Non-aqueous patch for the relief of pain

Abstract

[Problem] If lidocaine is composed of non-aqueous patch, the adhesive power of the preparation tends to get lower, as the composition amount of lidocaine is higher. It is popular to solve lidocaine in dissolving agent in order to compose lidocaine in patch and release effective amount into skin. However, if the amount of dissolving agent gets higher, the adhesive power gets extremely lower, so that an long-time attachment is difficult. [Solution] A non-aqueous patch comprising lidocaine and/or its reactant, and a dissolving agent which are contained in a base of plaster, the plaster being hold by a support, of which strength of 50% stretched to longitudinal direction is less than 2000 g/50 mm and of biaxially-oriented stretch cloth.

Claims

1. A method of relieving pain in an individual in need thereof, comprising applying a non-aqueous patch to the skin of the individual in need thereof, wherein the non-aqueous patch comprises 0.5 to 7 mass % lidocaine, and a dissolving agent comprising an organic acid and a polyalcohol, wherein the lidocaine and the dissolving agent are in a plaster, the plaster being held by a support, the support has a stretch strength of less than 2,000 g/50 mm when the support is stretched by 50% longitudinal extension; and the support comprises a biaxially-oriented stretch cloth, the organic acid is isostearic acid, which is present in the plaster in an amount of 0.9 mass % to 2.5 mass %, and the polyalcohol is dipropylene glycol, which is present in the plaster in an amount of 0.2 mass % to 1.5 mass % dipropylene glycol.

2. The method of claim 1, wherein the pain is muscle pain, arthritic pain, or lumbar pain.

3. The method of claim 1, wherein the non-aqueous patch is applied to the back of the individual in need thereof.

4. The method of claim 1, wherein the non-aqueous patch is applied to the individual in need thereof for up to and including 12 hours.

5. The method of claim 1, wherein the non-aqueous patch is applied to the individual in need thereof for at least 12 hours, and the area of the non-aqueous patch remaining on the skin compared to the area of the non-aqueous patch initially applied to the individual in need thereof is at least 90%.

6. The method of claim 1, wherein the non-aqueous patch is applied for at least 12 hours, and the amount of lidocaine remaining in the non-aqueous patch compared to the amount of lidocaine in the non-aqueous patch immediately prior to application to the individual in need thereof is less than 80%.

7. The method of claim 1, wherein the adhesive power of the patch is from 0.4N/width 25 mm to 5N/width 25 mm.

8. The method of claim 1, wherein the release ratio of lidocaine from the plaster is more than 6%, after 12 hours attachment to the skin.

9. The method of claim 1, wherein the amount of lidocaine is 0.1 to 1 mg/cm.sup.2 of the plaster.

10. The method of claim 1, wherein the plaster consists of lidocaine, isostearic acid and dipropylene glycol, an elastomer, a terpene resin, butylated hydroxytoluene, liquid paraffin and light anhydrous silicic acid.

11. The method of claim 10, wherein the elastomer consists of a combination of styrene isoprene and polyisobutylene.

12. The method of claim 1, wherein the lidocaine is dissolved in the dissolving agent.

13. The method of claim 10, wherein the lidocaine, the polyalcohol and the organic acid are combined prior to the addition of the elastomer, the terpene resin, the butylated hydroxytoluene, the liquid paraffin and the light anhydrous silicic acid.

14. A method of relieving muscle pain, arthritic pain, or lumbar pain in an individual in need thereof, comprising applying a non-aqueous patch to the skin of the individual in need thereof, wherein the non-aqueous patch comprises 0.5 to 7 mass % lidocaine, and a dissolving agent comprising an organic acid and a polyalcohol, wherein the lidocaine and the dissolving agent are in a plaster, the plaster being held by a support, the support has a stretch strength of less than 2,000 g/50 mm when the support is stretched by 50% longitudinal extension, the support comprises a biaxially-oriented stretch cloth, the organic acid is isostearic acid, which is present in the plaster in an amount of 0.9 mass % to 2.5 mass %, and the polyalcohol is dipropylene glycol, which is present in the plaster in an amount of 0.2 mass % to 1.5 mass % dipropylene glycol; and wherein the non-aqueous patch is applied to the individual in need thereof for at least 12 hours, and the area of the non-aqueous patch remaining on the skin compared to the area of the non-aqueous patch initially applied to the individual in need thereof is at least 90%, and the amount of lidocaine remaining in the non-aqueous patch compared to the amount of lidocaine in the non-aqueous patch immediately prior to application to the individual in need thereof is less than 80%.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 shows the ratio of the remaining drug.

DESCRIPTION OF EMBODIMENTS

(2) Examples of the present invention are described with reference to Table 1.

Example 1

(3) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(4) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(5) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(6) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 47.6 mass %

(7) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 0.9 mass %

(8) Dipropylene glycol (produced by NOF Corporation): 0.2 mass %

(9) Lidocaine: 0.5 mass %

(10) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(11) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(12) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the lidocaine, Dipropylene glycol, and Isostearic acid, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution.

(13) The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 140 g/m.sup.2. A polyester knitted fabric, of which strength of 50% stretched to longitudinal direction was 1600 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Example 2

(14) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(15) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(16) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(17) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 45.4 mass %

(18) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.8 mass %

(19) Dipropylene glycol (produced by NOF Corporation): 0.5 mass %

(20) Lidocaine: 1.5 mass %

(21) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(22) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(23) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and lidocaine, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution.

(24) The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 140 g/m.sup.2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 1000 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Example 3

(25) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(26) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(27) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(28) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 44.9 mass %

(29) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.8 mass %

(30) Dipropylene glycol (produced by NOF Corporation): 0.5 mass %

(31) Lidocaine: 2 mass %

(32) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(33) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(34) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and and lidocaine followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution. The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 160 g/m.sup.2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 500 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Example 4

(35) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(36) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(37) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(38) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 38 mass %

(39) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 2.5 mass %

(40) Dipropylene glycol (produced by NOF Corporation): 1.5 mass %

(41) Lidocaine: 7 mass %

(42) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.7 mass %

(43) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(44) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and lidocaine, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution. The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 160 g/m.sup.2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 500 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Comparative Example 1

(45) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(46) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(47) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 2 mass %

(48) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 63.4 mass %

(49) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.8 mass %

(50) Dipropylene glycol (produced by NOF Corporation): 0.5 mass %

(51) Lidocaine: 1.5 mass %

(52) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(53) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(54) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisoprene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and lidocaine, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution. The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 140 g/m2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 3000 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Comparative Example 2

(55) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers ICK.): 20 mass %

(56) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(57) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(58) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 28.2 mass %

(59) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 12 mass %

(60) Dipropylene glycol (produced by NOF Corporation): 7 mass %

(61) Lidocaine: 2 mass %

(62) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(63) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(64) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and lidocaine, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution. The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 140 g/m.sup.2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 3000 g/50 mm, was pasted to the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

Comparative Example 3

(65) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 20 mass %

(66) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 10 mass %

(67) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 20 mass %

(68) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 44.9 mass %

(69) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.8 mass %

(70) Dipropylene glycol (produced by NOF Corporation): 0.5 mass %

(71) Lidocaine: 2 mass %

(72) Light anhydrous silicic acid (trade name “Sylysia 350”, produced by Fuji Silysia Chemical Ltd.): 0.5 mass %

(73) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.3 mass %

(74) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, terpene resin, light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin were placed in a dissolution mixer and dissolved under heating at 150° C. A solution separately prepared by mixing the isostearic acid, dipropylene glycol, and lidocaine, followed by dissolution at 80° C., was added thereto, and the mixture was mixed under heating at 140° C. until the mixture became homogeneous, thereby obtaining a plaster solution. The plaster solution was applied to a polyester film treated with silicon so that the plaster weight was 160 g/m.sup.2. A polyester non-woven fabric, of which strength of 50% stretched to longitudinal direction was 5000 g/50 mm, was pasted the film and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

(75) TABLE-US-00001 TABLE 1 Example No. Comparative Comparative Comparative Component Example 1 Example 2 Example 3 Example 4 Example 1 Example 2 Example 3 Styrene-isoprene-styrene 20 20 20 20 20 20 20 block copolymer polyisobutylene 10 10 10 10 10 10 10 Terpene resin 20 20 20 20 2 20 20 Liquid paraffin 47.6 45.4 44.9 38 63.4 28.2 44.9 Isostearic acid 0.9 1.8 1.8 2.5 1.8 12 1.8 Light anhydrous 0.2 0.5 0.5 1.5 0.5 7 0.5 silicic acid Dibutylhydroxytoluene 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Lidocaine 0.5 1.5 2 7 1.5 2 2 Total 100 100 100 100 100 100 100

(76) The preparations obtained in Examples 1 to 4 and Comparative Examples 1 to 3 were subjected to the following tests.

(77) Adhesive Power Test

(78) 180 degree taking off method of Adhesive power test defined in Z0237 of JIS (Japanese Industrial Standards) was done.

(79) As shown in Table 2, example 1 to example 4 (hereinafter referred for present invention) indicate good adhesive power. But, comparative example 1 and comparative example 2 indicate low score. Since the preparation of comparative example 3 is similar to that of the present invention, its adhesive power is good in this test, however the adhesive power of comparative example 3 cannot be maintained in human skin adhesive test described as below.

(80) TABLE-US-00002 TABLE 2 Comparative Comparative Comparative Example 1 Example 2 Example 3 Example 4 Example 1 Example 2 Example 3 2.4 1.9 1.8 1.6 0.1 0.2 1.4
Human skin Adhesive Test

(81) The preparation product (14 cm×10 cm/a sheet) were attached to the examinees' back for 12 hours, with the condition of temperature from 25 to 28 degree centigrade, room inside, and no active motion. After 12 hours passed, the approximate area of remaining product on skin was measured as “adhesion remaining ratio”.

(82) If the adhesive portion remained curved, the adhesion area was measured by straight line in middle point. The adhesion remaining ratio of the present invention was more than 90%. In comparison, the preparation product of the comparative example 1 and 3 were fully fallen off, and the comparative example 2 was partially fallen off in adhesion test, and most part of comparative example 2 floated off to the skin, as the ratio of adhesion remaining for 14%.

(83) TABLE-US-00003 TABLE 3 Comparative Comparative Comparative Example 1 Example 2 Example 3 Example 4 Example 1 Example 2 Example 3 96% 94% 96% 93% 0% 14% 0%
Drug Remaining Test

(84) As shown in FIG. 1, the preparation product (14 cm×10 cm/a sheet) were attached to the examinees' back for 4 hours, 8 hours, and 12 hours. After each time period was passed, the preparation was removed. The amount of drug remaining in each preparation was measured to determine the drug remaining ratio on the premise that the amount of drug prior to attachment was 100%. In case of the preparation product removed, such removed preparation product was remained on the examinees' back and the examinees are lied down prone with relaxation. Then, the drug remaining test was continued.

(85) The drug remaining ratio after attachment for 12 hours was 96 to 99% in the comparative examples, while the results of all of the present invention products were 80% or less. According to this results, the amount of drug released into the human skin was 20% or more.