CN115227679A - Musk pain-relieving gel plaster and preparation method thereof - Google Patents

Abstract

The invention relates to the field of medicines, in particular to a musk analgesic gel plaster and a preparation method thereof. The gel plaster is water soluble matrix, and the active components of the product, including radix Aconiti, capsici fructus and radix Illicii Lanceolati, are obtained by percolating with high concentration ethanol solution, and the percolate concentrate has high content of liposoluble components. In the test process, the ethanol-extracted active component is found to generate more insoluble precipitates after being mixed with water-soluble components of belladonna fluid extract, artificial musk extract, methyl salicylate and camphor, and in addition, more lumps and scattered black plaques are generated when the ethanol-extracted active component is mixed with gel plaster matrix, and the preparation cannot be formed. The preparation method can ensure high fusion of the prescription medicine and the matrix, has good preparation stability, can be crosslinked and cured without the process of drying and dehydrating after forming, and can be crosslinked and cured after being coated and cut and directly filled into an inner bag.

Description

Musk analgesic gel patch and preparation method thereof

technical field

The invention relates to the field of medicine, in particular to a musk analgesic gel patch and a preparation method thereof.

Background technique

Musk analgesic ointment is a traditional Chinese medicine rubber ointment that has been on the market for many years. Its prescription includes artificial musk, Shengchuanwu, pepper, red fennel root, belladonna extract, methyl salicylate, and camphor. , blood circulation, analgesic effect, the main clinical rheumatic arthralgia, joint sprain, etc., the curative effect is remarkable. However, musk analgesic ointment is a rubber ointment, and the disadvantage of this dosage form is that it has poor air permeability, is highly irritating to the skin, is prone to allergic reactions, and has excessive adhesion during use, which is easy to adhere to body hair, thereby causing difficulty in peeling and sticking. Not only that, Musk analgesic ointment uses gasoline to dissolve natural rubber in production, so there are defects such as hidden dangers in production safety and environmental pollution.

The applicant has previously applied for the invention patent (application number is 201310653159.9) and the invention patent (application number is 201510119371.6) titled "Huoxue Pain Relief Paste and its preparation method" ), this invention patent discloses a kind of blood-activating pain-relieving and muscle-relieving pain-relieving balm and preparation method thereof based on the above-mentioned defect that the traditional Huoxuezhitong ointment and Shujinhuoluozhitong ointment are used for reference. The disclosed technical scheme, the applicant tried to prepare the seven-flavor traditional Chinese medicine of musk analgesic ointment and the matrix components (namely carbomer, povidone K30, Gelatin, sodium polyacrylate, disodium edetate, glycerin, ethyl paraben, ethanol and water) are combined to prepare musk analgesic gel patch, but the test found that the medicinal extract prepared by the above-mentioned technical scheme It cannot be dissolved evenly, and black insoluble particles and agglomerates appear in the paste after mixing with the matrix, which has poor viscoelasticity, is difficult to coat, and cannot be formed. is generic. Therefore, in order to obtain a prescription of musk analgesic gel patch with good viscosity, elasticity and formability, and good transdermal release, which can be used safely and effectively, it still needs to be further studied by technicians.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a kind of microbe suitable for commercial scale production which is easy to use, less irritating to the skin, good in curative effect and safe in production, the paste is easy to form, and prevents the volatilization of components such as camphor and methyl salicylate in the medicine. Emulsified musk pain relief gel patch.

In order to achieve the above object, the present invention adopts the following technical scheme: a musk analgesic gel patch, which is characterized in that: it comprises a medicinal active component and a matrix, and the matrix is prepared from the following raw materials according to parts by mass: Isopropyl myristate 0.1-2, polysorbate 80 is 0.1-2, propylene glycol 0.05-1, ethanol 0.1-0.5, skin penetrant 0.1-2, partially neutralized sodium polyacrylate 10-90, carbomer 5- 60. Cross-linking agent 0.1-2, disodium EDTA 0.1-2, tackifier 10-90, filler 5-20, pH adjuster 0.05-1, ethyl paraben 0.1-0.5, glycerin 60 -180, water 150-300.

The present invention designs the formula of the medicinal active ingredient of the musk analgesic gel patch according to the prescription of "Muxiang Analgesic Ointment" collected in the first part of the "Chinese Pharmacopoeia" of the 2020 edition. Specifically, the medicinal active ingredient is composed of the following parts by mass The raw materials are prepared from: artificial musk 0.015, Shengchuanwu 9, methyl salicylate 8, belladonna fluid extract 8, chili pepper 10, red fennel root 3, camphor 3.

In the matrix, the skin penetrant is one or more of azone, menthol, and dimethyl sulfoxide; the cross-linking agent is any one of aluminum glycerol, crystalline aluminum chloride, and magnesium sulfate; the thickening agent The agent is one or more of sodium carboxymethyl cellulose, povidone k30, povidone k90, gelatin, polyvinyl alcohol, polyvinylpyrrolidone; the filler is titanium dioxide, kaolin; the pH regulator Any of tartaric acid and citric acid.

Propylene glycol and polysorbate 80 act as co-solvents, which are beneficial to the uniform dissolution of ingredients such as medicinal extract and camphor. In addition, they act as co-emulsions during the formation of this product's microemulsion.

Isopropyl myristate is a skin penetrant, used in conjunction with propylene glycol and polysorbate 80 to form a microemulsion matrix, which not only promotes the dissolution of medicinal extracts that are mainly fat-soluble components, but also utilizes the carrier of microemulsion to promote penetration. The skin penetration rate of the drug is obviously improved, and the anti-inflammatory and analgesic effect of the drug is enhanced.

Gelatin and polyvinyl alcohol are tackifiers. Both of them in the matrix of this product not only increase the viscosity of the paste, but also increase the mechanical properties of the paste, and the viscoelasticity is better without destroying the integrity of the paste surface.

Most traditional gel pastes need to be placed under suitable temperature and humidity conditions for a certain period of time after coating, so that the paste can be cross-linked and cured before packaging. If it is directly packaged, the gel paste cannot be cross-linked and cured in the packaging bag. , of course, the product cannot be used normally, so the production efficiency of traditional gel paste is low, and at the same time, the process of airing also increases the risk of microbial contamination, especially the loss of matrix and drug components during the airing process. It is difficult to control the paste content of the adhesive paste, and the product quality fluctuates greatly, which is not conducive to commercial large-scale production. With the technical solution of the present invention, carbomer is a tackifier, which not only increases the viscosity of the matrix, but also is used in combination with gelatin, polyvinyl alcohol and other matrix components. , it can be cross-linked and cured in the inner bag, the production is efficient and simple, and it is suitable for commercial large-scale production.

Another object of the present invention is to provide a preparation method of musk analgesic gel patch, which can not only solve the problem of difficulty in forming the traditional musk analgesic formula when preparing the gel patch, but also simplifies the gel patch Cream making process.

In order to achieve the above object, the technical scheme adopted in the present invention is: 4. A preparation method of musk analgesic gel patch, comprising the following steps:

S1) chili pepper, Radix japonica, red fennel root are pulverized into coarse powder, and 90% ethanol is used as solvent to carry out percolation, and the percolation liquid is collected, concentrated into extract for subsequent use; artificial musk is ground into fine powder, and ether and no Immersion in water ethanol, pour out the supernatant, let stand, filter, and use the filtrate for later use.

S2) preparation of microemulsion solution: first, the extract and filtrate obtained in step S1) are added with ethanol and mixed uniformly, then methyl salicylate, belladonna extract, camphor are added and mixed uniformly, then propylene glycol, myristic acid are added Isopropyl ester, polysorbate 80, and shearing and stirring to obtain a 50-100 nm microemulsion solution; the uniform mixing is ultrasonic mixing, and the shearing and stirring are shearing and stirring at 5000-8000 rpm for 5-20 minutes.

This product extract is a medicinal material extracted with high concentration ethanol. After concentration, more insoluble components such as resin will be produced. Adding appropriate amount of ethanol and methyl salicylate and other components and ultrasonicating can accelerate the dispersion and dissolution to form a clear drug solution. It helps to reduce the particle size of microemulsion and improve the transdermal speed of drug-loaded microemulsion.

Compared with other microemulsion preparation methods, the present invention adopts the method of shearing and stirring at 5000-8000 rpm, which can quickly form a stable microemulsion structure, avoids the volatilization of the components of camphor and methyl salicylate in the pharmaceutical ingredients, and increases the stability.

S3) disperse sodium carboxymethyl cellulose with water, add carbomer, stir to swell the mixture to obtain matrix I; add povidone K30 to water and stir to dissolve to obtain matrix II; mix matrix II and matrix I, stir Matrix III is obtained; among them, matrix II is polyvinyl alcohol and water at 80-90 °C, stirring for 0.5-2 h to swell, cooling to 55-60 °C, adding gelatin and stirring for 0.5-1 h to swell, and cooling to 35 °C It can also be prepared by adding water to gelatin and polyvinyl alcohol, heating and stirring to swell, and letting it cool, instead of matrix II; matrix III is sodium carboxymethyl cellulose, carbomer and povidone K30 swelled separately and then mixed , at a speed of 50 to 200 rpm and stirring for 10 to 30 min.

S4) respectively adding tartaric acid and disodium edetate into water, stirring and dissolving to obtain matrix IV; dissolving ethyl paraben with ethanol to obtain matrix V; taking sodium polyacrylate, titanium dioxide and kaolin and mixing, adding glycerin and stirring evenly to obtain matrix VI.

S5) respectively adding the matrix III, matrix IV, matrix V and the microemulsion solution obtained in step S2) to matrix VI, and stirring to obtain a gel patch paste; the stirring is vacuum stirring, and the rotating speed is 50～200rpm, The stirring time is 10-60 min.

S6) Coat the paste prepared in step S5) on the non-woven fabric, apply the release film, cut into patches of a specified size, and put them into the inner bag of the package to obtain the musk analgesic gel patch.

The gel patch is a water-soluble matrix, and the active ingredients of this product, the raw chuanwu, pepper and red fennel root, are extracted from high-concentration ethanol solution, and the content of fat-soluble components in the concentrated solution is relatively high. . During the test, it was found that the alcohol-extracted active components were mixed with water-soluble ingredients such as belladonna extract, artificial musk extract, methyl salicylate and camphor, and more insoluble precipitation occurred. More clumps and scattered black patches were produced, and the formulation could not be formed. The preparation method of the present invention can ensure the high degree of fusion of the prescription drug and the matrix, the stability of the preparation is good, the cross-linking and curing can be performed without the process of drying the sheet after forming, and the product can be directly put into the inner bag after being coated and cut. Cross-linked curing.

Detailed ways

In order to further illustrate the technical solution disclosed in the present invention, the preparation method of musk analgesic gel patch comprises the following steps:

1) Preparation of medicinal material extraction solution: According to the prescription and preparation method of "Muxiang Analgesic Ointment" collected in the first edition of the 2020 edition of "Chinese Pharmacopoeia", the medicinal material extraction solution was prepared separately for later use.

2) Preparation of microemulsion solution: firstly add ethanol to the medicinal material extract prepared in step S1 and mix evenly, then add methyl salicylate, belladonna flow extract, camphor, ultrasonically mix evenly, then add propylene glycol, myristic acid Isopropyl ester, polysorbate 80, high-speed shearing and stirring to obtain 50-100nm micro-emulsion solution;

3) In step 2), the medium and high-speed shearing emulsification is performed by shearing at a speed of 5000-8000 rpm for 10 minutes to obtain a 50-100 nm micro-emulsion solution;

4) Preparation of Phase I: disperse sodium carboxymethyl cellulose with water, or add carbomer, stir to swell the mixture to obtain Phase I;

5) Preparation of Phase II: add povidone K30 to water and stir to dissolve to obtain Phase II, or add water to swell gelatin and polyvinyl alcohol to obtain Phase II.

6) In step 5), the gelatin and polyvinyl alcohol are swelled with water by adding water to polyvinyl alcohol at 80°C to 90°C for 0.5-2h to swell, and then let cool to 55°C to 60°C and then add gelatin and stir for 0.5-1h. Swell, let cool to 35℃～40℃ for later use;

7) Preparation of phase III: adding phase I obtained in step 4) to phase II obtained in step S5, and stirring at a rotational speed of 50-200 rpm for 10-30 min to obtain phase III;

8) Preparation of Phase IV: take an appropriate amount of water, add tartaric acid and disodium edetate respectively, stir to dissolve, and obtain Phase IV;

9) Preparation of Phase V: take by weighing ethyl hydroxybenzoate, dissolve with an appropriate amount of ethanol to obtain Phase V;

10) Preparation of Phase VI: Weigh sodium polyacrylate, titanium dioxide, aluminum glycerol and kaolin and mix, add glycerin and stir evenly to obtain Phase VI;

11) Preparation of gel paste: add phase III prepared in step S7, phase IV prepared in step S8, phase V prepared in step S9, and microemulsion solution prepared in step S2 into VI prepared in step S10 in turn. phase, at a rotational speed of 50 to 200 rpm, and vacuum-stirred for 10 to 30 minutes to obtain a gel patch paste;

12) Coating and molding of the gel patch: the gel paste prepared in step S11 is coated on the release film, coated with a non-woven fabric, cut into patches of a specified size, and packed into the inner packaging bag, that is, Get the musk analgesic gel patch.

According to the above steps, four examples are set, and a matrix group is used to prepare a product, and the specific formula is shown in Table 1 below:

Table 1 embodiment formula composition

Perform the following operations on the five groups of products in Table 1 above:

1. Characters and comprehensive evaluation

Properties: This product is a yellow to brown sheet-like gel patch with aroma.

The gel paste of this product has a smooth surface, uniform and fine texture, and can be pasted repeatedly. The comprehensive evaluation results of sensory indicators and initial viscosity are shown in Table 2.

Table 2 embodiment comprehensive scoring results

Note: The sensory evaluation indicators and standards are shown in the following table. The initial adhesion is based on the method under the first method of the four general rules of the Chinese Pharmacopoeia (2020 edition) 0952. The total evaluation score = initial adhesion steel ball number + comprehensive sensory score (See Table 3 for the scoring criteria);

Table 3 Sensory scoring standard comparison table

2. Acidity detection

Weigh about 1.00 g of the gel patch paste in the above embodiment, add 30 ml of water, stir to swell and disperse, and measure its acidity with a pH meter. The results are shown in Table 4.

Table 4 embodiment acidity inspection result

Example Example 1 Embodiment 2 Embodiment 3 Embodiment 4 Embodiment 5 acidity 5.12 5.35 5.41 5.67 5.87

3. Content detection

The content was determined according to high performance liquid chromatography.

Chromatographic conditions and system suitability test: use octadecylsilane bonded silica gel as filler; methanol-water (50:50) as mobile phase; detection wavelength is 280nm; flow rate is 1.0ml/min; column temperature is 40°C; the injection volume is 10 μl. The number of theoretical plates should not be less than 2000 calculated by capsaicin.

Preparation of reference substance solution: take capsaicin and dihydrocapsaicin reference substance, dissolve in methanol to prepare a solution of 20 μg each of capsaicin and dihydrocapsaicin per 1 ml.

Determination method: Take 1 stick (specification 7cm×10cm/stick) in the above-mentioned embodiment, cut it into small pieces, put it in a conical flask with stopper, add 50ml of methanol-tetrahydrofuran (1:1) mixed solution, ultrasonically treat it for 60min, The solution was poured into an evaporating dish, and 20 ml of methanol-tetrahydrofuran (1:1) mixed solution was added to the drug residues, and sonicated for 30 min. The mixed solution of tetrahydrofuran (1:1) was dissolved in stages and transferred to a 25ml volumetric flask. The methanol-tetrahydrofuran (1:1) mixed solution was used to make the volume to the mark, shaken up, filtered, and the subsequent filtrate was taken as the preparation test solution. Precisely draw 10 μl of the reference solution and the test solution, inject them into a liquid chromatograph, measure, and calculate the content of capsaicin and dihydrocapsaicin according to the area normalization method.

Each patch of this product contains capsaicin in the range of 0.5mg/patch to 1.0mg/g, and dihydrocapsaicin in the range of 0.3mg/patch to 0.7mg/g. The results are shown in Table 5.

Table 5 embodiment content detection result

Example Example 1 Embodiment 2 Embodiment 3 Embodiment 4 Embodiment 5 Capsaicin content (mg/stick) 0.56 0.76 0.93 0.86 / Dihydrocapsaicin content (mg/stick) 0.37 0.57 0.65 0.62 /

4. In vitro release evaluation

Franz diffusion cell was used to take samples of the musk analgesic ointment and the musk analgesic gel patch of the above-mentioned embodiment, and 6 copies were made in parallel. The polyethersulfone membrane was fixed between the diffusion cell and the receiving cell, the diffusion area was 2.21 cm ² , the receiving liquid was PEG400-95% ethanol-physiological saline (1:3:6), the magnetic stirring speed was 350 r/min, and the temperature was controlled. At (32±0.2) ℃, timing, at 0.5, 1, 2, 4, 6, 8, 12, and 24 h, all the receiving liquid was taken out, and the same volume of fresh receiving liquid was added at the same time. The receiving solution was used as the test solution, passed through a 0.20 μm microporous membrane, and the contents of capsaicin and methyl salicylate in the test sample were determined by high liquid chromatography (HPLC), and the cumulative release rate (Q) was calculated. , the results of capsaicin and methyl salicylate in the gel patch matrix within 24h release faster than the rubber patch, suggesting that the gel patch is more conducive to the exertion of efficacy, the results are shown in Table 6-7.

n＝6)Table 6 capsaicin 24h cumulative release rate results (

n=6)

n＝6)Table 7 methyl salicylate 24h cumulative release rate results (

n=6)

5. Evaluation of transdermal absorption

The SD rats were sacrificed by severed neck, and the abdominal rats were removed with an appropriate amount of depilatory agent. The rats were rinsed with normal saline, the skin was peeled off, the fat layer and fascia were removed, and they were placed in normal saline, and the intact and undamaged skin was selected. Franz diffusion cell was used to take samples of musk analgesic ointment and musk analgesic gel patch samples of each embodiment, and 6 copies were made in parallel. The treated rat skin was fixed between the diffusion cell and the receiving cell, the diffusion area was 2.21 cm ² , the receiving solution was PEG400-95% ethanol-physiological saline (1:3:6), the magnetic stirring speed was 350 r/min, and the control The temperature is (32±0.2) ℃, timing, at 0.5, 1, 2, 4, 8, 12 and 24h time points, all the receiving liquid are taken out, and the same volume of fresh receiving liquid is added at the same time. The receiving solution was used as the test solution, passed through a 0.20 μm microporous membrane, and the contents of capsaicin and methyl salicylate in the test sample were determined by high liquid chromatography (HPLC), and the cumulative release rate (Q) was calculated. , the results of capsaicin and methyl salicylate within 24h of the gel patch matrix through the amount of mouse skin faster than the rubber patch, suggesting that the gel patch is more conducive to the exertion of efficacy, the results are shown in Table 8-9.

n＝6)Table 8 Capsaicin 24h cumulative transdermal release rate results (

n=6)

n＝6)Table 9 methyl salicylate 24h cumulative release rate results (

n=6)

6. Influence of musk analgesic gel patch of the present invention on inflammation caused by xylene in mice

36 healthy male mice were selected and randomly divided into 3 groups, namely the control group, the Shexiang analgesic ointment group, and the Shexiang analgesic gel plaster group in Example 4, 12 in each group, and the mice in each experimental group were kept at The ointment was applied to the right ear once for 3 consecutive times. 1 hour after the last administration, the ointment was removed, and 0.05 mL of xylene was applied to the right ear. The left ear was used as a control. The same area of both ears was excised and weighed respectively to calculate the swelling degree of the right ear. The results show that there is no significant difference between the musk analgesic gel patch group of the prior art and the musk analgesic gel patch group of the present invention, as shown in Table 10 for details.

Table 10 Effects of xylene-induced ear swelling in mice (n=12,: X±s)

Compared with the control group: *ρ<0.05

8. Influence of musk analgesic gel patch of the present invention on pain caused by hot plate in mice

Adjust the temperature of the super constant temperature water bath at 55 °C ± 0.5 °C, preheat the hot plate for 10 min, take female healthy mice, and place one at a time on the hot plate. The required time (S) was taken as the pain threshold of the mouse. Those who licked the hind paws for less than 5s or more than 30s or jumped were discarded and 36 qualified mice were randomly divided into the control group, the Shujinhuoluozhitong ointment group, and the four musk analgesic gel plaster groups of Example 4. There were 12 mice in each group, and the mice in each experimental group applied the ointment to the hind legs once a day for 3 consecutive times. 1 hour after the last administration, the pain threshold of the mice was measured. The results show that there is no significant difference between the musk analgesic gel patch group of the prior art and the musk analgesic gel patch group of the present invention, as shown in Table 6.

Table 11 Effects on the pain threshold of hot plate in mice (n=12, x±s)

Compared with the control group: *ρ<0.05

9. Influence of musk analgesic gel patch of the present invention on acetic acid-induced writhing in mice

36 healthy male mice were selected and randomly divided into 3 groups, namely the control group, the musk analgesic ointment group, and the musk analgesic gel patch group of Example 4, with 12 mice in each group, and the abdominal hair of the mice was shaved before the experiment. , administered in the abdomen of the mice, repeated once after 1 hour, and then immediately intraperitoneally injected with 0.1 mL/10 g of 0.6% acetic acid solution to observe the writhing response of the mice, with typical hindlimb stretching, abdominal twisting, and abdominal muscle contractions As a standard, the writhing times of each group of animals were recorded within 15 min. The results show that there is no significant difference between the musk analgesic gel patch group of the prior art and the musk analgesic gel patch group of the present invention, as shown in Table 12 for details.

The effect of table 12 on the number of writhing in mice caused by acetic acid (η=12, χ ± s)

Compared with the control group: #ρ<0·01

Conclusion: The Shexiang Analgesic Analgesic Ointment group of the prior art and the Shexiang Analgesic Gel Patch Group of the present invention have obvious anti-inflammatory and analgesic effects. When used, the muscle-relieving and pain-relieving babu ointment of the present invention has a quicker effect than the musk analgesic and pain-relieving ointment of the prior art, has no obvious irritation and allergic reaction, fits comfortably, has high production safety, and causes environmental pollution. Low. In addition, an acute toxicity test was carried out on the musk analgesic gel patch of the present invention by using rabbits, and the results showed that no obvious systemic toxicity was found in the rabbits in the intact skin group and the damaged skin group.

10. The irritation test of the musk analgesic gel patch of the present invention to the skin

Take 12 healthy rabbits (2.3±0.2kg), half male and half male, and divide them into intact skin group and damaged skin group. 48 hours before administration, use 6% sodium sulfide solution to depilate both sides of the animal's back spine, each side The area is about 50cm ² , and 24 hours after hair removal, check whether the hair removal skin is injured due to hair removal. The damaged skin of the rabbit is made as follows: Use a scalpel to cut the hair removal and disinfected skin, and control the bleeding to the degree of oozing. The degree of skin damage on the left and right sides is basically the same.

The test adopts the same body left and right self-contrast method: the left and right hair removal areas are given embodiment four musk analgesic gel patch and blank control respectively, smear once a day, continuous administration for 7 days; 1, 24, 48 after stopping administration respectively , 72 hours to observe whether there is erythema and edema at the administration site, and at the same time pay attention to observe whether there is pigmentation, bleeding spots, rough skin, etc. at the administration site. The results showed that after continuous administration of the musk analgesic gel patch for 7 days, and observed within 72 hours, there were no irritating reactions such as erythema and edema in the rabbit intact skin group and the damaged skin group.

11. Allergy test of musk analgesic gel patch of the present invention to skin

Get 40 Hartley guinea pigs (300±30g), half male and half male, and divide into negative control group, positive control group (2,4-dinitrochlorobenzene), musk analgesic ointment group and embodiment four musk analgesic gel In the patch group, the hair on the left side of the animal spine was shaved with an electric razor 24 hours before administration. The drug (sensitizing dose) is directly applied or applied on the left dehaired skin, then covered with gauze, and then fixed with non-irritating tape and bandage, and the application time is at least 6 hours each time. After application, clean the administration site with lukewarm water. 13 days after the last administration, the hair on the right side of the spine of the animal was shaved with an electric razor, and the hair removal area was generally about 4cm×5cm as the stimulation administration area. 14 days after the last administration, the drug (provocative dose) was directly applied or smeared on the right depilated skin, then covered with gauze, and then fixed with non-irritating tape and bandage for about 6 hours.

During the sensitization period, the erythema and edema at the administration site of the animals, as well as the systemic reaction were observed once a day (observation 1 hour after the drug was removed on the day of sensitization administration); 14 days after the last sensitization, the test article was given again to challenge, 1 hour, 24 hours, 48 hours, and 72 hours after the drug was removed, the erythema and edema of the skin of the animals at the challenge administration site, and the systemic reaction were observed. Results The Shexiang Analgesic Ointment group had mild allergic reaction, but the Shexiang Analgesic Gel Patch group had no allergic reaction.

Claims (9)

1. a musk analgesic gel patch is characterized in that: comprise active pharmaceutical ingredient and matrix, and described matrix is prepared from following raw materials according to mass fraction: isopropyl myristate 0.1-2, polysorbate Ester 80 is 0.1-2, propylene glycol 0.05-1, ethanol 0.1-0.5, skin penetrant 0.1-2, partially neutralized sodium polyacrylate 10-90, carbomer 5-60, cross-linking agent 0.1-2, ethylene glycol Disodium amine tetraacetate 0.1-2, tackifier 10-90, filler 5-20, pH adjuster 0.05-1, ethyl paraben 0.1-0.5, glycerin 60-180, water 150-300. 2. according to the described musk analgesic gel patch of claim 1, it is characterized in that: described medicinal active ingredient is prepared from the raw material of following mass fraction: artificial musk 0.015, Shengchuanwu 9, salicylic acid methyl Ester 8, belladonna extract 8, pepper 10, red fennel root 3, camphor 3. 3. according to the described musk analgesic gel patch of claim 1, it is characterized in that: skin penetrant is one or more in azone, menthol, dimethyl sulfoxide; Any in crystalline aluminum chloride, magnesium sulfate; Described tackifier is a kind of in sodium carboxymethyl cellulose, povidone k30, povidone k90, gelatin, polyvinyl alcohol, polyvinylpyrrolidone or several kinds; the filler is titanium dioxide and kaolin; the pH adjuster is any one of tartaric acid and citric acid. 4. a preparation method of musk analgesic gel patch, comprising the steps: S1) chili pepper, Radix japonica, red fennel root are pulverized into coarse powder, and 90% ethanol is used as solvent to carry out percolation, and the percolation liquid is collected, concentrated into extract for subsequent use; artificial musk is ground into fine powder, and ether and no Immersion in water ethanol, pour out the supernatant, let stand, filter, and the filtrate is for use; S2) preparation of microemulsion solution: first, the extract and filtrate obtained in step S1) are added with ethanol and mixed evenly, then methyl salicylate, belladonna flow extract and camphor are added and mixed evenly, then propylene glycol, myristic acid are added Isopropyl ester, polysorbate 80, shearing and stirring to prepare 50-100nm microemulsion solution; S3) disperse sodium carboxymethyl cellulose with water, add carbomer, stir to swell the mixture to obtain matrix I; add povidone K30 to water and stir to dissolve to obtain matrix II; mix matrix II and matrix I, stir get matrix III; S4) respectively adding tartaric acid and disodium edetate into water, stirring and dissolving to obtain matrix IV; dissolving ethyl paraben with ethanol to obtain matrix V; taking sodium polyacrylate, titanium dioxide and kaolin and mixing, adding glycerin and stirring evenly to obtain matrix VI; S5) respectively adding matrix III, matrix IV, matrix V and the microemulsion solution obtained in step S2) to matrix VI, and stirring to obtain a gel patch paste; S6) Coat the paste prepared in step S5) on the non-woven fabric, apply the release film, cut into patches of a specified size, and put them into the inner bag of the package to obtain the musk analgesic gel patch. 5. the preparation method of musk analgesic gel patch according to claim 4, is characterized in that: in described step S2), described mixing is ultrasonic mixing, and described shearing stirring is shearing under 5000～8000rpm Cut and stir for 5 to 20 minutes. 6. The preparation method of the musk analgesic gel patch according to claim 4, characterized in that: the stirring in the step S5) is vacuum stirring, the rotating speed is 50～200rpm, and the stirring time is stirring 10～60min. 7. The preparation method of the musk analgesic gel patch according to claim 4, wherein the matrix II in the step S3) is that polyvinyl alcohol is added with water and stirred at a temperature of 80 to 90 ° C for 0.5 to 2 h to swell , let it cool to 55℃～60℃, add gelatin and stir for 0.5～1h to make it swell, and let it cool to 35℃～40℃. 8. according to the preparation method of the described musk analgesic gel patch of claim 4, it is characterized in that: the matrix III in described step S3) is sodium carboxymethyl cellulose, carbomer and povidone K30 to swell respectively Then mix again, and stir for 10 to 30 minutes at a speed of 50 to 200 rpm. 9. The preparation method of the musk analgesic gel patch according to claim 4, characterized in that: in the step S3), gelatin and polyvinyl alcohol are added with water, heated and stirred for swelling, and allowed to cool to replace the matrix II.