Medical device lubricant system and methods of use

Abstract

The present invention disclosed a lubricant system and methods of use. Said lubricant system comprises siloxane polymers with viscosity greater than 100 centistokes and cross-linking agents that can promote siloxane polymers curing rapidly in ambient conditions. The lubricant system comprises further hydroxy siloxane polymers, siloxane coupling agent, catalyst and volatile carrier solvents. The surfaces of medical devices are coated at least once, a solid lubrication film can be quickly formed, and the film has a very excellent lubricating performance and wide applications. The methods of use are simple, easy to implement and control, and is particularly suitable for rapid automatic production lines, and thus is of great economic value.

Claims

1. A medical device lubricant system, comprising an organic lubricant film having a three-dimensional structure formed on a medical device within five minutes of crosslinking cross-linkable siloxane polymers in the presence of a crosslinking agent at ambient temperature; wherein: the three-dimensional structure comprises a solid structure having a portion of the cross-linkable siloxane polymers stored uncrosslinked and liquid within the solid structure during the crosslinking; and the lubricant film is configured to release the liquid siloxane polymers as a liquid lubricant when pressure is applied thereto, wherein the siloxane polymers comprise a polymer having the following formula: ##STR00003## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 each independently represent an alkyl group, an aryl group, or a combination thereof, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 each independently have a chain length in a range of from 1 to 20, and a sum of m+n is an integer in a range of from 6 to 2,000.

2. The medical device lubricant system according to claim 1, wherein the crosslinking agent comprises a compound having the following formula:
R.sub.a.sup.1SiR.sub.b.sup.2(OR.sup.3).sub.4-a-b wherein: R.sup.1 represents a vinyl or alkyl group, R.sup.2 represents an amino group, R.sup.3 represents an alkyl, hydrogen, alkenyl, amino, acyl, aryl, carbonyl, or imine group, 0≤a≤2 is satisfied, and 0≤b<4 is satisfied.

3. The medical device lubricant system according to claim 2, wherein the lubricant film further comprises a siloxane coupling agent having the following formula:
—SiR.sub.x.sup.1(OR.sup.2).sub.3-x where: R.sup.1 represents a vinyl group or an alkyl group terminated with an amino, epoxy, or halogenated group; R.sup.2 represents a methyl or ethyl group; and 0≤x<2 is satisfied.

4. The medical device lubricant system according to claim 2, wherein R.sup.3 represents a ketoxime group as the imine group.

5. The medical device lubricant system according to claim 1, wherein a viscosity of the siloxane polymers is in a range of from 100 to 30,000 centistokes at a temperature of 25° C., and a weight average molecular weight of the siloxane polymers is in a range of from 6,000 to 90,000.

6. The medical device lubricant system according to claim 1, wherein the lubricant film further comprises a siloxane coupling agent having the following formula:
—SiR.sub.x.sup.1(OR.sup.2).sub.3-x where: R.sup.1 represents a vinyl group or an alkyl group terminated with an amino, epoxy, or halogenated group; R.sup.2 represents a methyl or ethyl group; and 0≤x<2 is satisfied.

7. The medical device lubricant system according to claim 1, wherein the lubricant film is formed in the presence of an organic tin catalyst.

8. The medical device lubricant system according to claim 1, wherein the lubricant film further comprises a volatile carrier solvent selected from the group consisting of a hydrofluoroether solvent and a chlorofluorocarbon solvent.

9. The medical device lubricant system according to claim 1, wherein: the solid structure of the lubricant film is microscopically porous; and the lubricant film is configured to partially and continuously release the liquid siloxane polymers under pressure caused by penetration or friction, which improves lubrication of the surface of the medical device, resulting in reduced frictional force and prolonged service life of the lubricant film, and avoidance of a situation in which there is no lubricant on a frictional surface of the medical device due to the lubricant being smeared away as the frictional surface slides.

10. The medical device lubricant system according to claim 1, wherein: the siloxane polymers have a viscosity in a range of from 100 centistokes to 30,000 centistokes at a temperature of 25° C.

11. A method for producing the medical device lubricant system according to claim 1, comprising: forming at least one layer of the lubricant film on a surface of the medical device by coating a composition comprising the siloxane polymers and the crosslinking agent on the surface of the medical device.

12. The method according to claim 11, wherein the composition is coated on the surface of the medical device by spraying, brushing, painting, or jet coating the composition on the surface, or dipping the surface of the medical device in the composition.

13. The method according to claim 11, wherein the lubricant film is formed on a metallic and/or polymer surface of the medical device.

14. A medical device lubricant system, comprising an organic lubricant film having a three-dimensional structure formed on a medical device within five minutes of crosslinking cross-linkable siloxane polymers in the presence of a crosslinking agent at ambient temperature; wherein: the three-dimensional structure comprises a solid structure having a portion of the cross-linkable siloxane polymers stored uncrosslinked and liquid within the solid structure during the crosslinking; and the lubricant film is configured to release the liquid siloxane polymers as a liquid lubricant when pressure is applied thereto, wherein the siloxane polymers comprise hydroxy siloxane polymers having the following formula: ##STR00004## where: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each independently represent an alkyl group, an aryl group, trifluoro propyl, or a combination thereof, and a sum of m+n is an integer in a range of from 150 to 1,000.

15. The medical device lubricant system according to claim 14, wherein the crosslinking agent comprises a compound having the following formula:
R.sub.a.sup.1SiR.sub.b.sup.2(OR.sup.3).sub.4-a-b wherein: R.sup.1 represents a vinyl or alkyl group, R.sup.2 represents an amino group, R.sup.3 represents an alkyl, hydrogen, alkenyl, amino, acyl, aryl, carbonyl, or imine group, 0≤a≤2 is satisfied, and 0≤b<4 is satisfied.

16. The medical device lubricant system according to claim 14, wherein a viscosity of the hydroxy siloxane polymers is in a range of from 1,000 to 8,000 centistokes at a temperature of 25° C., and a weight average molecular weight of the hydroxy siloxane polymers is in a range of from 30,000 to 60,000.

Description

EXAMPLES

(1) The following are examples of the technical aspects of the present invention. Obviously, the examples are only exemplary of the technical aspects of the present invention, not in its entirety. All other embodiments, obtained by persons of skills in the field from or out of the subject invention without having to put in any creative effort, falls within the protective scope of the present invention.

Example 1

(2) Example 1 demonstrates a comparison of the performance of a double layers of lubricant coated on the surface of injection needles according to the present invention versus a comparative product of international famous brand and of the same type.

(3) Test method according to Chinese national standard GB/18671-2009 was used to test the performance of different lubricants coated on the surface of injection needles by measuring their penetration forces. Materials used for penetration tests are polyurethane films that have a thickness of 0.35 mm±0.05 mm and a shore (A) hardness of 85±10 to simulate human skins. Prior to testing, the polyurethane films are stored at 22° C.±2° C. for 24 hours, and tests are conducted at the same temperature.

(4) A continuous piece of said polyurethane film is clamped to the fixing device, making sure there is no tension in the polyurethane film. The needle to be tested is fixed on the penetration device, the needle axis is perpendicular to the surface of the polyurethane film, the needle tip points to the center of the circular area of the polyurethane film to be tested, and the penetration device moves at a speed of 100 mm/minute. For each penetration, the area to be punctured on the polyurethane film is not previously used and punctured. 4 punctures are conducted for each needle in accordance with the Chinese national standard, peak penetration force for each puncture is recorded as merits to evaluate and compare the performance of different lubricants.

(5) In the present invention, each penetration force test value is the mean value of not less than 50 needle samples tested of the same batch.

(6) In comparative sample 1, 31G×8 mm pen needles of international famous brand are tested according to Chinese national standard GB/18671-2009, and results are placed in table 2.

(7) Independently, a needle lubricant was prepared in accordance with the present invention as Sample 2 according to the formulation in Table 1:

(8) TABLE-US-00001 TABLE 1 Sample 2 Weight % 100 cst α,ω dihydroxy polydimethylsiloxane 100 (Shandong Da-Yi Chemical Industry Co., Ltd. OH501-100) 12500 cst polydimethylsiloxane (Dow Corning DC-360) 47.50 1000 cst α,ω dihydroxy polydimethylsiloxane 47.50 (Shandong Da-Yi Chemical Industry Co., Ltd. OH501-100) cross-linking agent (Aladdin T110596/Hangzhou Guibao 3.28 Chemical Co., Ltd.) coupling agent (Aladdin A107148) 1.48 catalyst (Alfa B23612) 0.24

(9) Except for 100 cst α,ω dihydroxy polydimethylsiloxane, all other substances are mixed uniformly in no moisture condition according to a certain sequence after they are treated such as dewatering, then they are dissolved in CFC type of volatile solvent and uniformly mixed in an appropriate manner where the CFC type of volatile solvents accounts for the total mass of 92%, as Component A,

(10) 100 cst α,ω dihydroxy polydimethylsiloxane is dissolved in CFC type of volatile solvent and uniformly mixed in an appropriate manner after it is treated such as dewatering where the 100 cst α,ω dihydroxy polydimethylsiloxane accounts for the total weight of 3%, as Component B.

(11) The cross-linking agent in table 1 is a mixture of ethyl silicate with ketoxime siloxanes, their molar ratio is 1:1.

(12) 31G pen needles are coated with lubricants as described above. Component A is applied first, after 15 seconds in ambient temperature, Component B is applied.

(13) Penetration forces of sample 2 are tested according to Chinese national standard GB/18671-2009, and results are also placed in table 2.

(14) TABLE-US-00002 TABLE 2 Sample 1 (Comparative Sample) Sample 2 Mean Mean Times of Penetration Normal- Penetration Normal- Penetration Forces(g) ization Forces(g) ization 1 37.75 1.00 31.63 0.84 2 38.78 1.00 32.65 0.84 3 38.78 1.00 33.67 0.87 4 39.80 1.00 36.73 0.92

(15) From the results of table 2 it can be seen that all penetration forces of sample 2 are less than those of comparative sample 1. For first and second times puncture, the penetration forces of the sample 2 after normalization are only equivalent to 84% of those of comparative sample 1, even with 4-times puncture the lubricant performance of sample 2 is better than that of the comparative sample 1, the penetration force of sample 2 is equivalent to 92% of that of comparative sample 1.

Example 2

(16) Example 2 demonstrates a comparison of the performance of a single layer of organic siloxane compounds coated on the surface of needles according to the present invention versus comparative sample 1.

(17) Independently, a needle lubricant was prepared in accordance with the present invention as Sample 3 according to the formulation in table 3:

(18) TABLE-US-00003 TABLE 3 Sample 3 weight % 12500 cst polydimethylsiloxane (Dow Corning DC-360) 48.00 1000 cst α,ω dihydroxy polydimethylsiloxane 48.00 (Shandong Da-Yi Chemical Industry Co., Ltd. OH501-100) cross-linking agent (Aladdin T110596/Hangzhou Guibao 2.32 Chemical Co., Ltd.) coupling agent (Aladdin A107148) 1.48 catalyst (Alfa B23612) 0.20

(19) Substances in table 3 are mixed uniformly in no moisture condition according to a certain sequence after they are treated such as dewatering, then they are dissolved in CFC type of volatile solvent and uniformly mixed in an appropriate manner where the CFC type of volatile solvents accounts for the total mass of 92%.

(20) The cross-linking agent in Table 3 is a mixture of ethyl silicate with ketoxime siloxanes, their molar ratio is 3:1.

(21) In the same manner as in example 1, penetration forces of sample 3 are tested and results are placed in table 4.

(22) TABLE-US-00004 TABLE 4 Sample 1 (Comparative Sample) Sample 3 Mean Mean Times of Penetration Normal- Penetration Normal- Penetration Forces(g) ization Forces(g) ization 1 37.75 1.00 30.61 0.81 2 38.78 1.00 32.65 0.84 3 38.78 1.00 33.67 0.87 4 39.80 1.00 34.69 0.87

(23) From the results of table 4 it can be seen that all penetration forces of sample 3 are less than those of comparative sample 1. The penetration forces of the sample 3 after normalization are only equivalent to 81% of those of comparative sample 1, reduced 19%, even with 4-times puncture the lubricant performance of sample 3 is better than that of the comparative sample 1, the penetration force of sample 3 is equivalent to 87% of that of comparative sample 1, reduced 13%.

Example 3

(24) Example 3 demonstrates a comparison of the performance of coating the coupling agent alone first as a primer to the surface of needles, then coating the rest of compounds after the solvent is volatilized according to the present invention versus comparative sample 1.

(25) Independently, a needle lubricant was prepared in accordance with the present invention as Sample 4 according to the formulation in table 5:

(26) TABLE-US-00005 TABLE 5 Sample 4 Weight % coupling agent (Aladdin A107148) 100 12500 cst polydimethylsiloxane (Dow Corning DC-360) 48.72 1000 cst α,ω dihydroxy polydimethylsiloxane 48.72 (Shandong Da-Yi Chemical Industry Co., Ltd. OH501-100) cross-linking agent (Aladdin T110596/Hangzhou Guibao 2.35 Chemical Co., Ltd.) catalyst (Alfa B23612) 0.21

(27) The coupling agent in table 5 is dissolved in CFC type of volatile solvent after it is treated where coupling agent accounts for the total weight of 3%, as Component C.

(28) All other substances in table 5 are mixed uniformly in no moisture condition according to a certain sequence, then they are dissolved in CFC type of volatile solvent and uniformly mixed in an appropriate manner where the CFC type of volatile solvents accounts for the total mass of 92%, as Component D.

(29) The cross-linking agent in Table 5 is a mixture of ethyl silicate with ketoxime siloxanes, their molar ratio is 3:1.

(30) 31G pen needles are coated with lubricants as described above. Component C is applied first, after 15 seconds in ambient temperature, Component D is applied.

(31) In the same manner as in example 1, penetration forces of sample 4 are tested and results are placed in table 6.

(32) TABLE-US-00006 TABLE 6 Sample 1 (Comparative Sample) Sample 4 Mean Mean Times of Penetration Normal- Penetration Normal- Penetration Forces(g) ization Forces(g) ization 1 37.75 1.00 34.69 0.92 2 38.78 1.00 35.71 0.92 3 38.78 1.00 36.73 0.96 4 39.80 1.00 37.75 0.95

(33) From the results of table 6 it can be seen that all penetration forces of sample 4 are less than those of comparative sample 1. The penetration forces of the sample 4 after normalization are only equivalent to 92% of those of comparative sample 1, and with 4-times puncture the penetration force of sample 4 is equivalent to 95% of that of comparative sample 1.

Example 4

(34) Example 4 demonstrates a comparison of the performance of lubricant coated on the surface of non-patient end (NP) needles of pen needles according to the present invention penetrating the rubber septum of injection pen refills versus a comparative product of international famous brand and of the same type (sample 6).

(35) Independently, a needle lubricant was prepared in accordance with the present invention as Sample 5 according to the formulation in table 7:

(36) TABLE-US-00007 TABLE 7 Sample 5 weight % 100 cst polydimethylsiloxane (Dow Corning DC-360) 50.00 12500 cst polydimethylsiloxane (Dow Corning DC-360) 18.00 1000 cst α,ω dihydroxy polydimethylsiloxane 25.00 (Shandong Da-Yi Chemical Industry Co., Ltd. OH501-100) cross-linking agent (Aladdin T110596/Hangzhou Guibao 3.50 Chemical Co., Ltd.) coupling agent (Aladdin A107148) 3.10 catalyst (Alfa B23612) 0.40

(37) Substances in table 7 are mixed uniformly in no moisture condition according to a certain sequence, then they are dissolved in CFC type of volatile solvent and uniformly mixed in an appropriate manner where the CFC type of volatile solvents accounts for the total mass of 97%.

(38) The cross-linking agent in Table 7 is a mixture of ethyl silicate with ketoxime siloxanes, their molar ratio is 2:1.

(39) Materials used for penetration tests are rubber septum of injection pen refills, needles coated with lubricant are the non-patent end needles of pen needles, all other conditions are the same as example 1. Penetration forces are measured for sample 5 and sample 6, and results are placed in table 8.

(40) TABLE-US-00008 TABLE 8 Sample 6 (Comparative Sample) Sample 5 Mean Mean Times of Penetration Normal- Penetration Normal- Penetration Forces(g) ization Forces(g) ization 1 109.18 1.00 85.71 0.79 2 119.39 1.00 103.06 0.86 3 126.53 1.00 114.28 0.90 4 138.77 1.00 123.47 0.89

(41) From the results of table 8 it can be seen that all penetration forces of sample 5 are less than those of comparative sample 6. The penetration forces of the sample 5 after normalization are only equivalent to 79% of those of comparative sample 6, reduced 21%, even with 4-times puncture the lubricant performance of sample 5 is better than that of the comparative sample 6, the penetration force of sample 6 is equivalent to 89% of that of comparative sample 6, reduced 11%.

(42) If one of the cross-linking agents in above examples, ketoxime siloxanes, directly contact with human skin, they can cause allergic skin reactions. However when they are used as cross-linking agents, hydrolysis crosslinking reactions will occur to the ketoxime siloxanes in ambient condition, releasing all the ketoxime substance and forming solid three-dimensional structure of organic siloxane films. The above mentioned ketoxime substances at ambient temperature are extremely volatile, leaving only the non-toxic organic siloxanes. In the above examples, each needle theoretically releases 0-3 μg of ketoximino substance, the residual amount is not detected after volatilizing in ambient condition.

(43) Although the present invention a medical device lubricant system and methods of use are only applied to the lubrication of pen needles as examples, when they are applied to medical grade metallic and non-metallic surfaces of medical devices, such as injection and infusion needles, surgical suture needles, scalpels, medical catheters, and the like, their excellent lubrication performance is also significantly.

(44) Although illustrative embodiments of the present invention have been described herein with reference to the examples, it is not intend to restrict the protective scope of the invention. Any equivalent structural or procedural change made from or out of the description of this invention or direct or indirect use thereof in any related technical field fall within the protective scope of this patent.