U.S. patent application number 09/978415 was filed with the patent office on 2002-02-07 for two phase thermally deformable biocompatible absorbable polymer matrix for use in medical devices.
Invention is credited to Cooper, Kevin.
Application Number | 20020016596 09/978415 |
Document ID | / |
Family ID | 21997215 |
Filed Date | 2002-02-07 |
United States Patent
Application |
20020016596 |
Kind Code |
A1 |
Cooper, Kevin |
February 7, 2002 |
Two phase thermally deformable biocompatible absorbable polymer
matrix for use in medical devices
Abstract
An absorbable biocompatible polymeric matrix is described. The
matrix has a continuous phase that is preferably amorphous. The
matrix also has a disperse phase of low melting biocompatible
material that acts as scattering centers for light and melts at a
temperature lower than the continuous phase of the matrix. This
matrix is especially useful in a variety of medical devices. When
this matrix is heated to about the melting temperature of the
dispersed phase the matrix undergoes a visual change. This provides
a visual cue to a surgeon using the medical devices as to when the
device can be safely shaped or manipulated without imparting undue
stress to the device. As the medical device cools below the
temperature at which it may be safely deformed the matrix resumes
its original appearance signalling that it may no longer be safely
shaped or manipulated.
Inventors: |
Cooper, Kevin; (Warren,
NJ) |
Correspondence
Address: |
AUDLEY A. CIAMPORCERO JR.
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
21997215 |
Appl. No.: |
09/978415 |
Filed: |
October 16, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09978415 |
Oct 16, 2001 |
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09497060 |
Feb 2, 2000 |
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09497060 |
Feb 2, 2000 |
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09055342 |
Apr 6, 1998 |
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Current U.S.
Class: |
606/77 |
Current CPC
Class: |
A61L 27/18 20130101;
A61L 29/06 20130101; C08L 67/04 20130101; C08L 67/04 20130101; C08L
67/04 20130101; C08L 67/04 20130101; C08L 67/04 20130101; C08L
69/00 20130101; A61L 27/50 20130101; A61L 31/06 20130101; A61L
31/06 20130101; A61L 15/42 20130101; A61L 27/18 20130101; A61L
29/06 20130101; A61L 15/26 20130101; A61L 15/26 20130101 |
Class at
Publication: |
606/77 |
International
Class: |
A61F 002/30 |
Claims
We claim:
1. An absorbable polymeric matrix for use in medical devices that
provides a visual cue when heated so that the absorbable polymeric
matrix may be deformed without significantly reducing the strength
of a device made from the absorbable polymeric matrix.
2. The absorbable polymeric matrix of claim 1 wherein the
absorbable polymeric matrix is made from biocompatible aliphatic
polyesters.
3. The absorbable polymeric matrix of claim 1 wherein the
absorbable polymeric matrix comprises a continuous phase and a
dispersed phase.
4. The absorbable polymeric matrix of claim 3 wherein the
continuous phase is an amorphous aliphatic polyester selected from
the group consisting of amorphous polylactide, amorphous
polyglycolide, amorphous poly-1,4-dioxan-2-one, amorphous
polytrimethylene carbonate and miscible blends thereof.
5. The absorbable polymeric matrix of claim 3 wherein the dispersed
phase is an aliphatic polyester selected from the group consisting
of poly(.epsilon.-caprolactone); copolymers of
.epsilon.-caprolactone and with up to 40 mole percent of a second
monomer selected from the group consisting of lactide, lactic acid,
glycolide, glycolic acid, 1,4-dioxan-2-one, and trimethylene
carbonate; copolymers of .epsilon.-caprolactone or trimethylene
carbonate with greater than 60 mole percent 1,4-dioxan-2-one but
less than 90 mole percent and blends thereof.
6. The absorbable polymeric matrix of claim 3 wherein the dispersed
phase comprises from about 1 to about 50 weight percent of the
absorbable polymeric matrix.
7. The absorbable polymeric matrix of claim 6 wherein the dispersed
phase comprises from about 2 to about 20 weight percent of the
absorbable polymeric matrix.
8. A medical device that at least a portion thereof is formed from
an absorbable polymeric matrix that provides a visual cue when
heated that the absorbable polymeric matrix may be deformed without
significantly reducing the strength of the portions of the medical
device made from the absorbable polymeric matrix wherein the visual
cue disappears when the absorbable polymeric matrix cools to a
temperature at which deformation would reduce the strength of the
absorbable polymeric matrix.
9. The medical device of claim 8 wherein the medical device is
selected from the group consisting of burn dressings, hernia
patches, medicated dressings, facial substitutes, gauze, fabric,
sheet, felt, sponge for liver hemostasis, gauze bandages, arterial
graft or substitutes, bandages for skin surfaces, burn dressings,
bone substitutes, needles, intrauterine devices, tubes, surgical
instruments, vascular implants, vascular supports, vertebral discs,
extracorporeal tubing, artificial skin, stents, suture anchors,
injectable defect fillers, preformed defect fillers, bone waxes,
cartilage replacements, hemostatic barriers, tissue scaffolds,
monofilament sutures and braided sutures, pins, rods and
plates.
10. The medical device of claim 8 wherein the medical device is
selected from the group consisting, bone substitutes, vertebral
discs, pins, rods and plates.
11. The medical device of claim 8 wherein the absorbable polymeric
matrix comprises a continuous phase and a dispersed phase.
12. The medical device of claim 11 wherein the continuous phase is
an amorphous aliphatic polyester selected from the group consisting
of amorphous polylactide, amorphous polyglycolide, amorphous
poly-1,4-dioxan-2-one, amorphous polytrimethylene carbonate and
miscible blends thereof.
13. The medical device of claim 12 wherein the dispersed phase is
an aliphatic polyester selected from the group consisting of
poly(.epsilon.-caprolactone); copolymers of .epsilon.-caprolactone
and with up to 40 mole percent of a second monomer selected from
the group consisting of lactide, lactic acid, glycolide, glycolic
acid, 1,4-dioxan-2-one, and trimethylene carbonate; copolymers of
.epsilon.-caprolactone or trimethylene carbonate with greater than
60 mole percent 1,4-dioxan-2-one but less than 90 mole percent and
blends thereof.
14. A method of shaping a surgical article having a portion thereof
formed from an absorbable polymeric matrix comprises heating that
portion of the surgical article that is formed from the absorbable
polymeric matrix until a visual cue is provided by the absorbable
polymeric matrix that the portion of the surgical article made from
the absorbable polymeric matrix may be safely shaped, then shaping
that portion of the surgical article to the desired final shape
while the visual cue is present and allowing the surgical article
to cool.
15. The process of claim 14 wherein the surgical article is heated
to a temperature in the range of from about 40.degree. C. to about
65.degree. C.
16. The process of claim 14 wherein the surgical article is heated
in a biocompatible liquid medium.
17. The process of claim 14 wherein the surgical article is
selected from the group consisting, bone substitutes, vertebral
discs, pins, rods and plates.
18. The process of claim 14 wherein the absorbable polymeric matrix
has a continuous phase that is an amorphous aliphatic polyester
selected from the group consisting of amorphous polylactide,
amorphous polyglycolide, amorphous poly-1,4-dioxan-2-one, amorphous
polytrimethylene carbonate and miscible blends thereof.
19. The process of claim 18 wherein the absorbable polymeric matrix
has a dispersed phase that is an aliphatic polyester selected from
the group consisting of poly(.epsilon.caprolactone); copolymers of
.epsilon.-caprolactone and with up to 40 mole percent of a second
monomer selected from the group consisting of lactide, lactic acid,
glycolide, glycolic acid, 1,4-dioxan-2-one, and trimethylene
carbonate; copolymers of e-caprolactone or trimethylene carbonate
with greater than 60 mole percent 1,4-dioxan-2-one but less than 90
mole percent and blends thereof.
20. The process of claim 19 wherein the dispersed phase comprises
from about 2 to about 20 weight percent of the absorbable polymeric
matrix.
Description
FIELD OF THE INVENTION
[0001] The general field to which the invention relates to is
devices made of absorbable polymer matrices. Specifically,
absorbable polyester matrices for use in a thermally deformable
plating system for the fixation of bone and cartilage, especially
hard tissue of the cranium.
BACKGROUND OF THE INVENTION
[0002] Synthetic absorbable biocompatible polymers are well known
in the art. Such polymers are typically used to manufacture medical
devices, which are implanted in body tissue and absorb over time.
Synthetic absorbable biocompatible polymers include homopolymers,
copolymers (random, block, segmented and graft) of monomers such as
glycolic acid, glycolide (d, l, meso and mixtures thereof), lactic
acid, lactide, .epsilon.-caprolactone, trimethylene carbonate and
p-dioxanone. Numerous U.S. patents describe these polymers
including U.S. Pat. Nos. 5,431,679; 5,403,347; 5,314,989;
5,431,679; 5,403,347; and 5,502,159.
[0003] There is a constant need in this art for new polymer
compositions having improved physical properties when molded or
extruded into medical devices and further having excellent in vivo
properties. For example, it is known that copolymers of lactide and
glycolide have good in vivo properties (U.S. Pat. No. 5,569,250).
These materials are also generally known in the art to be single
phase, amorphous or semi-crystalline copolymers with melting points
exceeding 100.degree. C., and no low melting or immiscible
component.
[0004] Heat deforming of absorbable devices, such as plates, has
also been described in U.S. Pat. No. 5,569,250. However, one
drawback of such devices is their lack of a visual cue to aid the
surgeon in knowing the precise time that they can begin deforming
the device. This is critical to the device, because premature
bending or otherwise manipulating it before it has relaxed (i.e.,
heated above its Tg or Tm) can cause stresses to form in the part,
weakening it, especially in clinical situations.
[0005] Unfortunately, U.S. Pat. No. 5,569,250 does not recognize
that absorbable plates, rods and pins, for example, could be
manufactured from a polymeric material that provides a visual cue
to a surgeon during surgery to assist him/her in appropriately
applying the device to the surgical site.
[0006] Therefore, what is needed in this art is a novel device that
provides a visual cue during its application (i.e., deformation
during heating) to indicate when it can be safely manipulated or
shaped.
[0007] The surgical devices of the present invention provide a
visual cue to surgeons indicating when the surgical device may be
contoured or shaped.
SUMMARY OF THE INVENTION
[0008] We have discovered an absorbable polymeric matrix that
provides a visual cue when heated that the absorbable polymeric
matrix may be deformed without significantly reducing the strength
(due to internal stress concentration) of a device made from the
polymeric matrix. These polymeric matrices are especially well
suited for use in implantable surgical devices such as plates,
pins, rods and the like that need to be shaped during medical
procedures to accommodate the patient. The method of shaping a
surgical article containing these absorbable polymeric matrices
comprises heating the surgical article until a visual cue is
provided by the absorbable polymeric matrix that the portion of the
surgical article made from the absorbable polymeric matrix may be
safely shaped, then shaping that portion of the surgical article to
the desired final shape and allowing the surgical article to
cool.
[0009] The foregoing and other features and advantages of the
invention will become more apparent from the following description
and accompanying examples.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 photographically illustrates the visual cue of the
device of the present invention. The burr hole cover plate on the
left is opaque at room temperature, while the plate on the right
has been heated to 55.degree. C. is nearly transparent.
DETAILED DESCRIPTION OF THE INVENTION
[0011] The biocompatible polymeric materials described herein are
matrices having a continuous phase and a disperse phase. The
continuous phase is generally composed of an amorphous
biocompatible polymeric material. The dispersed phase is composed
of a biocompatible material with a low melting point. The dispersed
phase is believed to provide scattering centers in the matrix that
when heated become transparent. This provides the surgeon a visual
cue of when to bend and shape the medical device formed from the
matrix. In applications that require shaping the device, such as
cranial plating over a variety of bony contours, the present
invention is far superior to the devices disclosed in the prior
art.
[0012] The polymeric materials of the present invention are formed
of a polymeric matrix with a continuous phase and a dispersed phase
of a lower melting crystalline material forming a second distinct
phase. The continuous phase is preferably formed from amorphous
biocompatible polymers. Suitable amorphous biocompatible polymers
include, but are not limited to, amorphous aliphatic ester polymers
selected from the group consisting of amorphous polylactide
(including D-lactide, L-lactide, mixtures of D-lactide and
L-lactide, as well as, lactic acid polymers), amorphous
polyglycolide (including polyglycolic acid polymers), amorphous
poly-1,4-dioxan-2-one, amorphous polytrimethylene carbonate (also
known as poly-1,3-dioxan-2-one) and copolymers and blends thereof.
For crystalline compositions the polymers will have a melting point
above 80.degree. C. and most preferably above 70.degree. C.
[0013] The dispersed phase is a semi-crystalline polymer that will
form a separate phase in the continuous matrix and melt at a
temperature between about 40.degree. C. to about 65.degree. C., and
most preferably will melt at a temperature in the range of from
about 40.degree. C. to about 55.degree. C. Suitable absorbable
biocompatible polymers that may used especially in association with
the aliphatic ester polymers listed for the dispersed phase
include, but are not limited to, biocompatible absorbable polymers
selected from the group consisting of poly(.epsilon.caprolactone);
copolymers of .epsilon.-caprolactone and with up to 40 mole percent
of a second monomer selected from the group consisting of lactide
(lactic acid), glycolide (glycolic acid), 1,4-dioxan-2-one, and
trimethylene carbonate; and copolymers of .epsilon.-caprolactone or
trimethylene carbonate with greater than 60 mole percent
1,4-dioxan-2-one, but less than 90 mole percent.
[0014] Additionally, the dispersed phase may be formed from low
melting biocompatible organic molecules of an appropriate size to
act as scattering sites that may be blended with the matrix without
adversely affecting the chemical or mechanical properties of the
matrix polymer for its intended use. One suitable organic material
is polyethylene glycol (PEG).
[0015] Additionally, the continuous phase and the dispersed phase
could also be provided by using block copolymers composed of the
continuous phase and dispersed phase polymers described above,
provided that the block copolymers formed two distinct phases,
wherein the dispersed phase block forms scattering sites and the
dispersed phase has a melting point in the temperature range
previously described.
[0016] Generally, the amount of biocompatible material in the
dispersed phase will be that amount sufficient to provide a visual
cue when the biocompatible materials in the dispersed phase become
transparent or melt or otherwise visually changes during heating of
the device. By way of a guideline, but not limiting the scope of
the present invention, for the combination of the continuous phase
aliphatic polyesters previously listed with the dispersed phase
biocompatible absorbable polymers previously listed, it is
preferred that the weight percent of dispersed polymer comprise in
the range of from about 1 to about 50 and most preferable from
about 2 to about 20. The weight percentages being based on the
total weight percent of the matrix polymers equaling 100
percent.
[0017] In a medical procedure the device will be shaped to
accommodate the patients individual anatomy or the particular
surgical requirements. The medical device would be heated
preferably in a liquid media until the medical device provides a
visible cue that it may be shaped (without imparting undue stress
to the medical device). In one preferred embodiment of the present
invention when heated the absorbable polymer matrices under goes a
reversible visual change when a substantial amount of the dispersed
polymer phase becomes clear by melting. The scattering sites when
transparent no longer scatter light and the absorbable polymeric
matrix will appear clear as long as the dispersed phase remains
above its melting point. For the absorbable polymeric matrix
described above the surgeon would heat the matrix to a temperature
from about 40.degree. C. to about 65.degree. C. until it becomes
nearly transparent. While the matrix appears clear the surgeon will
be able to safely shape the device.
[0018] The polymers of the present invention will typically be
synthesized in a ring opening polymerization. That is, the
aliphatic lactone monomers lactide, glycolide,
.epsilon.-caprolactone, p-dioxanone, and trimethylene carbonate are
polymerized in the presence of an organometallic catalyst and an
initiator at elevated temperatures. The organometallic catalyst is
preferably tin based, e.g., stannous octoate, and is present in the
monomer mixture at a molar ratio of monomer to catalyst ranging
from about 10,000/1 to about 100,000/1. The initiator is typically
an alkanol (including diols and polyols), a glycol, a hydroxyacid,
or an amine, and is present in the monomer mixture at a molar ratio
of monomer to initiator ranging from about 100/1 to about 5000/1.
The polymerization is typically carried out at a temperature range
from about 80.degree. C. to about 240.degree. C., preferably from
about 100.degree. C. to about 220.degree. C., until the desired
molecular weight and viscosity are achieved.
[0019] The polymer blends of the present invention are manufactured
in a conventional manner, preferably in the following manner. The
homopolymers and copolymers, prepared as described above, are
individually charged into a conventional mixing vessel or reactor
vessel having a conventional mixing device mounted therein, such as
an impeller or equivalents thereof. Then, the polymers and
copolymers are mixed at a temperature of about 100.degree. C. to
about 230.degree. C., more preferably from about 160.degree. C. to
about 200.degree. C., for about 5 to about 90 minutes, more
preferably for about 10 to about 45 minutes, until a uniformly
dispersed polymer blend is obtained. Then, the polymer blend is
further processed by removing it from the mixing device, cooling to
room temperature, grinding, and drying under pressures below
atmospheric at elevated temperatures for a period of time using
conventional apparatuses and processes.
[0020] Additionally, a minor amount (less than 5, preferably less
than 3 weight percent weight percent) of additional lactone
monomers selected from the group consisting of 1,3-dioxan-2-one,
p-dioxanone, delta-valerolactone, beta-butyrolactone,
epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha,
alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate,
3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione,
gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one,
6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicycloctane-7-one and
combinations of two or more thereof may be added.
[0021] Under the above described conditions, the polymers and
blends composed of glycolide, .epsilon.-caprolactone, p-dioxanone,
lactide and trimethylene carbonate will typically have a weight
average molecular weight of about 20,000 grams per mole to about
300,000 grams per mole, more typically about 40,000 grams per mole
to about 200,000 grams per mole, and preferably about 60,000 grams
per mole to about 150,000 grams per mole. These molecular weights
provide an inherent viscosity between about 0.5 to about 4.0
deciliters per gram (dL/g), more typically about 0.7 to about 3.5
dL/g, and most preferably about 1.0 to about 3.0 dL/g as measured
in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at
25.degree. C. Also, it should be noted that under the above
described conditions, the residual monomer content would be less
than about 5 weight percent.
[0022] Articles such as medical devices are molded from the
polymers and blends of the present invention by use of various
injection and extrusion molding equipment equipped with dry
nitrogen atmospheric chamber(s) at temperatures ranging from about
100.degree. C. to about 230.degree. C., more preferably 140.degree.
C. to about 200.degree. C., with residence times of about 1 to
about 20 minutes, more preferably about 2 to about 10 minutes.
[0023] The polymers and blends of the present invention can be melt
processed by numerous methods to prepare a vast array of useful
devices. These materials can be injection or compression molded to
make implantable medical and surgical devices, including wound
closure devices. The preferred devices are orthopedic plates, pins
and rods.
[0024] Alternatively, the blends and polymers can be extruded to
prepare fibers. The materials of the present invention may also be
spun as multifilament yarn and woven or knitted to form sponges or
gauze, (or non-woven sheets may be prepared) or used in conjunction
with other molded compressive structures such as prosthetic devices
within the body of a human or animal where it is desirable that the
structure have high tensile strength and desirable levels of
compliance and/or ductility. Useful embodiments include tubes,
including branched tubes, for artery, vein or intestinal repair,
nerve splicing, tendon splicing, sheets for tying up and supporting
damaged surface abrasions, particularly major abrasions, or areas
where the skin and underlying tissues are damaged or surgically
removed.
[0025] Additionally, the polymers and blends can be molded to form
films which, when sterilized, are useful as adhesion prevention
barriers.
[0026] In another embodiment of the present invention, the polymers
and blends can be used as a drug delivery matrix. To form this
matrix, the polymer would be mixed with a therapeutic agent. The
variety of different therapeutic agents that can be used in
conjunction with the polymers of the present invention is vast. In
general, therapeutic agents which may be administered via the
pharmaceutical compositions of the invention include, without
limitation: antiinfectives such as antibiotics and antiviral
agents; analgesics and analgesic combinations; anorexics;
antihelmintics; antiarthritics; antiasthmatic agents;
anticonvulsants; antidepressants; antidiuretic agents;
antidiarrheals; antihistamines; antiinflammatory agents;
antimigraine preparations; antinauseants; antineoplastics;
antiparkinsonism drugs; antipruritics; antipsychotics;
antipyretics, antispasmodics; anticholinergics; sympathomimetics;
xanthine derivatives; cardiovascular preparations including calcium
channel blockers and beta-blockers such as pindolol and
antiarrhythmics; antihypertensives; diuretics; vasodilators
including general coronary, peripheral and cerebral; central
nervous system stimulants; cough and cold preparations, including
decongestants; hormones such as estradiol and other steroids,
including corticosteroids; hypnotics; immunosuppressives; muscle
relaxants; parasympatholytics; psychostimulants; sedatives; and
tranquilizers; and naturally derived or genetically engineered
proteins, polysaccharides, glycoproteins, or lipoproteins.
[0027] The drug delivery matrix may be administered orally,
parenterally, subcutaneously, vaginally or anally. Matrix
formulations may be formulated by mixing one or more therapeutic
agents with the polymer. The therapeutic agent, may be present as a
liquid, a finely divided solid, or any other appropriate physical
form. Typically, but optionally, the matrix will include one or
more additives, such as diluents, carriers, excipients, stabilizers
or the like.
[0028] The amount of therapeutic agent will depend on the
particular drug being employed and medical condition being treated.
Typically, the amount of drug represents about 0.001% to about 70%,
more typically about 0.001% to about 50%, most typically about
0.001% to about 20% by weight of the matrix.
[0029] The quantity and type of polymer incorporated into the drug
delivery matrix will vary depending on the release profile desired
and the amount of drug employed.
[0030] Upon contact with body fluids, the polymer undergoes gradual
degradation (mainly through hydrolysis) with concomitant release of
the dispersed drug for a sustained or extended period. This can
result in prolonged delivery (over, say 1 to 5,000 hours,
preferably 2 to 800 hours) of effective amounts (say, 0.0001
mg/kg/hour to 10 mg/kg/hour) of the drug. This dosage form can be
administered as is necessary depending on the subject being
treated, the severity of the affliction, the judgment of the
prescribing physician, and the like.
[0031] Following this or similar procedures, those skilled in the
art will be able to prepare a variety of formulations.
[0032] Furthermore, the polymers and blends of the present
invention can be processed by conventional techniques to form
foams, which are useful as hemostatic barriers, bone substitutes,
and tissue scaffolds.
[0033] In more detail, the surgical and medical uses of the
filaments, films, foams and molded articles of the present
invention include, but are not necessarily limited to knitted
products, woven or non-woven, and molded products including:
[0034] a. burn dressings
[0035] b. hernia patches
[0036] c. medicated dressings
[0037] d. fascial substitutes
[0038] e. gauze, fabric, sheet, felt or sponge for liver
hemostasis
[0039] f. gauze bandages
[0040] g. arterial graft or substitutes
[0041] h. bandages for skin surfaces
[0042] i. burn dressings
[0043] j. bone substitutes
[0044] k. needles
[0045] l. intrauterine devices
[0046] m. draining or testing tubes or capillaries
[0047] n. surgical instruments
[0048] o. vascular implants or supports
[0049] p. vertebral discs
[0050] q. extracorporeal tubing for kidney and heart-lung
machines
[0051] r. artificial skin and others
[0052] s. stents
[0053] t. suture anchors
[0054] u. injectable defect fillers
[0055] v. preformed defect fillers
[0056] w. tissue adhesives and sealants
[0057] x. bone waxes
[0058] y. cartilage replacements
[0059] z. hemostatic barriers
[0060] aa. tissue scaffolds
[0061] bb. monofilament and braided sutures
[0062] cc. orthopedic, spinal and nuerosurgical plates, rods and
pins.
[0063] The following non-limiting examples are illustrative of the
principles and practice of this invention. Numerous additional
embodiments within the scope and spirit of the invention will
become apparent to those skilled in the art.
EXAMPLES
[0064] The examples describe an opaque plating system that
comprises a polymer or polymer blends that when heated is
transparent then opaque again upon cooling to body temperature.
[0065] In the synthetic process, the high molecular weight
aliphatic polyesters are prepared by a method consisting of
reacting lactone monomers via a ring opening polymerization at
temperatures of 100.degree. C. to 230.degree. C. for 2 to 24 hours
under an inert nitrogen atmosphere until the desired molecular
weight and viscosity are achieved.
[0066] In the blending process, the polymer blends of the present
invention are prepared by individually charging the synthesized
aliphatic homo- and co-polyesters into a conventional mixing
vessel. The homopolymers and copolymers are mixed at a temperature
of 100.degree. C. to 230.degree. C., for 5 to 90 minutes until a
uniformly dispersed polymer blend is obtained.
[0067] In the examples which follow, the blends, polymers and
monomers were characterized for chemical composition and purity
(NMR, FT-IR), thermal analysis (DSC), melt rheology (melt stability
and viscosity), molecular weight (inherent viscosity), and baseline
mechanical properties (Instron stress/strain).
[0068] Inherent viscosities (I.V., dL/g) of the blends and polymers
were measured using a 50 bore Cannon-Ubbelhode dilution viscometer
immersed in a thermostatically controlled water bath at 25.degree.
C. utilizing chloroform or HFIP (hexafluoroisopropanol) as the
solvent at a concentration of 0.1 g/dL.
[0069] Several examples will be described in the following few
pages. Parts and percentages where used are parts and percentages
as specified as weight or moles.
Example 1
[0070] Synthesis of a 85:15 (mol/mol) poly(lactide-co-glycolide)
copolymer
[0071] The method described below and utilized in this example is
similar to those described in U.S. Pat. Nos. 4,643,191, 4,653,497,
5,007,923, 5,047,048 which are incorporated by reference, and is
known to those skilled in the art.
[0072] To a flame dried 500 mL 1-neck round bottom flask equipped
with an overhead mechanical stirrer and nitrogen inlet, 268 grams
(1.86 moles) of L(-) lactide, 38.4 grams (0.330 moles) of
glycolide, 0.53 grams (7.times.10.sup.-3 moles) of glycolic acid
initiator, and 131 microliters of a 0.33 M solution of stannous
octoate catalyst were added.
[0073] The assembly was then placed in a high temperature oil bath
at 185.degree. C. The stirred monomers quickly began to melt. The
low viscosity melt quickly increased in viscosity. Mechanical
stirring of the high viscosity melt was continued for a total
reaction time of 4 hours.
[0074] The 85:15 (mol/mol) poly(lactide-co-glycolide) copolymer was
removed from the bath, cooled to room temperature under a stream of
nitrogen, isolated and ground. The polymer was then dried under
vacuum at 110.degree. C. for 24 hours. Inherent viscosity using
HFIP as a solvent was 1.90 dL/g.
Example 2
[0075] Synthesis of a 95:5 (mol/mol)
poly(.epsilon.-caprolactone-co-p-diox- anone) copolymer
[0076] The method described below in this example is similar to
those described in U.S. Pat. Nos. 4,643,191, 4,653,497, 5,007,923,
5,047,048 which are incorporated by reference, and is known to
those skilled in the art.
[0077] To a flame dried 500 mL 1-neck round bottom flask equipped
with an overhead mechanical stirrer and nitrogen inlet, 262.43
grams (2.3 moles) of .epsilon.-caprolactone, 12.38 grams (0.12
moles) of p-dioxanone, 0.84 grams (0.011 moles) of glycolic acid
initiator, and 147 microliters of a 0.33 M solution of stannous
octoate catalyst were added.
[0078] The assembly was then placed in a high temperature oil bath
at 190.degree. C. The stirred monomers quickly began to melt. The
low viscosity melt quickly increased in viscosity. Mechanical
stirring of the high viscosity melt was continued for a total
reaction time of 24 hours.
[0079] The 95:5 (mol/mol)
poly(.epsilon.-caprolactone-co-p-dioxanone) copolymer was removed
from the bath, cooled to room temperature under a stream of
nitrogen, isolated and ground. The polymer was then dried under
vacuum at 40.degree. C. for 24 hours. Inherent viscosity using HFIP
as a solvent was 1.77 dL/g.
Example 3
[0080] Blending of a 85:15 (mol/mol) poly(lactide-co-glycolide)
copolymer with a 95:5 (mol/mol)
poly(.epsilon.-caprolactone-co-p-dioxanone) copolymer at a blended
weight ratio of 95:5
[0081] 29.45 grams of a 85:15 (mol/mol) poly(lactide-co-glycolide)
prepared as described in Example 1 was melt blended with 1.55 grams
of the 95:5 (mol/mol) poly(.epsilon.caprolactone-co-p-dioxanone)
copolymer of Example 2 at a weight ratio of 95:5 in a Brabender
Plasti-corder mixer at a temperature of 170.degree. C. for 23
minutes. The resulting blend was removed from the Brabender mixer,
cooled, ground and dried under vacuum at 50.degree. C. for 24
hours. Inherent viscosity using HFIP as a solvent was 1.90
dL/g.
Example 4
[0082] Blending of a 85:15 (mol/mol) poly(lactide-co-glycolide)
copolymer with a 95:5 (mol/mol)
poly(.epsilon.-caprolactone-co-p-dioxanone) copolymer at a blended
weight ratio of 80:20
[0083] 24.8 grams of a 85:15 (mol/mol) poly(lactide-co-glycolide)
prepared as described in Example 1 was melt blended with 6.2 grams
of the 95:5 (mol/mol) poly(.epsilon.-caprolactone-co-p-dioxanone)
copolymer of Example 2 at a weight ratio of 80:20 in a Brabender
Plasti-corder mixer at a temperature of 170.degree. C. for 23
minutes. The resulting blend was removed from the Brabender mixer,
cooled, ground and dried under vacuum at 50.degree. C. for 24
hours. Inherent viscosity using HFIP as a solvent was 1.83
dL/g.
Example 5
[0084] Blending of a 85:15 (mol/mol) poly(lactide-co-glycolide)
copolymer with a 95:5 (mol/mol)
poly(.epsilon.-caprolactone-co-p-dioxanone) copolymer at a blended
weight ratio of 60:40
[0085] 18.6 grams of a 85:15 (mol/mol) poly(lactide-co-glycolide)
prepared as described in Example 1 was melt blended with 12.4 grams
of the 95:5 (mol/mol) poly(.epsilon.-caprolactone-co-p-dioxanone)
copolymer of Example 2 at a weight ratio of 60:40 in a Brabender
Plasti-corder mixer at a temperature of 170.degree. C. for 23
minutes. The resulting blend was removed from the Brabender mixer,
cooled, ground and dried under vacuum at 50.degree. C. for 24
hours. Inherent viscosity using HFIP as a solvent was 1.80
dL/g.
Example 6
[0086] Synthesis of a 60:40 (mol/mol)
poly(.epsilon.-caprolactone-co-L-lac- tide) copolymer
[0087] The method described below in this example is similar to
those described in U.S. Pat. Nos. 4,643,191, 4,653,497, 5,007,923,
5,047,048 which are incorporated by reference, and is known to
those skilled in the art.
[0088] To a flame dried 500 mL 1-neck round bottom flask equipped
with an overhead mechanical stirrer and nitrogen inlet, 165.75
grams (1.45 moles) of .epsilon.-caprolactone, 139.68 grams (0.97
moles) of L-lactide, 0.84 grams (0.011 moles) of glycolic acid
initiator, and 147 microliters of a 0.33 M solution of stannous
octoate catalyst are added.
[0089] The assembly is then placed in a high temperature oil bath
at 190.degree. C. The stirred monomers quickly began to melt. The
low viscosity melt quickly increased in viscosity. Mechanical
stirring of the high viscosity melt is continued for a total
reaction time of 24 hours.
[0090] The 60:40 (mol/mol)
poly(.epsilon.-caprolactone-co-L-lactide) copolymer is removed from
the bath, cooled to room temperature under a stream of nitrogen,
isolated and ground. The polymer is then dried under vacuum at
40.degree. C. for 24 hours. Inherent viscosity using HFIP as a
solvent is 1.92 dL/g.
Example 7
[0091] Injection molding a circular plate (of FIG. 1) of a blend of
85:15 poly(lactide-co-glycolide) copolymer and 95:5
poly(.epsilon.-caprolactone- -co-p-dioxanone) copolymer at a
blended weight ratio of 95:5
[0092] 1.5 Kg of a blend as formed in Example 3 was added to a
nitrogen purged hopper of a 28 ton Engel injection molder equipped
with an 18 mm diameter barrel to form a circular plate as shown in
FIG. 1. Three heating zones of 180, 170, and 140.degree. C. were
employed to melt the blend as it entered the barrel. A nozzle
temperature of 185.degree. C. with an injection pressure of 700 psi
and a speed of 2 in/s were used to feed the molten material down
the barrel. Each injection produced a single part in a single
cavity mold. A temperature of 45.degree. C. was used in the mold to
optimize the stress levels in the part. Using this process 2 parts
are formed per minute.
Example 8
[0093] A circular burr hole cover plate (as illustrated in FIG. 1)
was manufactured from the matrix described in Example 3 by the
injection molding process described in Example 7. The plate was
then immersed in a vessel containing a biocompatible heat transfer
medium (i.e. warm water, . . . at a temperature of about
50-60.degree. C., until the plate became clear. This visual cue
signals the surgeon that the plate may be removed from the vessel
and shaped by bending it without causing damage to the plate. The
surgeon would then secure the plate to a fracture site in a
conventional manner using conventional fasteners (i.e. rivets, pins
and screws).
* * * * *