Non-aqueous patch

Abstract

Non-aqueous patches comprising lidocaine, which is not dissolved and is present in a crystalline state, have poor permeability to the skin. Therefore, non-aqueous patches have a high concentration of lidocaine. It is pointed out that lidocaine has an adverse effect on the heart. Prolonged use of a high concentration of lidocaine causes side effects, such as shock, rubor, and irritating sensation. External preparations comprising more than 5 mass % of lidocaine are designated as powerful drugs, and cannot be used as household (nonprescription) medicine. Provided is a non-aqueous patch that is effective to relieve muscle pain, the non-aqueous patch comprising lidocaine and/or its reactant, and a dissolving agent composed of an organic acid and a polyalcohol, which are contained in a base.

Claims

1. A non-aqueous patch comprising a plaster comprising 0.5 to 7 mass % lidocaine, a dissolving agent, and an elastomer, wherein the amount of lidocaine is 196 mg or less and the amount of plaster is 0.84 to 2.8 g, the dissolving agent comprises dipropylene glycol and isostearic acid, and the isostearic acid is present in the plaster in an amount of 1.4 to 2.1 mass %.

2. The non-aqueous patch of claim 1, wherein the elastomer consists of polyisobutylene and styrene isoprene rubber.

3. The non-aqueous patch of claim 1, wherein the plaster comprises 10 mass % to 40 mass % of the elastomer.

4. The non-aqueous patch of claim 1, wherein the plaster comprises 20 mass % to 40 mass % of the elastomer.

5. The non-aqueous patch of claim 1, wherein the plaster further comprises a terpene resin.

6. The non-aqueous patch of claim 1, wherein after application to a human for 12 hours, the amount of lidocaine remaining in the non-aqueous patch is 80% or less than the amount prior to application.

7. The non-aqueous patch of claim 1, wherein the amount of lidocaine is 0.1 to 1 mg/cm.sup.2 of the plaster.

8. The non-aqueous patch of claim 1, wherein the lidocaine is completely dissolved in the dissolving agent.

9. The non-aqueous patch of claim 1, wherein the lidocaine is completely dissolved in the plaster.

10. The non-aqueous patch of claim 1, wherein the mass of the plaster is from about 60 to about 200 g/m.sup.2.

11. The non-aqueous patch of claim 1, wherein the mass of the plaster is from 80 to 180 g/m.sup.2.

12. The non-aqueous patch of claim 1, wherein the non-aqueous patch further comprises a tackifier resin selected from the group consisting of terpene resin, rosin-based resin, alicyclic petroleum resin, phenolic resin and combinations thereof.

13. The non-aqueous patch of claim 1, wherein the non-aqueous patch further comprises liquid paraffin.

14. The non-aqueous patch of claim 1, wherein the plaster is held by a substrate selected from the group consisting of nonwoven fabric, woven fabric, knitted fabric or a combination thereof.

15. The non-aqueous patch of claim 1, wherein the plaster is adhered to a polyester woven fabric.

16. A method of treating 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 a plaster comprising 0.5 to 7 mass % lidocaine, a dissolving agent, and an elastomer, wherein the amount of lidocaine is 196 mg or less and the amount of plaster is 0.84 to 2.8 g, the dissolving agent comprises dipropylene glycol and isostearic acid, and the isostearic acid is present in the plaster in an amount of 1.4 to 2.1 mass %.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a graph showing the ratio of the remaining drug.

(2) FIG. 2 is a graph showing blood levels.

(3) Description of Embodiments.

(4) FIG. 3 shows a table summarizing examples of formulations disclosed herein.

(5) FIG. 4 shows a table summarizing ball tack scores for various examples disclosed herein.

(6) Examples of the present invention are summarised in a table shown in FIG. 3.

EXAMPLE 1

(7) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 18 mass %

(8) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 5 mass %

(9) Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced by Arakawa Chemical Industries, Ltd.): 12 mass %

(10) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 10 mass %

(11) Lidocaine: 7 mass %

(12) 1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1.5 mass %

(13) Oleic acid (“Purified Oleic Acid”, produced by NOF Corporation): 2 mass %

(14) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 43.8 mass %

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

(16) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.2 mass %

(17) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin ester, 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, 1,3-butylene glycol, and oleic 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. 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 woven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:0.5 by mass ratio.

EXAMPLE 2

(18) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 15 mass %

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

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

(21) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 48.3 mass %

(22) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.5 mass %

(23) Lidocaine: 3 mass %

(24) 1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1.5 mass %

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

(26) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.2 mass %

(27) 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, lidocaine, and 1,3-butylene glycol, 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 woven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:1 by mass ratio.

EXAMPLE 3

(28) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 18 mass %

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

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

(31) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 46.9 mass %

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

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

(34) Lidocaine: 2 mass %

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

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

(37) 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, lidocaine, and dipropylene glycol, 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 nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:1.15 by mass ratio.

EXAMPLE 4

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

(39) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 8 mass %

(40) Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced by Arakawa Chemical Industries, Ltd.): 20 mass %

(41) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 48.2 mass %

(42) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.5 mass %

(43) Lidocaine: 0.5 mass %

(44) 1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1 mass %

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

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

(47) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin ester, 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, lidocaine, and 1,3-butylene glycol, 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 nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:5 by mass ratio.

EXAMPLE 5

(48) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 18 mass %

(49) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 5 mass %

(50) Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced by Arakawa Chemical Industries, Ltd.): 12 mass %

(51) Terpene resin (trade name “YS resin 1150N”, produced by Yasuhara Chemical Co., Ltd.): 10 mass %

(52) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 38.1 mass %

(53) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 2.1 mass %

(54) Lidocaine: 7 mass %

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

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

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

(58) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin ester, 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, lidocaine, and dipropylene glycol, 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 100 g/m.sup.2. A polyester nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:1.3 by mass ratio.

EXAMPLE 6

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

(60) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 8 mass %

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

(62) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 49.165 mass %

(63) Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.4 mass %

(64) Lidocaine: 0.7 mass %

(65) Dipropylene glycol (produced by NOF Corporation): 0.035 mass %

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

(67) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.2 mass %

(68) 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, lidocaine, and dipropylene glycol, 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 150 g/m.sup.2. A polyester nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm). In this preparation, the proportion of lidocaine and dissolving agent was 1:2.05 by mass ratio.

COMPARATIVE EXAMPLE 1

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

(70) Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 5 mass %

(71) Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced by Arakawa Chemical Industries, Ltd.): 15 mass %

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

(73) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 48.2 mass %

(74) Polysorbate 80 (produced by NOF Corporation): 4 mass %

(75) Lidocaine: 2 mass %

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

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

(78) The production method using these materials according to the above formulation was as follows. The styrene-isoprene-styrene block copolymer, polyisoprene, hydrogenated rosin ester, 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 Polysorbate 80 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 nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

COMPARATIVE EXAMPLE 2

(79) Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced by Kraton JSR Elastomers K.K.): 15 mass %

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

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

(82) Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation): 51.3 mass %

(83) Lidocaine: 3 mass %

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

(85) Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu Chemical Industry Co., Ltd.): 0.2 mass %

(86) 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. The lidocaine 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 nonwoven fabric was pasted thereto and cooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).

(87) FIG. 3 summarizes the exemplary formulations in a table.

(88) The preparations obtained in Examples 1 to 6 and Comparative Examples 1 and 2 were subjected to the following tests.

(89) Adhesion Test

(90) A ball tack adhesion test was performed according to the test method described in Drug Approval and Licensing Procedures in Japan. As shown in FIG. 4, Examples 1 to 6 (hereinafter referred to the “invention products”) showed excellent adhesion. The adhesion of Comparative Example 1 was about half of those of the invention products. Comparative Example 2 had satisfactory adhesion, because no dissolving agent was used.

(91) Drug Remaining Test

(92) As shown in FIG. 1, the preparations were attached to the human skin for 4 hours, 8 hours, and 12 hours. After each time period was passed, the preparations were 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%.

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

(94) Blood Level Test

(95) The preparations were attached to the human skin for 12 hours and then removed. 4 hours, 8 hours, and 12 hours after the attachment of the preparations, and 24 hours after the removal of the preparations, the blood was extracted, and the level of lidocaine in the blood was measured. FIG. 2 is a graph showing the results.

(96) The results reveal that the preparations comprising a dissolving agent composed of isostearic acid and dipropylene glycol showed generally good results.