyl acid
or equivalent, e.g., lactic acid or lactide, will result in a
compound having two polylactides (repeating lactide units)
extending from either end of the ethylene glycol initiator, and
also having a hydroxyl group at each of the two termini of the
polylactide chains. In one aspect, compositions of the present
disclosure include a macromer as the photochemically reactive
component, and/or a macromer as the thermally reactive
component.
[0031] Compounds having two or more hydroxyl groups are exemplary
thermally reactive compounds of the present disclosure. Such
hydroxyl-containing compounds are thermally reactive with compounds
having complementary functional groups, such as epoxide or
isocyanate groups. Thus, a composition of the present disclosure
may have a first compound with two or more hydroxyl groups and a
second compound with two or more functional groups that are
thermally reactive with hydroxyl groups. In one aspect, the
hydroxyl group is an example of a nucleophilic group, and the
epoxide is an example of an electrophilic group. Thus, in one
aspect, a thermally reactive composition of the present disclosure
may be described as having a compound with two or more nucleophilic
groups and a compound having two or more electrophilic groups.
[0032] In addition to being compounds that are useful in thermally
curable compositions as disclosed herein, hydroxyl-containing
compounds are also useful starting materials for preparing
photoreactive compounds. For example, as disclosed herein, hydroxyl
groups may be converted to thiol-containing groups. In addition,
hydroxyl groups may be converted to groups having an ethylenically
unsaturated portion. Thus, the backbones of the hydroxyl-containing
compounds as disclosed herein may also be present as the backbone,
or a portion of the backbone, of a photochemically reactive
compound in the compositions disclosed herein. It should be
understood that when the present disclosure provides a compound
having two or more hydroxyl groups, the present disclosure
simultaneously provides that the backbone of that
hydroxyl-containing compound is optionally present in a
photochemically reactive compound of the present disclosure.
Poly.DELTA. Compounds
[0033] In one aspect, the present disclosure provides compositions
that include two poly.DELTA. compounds denoted herein as
poly.DELTA.1 and poly.DELTA.2. The compound poly.DELTA.1 has
multiple (hence the term "poly") .DELTA.1 groups, where a .DELTA.1
group is thermally reactive with a .DELTA.2 group. The compound
poly.DELTA.2 has multiple .DELTA.2 groups, where a .DELTA.2 group
is thermally reactive with a .DELTA.1 group. Each of poly.DELTA.1
and poly.DELTA.2 is an organic compound. The term "thermally
reactive" means that heat must be applied to a composition
comprising poly.DELTA.1 and poly.DELTA.2 in order for .DELTA.1 and
.DELTA.2 to react with one another. At room temperature, i.e.,
about 22.degree. C., and in the absence of a catalyst, .DELTA.1 and
.DELTA.2 do not react to any appreciable extent with one another.
In one embodiment, the compositions of the present disclosure do
not include a catalyst to increase the rate of a thermal reaction.
Upon reaction, .DELTA.1 and .DELTA.2 form one or more covalent
bonds so that poly.DELTA.1 and poly.DELTA.2 become part of a
polymeric network, optionally a crosslinked polymeric network.
[0034] In one aspect, a polyhydric compound (also referred to as a
polyol) is a poly.DELTA. compound. For example, an aliphatic polyol
having an alkylene group may be used as a poly.DELTA.. Exemplary
alkylene groups include ethylene, propylene (branched or straight
chain), butylene (branched or straight chain), hexylene (branched,
straight chain or cyclic) and octylene (branched, straight chain,
or cyclic). Exemplary polyols having more than two hydroxyl groups,
which may be used when crosslinking is desired, include
trimethylolpropane, glycerol, pentaerythritol, 1,2,4-butanetriol,
and 2,3,4-pentanetriol.
[0035] In one aspect, an aromatic diol may be used as a
poly.DELTA.. Examples include catechol, resorcinol, hydroquinone
and the reactions products thereof, for example, the reaction
product of reaction products of resorcinol and ethylene carbonate.
Other suitable aromatic diols include bisphenol A and
4,4'-dihydroxybiphenyl.
[0036] In one aspect, a polyether diol may be used as a poly.DELTA.
compound. The polyether diol will introduce polyoxyalkylene
segments, in other words polyether segments, into a cured
composition. The polyether diol may comprise a homopolymer of
oxyalkylene groups, or a copolymer of two different oxyalkylene
groups. The copolymer may be a random or block copolymer, for
example, a diblock copolymer, or a triblock copolymer. Exemplary
oxyalkylene moieties include oxyethylene, oxypropylene,
oxytrimethylene, and oxytetramethylene.
[0037] In one aspect, a polycarbonate diol may be used as a
poly.DELTA.. Examples include trimethylene carbonate,
poly(hexamethylene carbonate) diol, poly(ethylene-carbonate) diol,
poly(propylene-carbonate) diol, and poly(butylene-carbonate)
diol.
[0038] An exemplary poly.DELTA. macromer may have a polyaxial
central core (CC) and 2-4 arms having repeating units. Such
poly.DELTA. macromers may be referred to herein as polyaxial
macromers. In one embodiment, at least two of the arms terminate in
a nucleophilic group, e.g., a hydroxyl group or an amine group. In
one aspect, the repeating units are all the same, i.e., the arms
are a homopolymer. In one aspect, the repeating units not all the
same, i.e., the arms are a copolymer. The copolymer may be a random
or block copolymer. For example, and as discussed further below,
the arms may have the formula (A)-(B) or (B)-(A) extending from the
central core. The arms may be biodegradable or
non-biodegradable.
[0039] In one aspect, the arms include ester groups, and the arms
may be said to be polyesters. In order to form an ester group, the
arms may be prepared, in whole or in part, from hydroxy acids or
equivalent. Exemplary hydroxy acids and equivalents include
glycolic acid (and its equivalent, glycolide), lactic acid (and its
equivalent, lactide), .epsilon.-caprolactone (C), and p-dioxanone.
In one aspect, the arms are all formed from the same monomer, so
that the polyaxial macromer has homopolymeric arms. In one aspect,
the arms may include a carbonate group. In order to form a
carbonate group, the arms may be prepared, in whole or in part,
from trimethylene carbonate (also denoted herein as "T").
[0040] In one aspect, the poly.DELTA. compound may be a polyaxial
macromer having a central core and a plurality, e.g., 2-4,
copolymeric arms extending from the central core, each arm ending
(i.e., terminating) in a thermally reactive group, e.g., a hydroxyl
group. The compound may be represented by the formula
CC-[arm.DELTA.].sub.n where CC represents the central core and n is
selected from a number within the ranges of 2-18, or 2-14, or 2-8,
or 2-6, or 2-4. Each arm is formed by the polymerization of
monomers selected from two groups, the two groups being denoted as
group A and group B. Thus, more specifically, in compounds of the
present disclosure, CC-[arm.DELTA.].sub.n may be written as either
CC-[(A)p-(B)q-OH]n, or CC-[(B)q-(A)p-OH]n where each of (A)p-(B)q
and (B)q-(A)p represents an arm. Optionally, the terminal
functional group of the arm may be shown, where an exemplary
terminal functional group is hydroxyl. In the formula, A represents
the polymerization product of one or more monomers comprising, and
optionally selected only from, trimethylene carbonate (T or TMC)
and caprolactone (C or CAP), and p represents the number of
monomers that have been polymerized to form the polymerization
product A, where p is selected from 1-40, or 1-30, or 1-20, or
1-10. In the formula, B represents the polymerization product of
one or more monomers comprising, and optionally selected only from,
glycolide (G or GLY), lactide (L or LAC) and p-dioxanone (D or
DOX), and q represents the number of monomers that have been
polymerized to form the polymerization product B, where q is
selected from 1-40, or 1-30, or 1-20, or 1-10.
[0041] For example, when compounds of the formula
CC-[arm.DELTA.].sub.n are formed from a trifunctional central core,
and A is added to CC prior to the addition of B, then compounds of
the formula CC-[arm.DELTA.].sub.n may be written as
CC-[(A)p-(B)q-OH].sub.3. If, in this example, A is formed by the
polymerization of two Ts and one C, then p would be three and A
would be selected from TTT, TTC, TCT, TCC, CCC, CCT, CTC, and CTT,
independently within each arm. If, continuing with this example, B
is formed by the polymerization of one G, then q would be one and B
would be G. In this example, each arm would have a chemical formula
selected from TTTG, TTCG, TCTG, TCCG, CCCG, CCTG, CTCG, and CTTG.
This exemplary compound may be written as CC-[arm.DELTA.].sub.3
where each arm is independently selected from TTTG-OH, TTCG-OH,
TCTG-OH, TCCG-OH, CCCG-OH, CCTG-OH, CTCG-OH, and CTTG-OH, or
alternatively as either CC-[(T,T,C)-(G)-OH].sub.3 or
CC-[(T,T,C).sub.3-(G).sub.1-OH].sub.3.
[0042] In one aspect, the present disclosure provides a composition
comprising a compound having a bifunctional central core and 2 arms
extending from the central core, each arm terminating in a hydroxyl
group. In one embodiment, the present disclosure provides a
composition comprising a compound comprising a trifunctional
central core and either 2 or 3 arms extending from the central
core, each arm terminating in a hydroxyl group. In one embodiment,
the present disclosure provides a composition comprising a compound
comprising a tetrafunctional central core and either 2 or 3 or 4
arms extending from the central core, each arm terminating in a
hydroxyl group. Each arm in the compound may be a homopolymer or a
copolymer, and when a copolymer, may be a random copolymer or a
block copolymer, e.g., a block copolymer represented by the formula
(A)-(B) or (B)-(A). When the compound is prepared by reacting the
central core with monomers of Group A followed by reacting that
reaction product with monomer(s) selected from Group B, then the
compounds will have the formula CC-[(A)-(B)-OH]. However, when the
composition is prepared by reacting the central core with monomers
of Group B followed by reacting that reaction product with
monomer(s) selected from Group A, then the compounds will have the
formula CC-[(B)-(A)-OH].
[0043] In embodiments, the macromer will have a molecular weight of
less than 250,000 Da, or less than 200,000 Da, or less than 150,000
Da, or less than 100,000 Da, or less than 50,000 Da, or less than
25,000 Da, or less than 20,000 Da, or less than 15,000 Da, or less
than 10,000 Da, or less than 9,000 Da, or less than 8,000 Da, or
less than 7,000 Da, or less than 6,000 Da, or less than 5,000 Da,
or less than 1,000 Da.
[0044] In embodiments, the polyaxial macromers present in a
composition all contain the same central core. For example, all of
the macromer components of a composition are prepared from
trimethylolpropane or pentaerythritol. However, in one aspect, a
composition of the present disclosure contains a mixture of
polyaxial macromer components, for example, some of the macromer
components are triaxial, made from, e.g., trimethylolpropane, and
other macromer components of the same composition are tetraaxial,
made from, e.g., pentaerythritol.
[0045] In embodiments, the polyaxial macromers of the present
disclosure have relatively short arms, e.g., 1-10 monomer
residues/arm. A monomer residue, as used herein, refers to the
polymerization product of the monomer, i.e., the structure that the
monomer has after that monomer has been incorporated into a polymer
and is thus providing a monomer residue in that polymer. In one
embodiment, when the compounds of the disclosure are used in
additive printing, those compounds should be in a fluid state:
either the compounds themselves are fluid or the compounds are
dissolved in a solvent and/or diluent to provide a fluid
composition. If the arms are too long, a composition containing the
compound will typically be too viscous to be useful in additive
printing such as SLA, unless the composition contains a lot of
solvent or diluent to dilute the compound, in which case the
additive printing process may need to utilize an undesirably large
amount of solvent. Advantageously, when the arms are relatively
short, the compounds themselves may be fluid at the application
temperature of the additive printing process. In an aspect the
application temperature is room temperature, i.e., about 18.degree.
C. to about 23.degree. C., and the composition is a liquid at this
temperature.
[0046] In optional embodiments, the compounds and compositions of
the present disclosure containing such compounds, can be described
by one or more of the following features which characterize the A
region (also referred to as a block) of the polyaxial macromer:
have a block A which comprises residues formed from trimethylene
carbonate (TMC or T), i.e., which are the polymerization product or
residue of TMC; have a block A which comprises residues formed from
caprolactone (CAP or C); have a block A which comprises residues
formed from both TMC and CAP; at least 90% of the residues in block
A are residues formed from TMC or CAP; the compound comprises 1-45,
or 2-45 residues formed from TMC; the compound comprises 1-15 or
2-15 residues formed from TMC; the compound comprises 1-10 or 2-10
residues formed from TMC; region A has a molecular weight of from
102-2500 g/mol; region A has a molecular weight of 102-1000 g/mol;
region A has a molecular weight of 102-900 g/mol; each A region
comprises 2-45 monomer residues; each A region comprises 2-15
monomer residues; each A region comprises 2-10 monomer
residues.
[0047] In optional embodiments, the compounds and compositions of
the present disclosure containing such compounds, can be described
by one or more of the following features which characterize the B
block (also referred to as a region) of the polyaxial macromer:
each B block comprise 1-45 or 2-45 monomer residues; each B block
comprise 1-15 or 2-15 monomer residues; each B block comprises 1-10
or 2-10 monomer residues.
[0048] In one aspect, a polyamine is a poly.DELTA. compound. For
example, an aliphatic polyamine having an alkylene group may be
used as poly.DELTA.. Exemplary alkylene groups include ethylene,
propylene (branched or straight chain), butylene (branched or
straight chain), hexylene (branched, straight chain or cyclic) and
octylene (branched, straight chain, or cyclic). Exemplary
polyamines having more than two amine groups include
polypropylenimine tetramine (also known as Dab-Am-4) and
triethylenetetramine. The Huntsman Company sells many suitable
polyamines having more than two amine groups, for example
polyethertriamine (Huntsman product XTJ-566), JEFFAMINE.RTM. ST-404
polyetheramine (Huntsman product (XTJ-586), and JEFFAMINE.RTM.
T-403 polyetheramine.
[0049] In one aspect, an aromatic diamine may be used as a
poly.DELTA.. Examples include 1,2-diaminobenzene,
1,3-diaminobenzene, 1,4-diaminobenzene, toluene diamine (e.g.,
1,2-diamino-3-methylbenzene, 1,2-diamino-4-methylbenzene,
1,3-diamino-2-methylbenzene, 1,3-diaminoe-4-methylbenzene,
1,4-diamino-2-methylbenzene, 1,4-diamino-3-methylbenzene),
alkyl-substituted toluenediamine (e.g.,
3,5-diethyltoluene-2,4-diamine and 3,5-diethyltoluene-2,6-diamine),
and p-xylyenediamine.
[0050] In one aspect, a polyether diamine may be used as a
poly.DELTA. compound. When a polyether diamine is reacted with a
diisocyanate-containing poly.DELTA., the result will be a polyether
urea moiety. The polyether diamine may comprise a homopolymer of
oxyalkylene groups, or a copolymer of two different oxyalkylene
groups. The copolymer may be a random or block copolymer, for
example, a diblock copolymer, or a triblock copolymer. Exemplary
oxyalkylene moieties include oxyethylene, oxypropylene,
oxytrimethylene, and oxytetramethylene.
[0051] In one aspect, a polyisocyanate is a poly.DELTA. compound.
An exemplary polyisocyanate compound is an aliphatic
polyisocyanate, such as, without limitation, tetramethylene
diisocyanate, 1-lysine diisocyanate, lysine ethyl ester
diisocyanate, hexamethylene diisocyanate, octamethylene
diisocyanate, decamethylene diisocyanate, dodecamethylene
diisocyanate, and cyclohexane bis-(methylene isocyanate). Another
exemplary polyisocyanate compound is an aromatic polyisocyanate,
such as, without limitation, methylene 4,4,-diphenyl diisocyanate
(MDI), 2,4-toluenediisocyanate (TDI), 1,5-naphthalene diisocyanate,
and isophorone diisocyanate.
[0052] In one aspect, the polyisocyanate poly.DELTA. is a macromer
having multiple isocyanate groups. Such macromers may be referred
to herein a polyisocyanate macromer. Polyisocyanate macromers may
be prepared from the corresponding polyhydroxylated macromers by
reaction of the polyhydroxylated macromer with a diisocyanate,
e.g., hexamethylene diisocyanate.
[0053] Exemplary polyisocyanate macromers are the reaction product
of reactants comprising or consisting of a diisocyanate and either
or both of a diamine and a diol, e.g., a polyetherdiamine or a
polyetherdiol. Such polyisocyanate macromers have terminal
isocyanate groups which are reactive with additional polyamine
and/or polyhydric compounds. For example, a diisocyanate may be
used to form a macromer by reaction with either a diamine or a diol
to provide a poly.DELTA. compound (e.g., a poly.DELTA.2 compound)
having terminal isocyanate groups. This poly.DELTA.2 polyisocyanate
macromer may then be thermally reacted with additional diamine or
diol (a poly.DELTA.1 compound) to form a thermocured polymer in a
composition of the present disclosure.
[0054] In one aspect the present disclosure provides a
polyisocyanate macromer which is the reaction product of a
polyisocyanate, e.g., a diisocyanate, and a polyol, e.g., a diol
such as a polyetherdiol. Optionally, any one or more of the
following may be used to further describe this polyisocyanate
macromer and its preparation: the polyol is a diol and the
polyisocyanate is a diisocyanate, the diol may be a polyetherdiol
comprising at least one type of oxyalkylene sequence selected from
the group consisting of oxyethylene, oxypropylene, oxytrimethylene
and oxytetramethylene sequences; the polyol may be an aliphatic
polyol having an alkylene group, where exemplary alkylene groups
include ethylene, propylene (branched or straight chain), butylene
(branched or straight chain), hexylene (branched, straight chain or
cyclic) and octylene (branched, straight chain, or cyclic).
Exemplary polyols having more than two hydroxyl groups, which may
be used when crosslinking is desired, include trimethylolpropane,
glycerol, pentaerythritol, 1,2,4-butanetriol, and
2,3,4-pentanetriol. The polyol may be an aromatic diol, where
examples include catechol, resorcinol, hydroquinone and the
reactions products thereof, for example, the reaction products of
resorcinol and ethylene carbonate. Other suitable aromatic diols
include bisphenol A and 4,4'-dihydroxybiphenyl.
[0055] In one aspect, a polyisocyanate macromer which is the
reaction product of a polyisocyanate, e.g., a diisocyanate, and a
polyol, e.g., a diol such as a polyetherdiol, provides a
poly.DELTA.2 compound which may be reacted with a poly.DELTA.1
compound such as a polyamine. The reaction product may be described
in terms of its structural components rather than in terms of the
reactants by which it may be formed. In one aspect the polymer
chain is a polyurea, having a plurality of urea groups separated
alternately by aliphatic groups (contributed by the aliphatic
diamine) and polymeric blocks (contributed by the macromer). In
other words, the structure may be described by
repeating--[urea-aliphatic-urea-polymer block]--units. The polymer
block is a polyurethane, having a plurality of urethane (also known
as carbamate) groups separated alternatively by aliphatic groups
(contributed by the diisocyanate) and polyether groups. In other
words, the structure of the polymer block may be described by
repeating--[urethane-aliphatic-urethane-polyether]--units. The
polyether segments may optionally be selected from oxyethylene,
oxypropylene, oxytrimethylene and oxytetramethylene, and in one
embodiment the polymer chain contains more than one of these
polyether segments, for example, the polymer contains oxyethylene,
oxypropylene and oxytetramethylene groups, where optionally the
oxyethylene and oxypropylene are arranged in a block copolymer
arrangement (e.g., oxyethylene block-oxypropylene block-oxyethylene
block). The polymer block may also be referred to as a polyether
polyurethane, and the polymer itself may be referred to as a poly
ether urethane urea.
[0056] When the composition includes a polyisocyanate as a
poly.DELTA. compound, e.g., as poly.DELTA.2, the composition will
also include a compound that is reactive with a polyisocyanate,
i.e., a poly.DELTA.1 compound such as a polyhydric compound, where
reaction of a polyisocyanate and a polyhydric compound create
urethane groups. Another example of an isocyanate reactive group is
an amine group, so that when a composition contains a
polyisocyanate as poly.DELTA.2, the composition may also include a
polyamine compound as poly.DELTA.1, where reaction of a
polyisocyanate and a polyamine creates urea groups.
[0057] In one aspect, the poly.DELTA. compound is a polyepoxide.
Exemplary polyepoxides include, without limitation, a diepoxide, a
triepoxide and a tetraepoxide. In one aspect poly.DELTA.2 is a
diepoxide. Exemplary polyepoxides include diepoxybutane (also known
as butane diepoxide, butadiene diepoxide, or
1,2:3,4-diepoxybutane); 1,2,7,8-diepoxyoctane; 1,4-butanediol
diglycidyl ether; polyglycerol polyglycidyl ether; ethylene glycol
diglycidyl ether; polyethylene glycol diglycidyl ether with
molecular weight of about 500 to about 6,000; and polypropylene
glycol diglycidyl ether with molecular weight of about 500 to about
6,000.
[0058] The present disclosure provides poly.DELTA. compounds
wherein .DELTA. is hydroxyl. Such compounds may be converted to
poly.DELTA. compounds wherein .DELTA. is epoxy to provide
polyepoxide compounds of the present disclosure. For instance, a
polyhydroxyl compound may be reacted with an excess number of
equivalents of epichlorohydrin, followed by treatment with base
such as sodium hydroxide, to convert the hydroxyl groups to epoxy
groups.
[0059] In an aspect, .DELTA.1 is a nucleophilic group. In one
embodiment, poly.DELTA.1 has multiple hydroxyl (--OH) groups. In
one embodiment, poly.DELTA.1 has multiple amine groups
(--NH.sub.2). In an embodiment, poly.DELTA.1 is not reactive with
itself. In an embodiment, the only reactive groups present on
poly.DELTA.1 are the .DELTA.1 groups, and all of the .DELTA.1
groups are the same, e.g., they are all hydroxyl groups. In an
embodiment, the poly.DELTA.1 has two .DELTA.1 groups. In an
embodiment, the poly.DELTA.1 has three .DELTA.1 groups. In an
embodiment, the poly.DELTA.1 has four .DELTA.1 groups. In an
embodiment, the poly.DELTA.1 has more than four .DELTA.1 groups.
All other factors being equal, the more .DELTA.1 groups present as
part of poly.DELTA.1, the more crosslinking will occur from a
composition comprising poly.DELTA.1.
[0060] In one aspect, .DELTA.2 is an electrophilic group. In one
embodiment, poly.DELTA.2 has multiple epoxide (--CH(O)CH--) groups.
In one embodiment, poly.DELTA.2 has multiple isocyanate
(--N.dbd.C.dbd.O) groups. In an embodiment, poly.DELTA.2 is not
reactive with itself. In an embodiment, the only reactive groups
present on poly.DELTA.2 are the .DELTA.2 groups, and all of the
.DELTA.2 groups are the same, e.g., they are all isocyanate groups.
In an embodiment, the poly.DELTA.2 has two .DELTA.2 groups. In an
embodiment, the poly.DELTA.2 has three .DELTA.2 groups. In an
embodiment, the poly.DELTA.2 has four .DELTA.2 groups. In an
embodiment, the poly.DELTA.2 has more than four .DELTA.2 groups.
All other factors being equal, the more .DELTA.2 groups present as
part of poly.DELTA.2, the more crosslinking will occur from a
composition comprising poly.DELTA.2.
[0061] In one aspect, poly.DELTA.1 is a polyhydroxyl compound while
poly.DELTA.2 is a polyepoxide.
[0062] In one aspect, poly.DELTA.1 is a polyhydroxyl compound while
poly.DELTA.2 is a polyisocyanate.
[0063] In one aspect, poly.DELTA.1 is a polyamine compound while
poly.DELTA.2 is a polyepoxide.
[0064] In one aspect, poly.DELTA.1 is a polyamine compound while
poly.DELTA.2 is a polyisocyanate.
[0065] In one aspect, poly.DELTA.1 is a polythiol compound while
poly.DELTA.2 is a polyepoxide.
[0066] In one aspect, poly.DELTA.1 is a polythiol compound while
poly.DELTA.2 is a polyisocyanate.
[0067] In one aspect, a composition of the present disclosure
includes a photoinitiator.
Polyhv Compounds
[0068] Polyhv compounds of the present disclosure contain a
plurality of photopolymerizable groups, hv. Exemplary
photopolymerizable groups are ethylenically unsaturated groups, and
an exemplary polyhv compound having ethylenically unsaturated
groups may be denoted as polyEU. Another exemplary
photopolymerizable group is a thiol group, and an exemplary polyhv
compound having thiol groups may be denoted as polySH.
[0069] In one aspect, the present disclosure provides multi-arm
compounds as described herein, wherein an arm terminates in a hv
group, and that hv group is photopolymerizable. In one embodiment,
exemplary hv groups may contain a thiol group which is
photopolymerizable. In one embodiment, exemplary hv groups may
contain a carbon-carbon double bond which is photopolymerizable,
e.g., the arm may comprise a vinyl group such as present in an
acrylate or methyacrylate group, each having a photopolymerizable
carbon-carbon double bond.
[0070] The hv group containing a photopolymerizable component,
e.g., a photopolymerizable thiol or carbon-carbon double bond, may
be introduced into a multi-arm compound as described herein by
reaction of the terminal hydroxyl group with a suitable reagent.
Methods to convert a hydroxyl group to thiol-containing group or a
carbon-carbon double bond containing group are generally known and
may be utilized to prepare compounds of the present disclosure,
where examples are provided herein.
[0071] While the hv group will contain a photoreactive group, and
in particular a photoreactive group that allows for polymerization
of the hv-containing macromer, the hv group may also contain
additional atoms which influence the photoreactivity of the
photoreactive group, e.g., a carbonyl group adjacent to the
carbon-carbon double bond as illustrated herein, and/or which were
used to introduce the photoreactive group to the macromer, e.g., a
succinate ester may be used to introduce a thiol group, as
illustrated herein.
[0072] For example, to convert a hydroxyl group to a hv group
containing a photopolymerizable carbon-carbon double bond (polyEU),
a multi-arm compound having a terminal hydroxyl group as described
herein may be reacted with a reactive acrylate, methacrylate, or
norbornenyl compound, such as methacrylic anhydride, acrylic
anhydride, methyl-5-norbornene-2,3-dicarboxylic anhydride,
5-norbornene-2,3-dicarboxylic anhydride, methacryloyl chloride, or
acryloyl chloride.
[0073] For example, to convert a hydroxyl group to a hv group
containing a photopolymerizable thiol group (polySH), a multi-arm
compound having a terminal hydroxyl group as disclosed herein may
undergo an esterification reaction. One method for esterification
is to add stoichiometric amounts of macromer and a mercapto
carboxyl acid compound in the presence of a carbodiimide (e.g.,
N,N'-dicyclohexylcarbodiimide) and a catalyst (e.g.,
dimethylaminopyridine). Exemplary mercapto carboxyl acids include,
but are not limited to, the following compounds:
3-mercaptopropionic acid, thiolactic acid, thioglycolic acid,
mercaptobutyric acid, mercaptohexanoic acid, mercaptobenzoic acid,
mercaptoundecanoic acid, mercaptooctanoic acid, and n-acetyl
cysteine. For example, a multi-arm compound having a terminal
hydroxyl group as disclosed herein may be reacted with thiolactic
acid, in which case the resulting Q group has the formula
--C(.dbd.O)--CH.sub.2--SH attached to the terminal oxygen of the
multi-arm compound.
[0074] Another exemplary method of forming thiol functionalized
macromer (polySH) is to first modify a corresponding hydroxyl
terminated macromer to form terminal carboxylic acid groups. One
example of this is to react the hydroxyl terminated macromer with a
succinic anhydride. With terminal carboxylic acid groups, the
macromer can be reacted with mercapto alcohols by an esterification
reaction or with mercapto amines to form amide bonds. Some examples
of mercapto alcohols include, but are not limited to, the
following: mercapto propanol, mercaptohexanol, mercaptooctanol, and
mercapto undecanol. Some examples of mercapto amines include, but
are not limited to, the following: cysteine, glutathione,
6-amino-1-hexanethiol hydrochloride, 8-amino-1-octanethiol
hydrochloride, and 16-amino-1-hexadecanethiol hydrochloride. For
example, a multi-arm compound having a terminal hydroxyl group as
disclosed herein may be reacted with succinic anhydride to form an
intermediate which is then reacted with cysteine to introduce a
terminal thiol group, in which case the polySH compound includes a
portion having the formula
--C(.dbd.O)CH.sub.2CH.sub.2C(.dbd.O)NH--C(COOH)--CH.sub.2SH
attached to the terminal oxygen of the multi-arm compound.
[0075] Yet another method for forming thiol functionalized macromer
polySH is to react a macromer having terminal hydroxyl groups with
a lactone monomer having pendant thiol groups. This would occur in
a third step ring opening polymerization.
[0076] In one aspect, the polySH compound is a macromer known as a
thiomer. In some aspects, the thiol compound is a multi-arm
poly(ethylene glycol) (PEG) comprising at least two free thiol
groups or a multi-arm poly(ethylene oxide) comprising at least two
free thiol groups. Exemplary thiomers include, without limitation,
4arm-PEG2K-SH, 4arm-PEGSK-SH, 4arm-PEG10K-SH, 4arm-PEG20K-SH, 4-arm
poly(ethylene oxide) thiol-terminated, 8arm-PEG10K-SH (hexaglyerol
core), 8arm-PEG10K-SH (tripentaerythritol core), 8arm-PEG20K-SH
(hexaglyerol core), 8arm-PEG20K-SH (tripentaerythritol core), and
8-arm poly(ethylene oxide) thiol-terminated. These thiomers are
available from Millipore Sigma (formerly Sigma Aldrich).
[0077] In one aspect, polySH is not a macromer, but is instead a
small molecule having a molecular weight of less than 1000 daltons.
Optionally, the small molecule polySH may be water soluble.
Examples of such polySH compounds include dithiol compounds,
trithiol compounds, and tetrathiol compounds. Exemplary polySH
compounds include, without limitation, dithiothreitol (DTT);
1,2-ethanedithiol; 1,3-propanedithiol; 1,4-butanedithiol;
1,5-pentanedithiol; 1,6-hexanedithiol; 1,7-heptanedithiol;
1,8-octanedithiol; 1,9-nonanedithiol; 1,10-decanedithiol;
1,11-undecanedithiol; 1,12-dodecanedithiol; 1,13-tridecanedithiol;
1,14-tetradecanedithiol; 1,16-hexadecanedithiol; dithiolbutylamine
(DTBA); tetra(ethylene glycol) dithiol; hexa(ethylene glycol)
dithiol; 2-mercaptoethyl ether; 2,2'-thiodiethanethiol;
2,2'-(ethylenedioxy)diethanethiol; propane-1,2,3-trithiol;
trimethylolpropane tris(2-mercaptoacetate); trimethylolpropane
tris(3-mercaptoacetate); pentaerythrityl tetrathiol;
pentaerythritol tetrakis(3-mercaptopropionate);
1,2-dithiane-4,5-diol; lipoic acid (alpha lipoic acid and beta
lipoic acid); 3H-1,2-dithiole; 3-propyl-1,2-dithiolane;
3-acetyl-1,2-dithiolane; 1,2-dithiolane-4-carboxylic acid;
1,2-dithiolane-3-pentanol; 1,2,4-dithiazolidine; 1,2-dithiane;
1,2-dithiepane; 1,2-dithiocane; and 1,2-dithiocane-3,8-diol.
Photoinitiators
[0078] A photoinitiator refers to an organic (carbon-containing)
molecule that creates reactive species when exposed to radiation.
In one embodiment the photoinitiator creates a radical reactive
species, as opposed to, e.g., a cationic or anionic reactive
species. Photoinitiators are well known components for the
preparation of photopolymers which find use in photo-curable
coatings, adhesives and dental restoratives.
[0079] Type I photoinitiators are unimolecular free-radical
generators; that is upon the absorption of UV-visible light a
specific bond within the initiator's structure undergoes homolytic
cleavage to produce free radicals. Homolytic cleavage is a bonding
pair of electron's even scission into to free radical products.
Examples of homolytic cleavage in several common classes of Type I
photoinitiators: benzoin ethers, benzyl ketals,
.alpha.-dialkoxy-aceto-phenones, .alpha.-hydroxy-alkyl-phenones,
and acyl phosphine oxides. Exemplary commercially available Type I
photoinitiators, available from, for example, BASF, BASF SE,
Ludwigshafen, Germany, include, but are not limited to,
Irgacure.TM. 369, Irgacure.TM. 379, Irgacure.TM. 907, Darocur.TM.
1173, Irgacure.TM. 184, Irgacure.TM. 2959, Darocur.TM. 4265,
Irgacure.TM. 2022, Irgacure.TM. 500, Irgacure.TM. 819, Irgacure.TM.
819-DW, Irgacure.TM. 2100, Lucirin.TM. TPO, Lucirin.TM. TPO-L,
Irgacure.TM. 651, Darocur.TM. BP, Irgacure.TM. 250, Irgacure.TM.
270, Irgacure.TM. 290, Irgacure.TM. 784, Darocur.TM. MBF, Ivocerin,
hand Irgacure.TM. 754, lithium
phenyl-2,4,6-trimethylbenzoylphosphinate, magnesium
phenyl-2,4,6-trimethylbenzoylphosphinates, and sodium
phenyl-2,4,6-trimethylbenzoylphosphinates
[0080] Type II photoinitiators require a co-initiator, usually an
alcohol or amine, functional groups that can readily have hydrogens
abstracted, in addition to the photoinitiator. The absorption of
UV-visible light by a Type-II photoinitiator causes an excited
electron state in the photoinitiator that will abstract a hydrogen
from the co-initiator, and in the process, splitting a bonding pair
of electrons. Benzophenone, thioxanthones, and benzophenone-type
photoinitiators are the most common Type II photoinitiators.
Further examples of some common Type II photoinitiators include
riboflavin, Eosin Y, fluorescein, rose Bengal, and camphorquinone.
Once the free-radicals are generated, the polymerization mechanism
is similar to any free-radical polymerization process.
[0081] Optionally, a composition of the present disclosure includes
at least one photoinitiator component, typically in a total
concentration of less than 2 wt %, or less than 1.5 wt %, or less
than 1 wt %, or less than 0.9 wt %, or less than 0.8 wt %, or less
than 0.7 wt %, or less than 0.6 wt %, or less than 0.5 wt %, or
less than 0.25 wt %, or less than 0.1 wt % based on the total
weight of photoreactive compounds.
Optional Ingredients
[0082] A composition of the present disclosure may contain an
optional ingredient, such as one, two, or a plurality of optional
ingredients. Exemplary optional ingredients are described
herein.
[0083] In one aspect, a colorant, such as a dye, may be included in
the compositions of the present disclosure, and the corresponding
cured product. The addition of a dye can achieve the purpose of
tailoring a formulation to a desired color. In one aspect, the dye
is a non-toxic, biocompatible dye. Such dyes may be present at
concentrations of about 2 wt. % or less based on the total weight
of the composition. See, for example, PCT/US2016/059910, which is
incorporated herein for its teaching of the use of dyes. In one
embodiment, the dye is present at a concentration of about 0.1-0.3
wt %, which is the FDA-recommended amount for the dye D&C
Violet when present in an absorbable suture products. In one
embodiment, the dye is present at a concentration of less than 0.5
wt %. In some cases, the dye may impart toxicity to the
photopolymerized composition of the present disclosure, if that dye
is present at too high of a concentration.
[0084] In one aspect, a light reflective material component
comprising a light reflective material may be suspended in the
composition, where the light reflective material component
modulates the light dose of the composition when compared to the
light dose of the composition without the light reflective
material. Suitable light reflective materials for optional
inclusion in the compositions of the present disclosure are
provided in U.S. Provisional Patent Application Ser. No. 62/653584,
entitled Methods and Compositions for Photopolymerizable Additive
Manufacturing, filed Apr. 6, 2018 by Applicant Poly-Med, Inc.,
having inventors M. A. Vaughn and P. Saini, which is incorporated
herein in its entirety.
[0085] A suitable light reflective material comprises light
reflective material that reflects UV light, visible light or both.
For example, a light reflective material may be or comprise a
particulate light reflective material sized less than 500 microns,
or sized less than 30 microns, or sized less than 5 microns, or
sized less than 1 micron. A light reflective material may be
shaped, for example, as a sphere, cube, cone, cuboid, cylinder,
pyramid, prism, polyhedron, or irregular shape, or mixtures
thereof. In one aspect, a light reflective material has a smooth
surface.
[0086] In an aspect, a light reflective material may comprise an
inorganic solid including but not limited to titanium dioxide, zinc
oxide, barium sulfate, tricalcium phosphate, dicalcium phosphate,
monocalcium phosphate, dicalcium diphosphate, calcium triphosphate,
hydroxyapatite, apatite, and tetracalcium phosphate. In an aspect,
the light reflective material may comprise organic compounds
comprising aliphatic polymers and copolymers including but not
limited to polyesters, polyurethanes, polyethers, polyanhydrides,
polyamides, polycarbonates, polyketones, polyethylene,
polypropylene, polyvinyl alcohol, polytetrafluoroethylene,
polyvinyl chloride, polyimides, and polyhydroxy alkanoates or
combinations thereof. In an aspect, the light reflective material
may comprise organic compounds comprising aromatic polymers and
copolymers including but not limited to polyesters, polyurethanes,
polyethers, polyanhydrides, polyketones, polyamides,
polycarbonates, and polyimides or combinations. In an aspect, the
light reflective material may comprise organic compounds comprising
naturally derived polymers and derivatives including but not
limited to cyclodextrins, starch, hyaluronic acid, deacetylated
hyaluronic acid, chitosan, trehalose, cellobiose, maltotriose,
maltohexaose, chitohexaose, agarose, chitin 50, amylose, glucans,
heparin, xylan, pectin, galactan, glycosaminoglycans, dextran,
aminated dextran, cellulose, hydroxyalkylcelluloses,
carboxyalkylcelluloses, fucoidan, chondroitin sulfate, sulfate
polysaccharides, mucopolysaccharides, gelatin, zein, collagen,
alginic acid, agar, carrageean, guar gum, gum arabic, gum ghatti,
gum karaya, gum konjak, gum tamarind, gum tara, gum tragacanth,
locust bean gum, pectins, and xanthan gum. In an aspect, the light
reflective material may comprise crystalline organic compounds
comprising crystalline aliphatic and aromatic polymers. In an
aspect, the light reflective material may comprise crystalline
organic compounds comprising crystalline naturally derived polymers
and derivatives. In an aspect, a light reflective material may
comprise crystalline amino acids and their derivatives. In an
aspect, a light reflective material may comprise crystalline fatty
acids and their derivatives, including but not limited to palmitic
acid, ascorbyl palmitate, lauric acid, glycerol monolaurate,
myristic aid, and capric acid. In an aspect, a light reflective
material may comprise crystalline peptides.
[0087] In one aspect, the compositions of the present disclosure
may contain a diluent. The diluent may be reactive or non-reactive.
A reactive diluent undergoes a photopolymerization reaction when
exposed to light (UV or visible light) while a non-reactive diluent
is inert to such light exposure. An exemplary reactive diluent is
PEG-diacrylate (PEG-DA or PEGDA).
[0088] In one aspect, a bioactive agent may be included in a
composition of the present disclosure, and the corresponding cured
product. Examples of such bioactive agents include, but are not
limited to, fibrosis-inducing agents, antifungal agents,
antibacterial agents and antibiotics, anti-inflammatory agents,
anti-scarring agents, immunosuppressive agents, immunostimulatory
agents, antiseptics, anesthetics, antioxidants, cell/tissue growth
promoting factors, anti-neoplastic, anticancer agents and agents
that support ECM integration.
[0089] Examples of fibrosis-inducing agents include, but are not
limited to talcum powder, metallic beryllium and oxides thereof,
copper, silk, silica, crystalline silicates, talc, quartz dust, and
ethanol; a component of extracellular matrix selected from
fibronectin, collagen, fibrin, or fibrinogen; a polymer selected
from the group consisting of polylysine,
poly(ethylene-co-vinylacetate), chitosan, N-carboxybutylchitosan,
and RGD proteins; vinyl chloride or a polymer of vinyl chloride; an
adhesive selected from the group consisting of cyanoacrylates and
crosslinked poly(ethylene glycol)-methylated collagen; an
inflammatory cytokine (e.g., TGF.beta., PDGF, VEGF, bFGF,
TNF.alpha., NGF, GM-CSF, IGF-a, IL-1, IL-1.beta., IL-8, IL-6, and
growth hormone); connective tissue growth factor (CTGF); a bone
morphogenic protein (BMP) (e.g., BMP-2, BMP-3, BMP-4, BMP-5, BMP-6,
or BMP-7); leptin, and bleomycin or an analogue or derivative
thereof. Optionally, the device may additionally comprise a
proliferative agent that stimulates cellular proliferation.
Examples of proliferative agents include: dexamethasone,
isotretinoin (13-cis retinoic acid), 17-.beta.-estradiol,
estradiol, 1.alpha.,25-dihydroxyvitamin D.sub.3,
diethylstibesterol, cyclosporine A, L-NAME, all-trans retinoic acid
(ATRA), and analogues and derivatives thereof. See, e.g., US
2006/0240063, which is incorporated by reference in its entirety.
Examples of antifungal agents include, but are not limited to,
polyene antifungals, azole antifungal drugs, and Echinocandins.
Examples of antibacterial agents and antibiotics include, but are
not limited to, erythromycin, penicillins, cephalosporins,
doxycycline, gentamicin, vancomycin, tobramycin, clindamycin, and
mitomycin. Examples of anti-inflammatory agents include, but are
not limited to, non-steriodal anti-inflammatory drugs such as
ketorolac, naproxen, diclofenac sodium and fluribiprofen. Examples
of anti-scarring agents include, but are not limited to cell-cycle
inhibitors such as a taxane, immunomodulatory agents such as
serolimus or biolimus (see, e.g., US 2005/0149158, which is
incorporated by reference in its entirety). Examples of
immunosuppressive agents include, but are not limited to,
glucocorticoids, alkylating agents, antimetabolites, and drugs
acting on immunophilins such as ciclosporin and tacrolimus.
Examples of immunostimulatory agents include, but are not limited
to, interleukins, interferon, cytokines, toll-like receptor (TLR)
agonists, cytokine receptor agonist, CD40 agonist, Fc receptor
agonist, CpG-containing immunostimulatory nucleic acid, complement
receptor agonist, or an adjuvant. Examples of antiseptics include,
but are not limited to, chlorhexidine and tibezonium iodide.
Examples of anesthetic include, but are not limited to, lidocaine,
mepivacaine, pyrrocaine, bupivacaine, prilocalne, and etidocaine.
Examples of antioxidants include, but are not limited to,
antioxidant vitamins, carotenoids, and flavonoids. Examples of cell
growth promoting factors include, but are not limited to, epidermal
growth factors, human platelet derived TGF-.beta., endothelial cell
growth factors, thymocyte-activating factors, platelet derived
growth factors, fibroblast growth factor, fibronectin or laminin.
Examples of antineoplastic/anti-cancer agents include, but are not
limited to, paclitaxel, carboplatin, miconazole, leflunamide, and
ciprofloxacin. Examples of agents that support ECM integration
include, but are not limited to, gentamicin
[0090] The compositions and corresponding cured articles of the
present disclosure may contain a mixture of bioactive agents in
order to obtain a desired effect. Thus, for example, an
antibacterial and an anti-inflammatory agent may be combined in a
single article to provide combined effectiveness.
[0091] Other optional components of the photopolymerizable
composition are a reactive diluent, a non-reactive diluent, a
solvent, a stabilizer, a thixotropic material, a tracer material
and a conductive material. The stabilizer, when present, may
optionally be selected from the group consisting of tocopherol,
gallic acid, ester of gallic acid, butylated hydroxyanisole and
combinations thereof. By addition of the appropriate component, a
photopolymerized composition (e.g., an article, or piece) of the
present disclosure may be colored due to the presence of a dye, or
may have any other desired attribute such as having at least a
portion of the article that is, but is not limited to, fluorescent,
radioactive, reflective, flexible, stiff, pliable, breakable, or a
combination thereof.
[0092] In one aspect, a composition of the present disclosure
comprising polyhv or a poly.DELTA. is polymerized in the absence of
water, e.g., water is not a diluent in the composition.
Specifically, in one aspect, the composition which forms a single
or double network, or the single or double network itself, has a
moisture (water) content of less than 2500 ppm, or less than 1000
ppm, or less than 500 ppm of water. In one aspect, the photocurable
composition of the present disclosure that provides a single
network, is an anhydrous composition in that it does not contain
more than adventitious water. In one aspect, the photocurable and
thermocurable composition of the present disclosure that provides a
double network, is an anhydrous composition in that it does not
contain more than adventitious water. An anhydrous composition of
the present disclosure is not, for example, a hydrogel.
[0093] One challenge to creating formulations with both
ethylenically unsaturated compounds and thiol compounds is their
tendency to polymerize upon mixing at room temperature prior to the
application of stimuli such as light or heat. Therefore, this can
greatly limit the application of these formulations as the working
time where their viscosity is constant can be short. Specifically
for additive manufacturing using vat photopolymerization, these
formulations have issues with a changing viscosity over time. In
the present disclosure, biocompatible stabilizers are outlined than
may give stability for at least 24 hrs, which should be useful in
addressing work time for vat photopolymerization. In an aspect, one
or more stabilizer compounds may be included in a composition of
the present disclosure, and the corresponding cured product.
[0094] In one embodiment, the composition of the poly(SH) or
poly(EU) includes a stabilizer. The stabilizer may be included in
the poly(SH), poly(EU) or a combination thereof. In one aspect, the
stabilizer is an add-in component. In another aspect, the
stabilizer is included as in add-in dissolved in a monomer,
diluent, solvent, or combination thereof. In one aspect, the
stabilizer is an anti-oxidant. In another aspect, the stabilizer is
an acid. Preferably, the acid stabilizer has a pKa between 1 and 5.
In another aspect, the stabilizer is selected from a phosphite and
phosphonate compound. In another aspect, the stabilizer may include
an anti-oxidant, acid, phosphite, phosphonate, and combinations
thereof. Examples of anti-oxidant stabilizers include but are not
limited to hydroquinone, mono-tertiary-butyl hydroquinone (MTBHQ),
2,5-di-tertiary-butyl-hydroquinone (DTBHQ), p-methoxyphenol,
butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA),
2,6-di-tert-butyl-p-cresol,
2,2-methylene-bis-(4-methyl-6-tert-butyl)phenol (MBETBP),
p-tert-butyl catechol,
1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)be-
nzene (Anox 330.TM., Irganox 1330.TM.), hydroxytoluene butyl ether,
tocopherol (all isomers), esters of tocopherol, pyrogallol, lauryl
gallate, esters of gallic acid, or combinations thereof. Examples
of acid stabilizers may include but are not limited to phosphonic
acid, phosphorous acid, oxalic acid, succinic acid, gallic acid,
ascorbic acid, phenyl phosphonic acid, or combinations thereof.
Examples of phosphite and phosphonate stabilizers may include but
are not limited to triphenyl phosphite, diphenyl isodecyl
phosphite, diphenyl isooctylphosphite, or combinations thereof. In
one aspect, the stabilizer is soluble in the poly(SH) and/or
poly(EU) formulation. Preferably, the stabilizer is added in
concentrations that achieve biocompatibility. Preferably, a
biocompatible stabilizer comprises of tocopherol, gallic acid,
ester of gallic acid, butylated hydroxyanisole, or combinations
thereof. In one aspect, the stabilizer concentration is less than
100,000 ppm, more preferably less than 50,000 ppm, more preferably
less than 15,000 ppm, more preferably less than 15,000 ppm, more
preferably less than 5,000 ppm, more preferably less than 3,000 ppm
and even more preferably less than 1,500 ppm.
Photopolymerization Reaction Conditions
[0095] The photopolymerizable compounds polyhv (including polyEU
and polySH) as described herein having photopolymerizable groups,
and the compositions of the present disclosure that include such
compounds, will undergo polymerization upon sufficient exposure to
light of appropriate wavelength, optionally in the presence of a
photoinitiator, and further optionally in the presence of other
components. The choice of appropriate wavelength, time of exposure,
and curing agent identity and amount, is selected in view of
identity and quantity of the hv group in the compounds and
compositions, as is conventional in the art. Photopolymerization is
sometimes referred to radiation curing, in which case the
photoinitiator may be referred to as the curing agent.
[0096] In an aspect, a photoinitiator component in a composition of
the present disclosure comprises a Type I photoinitiator. In an
aspect, a photoinitiator component in a composition of the present
disclosure comprise a Type II photoinitiator. In an aspect, a
combination of a Type I and a Type II photoinitiator is present in
photopolymerization composition of the present disclosure.
[0097] In any of the photopolymerizable compounds and composition
as described herein, hv may be a carbon-carbon double bond, e.g., a
vinyl group. Exemplary vinyl groups are an acrylate group and a
methacrylate group. Another exemplary carbon-carbon double bond is
present in norbornenyl. In additional aspects, the
photopolymerizable compound having one or more hv groups undergoes
photopolymerization when exposed to light having a wavelength of
300-450 nm, or 300-425 nm, or 350-450 nm, or 350-425 nm, or 365-405
nm, or 450-550 nm, as examples. In one embodiment, the polyhv
compound and related composition undergoes photopolymerization when
exposed to UV radiation.
[0098] In any of the photopolymerizable compounds and composition
as described herein, hv may be a thiol group. In additional
aspects, the photopolymerizable compound polySH having one or more
SH groups undergoes photopolymerization when exposed to actinic
radiation, for example, light having a wavelength of 300-450 nm, or
300-425 nm, or 350-450 nm, or 350-425 nm, or 365-405 nm, or 450-550
nm, as examples. In one embodiment, the polySH compound and related
compositions undergoes photopolymerization when exposed to UV
radiation. In one embodiment, the polySH compound and related
compositions undergoes photopolymerization when exposed to visible
radiation.
[0099] In one aspect, the present disclosure provides a composition
comprising a compound having multiple photopolymerizable thiol
groups and a compound having multiple photopolymerizable
ethylenically unsaturated groups. The thiol groups and the
ethylenically unsaturated groups are reactive with one another in
the presence of a photoinitiator and upon exposure to suitable
actinic radiation. The actinic radiation may alternatively be
referred to as light, and the compositions may be referred to as
light-reactive. This reaction may be referred to as
photopolymerization or curing.
[0100] Suitable photoinitiators have been described elsewhere
herein. In order for the photoinitiator to successfully cure the
light-reactive composition, it is necessary that the absorption
bands of the photoinitiator overlap with the emission spectrum of
the light source used for curing. Optionally, photopolymerizable
compositions disclosed herein comprise at least one photoinitiator
that absorbs a wavelength of light in a range between about 10 nm
to about 770 nm, or between about 100 nm to about 770 nm, or
between about 200 nm to about 770 nm, and all wavelengths
thereinbetween the stated range. In an aspect, a photoinitiator
component comprises a photoinitiator that absorbs a wavelength of
light of greater than or equal to 300 nm, up to about 770 nm. In an
aspect, a photoinitiator component comprises a photoinitiator that
absorbs a wavelength of light of greater than or equal to 365 nm,
up to about 770 nm. In an aspect, a photoinitiator component
comprises a photoinitiator that absorbs a wavelength of light of
greater than or equal to 375 nm, up to about 770 nm. In an aspect,
a photoinitiator component comprises a photoinitiator that absorbs
a wavelength of light of greater than or equal to 400 nm, up to
about 770 nm. The photopolymerization conditions of the present
disclosure will include exposure of the light-reactive composition
to a spectrum of wavelengths from an emission source that can and
does provide the desired spectrum of wavelengths suitable for
photopolymerization of the composition. Choice of wavelength will
depend on the identity of the photoinitiator. Suppliers of
commercially available photoinitiators indicate the appropriate
wavelength for that particular photoinitiator.
[0101] Free radical generating photoinitiators may be used to
achieve polymer curing according to the present disclosure. These
photoinitiators may be used to cure a mixture of thiol-containing
compounds and ethylenically unsaturated compounds such as disclosed
herein. There are two types of free-radical generating
photoinitiators, designated as Type I and Type II photoinitiators,
which may be used according to the present disclosure, and which
are described elsewhere herein.
[0102] Photopolymerizable compositions disclosed herein are made by
combining the desired components, typically with stirring to
achieve a homogeneous composition. The desired components may be
mixed using a homogenizer. For example, a composition as disclosed
herein may be prepared by combining ingredients such as those
identified above. Optionally, the desired components may include a
dispersion agent to aid in suspension. The listed components may
optionally be heated prior to mixing. The listed components may
optionally be placed under vacuum to remove gas bubbles.
[0103] In an aspect, the present disclosure provides a composition
comprising a first organic compound (polySH) having multiple thiol
groups (SH), a second organic compound (polyEU) having multiple
ethylenically unsaturated groups (EU), and a photoinitiator. The
relative amounts of polySH and polyEU in the composition may be
described in terms of an SH to EU equivalents ratio of X:Y, where X
represents the equivalents of SH, Y represents the equivalents of
EU, and the total of X and Y is 100. In one aspect, X ranges from
25-75 and Y ranges from 75-25 and the sum of X and Y is 100. In one
aspect, X ranges from 30 to 70 and Y ranges from 70 to 30 and the
sum of X and Y is 100. In one aspect, X ranges from 40 to 60 and Y
ranges from 60 to 40 and the sum of X and Y is 100. In one aspect,
X ranges from 45 to 55 and Y ranges from 55 to 45 and the sum of X
and Y is 100. In one aspect, the equivalents of X are approximately
equal to the equivalents of Y.
Thermal Reaction Conditions
[0104] As discussed herein, compositions of the present disclosure
may contain poly.DELTA.1 and poly.DELTA.2, which are reactive with
one another upon exposure to elevated temperature. The specific
elevated temperature, and the time necessary to achieve reaction
between poly.DELTA.1 and poly.DELTA.2 at that specific elevated
temperature, will depend on the specific identities of .DELTA.1 and
.DELTA.2. For many reactions between a nucleophile and an
electrophile, a temperature of about 100.degree. C. for 30 minutes
to 5 hours is sufficient.
[0105] In one aspect, the present disclosure provides a composition
comprising a first organic compound (polyhv) having multiple
photopolymerizable groups (hv), a photoinitiator, a second organic
compound (poly.DELTA.1) having multiple reactive groups .DELTA.1,
and a third organic compound (poly.DELTA.2) having multiple
reactive groups .DELTA.2, where .DELTA.1 reacts with .DELTA.2 upon
contact and exposure to a temperature of greater than about
50.degree.C. The relative amounts of poly.DELTA.1 and poly.DELTA.2
in the composition may be described in terms of a .DELTA.1 to
.DELTA.2 equivalents ratio of X:Y, where X represents the
equivalents of .DELTA.1, Y represents the equivalents of .DELTA.2,
and the total of X and Y is 100. In one aspect, X ranges from 25-75
and Y ranges from 75-25 and the sum of X and Y is 100. In one
aspect, X ranges from 30 to 70 and Y ranges from 70 to 30 and the
sum of X and Y is 100. In one aspect, X ranges from 40 to 60 and Y
ranges from 60 to 40 and the sum of X and Y is 100. In one aspect,
X ranges from 45 to 55 and Y ranges from 55 to 45 and the sum of X
and Y is 100. In one aspect, the equivalents of X are approximately
equal to the equivalents of Y.
[0106] In order to expose the composition to elevated temperature,
the composition may be placed into an oven. Alternatively, a heat
lamp may be directed to the composition, where the head lamp
provides infrared radiation that will heat the composition.
Additive Manufacturing
[0107] Methods disclosed herein include methods for using curable
compositions to make articles, particularly non-toxic and
biodegradable articles. For example, a composition disclosed herein
may be used as a curable ink or resin in 3-D printing methods. For
example, a curable composition as disclosed herein may be used as
curable ink or resin in vat polymerization process for 3-D
printing. Exemplary vat polymerization processes include
stereolithography (SLA, also known as SL), digital light processing
(DLP.TM.; Texas Instrument), daylight polymer printing (DPP),
Carbon digital light synthesis (Carbon DLS.TM.; Carbon, Inc.) and
continuous liquid interface production (CLIP.TM.; Carbon, Inc.).
Other suitable methods of additive manufacturing an article using
the curable compositions of the present disclosure include binder
jetting, material jetting, material extrusion, computed axial
lithography, and 2 photon polymerization printing. The present
disclosure provides for the use of the curable compositions as
disclosed herein in any of the mentioned 3D printing processes.
[0108] Thus, in one aspect, the present disclosure provides a
method for vat polymerization, e.g., SLA printing an article, which
comprises exposing for a time with light, a photopolymerizable
composition comprising at least one photopolymerizable composition
as disclosed herein including at least one photoinitiator component
that is typically in a total concentration of less than 1.0 wt %.
Any of the photopolymerizable compositions disclosed herein may be
used in the method for SLA printing an article. For example, the
composition may contain polyhv in addition to poly.DELTA.1 and
poly.DELTA.2. As another example, the composition may contain
polyEU and polySH. Optionally, the photopolymerizable composition
may comprise a reactive diluent or a nonreactive diluent. A
reactive diluent is a diluent that participates in the
polymerization reaction, for example, the reactive diluent is
polymerized with, for example, a macromer. A photopolymerizable
composition of the present disclosure may comprise a stabilizer,
for example, a free radical stabilizer.
[0109] A method for printing an article by SLA according to the
present disclosure may comprise a secondary curing step comprising
curing the printed article with thermal energy. A secondary curing
step involves exposing at least a portion of the printed article to
thermal energy so that at least a portion of the printed article
undergoes a second, heat-induced polymerization reaction. For
example, some or all of an article may be exposed to a temperature
of about 100.degree. C. for about 30 minutes to 5 hours. A
secondary curing step may be used to change the properties of the
printed article.
[0110] A method for printing an article by SLA according to the
present disclosure may comprise pre- and/or post-treatments of a
printed article. For example, the printed article may be rinsed
after printing, before or after a thermal curing step.
[0111] A printed article is the article resulting after a 3-D
printing period is completed. The printed article may be a
structure or a portion of a structure. The printed article may be
in the form of a film, such as a coating that is printed onto a
surface. As used herein, the term printing is used to mean
contacting a polymeric composition with a surface and causing the
polymeric composition to further polymerize. Printing may involve
contacting a polymeric composition with a surface that is then
exposed to UV and/or visible light so that the polymeric
composition undergoes further polymerization. The surface that the
polymeric composition contacts may be any surface including a
polymerized layer of the polymeric composition. As mentioned
previously, the printed article may undergo a second curing step,
by being exposed to elevated temperature.
[0112] A printed article may or may not contain residual amounts of
components of a curable composition. For example, a printed article
may comprise diluent or photopolymerized diluent, or
photoinitiator. In an aspect, a printed article or a curable
composition may have additives. Additives may include thixotropic
materials, colorants, tracer materials or conductive materials. For
example, an additive may be a dye. A printed article may be colored
due to the presence of a dye, or may have any desired attribute
such as having at least a portion of the article that is, but is
not limited to, fluorescent, radioactive, reflective, flexible,
stiff, pliable, breakable, or a combination thereof.
[0113] In a common vat printing process, a build platform is
lowered from the top of the resin vat downwards by the layer
thickness. Actinic radiation is directed into the composition and
this light causing photopolymerization (photocuring) of the
composition. The build platform continue to move downwards and
additional layers are built upon the top of the previous layer.
After completion, the vat may be drained of excess resin and the
printed article collected. This printed article may be subjected to
additional treatment. For example, the printed article may be
washed to remove excess resin. As another example, particularly in
the case where the article contains poly.DELTA.1 and poly.DELTA.2,
the printed article may be exposed to thermal energy to cause
thermal curing to occur.
[0114] A method of forming an article by vat polymerization may
comprise directing actinic radiation to a vat of a
photopolymerizable composition comprising monomers or macromers
that are capable of undergoing polymerization, such as monomers or
macromers that have functional groups capable of undergoing
photopolymerization reactions to form oligomers and/or polymers,
such as the polyhv compounds disclosed herein.
[0115] In one aspect, the vat polymerization, e.g. using SLA, is
printing an article using a photopolymerizable composition, and
directing actinic radiation to the vat of composition at light
wavelength from about 10 nm to about 1 mm. As used herein, UV
radiation has a wavelength of from about 10-400 nm, while visible
radiation has a wavelength of 390-770 nm, and IR radiation has a
wavelength of 770 nm-1 mm. In one aspect, the actinic radiation is
comprised of one or more wavelengths and/or one or more radiations
sources. In an aspect, the photopolymerizable composition may
comprise a light reflective material component that causes
photopolymerization to occur in a shorter exposure time than would
occur without the light reflective material component under the
same polymerization conditions. Optionally, if the curable
composition contains thermally reactive components poly.DELTA.1 and
poly.DELTA.2, a thermal curing process will be performed before,
during, or after the photopolymerization process. Optionally, if
the curable composition contains thermally reactive components
poly.DELTA.1 and poly.DELTA.2, a thermal curing process will be
performed after the photopolymerization process.
[0116] In one aspect, the present disclosure provides a method of
printing an article using vat polymerization, e.g., SLA printing,
in a device suitable for printing by SLA. The method includes
providing a vat containing a curable composition as disclosed
herein comprising at least one photoinitiator that absorbs at a
wavelength of light from about 10 nm to about 770 nm. In an aspect,
a photoinitiator absorbs at a wavelength of light of greater than
or equal to 300 nm. In an aspect, a photoinitiator absorbs at a
wavelength of light of greater than or equal to 365 nm. In an
aspect, a photoinitiator absorbs at a wavelength of light of
greater than or equal to 375 nm. In an aspect, a photoinitiator
absorbs at a wavelength of light of greater than or equal to 400
nm. The photoinitiator in the curable composition is at least one
photoinitiator component that comprises a photoinitiator that is a
Type I, Type II, a cationic photoinitiator or a combination
thereof.
[0117] In one aspect, the present disclosure provides a method of
printing an article by vat polymerization, e.g., using SLA in a
device for printing by SLA, where the method comprises
photopolymerizing or curing a photopolymerizable composition at a
depth of less than 150 microns. In an aspect, a method disclosed
herein comprises photopolymerizing or curing a photopolymerizable
composition at a depth of from about 5 microns to about 50 microns,
and all depths thereinbetween.
[0118] In one aspect, the present disclosure provides a method of
printing an article by vat polymerization, e.g., using SLA in a
device for printing by SLA, where the method comprises
photopolymerizable compositions comprising a light reflective
material component comprising a light reflective material that is
absorbable in physiological conditions. In an aspect, a light
reflective material component comprises a light reflective material
that is biocompatible for biological organisms. In an aspect, a
light reflective material component comprises a light reflective
material that polymerizes with at least one of a photopolymerizable
macromer, a diluent, a light reflective material, or a combination
thereof.
[0119] In one aspect, the present disclosure provides an additive
manufacturing process comprising: (a) providing a vat containing a
first composition as disclosed herein comprising polyEU and polySH;
(b) directing actinic radiation from a light source into the first
composition in the vat, where the actinic radiation is effective to
induce polymerization of components of the composition so as to
form a second composition; (c) forming a solid article comprising
the second composition. The step (c) may be accomplished by
repeatedly directing actinic radiation at the first composition in
the vat, particularly as the build platform is moved. The second
composition will be or comprise a photopolymerization product of
polyEU and polySH.
[0120] In one aspect, the present disclosure provides an additive
manufacturing process comprising: (a) providing a vat containing a
first composition as disclosed herein containing polyhv,
poly.DELTA.1 and poly.DELTA.2; (b) directing actinic radiation from
a light source into the first composition in the vat, where the
actinic radiation is effective to induce polymerization of
photocurable components of the first composition so as to form a
second composition comprising photochemically cured composition;
and (c) applying thermal energy to the second composition
comprising photochemically cured composition so as to form a third
composition comprising photochemically cured composition and
thermally cured composition. The second composition will be or
comprise a photopolymerization product of polyhv. The third
composition will be or comprise a double network of the
photopolymerization product of polyhv in combination and the
thermally induced polymerization product of poly.DELTA.1 and
poly.DELTA.2.
[0121] In one aspect, the present disclosure provides a method of
manufacturing an article by 2 photon polymerization printing,
comprising curing a curable composition as disclosed herein to form
the article. In one aspect, the present disclosure provides a
method of manufacturing an article by computer axial lithography,
comprising curing a curable composition as disclosed herein to form
the article. In one aspect, the present disclosure provides a
method of manufacturing an article by material extrusion comprising
curing a curable composition as disclosed herein to form the
article. In one aspect, the present disclosure provides a method of
manufacturing an article by material jetting, comprising curing a
curable composition as disclosed herein to form the article. In one
aspect, the present disclosure provides a method of manufacturing
an article by binder jetting, comprising curing a curable
composition as disclosed herein to form the article. In one aspect,
the present disclosure provides a method of manufacturing an
article by continuous light interface production (CLIP), comprising
curing a curable composition as disclosed herein to form the
article. In one aspect, the present disclosure provides a method of
manufacturing an article by vat polymerization, comprising curing a
curable composition as disclosed herein to form the article.
Cured Compositions
[0122] The present disclosure comprises an article, additionally
referred to herein as a printed article or a solid article, which
may be made by the methods disclosed herein from the compositions
disclosed herein. In an aspect, an article may be a medical device.
In an aspect, an article may be a portion of a medical device. In
an aspect, an article may be porous. In an aspect, an article may
be biodegradable under physiological conditions. In an aspect, a
biodegradable article may have a degradation time of about three
days to about five years. In an aspect, an article may not be
biodegradable. In an aspect, a portion of an article may be
biodegradable and a second portion may be non-biodegradable or have
a different degradation time from the degradation time of the first
portion or the rest of the article.
[0123] As mentioned elsewhere, in one aspect, the cured composition
does not contain any appreciable amount of water. For example, in
aspects, the cured composition contains less than 2500 ppm water,
or less than 1000 ppm water, or less than 500 ppm water.
[0124] In one aspect, the cured composition will degrade in water
or when exposed to aqueous conditions. Thus, in one aspect, the
cured composition may be biodegradable, which may be particularly
useful when the cured composition is used to form a biodegradable
implantable medical device. In one aspect, the cured composition
degrades under aqueous conditions to form particulate material
rather than, e.g., forming a swollen material, i.e., a material
which has absorbed water and is in a swollen state. For example,
when the cured composition is placed into a degradation media
comprising water at a pH 7.0 to 7.4 phosphate buffer, or in
phosphate buffer saline, the cured composition will undergo
dissolution in the degradation media. Upon dissolution, such that
greater than 50 wt %, or greater than 60 wt %, or greater than 70
wt %, or greater than 80 wt %, or greater than 90 wt % of the total
weight of the cured composition has dissolved in the degradation
media, the undissolved material will have a particular morphology
rather than a swollen morphology.
[0125] In one aspect, the cured compositions of the present
disclosure demonstrate desirably low swelling when placed in
aqueous media. Swelling can be a serious problem when a cured
composition is in prolonged contact with aqueous media. For
example, when a cured composition is a component of, or all of, a
biodegradable implantable medical device, and that device is
implanted in a patient, the device may undergo both degradation
(which is desirable) and swelling (which may be undesirable).
Swelling may be a particular problem towards the end of the implant
degradation, i.e., after most of the implant has degraded. However,
the problem of swelling, particularly late stage swelling as may be
observed after a majority of the implant has degraded (i.e.,
greater than 50% weight loss, or greater than 60% weight loss, or
greater than 70% weight loss, or greater than 80% weight loss, or
greater than 90% weight loss), can be mitigated by use of the
curable compositions of the present disclosure.
[0126] The following are some exemplary embodiments of the present
disclosure. [0127] 1) A composition comprising a first organic
compound (polySH) having multiple thiol groups (SH), a second
organic compound (polyEU) having multiple ethylenically unsaturated
groups (EU), and a photoinitiator. A stabilizer may optionally be
present in the composition, where the stabilizer may optionally be
selected from the group consisting of tocopherol, gallic acid,
ester of gallic acid, butylated hydroxyanisole and combinations
thereof. [0128] 2) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 3-27, wherein the composition has an SH to EU
equivalents ratio of X:Y, where X ranges from 25-75 and Y ranges
from 75-25 and the sum of X and Y is 100. [0129] 3) The composition
of embodiment 1 or any embodiment of embodiment 1 as disclosed
herein, for example embodiment 2, wherein polySH is water soluble.
[0130] 4) The composition of embodiment 1 or any embodiment of
embodiment 1 as disclosed herein, for example embodiments 2 or 3,
wherein polySH is bioabsorbable. [0131] 5) The composition of
embodiment 1 or any embodiment of embodiment 1 as disclosed herein,
for example embodiments 2 or 3 or 4, wherein polySH is a macromer.
[0132] 6) The composition of embodiment 1 or any embodiment of
embodiment 1 as disclosed herein, for example embodiments 2 or 3 or
4, wherein polySH is a macromer having a molecular weight of
greater than 1,000 g/mol. [0133] 7) The composition of embodiment 1
or any embodiment of embodiment 1 as disclosed herein, for example
embodiments 2 or 3 or 4, wherein polySH has a molecular weight of
less than 500 g/mol. [0134] 8) The composition of embodiment 1 or
any embodiment of embodiment 1 as disclosed herein, for example any
of embodiments 2-7, wherein polyEU is water soluble. [0135] 9) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example any of embodiments 2-8, wherein
polyEU is bioabsorbable. [0136] 10) The composition of embodiment 1
or any embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-9 wherein EU of polyEU is acrylate. [0137] 11) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example embodiments 2-9, wherein EU of polyEU
is methacrylate. [0138] 12) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-9, wherein EU of polyEU is norbornenyl. [0139] 13)
The composition of embodiment 1 or any embodiment of embodiment 1
as disclosed herein, for example embodiments 2-7, wherein polyEU is
a macromer. [0140] 14) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-7, wherein polyEU is a macromer having a molecular
weight of greater than 1,000 g/mol. [0141] 15) The composition of
embodiment 1 or any embodiment of embodiment 1 as disclosed herein,
for example embodiments 2-14, wherein at least one of polySH and
polyEU further has multiple carbonyl groups, where optionally
polyEU has multiple carbonyl groups, or where optionally polySH and
polyEU each have multiple carbonyl group. [0142] 16) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example embodiments 2-15, wherein at least
one of polySH and polyEU further has multiple ester groups, where
optionally polyEU has multiple ester groups, or where optionally
polySH and polyEU each have multiple ester group. [0143] 17) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example embodiments 2-15, wherein at least
one polyEU and polySH further has multiple ester groups and
multiple carbonate groups, where optionally polyEU has both
multiple ester groups and multiple carbonate groups, or where
optionally both of polySH and polyEU further have both multiple
ester groups and multiple carbonate groups. [0144] 18) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example embodiments 2-15, wherein at least
one of polySH and polyEU further has multiple ester groups and
multiple urethane groups, where optionally polyEU has both multiple
ester groups and multiple urethane groups, or where optionally both
of polySH and polyEU further have both multiple ester groups and
multiple urethane groups. [0145] 19) The composition of embodiment
1 or any embodiment of embodiment 1 as disclosed herein, for
example embodiments 2-15, wherein at least one of polySH and polyEU
further has multiple carbonate groups and multiple urethane groups,
where optionally polyEU has both multiple carbonate groups and
multiple urethane groups, or where optionally both of polySH and
polyEU further have both multiple carbonate groups and multiple
urethane groups. [0146] 20) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-19, wherein the multiple SH of polySH is selected
from 2, 3 and 4. [0147] 21) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-20, wherein the multiple EU of polyEU is selected
from 2, 3 and 4. [0148] 22) The composition of embodiment 1 or any
embodiment of embodiment 1 as disclosed herein, for example
embodiments 2-21, which is free of volatile materials having a
boiling point of less than 110.degree. C. [0149] 23) The
composition of embodiment 1 or any embodiment of embodiment 1 as
disclosed herein, for example embodiments 2-22, which is anhydrous.
[0150] 24) The composition of embodiment 1 or any embodiment of
embodiment 1 as disclosed herein, for example embodiments 2-23,
which is fluid at room temperature of about 18.degree. C. to about
22.degree. C. [0151] 25) A composition comprising a photochemically
cured reaction product of the compositions of any of embodiments
1-24. [0152] 26) The composition of embodiment 25 which is
bioabsorbable. [0153] 27) The composition of embodiment 25 which is
a solid at 50.degree. C. [0154] 28) An additive manufacturing
process comprising: [0155] a. providing a vat containing a first
composition of any one of embodiment 1-24; [0156] b. directing
actinic radiation from a light source into the first composition in
the vat, where the actinic radiation is effective to induce
polymerization of components of the composition so as to form a
second composition; and [0157] c. forming a solid article
comprising the second composition. [0158] 29) A composition
comprising a first organic compound (polyhv) having multiple
photopolymerizable groups (hv), a photoinitiator, a second organic
compound (poly.DELTA.1) having multiple reactive groups .DELTA.1,
and a third organic compound (poly.DELTA.2) having multiple
reactive groups .DELTA.2, where .DELTA.1 reacts with .DELTA.2 upon
contact and exposure to a temperature of greater than 50.degree. C.
[0159] 30) The composition of embodiment 29 or any embodiment of
embodiment 29, wherein polyhv is bioabsorbable. [0160] 31) The
composition of embodiment 29 or any embodiment of embodiment 29,
for example embodiment 30, wherein polyhv is a macromer. [0161] 32)
The composition of embodiment 29 or any embodiment of embodiment
29, for example embodiment 30 or 31, wherein polyhv is a macromer
having a molecular weight of greater than 1,000 g/mol. [0162] 33)
The composition of embodiment 29 or any embodiment of embodiment
29, for example embodiment 30 or 31, wherein polyhv has a molecular
weight of less than 500 g/mol. [0163] 34) The composition of
embodiment 29 or any embodiment of embodiment 29, for example
embodiment 30 or 31, wherein polyhv is water soluble. [0164] 35)
The composition of embodiment 29 or any embodiment of embodiment
29, for example embodiment 30 to 34, wherein polyhv is polyEU
elected from acrylate and methyacrylate. [0165] 36) The composition
of embodiment 29 or any embodiment of embodiment 29, for example
embodiment 30 to 34, wherein hv of polyhv is norbornenyl. [0166]
37) The composition of embodiment 29 or any embodiment of
embodiment 29, for example embodiment 30 to 36, wherein .DELTA.1 is
a nucleophile and .DELTA.2 is an electrophile. [0167] 38) The
composition of embodiment 29 or any embodiment of embodiment 29,
for example embodiment 30 to 36, wherein .DELTA.1 is selected from
hydroxyl and amino. [0168] 39) The composition of embodiment 29 or
any embodiment of embodiment 29, for example embodiment 30 to 36,
wherein .DELTA.2 is selected from epoxide and isocyanate. [0169]
40) The composition of embodiment 29 or any embodiment of
embodiment 29, for example embodiment 30 to 39, wherein at least
one of polyhv, poly.DELTA.1 and poly.DELTA.2 further has multiple
carbonyl groups, where optionally polyhv has multiple carbonyl
groups, or where optionally polyhv and at least one of poly.DELTA.1
and poly.DELTA.2 has multiple carbonyl group. [0170] 41) The
composition of embodiment 29 or any embodiment of embodiment 29,
for example embodiment 30 to 39, wherein at least one of polyhv,
poly.DELTA.1 and poly.DELTA.2 further has multiple ester groups,
where optionally polyhv has multiple ester groups, or where
optionally polyhv and at least one of poly.DELTA.1 and poly.DELTA.2
has multiple ester group. [0171] 42) The composition of embodiment
29 or any embodiment of embodiment 29, for example embodiment 30 to
39, wherein at least one polyhv, poly.DELTA.1 and poly.DELTA.2
further has multiple ester groups and multiple carbonate groups,
where optionally polyhv has both multiple ester groups and multiple
carbonate groups, or where optionally polyhv and at least one of
poly.DELTA.1 and poly.DELTA.2 has both multiple ester groups and
multiple carbonate groups. [0172] 43) The composition of embodiment
29 or any embodiment of embodiment 29, for example embodiment 30 to
39, wherein at least one of polyhv, poly.DELTA.1 and poly.DELTA.2
further has multiple ester groups and multiple urethane groups,
where optionally polyhv has both multiple ester groups and multiple
urethane groups, or where optionally polyhv and at least one of
poly.DELTA.1 and poly.DELTA.2 has both multiple ester groups and
multiple urethane groups. [0173] 44) The composition of embodiment
29 or any embodiment of embodiment 29, for example embodiment 30 to
39, wherein at least one of polyhv, poly.DELTA.1 and poly.DELTA.2
further has multiple carbonate groups and multiple urethane groups,
where optionally polyhv has both multiple carbonate groups and
multiple urethane groups, or where optionally polyhv and at least
one of poly.DELTA.1 and poly.DELTA.2 has both multiple carbonate
groups and multiple urethane groups. [0174] 45) The composition of
embodiment 29 or any embodiment of embodiment 29, for example
embodiment 30 to 44, wherein the multiple hv of polyhv is selected
from 2, 3 and 4. [0175] 46) The composition of embodiment 29 or any
embodiment of embodiment 29, for example embodiment 30 to 44,
wherein the multiple .DELTA.1 of poly.DELTA.1 is selected from 2, 3
and 4. [0176] 47) The composition of embodiment 29 or any
embodiment of embodiment 29, for example embodiment 30 to 44,
wherein the multiple .DELTA.2 of poly.DELTA.2 is selected from 2, 3
and 4. [0177] 48) The composition of embodiment 29 or any
embodiment of embodiment 29, for example embodiment 30 to 47, which
is free of volatile materials having a boiling point of less than
110.degree. C. [0178] 49) The composition of embodiment 29 or any
embodiment of embodiment 29, for example embodiment 30 to 47, which
is anhydrous. [0179] 50) The composition of embodiment 29 or any
embodiment of embodiment 29, for example embodiment 30 to 47, which
is fluid at a temperature of about 18.degree. C. to about
22.degree. C. [0180] 51) A composition comprising a photochemically
cured reaction product and a thermally cured reaction product of
the compositions of any of embodiments 29-50. [0181] 52) The
composition of embodiment 51 which is bioabsorbable. [0182] 53) The
composition of embodiment 51 which is a solid at 50.degree. C.
[0183] 54) An additive manufacturing process comprising: [0184] a.
providing a vat containing a first composition of any one of
embodiments 29-50; [0185] b. directing actinic radiation from a
light source into the first composition in the vat, where the
actinic radiation is effective to induce polymerization of
components of the first composition so as to form a second
composition comprising photochemically cured composition; and
[0186] c. applying thermal energy to the second composition
comprising photochemically cured composition so as to form a third
composition comprising photochemically cured composition and
thermally cured composition.
[0187] The disclosure has been described broadly and generically
herein. Each of the narrower species and subgeneric groupings
falling within the generic disclosure also form part of the
disclosure. This includes the generic description of the disclosure
with a proviso or negative limitation removing any subject matter
from the genus, regardless of whether or not the excised material
is specifically recited herein.
[0188] It is also to be understood that as used herein and in the
appended claims, the singular forms "a," "an," and "the" include
plural reference unless the context clearly dictates otherwise, the
term "X and/or Y" means "X" or "Y" or both "X" and "Y", and the
letter "s" following a noun designates both the plural and singular
forms of that noun. In addition, where features or aspects of the
disclosure are described in terms of Markush groups, it is
intended, and those skilled in the art will recognize, that the
disclosure embraces and is also thereby described in terms of any
individual member and any subgroup of members of the Markush group,
and Applicants reserve the right to revise the application or
claims to refer specifically to any individual member or any
subgroup of members of the Markush group.
[0189] The following Examples are offered by way of illustration
and not by way of limitation. Chemicals were obtained from
commercial sources, e.g., MilliporeSigma (St. Louis, Mo., USA).
EXAMPLES
Example 1
Hydroxyl Terminated Precursor Polymers
[0190] In one aspect, the present disclosure provides compositions
that contain at least one of the compounds denoted as polyhv,
polySH, polyEU, poly.DELTA.1 and poly.DELTA.2. Optionally, each of
these compounds may be made from a precursor polymer having
hydroxyl groups in lieu of the hv or SH or EU or .DELTA.1 or
.DELTA.2 groups, where optionally the hv, SH, EU, .DELTA.1 or
.DELTA.2 group is joined to the precursor polymer through a
suitable linking group. The present Example illustrates the
preparation of exemplary hydroxyl-containing precursor
polymers.
[0191] Table 1 identifies 16 precursor polymers, uniquely labeled
as 3DP 1 through 3DP 16, which may generally be described as having
or including compounds of the general formula CC-[arm-OH] according
to the present disclosure. The term arm-OH refers to an arm that
terminates in a hydroxyl group (OH), i.e., has a hydroxyl end
group.
[0192] When the precursor polymer includes compounds that include
the formula CC-[(A)-(B)], i.e., when an arm is formed from residues
of monomers from Group A (any one or more of trimethylene carbonate
and .epsilon.-caprolactone) which are proximal to (adjacent to) the
central core, and residues of monomers from Group B (any one or
more of glycolide, lactide and p-dioxanone) which are the distal to
(furthest away from) the central core, such precursor polymers may
be prepared by reacting a functionalized central core, also
referred to herein as an initiator, with one or more monomers from
Group A, followed by reacting that reaction product (referred to
herein as a precursor prepolymer) with one or more monomers from
Group B. The result is a central core bonded to one or more arms,
each arm being hydroxyl terminated and having the formula
-(A)-(B)-OH. The preparation of such a precursor polymer is
illustrated in Example 1A below, where the central core is
trifunctional and the functionalized central core/initiator is
provided by trimethylolpropane.
Example 1A--Preparation of Triaxial 3DP-6 Precursor Polymer
[0193] Trimethylene carbonate (1.4 mol) and .epsilon.-caprolactone
(1.4 mol) were co-polymerized using trimethylolpropane (0.6 mol) as
initiator and stannous octoate (7.0.times.10.sup.-5 mol) as
catalyst, at 130.degree. C. for 72 hours to provide a polymer
precursor. Glycolide (1.1 mol) and additional stannous octoate
(2.1.times.10.sup.-4 mol) were combined with the polymer precursor
at 160.degree. C. for 3 hours to provide a precursor polymer having
polyglycolide grafts on the ends of the polymer precursor. The
amorphous liquid precursor polymer, thus obtained, was
devolatilized and characterized by .sup.1H NMR spectroscopy,
rheometry (viscosity 17,300 cP at shear rate 105 s.sup.-1),
differential scanning calorimetry (Tg=-45.degree. C.) and gel
permeation chromatography (Mn=1884 Da, PDI=1.80).
[0194] When the precursor polymer includes compounds that include
the formula CC-[(B)-(A)], i.e., when residues of monomers from
Group B (glycolide, lactide and p-dioxanone) are proximal to
(adjacent to) the central core, and residues of monomers from Group
A (trimethylene carbonate and caprolactone) are the distal to
(furthest away from) the central core, such precursor polymers may
be prepared by reacting a functionalized central core with one or
more monomers from Group B, followed by reacting that reaction
product with one or more monomers from Group A. The result is a
central core bonded to one or more arms, each arm being hydroxyl
terminated and having the formula -(B)-(A)-OH. The preparation of
such a precursor polymer is illustrated in Example 1B below, where
the central core is trifunctional and the functionalized central
core is provided by trimethylolpropane.
Example 1B--Preparation of Triaxial 3DP-4 Precursor Polymer
[0195] In a first step, glycolide (1.1 mol) was polymerized with
trimethylolpropane (0.6 mol) as initiator and stannous octoate
(7.times.10.sup.-5 mol) as catalyst, at 160.degree. C. for 3 hours
to provide a polymer precursor. After completion of the first step,
a mixture of equimolar amounts of trimethylene carbonate (1.4 mol)
and .epsilon.-caprolactone (1.4 mol) was co-polymerized onto ends
of the polymer precursor by adding more stannous octoate
(2.times.10.sup.-4 mol) and reacting at 130.degree. C. for 72
hours. The resulting amorphous liquid was devolatilized and
characterized by .sup.1H NMR spectroscopy, rheometry (viscosity
17,300 cP at shear rate 105 s.sup.-1), differential scanning
calorimetry (Tg=-45.degree. C.) and gel permeation chromatography
(Mn=1909 Da, PDI=1.83).
[0196] Following the procedures outlined in Examples 1A and 1B,
additional polyester precursor polymers were synthesized as
described in Table 1. All linear samples were synthesized with
1,3-propanediol as the bifunctional initiator, all trifunctional
prepolymers were prepared with trimethylolpropane, and 4-arm block
copolyester compositions were initiated by pentaerythritol as the
tetrafunctional initiator. In Table 1, M/I refers to the total
moles of monomers (M) used to prepare the arms divided by the moles
of initiator (I) (also referred to as the functionalized central
core) for each of the copolyesters identified in Table 1. Also in
Table 1, M/C refers to the total moles of monomers (M) used to
prepare the arms divided by the total moles of catalyst (C) used to
prepare each of the copolyester prepolymers identified in Table 1.
Each of the precursor polymers of Table 1 contains a B region,
which is characterized in the column titled G/L/p-D, which is
shorthand for Glycolide/Lactide/p-Dioxanone segment, and which may
either be proximal to the central core (in which case the location
of the B region is identified as being central to the precursor
polymer) or it is distal to the central core (in which case the
location of the B region is identified as being at the end of the
precursor polymer, and in which case the B region terminates in a
hydroxyl group).
[0197] Selected molecular weight results obtained by gel permeation
chromatography (GPC) for selected precursor polymers prepared as
illustrated in Example 1 are provided in Table 2. In Table 2, Mn
refers to number average molecular weight, Mw refers to weight
average molecular weight, PDI refers to polydispersity (i.e.,
Mw/Mn), and Da refers to Daltons.
TABLE-US-00001 TABLE 1 Precursor polymer compositions Prepolymer
Initiator Composition (mol %) Name M/I M/C Type G/L/p-D Glycolide
TMC Caprolactone D,L-lactide p-Dioxanone 3DP 1 14.3 14,333 Triaxial
Center 2.3 48.8 48.8 -- -- 3DP 2 7 14,333 Triaxial Center 2.3 48.8
48.8 -- -- 3DP 3 3.5 14,333 Triaxial Center 2.3 48.8 48.8 -- -- 3DP
4 7 14,000 Triaxial Center 28.6 35.7 35.7 -- -- 3DP 5 7 11,666
Linear Center 14.3 42.9 42.9 -- -- 3DP 6 7 14,000 Triaxial End 28.6
35.7 35.7 -- -- 3DP 7 7 11,666 Linear End 14.3 42.9 42.9 -- -- 3DP
8 7 14,000 4-arm Center 42.9 28.6 28.6 -- -- 3DP 9 7 14,000
Triaxial End 50 25 25 -- -- 3DP 10 7 11,666 Linear End 25 37.5 37.5
-- -- 3DP 11 7 14,000 Triaxial End 75 12.5 12.5 -- -- 3DP 12 7
11,666 Linear End 50 25 25 -- -- 3DP 13 7 14,000 Triaxial End -- 25
25 50 -- 3DP 14 7 14,000 Triaxial End -- 25 25 -- 50 3DP 15 7
11,666 Linear End -- 37.5 37.5 25 -- 3DP 16 7 11,666 Linear End --
37.5 37.5 -- 25 3DP 19 7 11,666 Linear End 20-40 15-35 40-60 -- --
3DP 20 7 11,666 Linear End 20-40 10-30 45-70 -- --
TABLE-US-00002 TABLE 2 3DP molecular weights (Mn and Mw) and
polydispersity indices (PDI) Precursor polymer Name Mn (Da) Mw (Da)
PDI 3DP 4 1909 .+-. 29 3490 .+-. 016 1.83 .+-. 0.03 3DP 5 2311 .+-.
23 3766 .+-. 18 1.63 .+-. 0.02 3DP 6 1884 .+-. 15 3386 .+-. 36 1.79
.+-. 0.02 3DP 7 2168 .+-. 141 3628 .+-. 87 1.68 .+-. 0.08 3DP 9
1554 .+-. 37 2569 .+-. 29 1.65 .+-. 0.03 3DP 10 1785 .+-. 30 2208
.+-. 73 1.24 .+-. 0.02 3DP 11 1389 .+-. 8 1829 .+-. 9 1.32 .+-.
0.01 3DP 12 1606 .+-. 5 2410 .+-. 17 1.50 .+-. 0.01 3DP 19 1837
.+-. 15 2936 .+-. 23 1.59 .+-. 0.02 3DP 20 1881 .+-. 37 2902 .+-.
22 1.54 .+-. 0.05
Example 2
Preparation of Methacrylated Compounds of the Present
Disclosure
Exemplary Polymer of Formula PolyEU
[0198] Table 3 identifies 8 EU-functionalized precursor polymers,
uniquely labeled as 3DP 4m (m standing for methacrylate, which is
an exemplary ethylenically unsaturated (EU) group) through 3DP 7m
and 3DP 9m through 3DP 12m, which may generally be described as
having or including compounds of the general formula CC-[arm-EU]
according to the present disclosure. The designation arm-EU refers
to an arm that terminates in a light-reactive ethylenically
unsaturated group, such as an acrylate ("a") or methacrylate ("m")
group.
[0199] The methacrylated polymers of Table 3 were prepared from the
corresponding precursor polymers of Table 1, that is, 3DP 4m was
prepared from 3DP 4, 3DP 5m was prepared from 3DP 5, etc.
Methacrylation of 3DP 6 to form 3DP 6m
[0200] The 3DP 6 precursor polymer (0.131 moles) was reacted with
an excess of methacrylic anhydride, in the presence of
3-tert-2-butyl-4-hydroxyanisole (6.724.times.10-4 moles), at
120.degree. C. for 24 hours. Residual methacrylic anhydride and
methacrylic acid by-products were removed from the crude polymer
using a rotary evaporator. The resulting amorphous liquid polymer
was characterized using .sup.1H NMR spectroscopy, rheometery
(viscosity 16,400 cP at shear rate 105 s-1), differential scanning
calorimetry (Tg=-38.degree. C.) and gel permeation chromatography
(Mn=2162 Da, PDI=1.75). Each 3DP formulation was methacrylated
following the procedure outlined above. The composition and
molecular weight results are outlined in Table 3, and the dynamic
viscosities are reported in Table 4. In Table 3, for 3DP 5m, 40.15
in the TMC column is the total mole % of TMC plus 1,3-propanediol
used to make 3DP 5m.
TABLE-US-00003 TABLE 3 Composition and molecular weight results of
nnethacrylated 3DP formulations Polymer Composition (mol %) Name
Glycolide TMC Caprolactone Methacrylate Mn Mw PDI 3DP 4m 19.91
28.43 24.66 27.00 -- -- -- 3DP 5m 9.93 40.15 32.87 17.05 2648 .+-.
82 3999 .+-. 56 1.51 .+-. 0.03 3DP 6m 19.94 24.36 28.87 27.43 2162
.+-. 14 3793 .+-. 24 1.75 .+-. 0.02 3DP 7m 9.89 39.38* 32.52 18.21
2328 .+-. 32 3551 .+-. 14 1.53 .+-. 0.02 3DP 9m 35.06 15.51 22.16
27.87 1585 .+-. 55 2946 .+-. 52 1.86 .+-. 0..03 3DP 10m 17.3 36.97*
27.78 17.95 2140 .+-. 11 2548 .+-. 13 1.19 .+-. 0.004 3DP 11m 50.23
9.34 13.60 26.83 2125 .+-. 4 2575 .+-. 6 1.21 .+-. 0.003 3DP 12m
32.02 26.00* 20.98 21.01 1670 .+-. 8 2588 .+-. 12 1.55 .+-. 0.01
3DP 19m -- -- -- -- 1826 .+-. 13 3009 .+-. 29 1.64 .+-. 0.01 3DP
20m -- -- -- -- 1984 .+-. 12 3022 .+-. 6 1.5 .+-. 0.09
TABLE-US-00004 TABLE 4 Dynamic viscosity of methacrylated 3DP
polymers Polymer Viscosity at 105 s.sup.-1 shear Name rate (cP) 3DP
4m 12,700 .+-. 141 3DP 5m 6,747 .+-. 35 3DP 6m 16,400 .+-. 346 3DP
7m 5,493 .+-. 38 3DP 19m 6555 .+-. 216 3DP 20m 3262 .+-. 26
Example 3
Preparation of Thiolated Compound of the Present Disclosure
Exemplary Polymers of Formula PolySH
[0201] A 500 mL 3-neck round bottomed flask equipped with a
mechanical stirrer and an addition funnel was charged with 3DP 6
(51.3 g; 0.0665 moles; see Table 1), thiolactic acid (17.243 mL;
20.623 g; 0.1943 moles) and dichloromethane (DCM) (200 mL) in a
nitrogen environment. The contents of the reaction vessel were
stirred at 200 rpm and the reaction vessel was cooled using an ice
bath. Separately, N,N'-dicyclohexylcarbodiimide (DCC) (44.5 g,
0.2157 moles) was dissolved in 200 mL DCM. The DCC in DCM solution
was then added to the reaction vessel drop wise using an addition
funnel over a period of 30 minutes. After the addition of DCC/DCM
solution had been completed, ice bath was removed.
4-Dimethylaminopyridine (DMAP) (2.366 g; 0.0193 moles) was added to
the reaction vessel using a powder funnel. The reaction mixture was
continued to stir in nitrogen environment at room temperature for
72 hours. DCM levels were replenished as it evaporated during the
reaction. After 72 hours, the reaction mixture was filtered under
suction. The filtrate was washed with 2.times.100 mL 0.25 M HCl and
1.times.100 mL deionized (DI) water. The organic phase from the
extraction was dried over activated molecular sieves (3 .ANG.) for
18 hours after which it was filtered under suction. The solvent was
removed under vacuum on a rotary evaporator to get a liquid
polymeric product (3DP 6t, where "t" indicates thiolated, also
referred to herein as a polySH polymer). The amorphous liquid
polymer, thus obtained, was characterized by .sup.1H NMR
spectroscopy, rheometry (viscosity=7690 at shear rate of 99
s.sup.-1), and gel permeation chromatography (Mn=1952 Da,
PDI=1.62). The table below outlines other thiolated 3DP compounds
with n-acetyl cysteine (NAC), thiolactic acid (TLA), and
thioglycolic acid (TGA). Each of these were synthesized based on
this exemplary synthesis procedure.
TABLE-US-00005 TABLE 5 Properties of Thiolated 3DP Polymers
Viscosity at 100 s.sup.-1 Polymer Composition (mol %) shear Name
Glycolide TMC Caprolactone Thiol rate (cP) Mn Mw PDI 3DP 6t 22.14
27.64 27.64 22.59 7690 2380 4579 1.92 (TLA) 3DP 6t 17.10 21.34
21.34 40.22 116,921 1952 3162 1.62 (NAC) 3DP 10t 16.89 25.33 25.33
32.45 42,592 2213 3629 1.64 (NAC) 3DP 19t 20.74 18.66 43.55 17.05
5295 2071 3165 1.54 (TLA) 3DP 19t 21.32 19.18 44.17 14.74 5904 2202
3487 1.58 (TGA) 3DP 20t 21.34 12.81 51.22 14.63 4461 2109 3052 1.45
(TGA)
Example 4
Preparation of Thiolated Compound of the Present Disclosure
Generally Described by the Formula PolySH
[0202] Polymers which have hydroxyl groups can be capped with a
moiety that replaces the hydroxyl group with a carboxylic acid
group. The carboxylic acid groups can then be substituted with a
thiol containing moiety via an amide or ester bond depending on the
functional unit of the substituent employed for bonding. For
instance, the hydroxyl end groups of a 3DP precursor polymer (see,
e.g., Table 1) can be reacted with succinic anhydride to form a
succinated intermediate (3DP-SA), which may in turn be reacted with
the amine group present in cysteine to provide a product (3DP
6-SA-Cys) having terminal free thiol groups, which provide
exemplary polySH compounds of the present disclosure. This approach
is illustrated by the present example.
[0203] Part 1--formation of 3DP 6-SA: A 250 mL 3-neck round
bottomed flask was charged with 3DP 6 (48.9 g; 0.0633 moles, Table
1). The system was placed under vacuum (<0.5 torr) at 40.degree.
C. for 18 hours to dry the pre-polymer. After 18 hours, the system
was purged with nitrogen and succinic anhydride (19.0 g; 0.1900
moles) was added to the reaction vessel. The reaction mixture was
stirred at 50 rpm at 120.degree. C. for 24 hours. The polymer thus
obtained was cooled to room temperature and devolatilized on rotary
evaporator to remove residual monomer at room temperature for 18
hours and further 24 hours at 110.degree. C. The structure of the
resulting clear amorphous polymer product was confirmed using
.sup.1H NMR.
[0204] Part 2--formation of 3DP 6-SA-Cys: A 100 mL 2-neck flask was
charged with 3DP 6-SA (10.1 g; 0.0093 moles), L-cysteine (3.39 g;
0.0280 moles) and dichloromethane (DCM) (30 mL). The reactants were
stirred at 200 rpm in nitrogen environment. Separately,
N'-dicyclohexylcarbodiimide (DCC) (6.35 g, 0.0307 moles) was
dissolved in 10 mL DCM. An ice bath was placed around the reaction
vessel and DCC/DCM solution was added dropwise. The ice bath was
removed after the addition of DCC/DCM solution had been completed
and the reactants were allowed to stir at room temperature for 72
hours in nitrogen environment. After 72 hours, the reaction mixture
was diluted with 50 mL DCM and filtered under suction. The filtrate
was washed with 2.times.50 mL 0.25 M HCl and 1.times.50 mL DI
water. The organic phase from the extraction was dried over
activated molecular sieves (3 .ANG.) for 18 hours after which it
was filtered under suction. The solvent was removed under vacuum on
a rotary evaporated to provide a waxy polymeric product (3DP
6-SA-Cys), the structure of which was confirmed by .sup.1H NMR
spectroscopy.
Example 5
Single Polymeric Network from PolyEU and PolySH
[0205] Thiol terminated 3DP polymers were mixed with methacrylated
3DP polymers in two different ratios. TPO-L photoinitiator was
added to each combination at a concentration of 0.5% (w/w) and the
formulation was mixed on a Flacktek high speed mixer for 2 minutes
at 2000 rpm followed by 3 minutes at 3000 rpm. The formulation was
cured into a film with 0.75 mm thickness. Films were cut into 75
mm.times.7.5 mm.times.0.75 mm specimens subjected to accelerated
degradation at 50.degree. C. in pH 7.4 phosphate buffer. In FIG. 1,
the degradation profiles of 50:50 and 25:75 3DP 6t TLA/3DP 10m
films are shown. The information in FIG. 1 shows the effect of
water swelling for polyEU/polySH single polymeric networks.
Example 6
Preparation of Isocyanate Terminated Compounds of the Present
Disclosure
Exemplary Polymers of Formula Poly.DELTA.
[0206] As mentioned in Example 1, hydroxyl-terminated polymers may
provide precursor compounds to poly.DELTA. compounds of the present
disclosure. Hydroxyl groups may be converted to thermally reactive
groups, e.g., isocyanate group as shown by the present example,
which illustrates diisocyanate capping of 3DP 10
[0207] A 250 mL 3-neck round bottomed flask equipped with a
mechanical stirrer and an addition funnel was charged with 3DP 10
(76.7 g; 0.0996 moles). The 3DP 10 was dried at 40.degree. C. under
reduced pressure for 3 days. After drying, the flask was purged
with dry nitrogen, and agitation was started at 220 rpms. The flask
was charged with 15 ml of anhydrous toluene and hexamethylene
diisocyante (HMDI; 33.5 ml; 0.209 moles). The reaction mixture
temperature was increased to 80.degree. C. for 2 hours and then
allowed to return to room temperature. The polymer mixture was then
transfer to a 1-neck flask and placed on a rotary evaporator. The
residual toluene and HMDI were removed under reduced pressure on
the rotary evaporator. The amorphous liquid polymer, thus obtained
was characterized by H.sup.1NMR spectroscopy (Polymer--70.3 wt %
Isocyanate--29.6 wt. %).
Example 7
Double Polymeric Network from PolyEU and
Poly.DELTA.1+Poly.DELTA.2
[0208] Double network films were prepared with a photopolymerized
methacrylate polymer network and a thermally cured interpenetrating
polymer network. 3DP 12m and 3DP 6 precursor polymer (an exemplary
poly.DELTA.1) were mixed in either a 50:50 or 70:30 ratio. TPO-L
photoinitiator was added to the mixture at a 0.5% (w/w)
concentration with respect to the weight of the methacrylated
polymer. Hexamethylenediisocynate (an exemplary poly.DELTA.2) was
added the mixture at a 45% of the number of moles of hydroxyl
groups in the precursor polymer (3:1 OH:polymer in case of 3DP6, a
triaxial polymer). The formulation was mixed using a Flacktek high
speed mixer for 2 minutes at 2000 rpm followed by 2 minutes at 3000
rpm. The formulation was then cured as a film of 0.75 mm thickness
for 10 minutes under UV light at an intensity of 30 mW/cm2. The
photocured film was further cured thermally at 100.degree. C. for 1
hour.
[0209] The film was cut up into test strips of 75 mm.times.7.5
mm.times.0.75 mm and subjected to accelerated degradation at
50.degree. C. in pH 7.4 phosphate buffer. Mass loss, water content
and mechanical properties of the material were analyzed at
different timepoints during the study. The results are shown in
FIG. 2. In FIG. 2, the data show the water swelling behavior for
urethane and methacrylated polyester double networks. The addition
of the urethane network increases the water swelling up to 25-30%
mass loss. After 25-30% mass loss, both the 50:50 3DP12m:3DP 6U and
3DP6u showed substantially less swelling.
Example 8
Mechanics of Poly(SH) and Poly(EU) Materials
[0210] To evaluate the properties of crosslinked 3DP polymer
blends, tensile specimens were created for mechanical testing. For
any particular polymer blend, a thiol-terminated 3DP polymer was
mixed with one or more methacrylated 3DP polymers (3DPX M) in 25:75
and 50:50 weight ratios where the thiolated polymer was synthesized
using thiolactic acid (3DPX TLA), N-acetyl-L-cysteine (3DPX NAC),
or thioglycolic acid (3DPX TGA) as described in Example 3. In
addition to methacrylated 3DP polymers, select blends at similar
ratios were studied with a diluent component of poly-ethylene
glycol diacrylate (PEGDA). A photoinitiator, ethyl
(2,4,6-trimethylbenzoyl) phenyl phosphinate (TPOL), was added at
0.5% (w/w) and the blend was mixed on a FlackTek high speed mixer
for two minutes at 2000 rotations per minute (rpm) followed by
three minutes at 3000 rpm.
[0211] Each liquid polymer blend was poured between two
UV-transparent acrylic sheets with 0.75 mm spacers and cured under
a 100 W UV Blak-Ray lamp for 10 minutes. The crosslinked film was
removed and cut into tensile specimens with dimensions of
0.75.times.7.5.times.75 mm. The film strips were subjected to
mechanical testing on an MTS test frame to evaluate their tensile
properties with at least four strips for each blend tested. The
test parameters for tensile testing are presented in Table 6. The
polymer blends studied and their corresponding tensile properties
are reported in Table 7.
TABLE-US-00006 TABLE 6 Testing Parameters Parameter Value Units
Test Inputs Break sensitivity 90 % Break threshold 0.5 Ibf Data
acquisition rate 70 Hz Test speed 2.5 mm/min Calculation Break
marker drop 50 % Inputs Break marker 0.1 Inch elongation Grip
separation 1 Inch Slack pre-load 1 Ibf Slope segment length 20 %
Yield offset 0.2 % Yield segment length 2 %
TABLE-US-00007 TABLE 7 Poly (SH) and Poly (EU) Photopolymerized
Tensile Mechanics Peak Stress Strain at Modulus (kPa) Break (%)
(MPa) 3DP6 M 29340 38 352 25:75 3DP6t TLA:3DP6 M 4020 23 23 50:50
3DP6t TLA:3DP6 M 750 19 4 3DP10 M 5950 31 21 PEGDA 575 4780 15 34
25:75 3DP6t TLA:PEGDA 575 1900 14 15 50:50 3DP6t TLA:PEGDA 575 800
13 7 25:75 3DP6t TLA:3DP10 M 1370 28 6 50:50 3DP6t TLA:3DP10 M 450
30 2 3DP19 M 6630 34 29 3DP20 M 6430 41 21 50:50 3DP19t TLA:3DP20 M
400 40 1 50:50 3DP19t TGA:3DP20 M 530 65 2
Example 9
Stability of Poly(SH) and Poly(EU) Compositions
[0212] Part 1--Polymer blends with and without stabilizers were
investigated for premature crosslinking. A thiol terminated
photo-reactive compound was mixed with a methacrylated
photo-reactive compound at a 50:50 ratio. Prospective stabilizing
compounds were each added to an aliquot of the reactive mixture at
varying concentrations. Each formulation blend was mixed on a
FlakTek high speed mixer for two minutes at 2000 rotations per
minute (rpm) followed by three minutes at 3000 rpm. An aliquot of
each blend was transferred to a petri dish and stored at room
temperature (RT) or 50.degree. C. The stability of the polymer
blends were qualitatively evaluated by the solidification of the
blend and the results are reported in table 8.
TABLE-US-00008 TABLE 8 Stability of methacrylate and thiol
terminated photo-reactive resins Concen- Storage Solidi-
Photo-reactive tration time Storage fication blends (50:50)
Stabilizer (Ppm) (hr) temp (Yes/No) 3DP 19m:3DP Citric acid 5000 16
RT Y 19t TLA 3DP 19m:3DP Succinic acid 5200 96 RT Y 19t TLA 3DP
19m:3DP Adipic acid 1000 48 RT Y 19t TLA TMPTM:TMPTT* Phosphoric
acid 500 48 50.degree. C. N 3DP 20m:3DP Lauryl gallate 9000 24 RT N
19t TGA 3DP 20m:3DP Tocopherol 12000 24 RT N 19t TGA 3DP 20m:3DP
Gallic acid 4000 24 RT N 19t TGA 3DP 20m:3DP Triphenyl- 9500 24 RT
N 19t TGA phosphite 3DP 20m:3DP Phenyl- 4000 24 RT N 19t TGA
phosphonic acid *--TMPTM: Trimethylolpropane trimethacrylate;
TMPTT: Trimethylolpropane tris(3-mercaptopropionate)
[0213] Part 2--A thiol-terminated polymer (3DP 19t TGA) was mixed
with a methacrylated polymer (3DP 20m) at a 50:50 weight ratio.
Selected stabilizers were each added to an aliquot of the liquid
polymer blend and the viscosity of the formulations were evaluated
by rheometry (25.degree. C. at shear rate 100 s-1) at 24 hours to
yield a quantitative measurement of stability. The initial
viscosity of the resin without a stabilizer was 3920.+-.20 cP.
Viscosities of stabilized polymer blends at 24 hours of storage at
room temperature are provided in table 9.
TABLE-US-00009 TABLE 9 Viscosity of stabilized 3DP 19t TGA and 3DP
20m blend after 24 hours of storage Viscosity at Stabilizer in
Concentration 24 hours polymer blends (ppm) Viscosity (cP) Increase
(%) No stabilizer -- Solidified -- Ascorbic acid 4400 Solidified --
BHA 4500 4044 3.2 BHT 5400 8797 124 Lauryl gallate 8700 3940 0.5
Gallic acid 5200 4056 3.5 Tocopherol 1000 4021 2.6 Tocopherol 10000
4113 4.9 Tocopherol 100000 3769 -3.9 Triphenyl phosphite 10000 4046
3.2
[0214] All references disclosed herein, including patent references
and non-patent references, are hereby incorporated by reference in
their entirety as if each was incorporated individually.
[0215] It is to be understood that the terminology used herein is
for the purpose of describing specific embodiments only and is not
intended to be limiting. It is further to be understood that unless
specifically defined herein, the terminology used herein is to be
given its traditional meaning as known in the relevant art.
[0216] Reference throughout this specification to "one embodiment"
or "an embodiment" and variations thereof means that a particular
feature, structure, or characteristic described in connection with
the embodiment is included in at least one embodiment. Thus, the
appearances of the phrases "in one embodiment" or "in an
embodiment" in various places throughout this specification are not
necessarily all referring to the same embodiment. Furthermore, the
particular features, structures, or characteristics may be combined
in any suitable manner in one or more embodiments.
[0217] As used in this specification and the appended claims, the
singular forms "a," "an," and "the" include plural referents, i.e.,
one or more, unless the content and context clearly dictates
otherwise. It should also be noted that the conjunctive terms,
"and" and "or" are generally employed in the broadest sense to
include "and/or" unless the content and context clearly dictates
inclusivity or exclusivity as the case may be. Thus, the use of the
alternative (e.g., "or") should be understood to mean either one,
both, or any combination thereof of the alternatives. In addition,
the composition of "and" and "or" when recited herein as "and/or"
is intended to encompass an embodiment that includes all of the
associated items or ideas and one or more other alternative
embodiments that include fewer than all of the associated items or
ideas.
[0218] Unless the context requires otherwise, throughout the
specification and claims that follow, the word "comprise" and
synonyms and variants thereof such as "have" and "include", as well
as variations thereof such as "comprises" and "comprising" are to
be construed in an open, inclusive sense, e.g., "including, but not
limited to." The term "consisting essentially of" limits the scope
of a claim to the specified materials or steps, or to those that do
not materially affect the basic and novel characteristics of the
claimed disclosure. In case of conflict, the present specification,
including explanations of terms, will control. In addition, all the
materials, methods, and examples are illustrative and not intended
to be limiting.
[0219] Any headings used within this document are only being
utilized to expedite its review by the reader, and should not be
construed as limiting the disclosure or claims in any manner. Thus,
the headings and Abstract of the Disclosure provided herein are for
convenience only and do not interpret the scope or meaning of the
embodiments.
[0220] Where a range of values is provided herein, it is understood
that each intervening value, to the tenth of the unit of the lower
limit unless the context clearly dictates otherwise, between the
upper and lower limit of that range and any other stated or
intervening value in that stated range is encompassed within the
disclosure. The upper and lower limits of these smaller ranges may
independently be included in the smaller ranges is also encompassed
within the disclosure, subject to any specifically excluded limit
in the stated range. Where the stated range includes one or both of
the limits, ranges excluding either or both of those included
limits are also included in the disclosure.
[0221] For example, any concentration range, percentage range,
ratio range, or integer range provided herein is to be understood
to include the value of any integer within the recited range and,
when appropriate, fractions thereof (such as one tenth and one
hundredth of an integer), unless otherwise indicated. Also, any
number range recited herein relating to any physical feature, such
as polymer subunits, size or thickness, are to be understood to
include any integer within the recited range, unless otherwise
indicated. As used herein, the term "about" means .+-.20% of the
indicated range, value, or structure, unless otherwise
indicated.
[0222] All of the U.S. patents, U.S. patent application
publications, U.S. patent applications, foreign patents, foreign
patent applications and non-patent publications referred to in this
specification and/or listed in the Application Data Sheet, are
incorporated herein by reference, in their entirety. Such documents
may be incorporated by reference for the purpose of describing and
disclosing, for example, materials and methodologies described in
the publications, which might be used in connection with the
presently described disclosure. The publications discussed above
and throughout the text are provided solely for their disclosure
prior to the filing date of the present application. Nothing herein
is to be construed as an admission that the inventors are not
entitled to antedate any referenced publication by virtue of prior
disclosure.
[0223] All patents, publications, scientific articles, web sites,
and other documents and materials referenced or mentioned herein
are indicative of the levels of skill of those skilled in the art
to which the disclosure pertains, and each such referenced document
and material is hereby incorporated by reference to the same extent
as if it had been incorporated by reference in its entirety
individually or set forth herein in its entirety. Applicants
reserve the right to physically incorporate into this specification
any and all materials and information from any such patents,
publications, scientific articles, web sites, electronically
available information, and other referenced materials or
documents.
[0224] In general, in the following claims, the terms used should
not be construed to limit the claims to the specific embodiments
disclosed in the specification and the claims, but should be
construed to include all possible embodiments along with the full
scope of equivalents to which such claims are entitled.
Accordingly, the claims are not limited by the disclosure.
[0225] Furthermore, the written description portion of this patent
includes all claims. Furthermore, all claims, including all
original claims as well as all claims from any and all priority
documents, are hereby incorporated by reference in their entirety
into the written description portion of the specification, and
Applicants reserve the right to physically incorporate into the
written description or any other portion of the application, any
and all such claims. Thus, for example, under no circumstances may
the patent be interpreted as allegedly not providing a written
description for a claim on the assertion that the precise wording
of the claim is not set forth in haec verba in written description
portion of the patent.
[0226] The claims will be interpreted according to law. However,
and notwithstanding the alleged or perceived ease or difficulty of
interpreting any claim or portion thereof, under no circumstances
may any adjustment or amendment of a claim or any portion thereof
during prosecution of the application or applications leading to
this patent be interpreted as having forfeited any right to any and
all equivalents thereof that do not form a part of the prior
art.
[0227] Other nonlimiting embodiments are within the following
claims. The patent may not be interpreted to be limited to the
specific examples or nonlimiting embodiments or methods
specifically and/or expressly disclosed herein. Under no
circumstances may the patent be interpreted to be limited by any
statement made by any Examiner or any other official or employee of
the Patent and Trademark Office unless such statement is
specifically and without qualification or reservation expressly
adopted in a responsive writing by Applicants.
* * * * *