U.S. patent application number 17/087195 was filed with the patent office on 2021-02-18 for method of reducing friction between syringe components.
The applicant listed for this patent is W. L. Gore & Associates, Inc.. Invention is credited to Michael P. Moritz.
Application Number | 20210046245 17/087195 |
Document ID | / |
Family ID | 1000005191015 |
Filed Date | 2021-02-18 |
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United States Patent
Application |
20210046245 |
Kind Code |
A1 |
Moritz; Michael P. |
February 18, 2021 |
Method Of Reducing Friction Between Syringe Components
Abstract
A method of making a syringe assembly includes providing a first
syringe component defining a first sliding surface that is
substantially free of lubricant. The first sliding surface is
contacted with water. The first sliding surface and the water in
contact with the first sliding surface are heated at a temperature
of at least 121.degree. C. The first sliding surface is dried.
Inventors: |
Moritz; Michael P.; (Media,
PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
W. L. Gore & Associates, Inc. |
Newark |
DE |
US |
|
|
Family ID: |
1000005191015 |
Appl. No.: |
17/087195 |
Filed: |
November 2, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15335112 |
Oct 26, 2016 |
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17087195 |
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13446900 |
Apr 13, 2012 |
9539394 |
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15335112 |
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61475851 |
Apr 15, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B08B 3/10 20130101; A61M
2207/00 20130101; A61M 5/3129 20130101; A61M 2005/3131 20130101;
B05D 5/08 20130101; A61M 5/28 20130101; Y10T 29/4984 20150115 |
International
Class: |
A61M 5/31 20060101
A61M005/31; B08B 3/10 20060101 B08B003/10; B05D 5/08 20060101
B05D005/08; A61M 5/28 20060101 A61M005/28 |
Claims
1. A method of treating a syringe assembly comprising: providing a
glass barrel having a glass sliding surface for sliding engagement
with a complementary component of a syringe assembly; applying
saturated steam to heat the glass sliding surface; maintaining the
saturated steam at a temperature at or above 120.degree. C. for at
least 60 minutes; and drying the glass sliding surface, wherein a
friction force of the glass sliding surface is reduced.
2. The method of claim 1, wherein the glass sliding surface is an
interior surface of the glass barrel.
3. The method of claim 2, wherein the glass sliding surface is
substantially free of silicone oil.
4. The method of claim 1, wherein the method is achieved within a
sterilization cycle.
5. The method of claim 1, wherein the glass sliding surface is
dried at about 90.degree. C. or greater.
6. The method of claim 1, comprising rinsing the glass sliding
surface with an organic solvent.
7. The method of claim 1, wherein the complementary component is a
syringe stopper or a syringe tip cap.
8. The method of claim 1, wherein the glass barrel contains therein
water for injection.
9. The method of claim 7, comprising removing the water for
injection prior to the drying.
10. The method of claim 1, comprising placing the barrel into an
autoclave prior to the application of saturated steam.
Description
BACKGROUND
[0001] Syringes used for delivery of medicaments are principally
constructed of a barrel and a stopper. The stopper is slidably
fitted within the syringe barrel and may have a stopper rod affixed
to it for actuation of the syringe and delivery of medicament. The
stopper is generally constructed of an elastomer, with silicone oil
applied. The silicone oil is applied to the stopper or barrel to
reduce sliding friction between the stopper and barrel and to
improve the seal between them, which can be helpful in ensuring a
full dose is administered. Ease of sliding can be important for
proper operation of pens and so-called auto injecting syringes. The
oil helps prevent jamming of such devices, which can otherwise lead
to trauma at the site of injection. The improved sealing provided
by silicone oil can also help ensure no foreign contaminants, such
as bacteria, enter the syringe.
[0002] Recently there has developed a trend favoring pre-filled
syringes which function to both store and deliver medicaments. Such
pre-filled syringes may offer cost savings to the pharmaceutical
industry and may improve safety, convenience and efficacy of
medicament delivery. Biopharmaceuticals are an important class of
pharmaceuticals that may increase the use of pre-filled syringes
and related devices (pens, auto injectors and the like). Such
biopharmaceuticals may include insulin, vaccines, antibodies, blood
products, hormones, cytokines, and the like. As more
pharmaceuticals and particularly biopharmaceuticals utilize
delivery in pre-filled syringes and similar devices, the challenges
of conventional syringe technology multiply.
[0003] Several aspects of traditional syringe construction present
a challenge for their use as pre-filled syringes. The use of
silicone oil is a concern, because the oil may degrade the
medicament and because a small amount of silicone may be injected
with it. The oil is of particular concern with regard to
biopharmaceuticals because it may cause aggregation of certain
proteins.
[0004] Another issue that arises in pre-filled syringes is that the
elastomer of the stopper may contain leachable and extractable
contaminants. These may also contaminate the medicament upon long
term storage in syringes. Trace amounts of residual monomer or
plasticizer or other impurities from the stopper can adversely
affect the therapeutic function or can have an adverse impact on
the patient once injected.
[0005] Among the many other considerations affecting pre-filled
syringe devices and similar devices and their components are the
need to be sterilized, stability with transport and storage for up
to a few years, optical clarity, the need to integrate into
existing filling equipment (including the durability requirements
for stopper cleaning and insertion into the syringe barrel),
leachables and extractables of all components of the syringe, and
the need to maintain sterility from filling through administering
of the contents, and finally user preferences and ergonomic
considerations. For a variety of considerations the pre-filled
syringe market uses both glass and plastic barrels.
[0006] Friction between stopper materials and syringe barrels can
be significant. As described above, lubricants such as silicone oil
are problematic. There is a need to reduce friction between stopper
and barrel without the use of oils or other lubricants that have
undesirable effects.
SUMMARY
[0007] Some aspects relate to a method of reducing sliding friction
between glass and a stopper material. The method includes exposing
glass to an aqueous solution at high temperature. For example, the
glass is optionally contacted with water for injection (WFI) water
and placed in an autoclave set at a temperature at or above
120.degree. C. Following the autoclave process, the glass is dried
at about 90.degree. C. Friction between a stopper material and
glass are thereby reduced significantly. In another aspect, the
method may include rinsing the glass, for example with an organic
solvent.
[0008] Other aspects relate to a method of making a syringe
assembly including providing a first syringe component defining a
first sliding surface that is substantially free of lubricant. The
first sliding surface is contacted with water, the first sliding
surface and the water in contact with the first sliding surface are
heated at a temperature of at least 121.degree. C., and the first
sliding surface is dried.
[0009] Still other aspects relate to a component of a syringe
assembly that is prepared for sliding engagement with a second,
complementary component of the syringe assembly by a process
including contacting the first sliding surface with WFI water.
Saturated steam is applied to heat the first sliding surface and
the WFI water in contact with the first sliding surface and the
first sliding surfaced is dried.
[0010] While multiple embodiments are disclosed, still other
embodiments of the present invention will become apparent to those
skilled in the art from the following detailed description, which
shows and describes illustrative embodiments of the invention.
Accordingly, the drawings and detailed description are to be
regarded as illustrative in nature and not restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a schematic view of a syringe assembly prepared
according to some embodiments.
[0012] FIG. 2 provides flow charts illustrating the methods of
Examples 2 to 5.
[0013] FIG. 3 is a chart reflecting functional forces of
Comparative Example 1 and Example 2.
[0014] While the invention is amenable to various modifications and
alternative forms, specific embodiments have been shown by way of
example in the drawings and are described in detail below. The
intention, however, is not to limit the invention to the particular
embodiments described. On the contrary, the invention is intended
to cover all modifications, equivalents, and alternatives falling
within the scope of the invention as defined by the appended
claims.
DETAILED DESCRIPTION
[0015] Various embodiments described herein address reducing
sliding friction between complementary sliding components in
syringe assemblies, such as friction reduction between a first,
softer component and a second, more rigid component of a syringe
assembly. For example, some embodiments relate to reducing friction
between a syringe stopper and a barrel, between a syringe tip cap
and a barrel, or between a syringe valve body and valve plug, or
other complementary syringe components. In some embodiments, the
first component (e.g., a stopper) includes an elastomeric material,
such as butyl rubber, and the second component (e.g., a syringe
barrel) includes a ceramic material, such as borosilicate glass.
While various embodiments are described in association with syringe
assembly applications, a variety of applications where reduced
friction is sought are contemplated.
[0016] FIG. 1 is a schematic view of a syringe assembly 10,
according to some embodiments. As shown, the syringe assembly 10
includes a syringe barrel 12, a stopper 14 that forms a
complementary fit with the syringe barrel 12, a plunger rod 16, a
tip cap or needle shield 18, and, in the case of a pre-filled
embodiment, a liquid 20, such as a medicament, for dispensing from
the syringe assembly 10. As shown, the syringe barrel 12 and the
stopper 14 are first and second complementary syringe components
that are slidably engaged with one another, the stopper 14 forming
a slidable seal within the syringe barrel 12. Although the syringe
barrel 12 and the stopper 14 are slidably engaged in a linear
relationship, it should be understood that other sliding
relationships (e.g., rotational sliding between a valve body and a
valve plug) are contemplated.
[0017] As shown, the syringe barrel 12 defines a bore or inner
surface 30, also described as a sliding surface. The syringe barrel
12 is formed of a suitable material, such as suitable ceramic,
polymeric, and metal materials. In some embodiments, the syringe
barrel 12 includes a substantially rigid or hard material, such as
a glass material. Although any of a variety of glass compositions
are contemplated, according to the examples that follow
borosilicate glass has been shown to be an effective material in
association with friction-reduction methods according to some
embodiments.
[0018] As indicated in FIG. 1, the stopper 14 defines an outer
surface 32 for slidably engaging the inner surface 30 of the
syringe barrel 12. In some embodiments, the stopper 14 includes a
softer material than the syringe barrel 12. For example, the
stopper 14 is optionally constructed with one or more barrier films
applied to an elastomeric core, where the barrier film(s) define
the outer surface 32 of the stopper 14. The elastomeric core can be
formed of a variety of elastomeric materials, including: Butyl
Rubber, Silicon, materials sold under the trade name "VITON", and
the like. The barrier film or films optionally include expanded
fluoropolymer films and, such as expanded polytetrafluoroethylene
films. Barrier films based on expanded PTFE help provide for thin
and strong barrier layers to leachables and extractables. Some
examples of suitable stopper designs utilizing expanded PTFE and
elastomeric materials are described in U.S. application Ser. No.
12/915,850, "SYRINGE STOPPER" by Ashmead et al., filed Oct. 29,
2010, the entire contents of which are incorporated herein by
reference for all purposes.
[0019] In some embodiment methods of reducing friction between the
stopper 14 and the syringe barrel 12 of the syringe assembly 10,
the syringe barrel 12 is filled with WFI water and sealed to
prevent leakage. A cap, a second stopper, or other sealing member
(not shown) different than the stopper 14 is optionally utilized to
seal the WFI water within the syringe barrel 12. In other
embodiments, the assembly 10, including the stopper 14 is filled
with WFI water. The WFI water filled syringe barrel 12 is exposed
to a source of heat, such as saturated steam. For example, the WFI
water filled syringe barrel 12 may be placed in an autoclave with
the temperature set at 121.degree. C. or above. The saturated steam
will heat the WFI water and the syringe barrel 12. The WFI water is
removed and the syringe barrel 12 is dried. Following drying, the
syringe barrel 12 is ready for use. Syringe assemblies with syringe
barrels thus prepared display lower frictional forces between the
syringe barrel 12 and the stopper 14.
[0020] In some embodiments, the syringe barrel 12 is rinsed with an
organic solvent after the syringe barrel 12 and associated WFI
water have been heated with steam. For example, a Hexane solvent
may be used to rinse the syringe barrel 12. After the rinsing step,
the syringe barrel 12 is dried. Drying may be conducted at room
temperature (RT) or at elevated temperatures (e.g., at about
90.degree. C. or greater, from about 70.degree. C. to about
110.degree. C., other at other temperature(s) as desired). The
following examples are illustrative of methods of preparing a
syringe assembly 10 with reduced friction according to some
embodiments. While various methods of reducing friction between the
syringe barrel 12 and the stopper 14 have been described, it should
be understood that in other implementations similar methodology is
applied to reduce friction between alternative or additional
components of the syringe assembly 10, such as between the syringe
barrel 12 and the tip cap 18, for example.
EXAMPLES
[0021] A syringe stopper was constructed in the following manner: A
layer of FEP about 0.5 mils in thickness (FEP 100, DuPont) was
laminated to a layer of densified expanded PTFE film [thickness: 1
mil; tensile strength: 13.85 ksi (longitudinal), 13.9 ksi
(transverse); modulus: 19.8 ksi (longitudinal), 20.7 ksi
(transverse); strain to break: 425% (longitudinal), 425%
(transverse)]. The two layers were stacked on top of each other in
a pin frame and heating to 380.degree. C. in an oven for 15
minutes. A layer of porous expanded PTFE [thickness: 27.5
micrometers, matrix tensile strength: 66.8 MPa (longitudinal), 75.8
MPa (transverse), strain to break: 131% (longitudinal), 91%
(transverse), bubble point: 22.6 psi] was placed on the densified
ePTFE-FEP laminate such that the porous expanded PTFE layer faced
the FEP layer in the laminate. These three layers were placed
between two smooth metal plates, the plates were clamped to a
clamping pressure of about 1 psi. The plates were then placed in an
oven at 305.degree. C. for 15 minutes. The resulting three layer
composite material (densified ePTFE--FEP--porous ePTFE) was then
cooled to about 40.degree. C.
[0022] This composite material was then thermoformed using heat and
vacuum to create a pre-form. The pre-form was constructed by
heating the composite to a sufficiently high temperature and then
drawing the composite over a male plug using differential pressure.
The composite material was loaded into the thermoforming apparatus
such that the densified ePTFE layer faced the plug. The composite
was heated using a hot air gun (Steinel HG2310) with air exit
temperature of 380.degree. C. by placing the gun about 5 mm away
from the surface of the composite. After 5 seconds, the film was
subjected to a vacuum of -85 kPa. The composite was continued to be
heated for another 15 seconds and cooled to about 40.degree. C.
under vacuum.
[0023] The resulting pre-form sample was then inverted and then
placed into a rubber molding cavity charged with 3.5 grams of
elastomer (50 Durometer halobutyl rubber), and the stopper was
formed by compression molding. The mold was built to geometry
specified for 1 mL "long" plunger per the ISO standard
ISO11040-5:2001(E), with an additional 2% shrinkage factor
incorporated.
[0024] The cavity was loaded in a press with both platens preheated
to 120.degree. C. The platens were closed to 55,500 lbs (about 8700
psi total internal pressure). The platens were then heated at
180.degree. C. for 5 minutes and then cooled under pressure to
40.degree. C. The pressure was released and the stopper was
ejected. The resulting stopper was washed using a detergent and
triple rinsed with de-ionized water. Stopper samples were then cut
from the release sheet using a razor blade. They were subjected to
two 30 minute cycles in an autoclave at 121.degree. C.
[0025] As constructed, the stoppers were used as in the following
examples, which reflect the improved sliding friction of the
present invention when compared to that of the comparative example.
A new stopper was used in each of the examples. FIG. 2 provides
flow charts illustrating the methods of Examples 2 to 5.
Comparative Example 1
"As delivered"
[0026] A borosilicate glass syringe (1 mL Long Schott form a 3 s
with a staked needle) was obtained. The syringe was obtained
without silicone oil applied. A stopper constructed as described
above was inserted into the barrel of the syringe and the Dynamic
force was measured. Results are reported in Table 1.
Example 2
[0027] A syringe according to the inventive method was constructed
in the following manner: A glass syringe free of silicone oil
identical to that used in Example 1 was filled with WFI grade water
and placed in an autoclave (121.degree. C. for 1 hr), the glass
syringe was then dried at 90.degree. C. for 60 minutes and allowed
to cool overnight. The stopper was then inserted into the syringe
and the dynamic force was measured to be 4.7N. Results are reported
in Table 1.
Example 3
[0028] A glass syringe free of silicone oil identical to that of
Example 1 was filled with WFI grade water and placed in an
autoclave (121.degree. C. for 1 hr), the glass syringe was then
removed from the autoclave, rinsed with hexane and dried at room
temperature overnight in a laboratory hood. Another stopper was
then inserted into this syringe and the dynamic force was measured
to be 1.1N. Results are reported in Table 1.
Example 4
[0029] A glass syringe free of silicone oil identical to that of
Comparative Example 1 was filled with WFI grade water and placed in
an autoclave (121.degree. C. for 1 hr), the glass syringe was then
removed from the autoclave and dried at room temperature overnight
in a laboratory hood. The stopper was then inserted into this
syringe and the dynamic force was measured to be 5.9N. Results are
reported in Table 1.
Example 5
[0030] A glass syringe free of silicone oil identical to that of
Comparative Example 1 was filled with WFI grade water and placed in
an autoclave (121.degree. C. for 1 hr), the glass syringe was then
removed from the autoclave and then dried at 90.degree. C. for 60
minutes. The syringe was then rinsed with hexane and allowed to dry
overnight in a laboratory hood. The stopper was then inserted into
this syringe and the dynamic force was measured to be 4.4 N.
Results are reported in Table 1.
Example 6
[0031] The syringe of Example 2 was tested per the dye ingress test
in USP <381> to evaluate the seal between the inside of the
syringe barrel and the stopper from Example 1. No significant dye
ingress was observed.
TABLE-US-00001 TABLE 1 Static Dynamic Force (N) Force (N)
Comparative 10.1 8.5 Example 1 Example 2 7.0 4.7 Example 3 7.3 1.1
Example 4 8.5 5.9 Example 5 6.4 4.4
[0032] As shown in Table 1, subjecting the glass syringe to the
treatments described in Examples 2 through 5 lower the dynamic and
static force of the stopper.
[0033] Test Methods:
[0034] Static and Dynamic Force Test
[0035] The test was performed as specified by I.S. EN ISO
7886-1:1998 Annex G, with the following exceptions: i) Syringe is
mounted so that nozzle is pointing down, ii) No liquid was
expelled; only air was expelled, and iii) Forces resulting from
travel from the total graduated capacity position to 20 mm from
that point were recorded. Static force is defined as the value at
the first inflection point in the force versus displacement graph.
Dynamic force is the value after the inflection point during
travel.
[0036] Tensile, Modulus, Strain to Break
[0037] Materials were evaluated for tensile strength, modulus and
strain to break according to ATM D882-10 using 0.25 inch by 3 inch
samples and a cross head rate of 20 inches/min and one inch gauge
length.
[0038] Various modifications and additions can be made to the
exemplary embodiments discussed without departing from the scope of
the present invention. For example, while the embodiments described
above refer to particular features, the scope of this invention
also includes embodiments having different combinations of features
and embodiments that do not include all of the described features.
Accordingly, the scope of the present invention is intended to
embrace all such alternatives, modifications, and variations as
fall within the scope of the claims, together with all equivalents
thereof.
* * * * *