TW520299B - Chin Su Kao pharmaceutical paster within a water soluble substrate compound and manufacture process thereof - Google Patents

Abstract

The present invention relates to a Chin Su Kao pharmaceutical paster within a water soluble substrate compound and manufacture process thereof, which is used for curing tendon contusion. The conventional external pharmaceutical paster is composed by oily substrate, which easily leads to allergy in derma, The Chin Su Kao water soluble colloid pharmaceutical paster in present invention has been passed through animal evaluation model to pick and weed out the formula of the Chin Su Kao pharmaceutical paster. The total manufacture process fits modern quality control and quality assurance for stabilizing the effect of the Chinese medicine.

Description

520299 _Case No. 87108001_ 年月 日 __ V. Description of the invention (1) The present invention is a gold silk paste with a water-soluble polymer as the matrix. The gold silk paste is a traditional plaster from the rule of certification. Treatment of bone and bone damage flash, rheumatoid malignant sore, rheumatic tendons and colds. Traditional Chinese medicine external preparations generally remain in the way of preparation before use, which is not very convenient. Traditional Chinese medicine patches such as gold silk paste and musk tongxue bone paste use oily colloids, which can easily cause skin irritation; and water-based patches on the market are patches containing western medicine or traditional Chinese medicine with western medicine; There are no patents or products of pure Chinese herbal medicine compound such as golden silk paste. The Republic of China Patent Application No. 7 7 1 0 5 5 5 4 (Announcement No. 1 3 3 3 3 4) relates to a transdermal patch containing cleopride (c 1 eb〇pr ide) and its manufacturing method. The composition of the polymer is polyvinyl alcohol, gelatin, polyacrylic acid, sodium polyacrylate, methylcellulose, carboxymethylcellulose, polyvinylpyrrolidone or gum or dextrin or its cross-linked reaction product. These are water-soluble The composition of polymers is complex and the available composition range is narrow. The Republic of China Patent Application No. 7 1 0 6 8 0 1 (Publication No. 1 799 5 9 0) is a vasodilator (nitroglycerin patch) with a pyrrolidone as a carrier. However, the patch The adhesive properties are not ideal. One of the objectives of the present invention is to use the characteristics of modern polymer materials to develop appropriate hydrocolloid formulations, thereby improving the shortcomings such as the stickiness, greasiness, and inconvenience of traditional prescriptions and Chinese herbal medicine patches. Another object of the present invention is to ensure the stabilization of the quality of traditional Chinese medicine patches through the control of modern analytical tests. The present invention has broken through the current situation of domestic oil-based plasters and changed to water-based patches with less skin irritation. At the same time, through the scientificization of traditional Chinese medicine preparations, the efficacy of traditional prescriptions and traditional Chinese herbal medicine preparations will be exerted to enhance the status of traditional Chinese medicine preparations.

Page 6 520299 V. Description of the invention (2) Amendment of the present invention to discuss the ancient 4) The medicine and prescription basis of the “YUYI” 糸 patch, which is the criterion of syndrome management (Ding, Xing Z, No. 2 and China Medical University) Dictionary; medicinal materials are angelica tail, Chuanbaixiang 1 8 7 5g > each of pig's teeth angle and grass Wuzhu Liuwei 11.2 5g, milk 300g to prepare Qiao = 7 said, white gum 3 °° g , 1150 grams, rosin, and strip extract. The medicinal materials are heated and refluxed with a 5% ethanol aqueous solution of 1 to 20 times > extraction and concentration. Each gram of raw medicinal materials is extracted and concentrated to 5 4 grams of dipped T. ° This concentrated extract of medicinal materials will be added to a suitable hydrocolloid at a ratio of 3% by weight, and mixed and coated to form a drug storage layer of the patch as shown in the first figure. 5 to 12% by weight of sodium polyacrylate, 1 to 20% by weight of carboxyvinyl polymer, and 1 to 10% by weight of poly (vinyl chloride), or 0.5 to 12% by weight of polyacrylic acid, 1 ~ 2 0% by weight carboxyethylene polymer and 1 ~ 5% by weight polyvinyl alcohol; or 0.5 ~ 1 2% by weight sodium polydiene acid, 1 ~ 20% by weight of carboxyvinyl polymer and 1 ~ 10% by weight of polyvinylpyrrolidone and 1 ~ 5% by weight of polyvinyl alcohol. The cross-linked reaction product of the present invention is composed of three layers: (1) The peeling layer is made of poly (fe) molecular substance. (2) The drug storage layer is made of water-soluble polymer colloid, and the extract of gold silk paste is distributed in the colloid in a matrix type. (3) Back layer: It is made of non-woven fabric or fiber material. Under normal circumstances, the size of the patch can be 20 × 20cm, and the thickness of the medicated honeycomb cloth can be 0.1-1.7. Concentrated extract contains 520299 ΓΤ ~ Τ-V. Description of the invention (3) --- The ratio is 2 to 10% by weight. Example 1 The method for making a gold silk paste patch is divided into (1) extraction and concentration of medicinal materials (2) Preparation of drug-containing colloids and (3) Coating and molding of drug-containing colloid patches. (1) ¾ The materials are Dangshuo, Chuanbaizhi, almonds, black ginseng, pig teeth angle and Caowu and other six flavors 1L 25g each, frankincense 18.75g, myrrh 1875g, white gum 300g, Hui 150g, rosin 300g, 13 times 95% ethanol The solution was heated under reflux to extract and concentrate. Each 100 grams of raw medicinal materials were extracted and concentrated to adjust to 5 4 grams of extract. (2) Preparation of medicated colloid: a. Mix 5.9 g of glycerin with 5.9 g of water, stir evenly, Then add 1 · 3 grams of carboxyvinyl polymer powder (C arb ο ρ ο 1-9 4 1), pour into the solution, stir and mix to form a colorless gelatinous solution of 10% carboxyvinyl polymer. Bottle cap, let stand for 24 hours and set aside; b. Pour 17.6 grams of sorbitol and 11.8 grams of glycerin into a beaker and stir to mix the two liquids; weigh and add polyvinylpyrrolidone 2 _ 5 grams, 2.5 grams of polyvinyl alcohol powder, stirred for 20 minutes; C · Another 8.8 grams of kaolin and 17 · 1 grams of pure water were combined and stirred to make 1 moist and disintegrate, then poured into the mixed solution of step b. After stirring for 20 minutes & add Car bopcH-9 41 colloidal material from step a and stir off for 30 minutes; add 1.5 g of sodium polyacrylate powder and stir for 30 minutes; d extract the condensed medicinal material Liquid 2.4 g, mint 1.6 g, methyl salicylate 0.8 g, propyl parahydroxybenzoate 0.016 g, para-hydroxyl

520299 _Case No. 87108001_ Year Month Amendment _ V. Description of the Invention (4) 0.1 4 g of methyl benzoate are mixed and dissolved; e. Combine the solution of step d and the solution of step c and stir: mix 2 In 0 minutes, drug-containing colloids are obtained. (3) Coating and molding of medicine-containing colloids: a. Fix the peeling layer with the test piece holder of the ointment coating machine, and set the coating machine at a constant temperature of 50 ° C; b. Set the coating knife and the peeling layer. At a distance of 1.0 mm, 80 g of the prepared drug-containing colloid was poured onto the surface of the release layer, and the colloid was rolled with a coating knife to apply it on the release layer. Send it to the air box to heat for 1 minute and exit; then, cover the back layer on the gel and remove the coated patch from the fixed frame; place it on the table, and then roll the surface with a roller, and Press the four sides of the patch; the shape and structure of the product are as shown in the first figure. The preparation method of the second embodiment is the same as that of the first embodiment, but the weight of the formula ingredients is changed as follows: 8.2 g of glycerol, 12.1 g of sorbitol, 5.0 g of polyvinylpyrrolidone, 16.9 g of water, kaolin 8 · 7g, polyvinyl alcohol 2.5g, 10% carboxy ethylene polymer (C arb ο ρ ο 1-9 4 1) colloidal solution 1 3.0g, polyacrylic acid solution 8.7 G (the sodium polyacrylate in step c in Example 1 was replaced by a 12% glycerol solution of sodium polyacrylate prepared in advance), 2.4 g of the extract of the concentrated medicinal material, 1.6 g of mint, and methyl salicylate 0. 8 grams, propyl p-benzoate 0.16 g, methyl p-hydroxybenzoate 0.1 14 g were prepared into 80 g of gold silk paste aqueous drug-containing colloid.

Page 9 520299 Amendment No. 87108001 Fifth, the description of the invention (5) In the third embodiment, the weight of the formula ingredients such as the preparation method are as in the example-the following: glycerin 1 2 · 6 grams, sorbitol 7R ancient ^ ^ 8 grams, 5.0 g of polyvinylpyrrolidone, 16.9 g of water, 8.7 g of kaolin, r., Nona polyvinyl alcohol 2.5 g, 10% carboxyethyl

Ene polymer (130 g of Carbopo 94U colloidal solution, 8.7 g of sodium polyacrylic acid solution (the sodium polyacrylate in step c in Example-was replaced with a 12% sodium polyacrylate glycerol solution prepared in advance), concentrated Extract of 24 g of medicinal herbs, 1.6 g of mint, 8 g of methyl salicylate, 0.16 g of propyl parahydroxybenzoate, 0.4 g of methyl parahydroxybenzoate 0.4 g 80 g of water-containing medicated gel colloid. 1 · Evaluation method for in vitro release of efficacy: A flat-mouth frosted Franz diffusion test device with a caliber of 20 mm and a volume of 6 · 8 mL was used. // Stainless steel mesh support patch with m pores. The experiment was performed at a constant temperature of 32 ° C with stirring and sampled regularly. The sample was filtered through a 0.45 / m filter membrane, and the filtrate was analyzed by HPLC.

HPLC analysis conditions: a. Chromatography tube: Inertsil 50DS-2 3.2x250mm. b. Mobile phase: acetonitrile: water (gradient stripping 100% to 100%, pH value adjusted to 3.0 with phosphoric acid)

Page 10 520299 __t? 4_871〇8〇Ql V. Description of the invention (6)

Correction c · Detection wavelength: 254nm. And three examples of in vitro release of three drug-containing colloidal formulas. Once confirmed by HPLC analysis, good release properties 2 · Test mode for analgesic and anti-inflammatory effects 2 ~ 1 Test for analgesic effects According to the method described by D, Amour and Smith, use A thermal stimulation analgesic instrument (Tail filck unit, UG0 Basile, Model ~ DS 2 0) was used to determine the pain response time of s · D · strain rats in response to radiant heat at a constant temperature (60 ° C. 5C) to determine the meaning of each. Reduce the analgesic effect of the drug. 2 Test mode of anti-inflammatory effect In this experiment, carrageenin-induced edema was used. SD rats were used as test subjects, weighing between 20.0 and 25.0 grams, regardless of gender, before application. The anti-inflammatory drug carrageeni η (1%, 0.03ml) was injected subcutaneously on the hind toe one hour, and then measured by P 1 ethysmometer at 1, 2, 3, and 4 hours to evaluate the anti-inflammatory effect.

Page 11 520299 _ Case No. 87108001_ Year Month Day Amendment V. Description of Invention (7) Example 1 Example 2 Example 3 Test Item Anti-inflammatory efficacy 86. 65% 83. 32% 81. 44¾ Analgesic efficacy 87. 58¾ 84 67¾ 84. 96¾ The three formulas of Examples 1, 2, and 3 all have high analgesic and anti-inflammatory effects, and the differences are not large. But formula one is better. 3 · Quality control of the patch: The product is cut into small pieces, shaken with methanol (MeOH) at 60 ° C for 30 minutes, filtered and concentrated, and the sample is filtered through a 0.4 // m filter membrane and injected into the HPLC analysis. Comparison of the HPLC chromatograms of the extracts of each patch showed that the in vitro release of the three formulations of Examples 1, 2, and 3 was consistent with the components of the patch. In terms of adhesive properties and the appearance of the patch, among the three formulations, the first formulation was the most adhesive and the color was whiter; the second formulation and the third formulation were weaker and the color was darker.

Page 12 520299 Case No. 87108001 Month Revision Amendment of the drawing is simple. The first picture is a schematic diagram of a water-based gold silk plaster patch. Document representative symbols: (1) peeling layer (2) drug storage layer (3) back layer

Page 13

Claims (1)

520299 Case No. 87108001 Amendment VI. Patent Application Scope 1. A water-based gold silk plaster patch, including: (1) a release layer composed of a polyolefin polymer; (2) a drug storage layer: composed of an aqueous polymer Constituted by the polymer of the compound, a concentrated extract containing gold silk paste is placed therein, which are 11.2 5 grams each of angelica tail, Chuanbai scallion, almonds, black ginseng, saponin serrata and grass black, and 18.75 grams of frankincense, 18.5 grams of myrrh, 300 grams of white gum, 150 grams of green onion, and 300 grams of rosin, add 1 to 20 times ethanol aqueous solution to heat under reflux for extraction, and concentrate; the aqueous polymer compound is 0 Crosslinking reaction product of 5-12% by weight of polyacrylic acid sodium, 1-20% by weight of carboxyvinyl polymer and 1-5% by weight of polyvinyl alcohol; and (3) Back layer: composed of non-woven fabric or fiber material . 2. The water-based golden silk plaster patch according to item 1 of the application scope, wherein the water-soluble polymer compound 1 to 5% by weight of polyvinyl alcohol can be replaced by 1 to 10% by weight of polyvinylpyrrolidone. 3. The water-based golden silk plaster patch as described in item 1 of the application scope, wherein the water-based polymer compound can further add 1 to 10% by weight of polyvinylpyrrolidone. 4. The water-based gold silk paste patch according to item 1 of the application scope, wherein the content of the gold silk paste concentrated extract solution in the medicinal layer is 2 to 10% by weight. 5 · —A method for preparing an aqueous transdermal patch containing traditional Chinese medicine gold silk paste, including the following steps: (1) Stir an appropriate amount of glycerin, water, and sorbitol: mix well, and add kaolin and water-based polymer compounds in a timely manner. The polymer compound is 0.5 to 12% by weight of sodium polyacrylate and 1 to 20% by weight of carboxyethylene polymer. Page 14 520299 Case No. 87108001 Modification VI. Application for patents and cross-linking reaction products made from 1 to 5% by weight of polyvinyl alcohol; (2) adding concentrated extract of golden silk paste, mint, salicylic acid A mixed solution of methyl ester, propyl parahydroxybenzoate and methyl parahydroxybenzoate can be used to obtain medicated colloids; the concentrated extract of golden silk paste is angelica tail, Chuanbai scallion, almond, black ginseng, and pork tooth saponin 11.25 grams of grass and black, 18.75 grams of frankincense, 18.75 grams of myrrh, 300 grams of white gum, 150 grams of green onion, 300 grams of rosin, and adding 1 to 20 times ethanol The aqueous solution is heated under reflux for extraction and concentration; and (3) Then, a drug-containing colloid is coated on the lining sheet, and then a release layer is coated thereon to form a water-soluble gold silk paste. 6. The method for preparing an aqueous transdermal patch containing Chinese medicine gold silk paste as described in item 5 of the scope of the patent application, wherein the aqueous polymer compound of step (1) 1 to 5% by weight of polyvinyl alcohol may be 1 to 10% by weight Polyvinylpyrrolidone replacement. 7. The method for preparing an aqueous transdermal patch containing Chinese medicine gold silk paste as described in item 5 of the scope of the patent application, wherein the aqueous polymer compound in step (1) can further add 1 to 10% by weight of polyvinylpyrrolidone. Page 15