U.S. patent application number 14/448432 was filed with the patent office on 2016-02-04 for extrudable tubing and solvent bonded fitting for delivery of medicinal fluids.
The applicant listed for this patent is Tekni-Plex, Inc.. Invention is credited to Philip D. Bourgeois, Joseph E. Olsavsky.
Application Number | 20160030728 14/448432 |
Document ID | / |
Family ID | 53783923 |
Filed Date | 2016-02-04 |
United States Patent
Application |
20160030728 |
Kind Code |
A1 |
Bourgeois; Philip D. ; et
al. |
February 4, 2016 |
EXTRUDABLE TUBING AND SOLVENT BONDED FITTING FOR DELIVERY OF
MEDICINAL FLUIDS
Abstract
Assembly, and method of fabricating an assembly including an
extruded polymeric tube and a prefabricated tubular polymer body
(fitment), the method including the steps of: extruding an outer
tubular surface of a thermoplastic propylene-based elastomer (PBE)
material; treating the outer surface along a selected axial length
at one end of the tube with a solvent; inserting the treated one
end into a hollow tubular passage of a prefabricated tubular body
having an inner passage wall of a polypropylene-based material; and
allowing the mated juncture to dry such that the treated outer
surface solvent bonds to the inner wall. The tubing is preferably a
coextruded tube having an innermost layer of a thermoplastic
ethylene-based olefinic material. The mating tubing and fitment
overcome the prior art problems of stress cracking, fluid
contamination and/or processing difficulties.
Inventors: |
Bourgeois; Philip D.;
(Perrysburg, OH) ; Olsavsky; Joseph E.;
(Waterville, OH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Tekni-Plex, Inc. |
King of Prussia |
PA |
US |
|
|
Family ID: |
53783923 |
Appl. No.: |
14/448432 |
Filed: |
July 31, 2014 |
Current U.S.
Class: |
604/506 ;
138/137; 156/244.13 |
Current CPC
Class: |
B29C 66/1224 20130101;
B29C 66/723 20130101; B29C 66/712 20130101; B29L 2023/007 20130101;
B29C 65/565 20130101; B29K 2105/0085 20130101; B29C 66/5344
20130101; B29C 66/1222 20130101; B29C 66/71 20130101; B29C 65/82
20130101; A61M 39/08 20130101; A61M 2207/00 20130101; B29K 2023/12
20130101; B29C 65/4895 20130101; C08J 5/12 20130101; B29C 66/73773
20130101; B29C 66/71 20130101; B29K 2023/12 20130101; B29C 66/71
20130101; B29K 2021/003 20130101; B29C 66/71 20130101; B29K 2023/06
20130101 |
International
Class: |
A61M 39/08 20060101
A61M039/08; A61M 5/158 20060101 A61M005/158; B29C 65/48 20060101
B29C065/48 |
Claims
1. A method of coaxially bonding a polymeric tube to a
prefabricated tubular body, the prefabricated tubular body defining
a hollow central tubular passage having a longitudinal axis bounded
by an inner wall of polypropylene based material, the method
comprising: extruding a mating polymeric tube having an outer
tubular wall surface comprising thermoplastic propylene-based
elastomer (PBE) material, and a central tubular passage having a
longitudinal axis and opposing ends, treating the outer surface of
the mating tube along a selected axial length at one of the end of
the tube with a solvent that causes the treated outer surface to
adhere to the inner wall of the tubular body on drying, inserting
the treated end of the mating tube coaxially into the central
tubular passage of the tubular body such that the outer surface of
the treated end mates with the inner wall of the tubular body along
the selected axial length to form a mated juncture, allowing the
mated juncture to dry such that the treated outer surface solvent
bonds to the inner wall.
2. The method of claim 1 wherein the solvent is selected from one
or more of cyclohexanone, cyclohexane, hexane, xylene,
tetrahydrofuran (THF), ethyl acetate (EA) and methyl ethyl ketone
(MEK).
3. The method of claim 2 wherein the solvent is selected from one
or more of cyclohexane, cyclohexanone, xylene, tetrahydrofuran, and
hexane.
4. The method of claim 2 wherein the PBE is a copolymer or blend of
propylene and an alpha-olefin.
5. The method of claim 4 wherein the PBE is a
propylene/alpha-olefin copolymer with semi-crystalline isotactic
propylene segments.
6. The method of claim 2 wherein the PBE is a blend of a first
polymer component (FPC) which is a predominately crystalline
stereoregular polypropylene, and a second polymer component (SPC)
which is a crystallizable copolymer of C2,C4-C20 alpha-olefin and
propylene.
7. The method of claim 4 wherein the alpha-olefin is ethylene.
8. The method of claim 1 wherein the tube has an inner wall
comprising a layer of a polyethylene (PE).
9. The method of claim 8, wherein the PE of the inner wall is a low
density polyethylene (LDPE), linear low density polyethylene
(LLDPE), high density polyethylene (HDPE) or blends thereof.
10. The method of claim 1 wherein the step of extruding comprises
coextruding an outer tubular layer of the PBE material with at
least one innermost tubular layer of a thermoplastic ethylene-based
olefinic material.
11. The method of claim 10 wherein the coextruded outer layer of
the mating tube is the PBE with an ethylene content of at least 9%
by weight and the innermost layer of the mating tube is
polyethylene.
12. The method of claim 1, wherein the tubular body comprises a
prefabricated body of PBE material.
13. The method of claim 12, wherein the PBE material of the tubular
body is a homopolymer polypropylene or a copolymer of predominately
propylene units and ethylene.
14. A bonded tubular assembly comprising: a prefabricated tubular
body defining a hollow central tubular passage having a
longitudinal axis bounded by an inner wall of propylene-based
material, an extruded tube having an extruded outer tubular wall
surface comprising thermoplastic propylene-based elastomer (PBE)
material, the mating tube having a central tubular passage having a
longitudinal axis and opposing ends, wherein one of the ends of the
mating tube is coaxially positioned within the central tubular
passage of the prefabricated tubular body such that the outer
surface of the one end of the mating tube is mated with the inner
wall of the tubular body along a selected axial length of the
mating tube, the mated outer surface and inner wall being solvent
bonded to each other.
15. The tubular assembly of claim 14 wherein the extruded tube is a
coextruded tube having an outer tubular layer of the PBE material
with at least one innermost tubular layer of a thermoplastic
ethylene-based olefinic material.
16. The tubular assembly of claim 15 wherein the coextruded outer
layer of the mating tube is the PBE material with an ethylene
content of at least 9% by weight and the innermost layer of the
mating tube is polyethylene.
17. The tubular assembly of claim 14 wherein the tube has an inner
wall forming the central tubular passage comprising a coextruded
layer of polyethylene (PE).
18. The tubular assembly of claim 15, wherein the PE is a low
density polyethylene (LDPE), linear low density polyethylene
(LLDPE), high density polyethylene (HDPE) or blends thereof.
19. A method of delivering an aqueous based or non-aqueous based
medicinal fluid or combination thereof to a patient comprising
inserting a fluid delivery member into the body, the member being
fluidly connected to the bonded tubular assembly of claim 14, and
delivering the medical fluid through the tube to the delivery
member.
20. The method of claim 14, wherein the medicinal fluid comprises
one or more of: the nonaqueous solvents selected from the group
consisting of: vegetable oils, ethyl oleate, propylene glycol, and
polyethylene glycols with molecular weights of 300 and 400.
21. The method of claim 14, wherein the medicinal fluid comprises
one or more of: synthetic and semisynthetic preparations as solvent
or mixed solvent based fluid preparations for injection to the
patient, selected from the group consisting of alcohols, esters,
ethers, amides, sulfoxides and pyrrolidones.
22. The method of claim 21, wherein the fluid preparations are
selected form the group consisting of ethyl alcohol; benzyl
alcohol; phenylethyl alcohol; propylene glycol; butylene glycol;
trichloro-t-butyl; polyoxyethylene glycol; ethyl ether;
phenoxyethanol; ethyl acetate ethyl oleate; benzyl benzoate;
N-methylacetamide; N,N-dimethylacetamide; dimethyl sulfoxide
(DMSO), and N-methyl 2-pyrrolidone (NMP).
Description
FIELD OF THE INVENTION
[0001] The present invention relates to the composition, structure,
assembly and method of making an extruded polymeric tube and
bonding the tube in a co-axial arrangement with a pre-fabricated
polymeric body (e.g., fitting) for delivery of fluids.
BACKGROUND
[0002] Plasticized polyvinyl chloride (PVC) tubing has been
utilized in the medical field for many decades. Over this time
period, there have been various post tube manufacturing operations
utilized to apply fitments at the end of the tube so as to
incorporate the tube into various medical assemblies, e.g.,
connected to an insulin pump or the like, or to a delivery member
(e.g. needle set) for the delivery of fluids to a patient(human or
other animal) for health maintenance or during operational
procedures. Typically, these various fitments include a region
where the tube is inserted into the fitment and it is then secured
(e.g., by adhesives or other chemical and non-chemical bonding
means) in liquid-tight engagement to the fitment. Fitments may be
made from various materials, including
acrylonitrile-butadiene-styrene (ABS) copolymers, polycarbonate
(PC), acrylic resins and other thermoplastic materials so chosen
for their mechanical properties, thermal stability and for the
ability to be precisely molded within very tight dimensional
tolerances.
[0003] During the assembly process of combining a tube with a
fitment, there is a stage where a bonding material, such as a UV
curable adhesive material, is applied with an applicator to the
external outer surface of the tube, and the tube is then physically
engaged into the fitment. At the conclusion of fitting the tube
into the fitment, this portion of the assembly is exposed to UV
(ultraviolet) light which activates the adhesive to cure into a
final solid form and the tube is adhesively bonded to the fitment.
The nature of the bonding which occurs is such that it takes a
certain amount of force to physically remove the tube portion from
the fitment, e.g., to prevent unintended dislodgement during use of
the assembly. This force is typically much larger after the
application and curing of the adhesive to the surfaces versus
simply a physical insertion of the tube into the fitment, in the
absence of the adhesive.
[0004] Plasticized PVC tubing has been demonstrated to be most
useful for all of these operations with a variety of fitments made
from the different materials types referenced above. However, for
at least environmental, regulatory and/or legislative reasons,
there is a need to avoid the use of plasticized PVC as the material
with which to make medical tubing. The potential for migration of
the plasticizer into the medicinal fluid has been cited as a
concern for some fluid types.
[0005] Other elastomeric materials also have chemical functionality
(esters, amide, etc.) that may have interactions with various
medicinal fluids. Thus, there is a need to provide a secure bonding
that does not require chemical functionality in the tube or fitment
that may potentially interact with the fluid being delivered by the
assembly.
[0006] Medicinal fluids--not just the solvent/fluid types, but the
medicinal fluid itself, may comprise balanced/stable colloids and
suspensions of the active pharmacological agents that are buffered
with surfactants and other dispersion/suspending agents. These
agents may preferentially adsorb to chemical functionalities of the
tube material/luer and thus affect the medicinal efficacy of the
fluid.
[0007] Still further, many of the common fitment materials (ABS,
PC, and acrylics) are amorphous materials that are subject to
crazing/cracking. Thus the ABS, PC, Acrylic, etc luers in common
usage today may have molded in stress which makes them especially
susceptible to cracking in the presence of solvents, either prior
to or during use. The nature of the medicinal fluids may cause
stress cracking of such amorphous materials or changes in
dimensions of the luers that cause leakage or failure.
[0008] Thus, there is an ongoing need for new tubing and fitment
assemblies that avoid the aforementioned problems of stress
cracking, chemical interactions, and processing difficulties of the
prior art.
SUMMARY OF THE INVENTION
[0009] The present invention contemplates the manufacture of an
extruded tube, preferably a multilayer coextruded tube of at least
two non-PVC containing polymeric materials (lacking chemical
functionality) that are coextruded, whereby the tubing materials
are bonded securely to each other and such that the outer tubing
layer of the two materials can be readily and securely solvent
bonded on an exposed outside surface to the inside surface of the
central channel of a tubular component, such as a luer or other
fitment. The tubing is particularly well adapted for bonding to a
fitment comprised of inert polypropylene based materials for use in
medical fluid delivery and treatment applications.
[0010] The present invention avoids the problems of the prior art
plasticized PVC tubing, and also avoids the problems of using UV
curable adhesives. These curable adhesives are expensive, and
require the additional step of exposure to UV light, which adds
considerably to the cost of assembling the tubing and fitment.
[0011] The invention further avoids the potential for fluid
contamination. It has been observed that the fluid being injected
through a tubing and fitment will often wet out the area of
engagement between the tubing and fitment, thereby encountering the
adhesive polymer material. The UV curable polymers may have
extractable uncured monomer or other components that are not
intended and would be detrimental to the patient if they become
part of the injected fluids delivered to the patient.
[0012] The present invention further eliminates the need for the
use of ester, urethane, or amide containing elastomers or other
chemical functionality, such as carbonyls or acid groups, that may
contact and interact with fluids being delivered through the tubing
or fitment.
[0013] In accordance with one embodiment of the invention, the
invention further avoids the use of fitment materials that are
prone to stress cracking in the presence of medicinal fluids.
[0014] In accordance with one embodiment of the invention, a method
is provided for coaxially bonding a polymeric tube to a
prefabricated tubular body, the prefabricated tubular body defining
a hollow central tubular passage having a longitudinal axis bounded
by an inner wall of polypropylene based material, the method
comprising: [0015] extruding a mating polymeric tube having an
outer tubular wall surface comprising of thermoplastic
propylene-based elastomer (PBE) material, and a central tubular
passage having a longitudinal axis and opposing ends, [0016]
treating the outer surface of the mating tube along a selected
axial length at one of the end of the tube with a solvent that
causes the treated outer surface to adhere to the inner wall of the
tubular body on drying, [0017] inserting the treated end of the
mating tube coaxially into the central tubular passage of the
tubular body such that the outer surface of the treated end mates
with the inner wall of the tubular body along the selected axial
length to form a mated juncture, [0018] allowing the mated juncture
to dry such that the treated outer surface solvent bonds to the
inner wall.
[0019] In one embodiment, the solvent is selected from one or more
of cyclohexanone, cyclohexane, hexane, xylene, tetrahydrofuran
(THF), ethyl acetate (EA) and methyl ethyl ketone (MEK).
[0020] In one embodiment, the solvent is selected from one or more
of cyclohexane, cyclohexanone, xylene, tetrahydrofuran, and
hexane.
[0021] In one embodiment, the PBE is a copolymer or blend of
propylene and an alpha-olefin.
[0022] In one embodiment, the PBE is a propylene/alpha-olefin
copolymer with semi-crystalline isotactic propylene segments.
[0023] In one embodiment, the PBE is a blend of a first polymer
component (FPC) which is a predominately crystalline stereoregular
polypropylene, and a second polymer component (SPC) which is a
crystallizable copolymer of C2,C4-C20 alpha-olefin and
propylene.
[0024] In one embodiment, the alpha-olefin is ethylene. The method
of claim 1 wherein the tube has an inner wall comprising a layer of
a polyethylene (PE).
[0025] In one embodiment, the PE of the inner wall is a low density
polyethylene (LDPE), linear low density polyethylene (LLDPE), high
density polyethylene (HDPE) or blends thereof.
[0026] In one embodiment, the step of extruding comprises
coextruding an outer tubular layer of the PBE material with at
least one innermost tubular layer of a thermoplastic ethylene-based
olefinic material.
[0027] In one embodiment, the coextruded outer layer of the mating
tube is the PBE with an ethylene content of at least 9% by weight
and the innermost layer of the mating tube is polyethylene.
[0028] In one embodiment, the tubular body comprises a
prefabricated body of PBE material.
[0029] In one embodiment, the PBE material of the tubular body is a
homopolymer polypropylene or a copolymer of predominately propylene
units and ethylene.
[0030] In accordance with another embodiment of the invention, a
bonded tubular assembly is provided comprising: [0031] a
prefabricated tubular body defining a hollow central tubular
passage having a longitudinal axis bounded by an inner wall of
propylene-based material, [0032] an extruded tube having an
extruded outer tubular wall surface comprised of thermoplastic
propylene-based elastomer (PBE) material, the mating tube having a
central tubular passage having a longitudinal axis and opposing
ends, [0033] wherein one of the ends of the mating tube is
coaxially positioned within the central tubular passage of the
prefabricated tubular body such that the outer surface of the one
end of the mating tube is mated with the inner wall of the tubular
body along a selected axial length of the mating tube, [0034] the
mated outer surface and inner wall being solvent bonded to each
other.
[0035] In one embodiment, the extruded tube is a coextruded tube
having an outer tubular layer of the PBE material with at least one
innermost tubular layer of a thermoplastic ethylene-based olefinic
material.
[0036] In one embodiment, the coextruded outer layer of the mating
tube is the PBE material with an ethylene content of at least 9% by
weight and the innermost layer of the mating tube is
polyethylene.
[0037] In one embodiment, the tube has an inner wall forming the
central tubular passage comprising a coextruded a layer of a
polyethylene (PE).
[0038] In one embodiment, the PE is a low density polyethylene
(LDPE), linear low density polyethylene (LLDPE), high density
polyethylene (HDPE) or blends thereof.
[0039] In accordance with one embodiment of the invention, a method
is provided of delivering an aqueous based or non-aqueous based
medicinal fluid or combination thereof to a patient comprising
inserting a fluid delivery member into the body, the member being
fluidly connected to the bonded tubular assembly, and delivering
the medical fluid through the tube to the delivery member.
[0040] In one embodiment, the medicinal fluid comprises one or more
of:
[0041] the nonaqueous solvents selected from the group consisting
of: vegetable oils, ethyl oleate, propylene glycol, and
polyethylene glycols with molecular weights of 300 and 400.
[0042] In one embodiment, the medicinal fluid comprises one or more
of: [0043] synthetic and semisynthetic preparations as solvent or
mixed solvent based fluid preparations for injection to the
patient, selected from the group consisting of alcohols, esters,
ethers, amides, sulfoxides and pyrrolidones.
[0044] In one embodiment, the fluid preparations are selected form
the group consisting of ethyl alcohol; benzyl alcohol; phenylethyl
alcohol; propylene glycol; butylene glycol; trichloro-t-butyl;
polyoxyethylene glycol; ethyl ether; phenoxyethanol; ethyl acetate
ethyl oleate; benzyl benzoate; N-methylacetamide;
N,N-dimethylacetamide; dimethyl sulfoxide (DMSO), and N-methyl
2-pyrrolidone, (NMP).
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] The accompanying drawings illustrate one or more
non-limiting examples of the invention.
[0046] FIG. 1 is a schematic perspective view of a portion of a
multilayer co-extruded tube according to one embodiment of the
invention, the tube having a terminal end portion of a selected
axial length AL.
[0047] FIG. 2 is a side cross-sectional view of the tube of FIG. 1
with its terminal end portion coaxially inserted and solvent bonded
within a central fluid flow channel end of a prefabricated tubular
body (luer).
[0048] FIG. 3 is a schematic flow chart of one method according to
the invention.
[0049] FIG. 4 is a schematic perspective view of a portion of a
monolayer tube according to another embodiment of the
invention.
[0050] FIG. 5 is a graph of measured bond strength values for
various embodiments of the invention utilizing different solvents
for bonding the extruded tube and luer fitting, all showing a
substantial improvement over an interference fit without solvent
bonding.
[0051] FIG. 6 is a graph similar to FIG. 5 showing significant
improvements in bonding strength for co-extruded tubing samples
filled with different fluids.
DETAILED DESCRIPTION
[0052] Reference is made to the exemplary embodiments of the
invention with reference to the Figures. Wherever possible, the
same reference numbers are used throughout the drawings to refer to
the same or like parts.
[0053] With reference to FIGS. 1, 2 a polymeric tube 10 according
to the invention is fabricated by co-extruding a first outer layer
12 comprised of an extrudable thermoplastic propylene-based
elastomer (PBE) material into bonding engagement with the outer
surface 14a of a first inner layer 14 comprised of an extrudable
thermoplastic ethylene-based olefinic material. One or more
additional intermediate or inner layers 19 of extrudable polymeric
materials can, as optionally desired, be co-extruded together with
the materials of layers 12, 14 into successive bonding engagement
with the layers 12, 14 to form a three or more layered tube 10.
Alternatively, a monolayer tube of the extrudable thermoplastic PBE
(same material as outer layer 12) may be used as shown in FIG. 4
and described below.
[0054] The propylene-based outer layer 12 is typically selected to
comprise a PBE that renders the material flexible for use as tubing
for delivery of a medicinal fluid depending on the intended
applications and also compatible with a propylene-based fitting
(e.g., luer) to enable solvent bonding thereto. Suitable PBEs are
described below.
[0055] In one embodiment, the present invention relates to a
polymeric tube for the delivery of medicinal fluids comprising a
propylene based elastomer (PBE) that exhibits substantially
equivalent mechanical performance to plasticized PVCs known in the
industry.
[0056] In one embodiment, the PBE polymers' composition of the
present invention is propylene/alpha-olefin copolymers with
semi-crystalline isotactic propylene segments. In one specific
embodiment, the PBE for use in the present invention have a
comonomer range of between 9 to 16%, preferably between 9 to 11%.
The comonomers are alpha-olefins. In addition, the PBE polymers may
have a narrow molecular weight distribution of 2-3. The molecular
weight distribution is induced Mw/Mn (also referred to as
polydispersity index or MWD).
[0057] In yet another embodiment, the suitable PBE for use in the
present invention is ExxonMobil Vistamaxx series (eg, 3020FL or
3980FL grades). One method of producing such a PBE is disclosed in
U.S. Pat. No. 6,927,258, which is incorporated by reference herein.
For examples, such a PBE is produced by blending a "first polymer
component" ("FPC") which is a predominately crystalline
stereoregular polypropylene with a "second polymer component"
("SPC") which is a crystallizable copolymer of C2, C4-C20
alpha-olefin (preferable ethylene) and propylene. Optional
components of the blend are SPC2, a crystallizable copolymer of C2,
C4-C20 alpha olefins (preferably ethylene). Other optional
components are fillers, colorants, antioxidants, nucleating agents,
lubricants and other process aids.
[0058] The FPC melts higher than 110 C (degrees Centigrade) and has
a heat of fusion of at least 75 J/g (Joules/gram), as determined by
DSC (Differential Scanning calorimetry) analysis. The crystalline
polypropylene can be either a homopolymer or a copolymer with other
alpha olefins. The SPC, and optionally the SPC2 if used, have
stereoregular propylene sequences long enough to crystallize. The
SPC has a melting point of less than 105 C and has a heat of fusion
of less than 75 J/g. The SPC2 has a melting point of less than 115
C and has a heat of fusion of less than 75 J/g. One embodiment is
blending isotactic polypropylene (FPC) with ethylene propylene
copolymers (SPC) having about 4 wt % to about 35 wt % ethylene so
as to ensure high compatibility with the FPC. The ratio of the FPC
to the SPC of the blend composition may vary in the range 2:98 to
70:30 by weight.
[0059] In one embodiment, the PBEs of the present invention have a
glass transition temperature (Tg) range of about -15 to -35 C. The
PBE of the present invention have a melt flow range (MFR) as
measured at 230 C of between 0.5 to 50 grams/10 minutes as per ASTM
D1238. In one embodiment, the PBE of the present invention have a
preferred Shore A hardness range of about 60 to 90 and have a
flexural modulus range of about 500 to 20,000 psi (pounds per
square inch) and more preferably of about 1,000 to 16,500 psi.
[0060] Alternatively, the outer layer may comprise a blend of
polypropylene and other olefinic polymers (e.g., polyethylene or
polyethylene-octene block copolymers); the blend should be
extrudable and compatible with both the inner layer and the fitment
to which it will be solvent bonded.
[0061] The thickness of outer layer 12 typically ranges between
about 0.0005 inches and about 0.050 inches. The thickness of the
outer layer will vary depending on cost of materials, desired
physical properties, extrusion equipment, intended use of the
tubing and fitment, and other design concerns.
[0062] The ethylene-based olefinic material of which the first
inner layer 14 is comprised is preferably a predominately
extrudable thermoplastic ethylene-based olefinic material. The
inner layer may be comprised of a polyethylene ("PE"), typically a
low density polyethylene ("LDPE"), linear low density polyethylene
("LLDPE"), high density polyethylene ("HDPE") or blends thereof.
The inner layer is extrudable, compatible with adjacent tube
layers, and where as it comprises the innermost layer that forms
the fluid delivery channel, substantially inert and approved for
use with the fluid. The thickness of the inner layer 14 typically
ranges between about 0.0005 inches and about 0.025 inches but again
will vary with overall tube dimensions and lengths, cost of
materials, extrusion equipment, intended use (application), and
other design concerns.
[0063] Both the first and second layer materials are thermoplastic
materials that are extrudable, processable as a melt at elevated
temperature, do not have significant creep, are of generally low
modulus and are flexible materials that can be stretched repeatedly
at room temperature with an ability to return to their approximate
original length if not stretched beyond their elastic yield
strain.
[0064] The inner layer 14 is non-polar and otherwise lacking
chemical functionality (functional groups) that would interact with
a medicinal fluid of the intended application. By medicinal fluid
it is meant any aqueous based fluid, non-aqueous based fluid, or
combination thereof acceptable for injection into a patient (human
or other animal) which includes the active pharmacological
substance or biological substance, the choice of which is for an
intended beneficial medical treatment of the patient. The active
pharmacological or biological substance to be injected (e.g., via
subcutaneous or intramuscular introduction, intravenous and other
parenteral means) may include but is not limited to insulin,
anti-inflammatories, anti-septics, cancer therapies, arthritis
therapies, other treatment therapies, protein and enzyme based
pharmaceuticals, nutrients, and other medicants. The active
pharmacological or biological substance may be delivered via any of
various aqueous, nonaqueous, or mixed solvents and other carrier
fluids. Of the nonaqueous solvents, the following are examples:
vegetable oils, ethyl oleate, propylene glycol, and polyethylene
glycols with molecular weights of 300 and 400. Synthetic and
semisynthetic preparations are also available as solvent or mixed
solvent based fluid preparations for injection to the patient;
examples include the alcohols (e.g., ethyl, benzyl, phenylethyl,
propylene glycol, butylene glycol, trichloro-t-butyl, etc.), ethers
and esters (e.g., polyoxytheylene glycol, ethyl ether,
phenoxyethanol, ethyl acetate ethyl oleate, benzl benzoate, etc.),
amides (e.g., N-methylacetamide and N,N-dimethylacetamide),
sulfoxides (e.g,. dimethyl sulfoxide, (DMSO)), pyrrolidones (e.g.,
N-methyl 2-pyrrolidone, (NMP)) and the like.
[0065] The active pharmacological substance or biological substance
is typically prepared as a stabilized mixture, suspension or
emulsion in combination with the aqueous, nonaqueous or solvent
based carrier fluid. Chemical interaction of the medicinal fluid
with the chemical functionalities of the tube and fitment during
conveyance to the patient, through adsorption or absorption of
components of the medicinal fluid, is to be avoided as it may
negatively affect the stability of the medicinal fluid and affect
the proper administration of the active pharmacological substance
or biological substance, thus negatively affecting the efficacy of
the intended medical treatment of the patient.
[0066] The fitments must also not have any negative interaction
with the medicinal fluid, either through direct solvation of the
fitment by components of the medicinal fluid or through
environmental stress cracking (ESC) of the fitment by the medicinal
fluid. Solvation of the fitment by the medicinal fluid leads to
loss of mechanical integrity of the fitment itself, decreases the
bond strength between the tube and fitment during use and is also a
means by which the dissolved fitment material may potentially be
injected to the patient during fluid conveyance. Environmental
stress cracking of the fitment leads to the mechanical failure of
the fitment due to continuously acting external and/or internal
stresses in the fitment due to the presence of surface active
substances (known as stress cracking agents) that may exist in the
form of surfactants, buffering agents or other suspending agents
utilized to produce stable medicinal solutions and suspensions in
which the fitment will come into contact with while in use. The ESC
of the fitment may also contribute to a decrease of the bond
strength between the tube and fitment. Although ESC results from
the interaction of the polymer used to make the fitment with
certain chemicals, it is usually not a chemical reaction between
the polymer and the active environment and is well in known in the
art. In practice, ESC occurs more readily in amorphous polymers
such as ABS (acrylonitrile-butadiene-styrene terpolymers), PC
(polycarbonate), PMMA (polymethyl methacrylate), PEMA (polyethyl
methacrylate), PS (polystyrene), rigid PVC, SAN
(styrene-acrylonitrile copolymer), all of which are commonly
utilized as materials for fitments, as well as in some
semi-crystalline thermoplastics like polyethylene. In the
production of various fitments utilized in the medical field,
injection molding is typically the process of choice and
manufacturing necessity and there exists the potential for
internally induced stresses in the final fitment due to the very
high polymer melt injection pressures utilized in the injection
molding process. Amorphous polymers (glassy polymers) exhibit a
higher tendency for this type of failure because their loose
structure facilitates fluid permeation into the polymer. The stress
acting agents which may exist in the medicinal fluid may promote
crazing, cracking or plasticization of the fitment. In amorphous
polymers, crack formation due to ESC is often preceded by craze
formation. Crazes are expanded regions held together by highly
drawn fibrils which bridge the micro-cracks and prevent their
propagation and coalescence. Semi-crystalline polymers such as PE
show brittle fracture under stress if exposed to stress cracking
agents. In such polymers, the crystallites are connected by the tie
molecules through the amorphous phase. The tie molecules play a
decisive role in the mechanical properties of the polymer, through
the transmission of load. Stress cracking agents act to lower the
cohesive forces which maintain the tie molecules in the
crystallites, thus facilitating their "pull-out" and
disentanglement from the lamellae.
[0067] in contrast, in accordance with the present invention,
polypropylene is a material which is desirable for use as the
fitment material as it has no known solvent at room temperature
which may be utilized in a medicinal fluid, and polypropylene is a
material in which ESC does not readily occur.
[0068] Returning to FIG. 2, the tubular body or fitment 20 to be
solvent bonded to the tube 10 is typically formed into the
configuration of a luer, plastic tube connector or other fitment
that is used in medical applications such as for connecting tubes
for delivery of medicinal fluids from a fluid source to a patient
or receptacle in a sterile manner where the fluid is sealed within
a closed system, the tubing and connector maintaining the fluid
contained within the sealed system. The tubular body 20 is most
preferably comprised of a prefabricated PBE material, utilizing
either a homopolymer polypropylene or a copolymer of predominately
propylene units and a compatible co-monomer, such as ethylene. The
polymeric material of which tubular body 20 is comprised can also
have optional components such as fillers, colorants, antioxidants,
nucleating agents, lubricants and other process aids.
[0069] As shown in FIGS. 1 and 2, the tube 10 has a terminal end
portion 11 having an outer surface 18 and a selected axial length
AL for purposes of insertion into passage 22 and solvent bonding to
the inner wall surface 22a of the central fluid passage 22 of
tubular body 20 (typically in the form of a luer). As shown in FIG.
2, the end portion 11 of the tube (after being coated with a
solvent for bonding to the fitment 20) is inserted into passage 22
of body 20 such that axis A1 of the tube 10 is generally coaxially
aligned with the axis A2 of the tubular body 20. The
cross-sectional diameter D2 of the passage 22 is preferably
complementary to the cross-sectional diameter D1 of the end portion
11 of the tube 10. The diameter D2 can be slightly smaller than D1
(e.g., 0.001 to about 0.015 inches smaller) in order to ensure a
snug fit of the end portion 11 within passage 22. On insertion of
end portion 11 into passage 22, the outer surface 18 engages
against the inner surface 22a of passage 22 and the solvent that
has been applied to surface 18 of tube end 11 prior to insertion is
spread over both surfaces 18 and 22a along substantially the entire
selected axial length AL.
[0070] The tubular body 20 typically has separate co-axially
aligned (A1-A2) hollow central passage portions 22, 24 respectively
that have different cross-sectional inner diameters D2 and D3,
where D3 is typically smaller than D2 thus forming a stop surface
25 against which the larger diameter D1 terminal end surface 17 of
the terminal end portion 11 of tube 10 (about the same or slightly
larger than D2) is stopped and abuts against on forcible manual
insertion of end portion 11 axially into and through passage
[0071] The solvent for treating outer surface 18 of the tube 10 is
typically selected from one or more hydrocarbons, such as
cyclohexanone, cyclohexane, hexane, xylene, tetrahydrofuran (THF),
ethyl acetate (EA) and methyl ethyl ketone (MEK). Solvent treatment
typically comprises applying the solvent to surface 18 of the end
portion 11 of tube 10 prior to inserting the end portion 11 into
the axial passage 22 of the tubular body 20.
[0072] FIG. 3 is a flow chart illustrating one method embodiment of
the invention. In the first step, a tube, such as multilayer tube
10 shown in FIGS. 1-2, is co-extruded as the mating tube to be
solvent bonded with the tubular body 20. In a next step, the outer
surface of the mating tube at one end portion is treated with
solvent, e.g., by applying a coating of the solvent. In a next
step, the treated end portion of the mating tube is inserted into a
central tubular passage of the tubular body, to form a mated
juncture along the coaxial mating portions of the outer surface of
the tube and central passage of the tubular body. In a next step,
the mated juncture is allowed to dry so that the solvent evaporates
such that a solvent bond is formed between the mating portion of
the outer surface of the tube and the central tubular passage of
the tubular body.
[0073] In an alternative embodiment, shown in FIG. 4, a monolayer
tube of the thermoplastic PBE material is provided. In this case,
the single layer tubular wall forms both the outer surface 18 for
solvent bonding with the central passage of the tubular body, and
the inner tubular surface 21 of the single layer forms the fluid
delivery passage that is intended, as previously described, to be
non-polar and otherwise lacking in chemical functionality that
would interact with a medicinal fluid of the intended
application.
[0074] Tubing samples according to various multilayer embodiments
were tested, as set forth below.
[0075] Tubing Test Samples: Tubing specimens were fabricated by
co-extrusion in multilayer form, with materials as specified below,
and using an extrusion tooling such as the "Tri Die" extrusion
apparatus manufactured by the Genca Division of General Cable
Company, Clearwater, Fla.: [0076] Outer Layer: Vistamaxx 3980FL, or
Vistamaxx 3020FL (ExxonMobil Chemical, Houston, Tex., USA) [0077]
Inner Layer: Westlake 808 LDPE (Westlake Chemical, Houston, Tex.,
USA) [0078] Solvents tested: [0079] ethyl acetate (EA) [0080]
methyl ethyl ketone (MEK) [0081] cyclohexanone [0082]
tetrahydrofuran (THF) [0083] hexane [0084] xylene [0085]
cyclohexane
[0086] The two material, two layer (2M2L) coextruded tubing
specimens were extruded with dimensions of: 0.152 inches
OD.times.0.090 inches ID and overall wall thickness =0.031 inches
The outer layer of the PBE had a thickness of 0.026 inches and the
inner layer of ethylene-based material had a thickness of 0.005
inches As known in the art, the extrusion or co-extrusion process
is carried out by melting the polymeric material(s), routing the
melted material(s) under pressure through a suitable die head to
form a tubular shaped extrudate or co-extrudate that is then cooled
through conventional water baths or water vacuum tanks to form an
end product. Tubing specimens so fabricated were then bonded to
commercially available luers as specified below and then pull
tested for bond strength. The test samples were prepared and test
equipment and parameters utilized were as follows.
[0087] Samples Prepared for Solvent Bonding: [0088] 1. Tube samples
were cut to 8 inches and the end of the tube was cleaned with 70%
isopropyl alcohol and allowed to air dry. [0089] 2. Solvent was
applied to 1/2 inch of the cleaned end of tube with small
applicator and inserted into the luer. [0090] 3. Tubes were set to
dry for 24 hours prior to mechanical testing (72.degree. F./50%
RH).
[0091] Mechanical Test Equipment and Parameters as described below
were used in the testing of tubing samples that were solvent bonded
to commercially available polypropylene luers. Mechanical test
equipment which can test samples in a tensile manner and record
forces on the sample are well known in the art; equipment such as
those manufactured by Instron (826 University Avenue, Norwood,
Mass., USA) or Lloyd Instruments Ltd (West Sussex, UK) are useful
for testing. Such instruments include load cells attached to a
moveable clamp and include an immovable clamp or jaw. Usually, a
sample is clamped between the top and bottom clamps and one clamp
is moved at a control rate and records the force which a sample is
experiencing whilst the clamp is moving. In the test described
below, the tube and luer assembly is secured within the equipment
clamps and the maximum force, in pounds, to remove the tube from
the luer is measured. Such a test is referred to as a pull test:
[0092] 1. Test equipment clamps are set 3 inches apart. [0093] 2.
Luer end of tube clamped in center of the upper clamp. [0094] 3.
Loose end of tube clamped in center of the lower clamp. [0095] 4.
The pull test is initiated and allowed to cycle through until the
tube is pulled from luer at a rate of 12 inches per minute. [0096]
5. The pound force (pounds, lbs) to pull the tube from the luer is
recorded and the tube is removed from the clamps. [0097] 6. Steps
1-5 are repeated for each sample (10.times.) for each type of
luer/tube combination.
[0098] Commercially available luer specimens used in the assembly
and pull tested were purchased from Qosina Inc., 150-Q Executive
Drive, Edgewood, N.J. 11717, USA (Qosina.com) with the following
identification and specifications: Part Number 65213, Female Luer
Lock Connector, 0.145 inch to 0.156 inch ID, 0.206 inch OD,
Material: Polypropylene.
[0099] As shown by the bond strength data summarized in FIG. 5, a
multi-layer (2 material, 2 layer) tube 10 having an outer surface
layer formed from the Vistamaxx.TM. 3980 FL (striped bars) or
Vistamaxx.TM. 3020 FL (unstriped bars) that is solvent bonded to
the least effective bonding solvent (ethyl acetate) still provides
a significant improvement in bonding strength to a polypropylene
luer, relative to a non-solvent bonded assembly that relies solely
on a mechanical interference fit. As shown by the data, the bonding
strength of the least effective solvent was at least about 3.5 lbs
as compared with a bonding strength of about 2.3-2.6 lbs based on a
mechanical interference fit alone (without solvent). A number of
solvents produced bond strengths greater than 4 lbs., ranging from
6.3 to 13.5 lbs.
[0100] FIG. 6 demonstrates the chemical compatibility of two
non-aqueous fluid systems, DMSO and NMP, respectively, with the
aforementioned Vistamaxx 3980 FL tubing samples according to one
embodiment of the invention. DMSO (dimethyl sulfoxide) and NMP
(N-methyl 2-pyrrolidone) are common fluid carriers or solvents
recognized by the US Food and Drug Administrtion for use in
medicinal fluids and are typically utilized, amongst other uses,
for solubilizing lipophilic pharmacological substances that are not
readily soluble in water. DMSO and NMP are also recognized to be
very aggressive to many polymers either as strong solvents or
stress crack agents. The data presents the pull test results for
samples made from Vistamaxx 3980FL as the outer layer, when
coextruded with an inner layer of polyethylene, and solvent bonded
to the polypropylene luer utilizing xylene or cyclohexane. After
preparation of the tube and luer assembly, the luer was heat
crimped to seal the luer at the end opposite to which the tube was
inserted. After the luer end was sealed, the tube and luer
assemblies were filled with either DMSO or NMP, and left at room
temperature conditions (72 F/50% R.H.) in a sealed glass jar. At 24
hours and 48 hours after filling, the DMSO and NMP were drained
from the tube and luer assemblies and the samples were pull tested.
As can be seen in FIG. 6, there was little or no degradation of
bond strength between the tube and luer over the stated time
periods. There was no noted swelling of the tube and no swelling or
cracking of the luer.
[0101] As is readily apparent, numerous modifications and changes
may readily occur to those skilled in the art. Hence, the
disclosure herein is not intended to limit the invention to the
exact construction and operation shown and described. All suitable
equivalents are included within the scope of the invention as
claimed.
* * * * *