Inflammation diminishing and pain relieving cataplasm capable of improving drug stability and preparation method thereof

Abstract

The invention discloses an anti-inflammatory and pain-relieving cataplasm capable of improving drug stability and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The inflammation diminishing and pain relieving cataplasm is prepared from the following raw material components: methyl salicylate, eucalyptus oil, synthetic menthol, camphor, borneol, thymol, belladonna liquid extract, diphenhydramine hydrochloride, DL-tartaric acid, gelatin, titanium dioxide, PVP, sorbitol, beta-cyclodextrin, dihydroxyaluminum aminoacetate, castor oil, partially neutralized sodium polyacrylate, glycerol and purified water. Through process improvement and inclusion of volatile materials in the formula with beta-cyclodextrin, the prepared inflammation-diminishing and pain-relieving cataplasm has the characteristics of good stability and capability of remarkably improving in-vitro drug release.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to an anti-inflammatory and analgesic cataplasm for improving drug stability and a preparation method thereof. Background Art

[0002] Hydrophilic matrix cataplasms were applied earlier in Japan. The first part of the Pharmacopoeia of the People's Republic of China (2000 edition) defines them as cataplasm agents, which refer to external preparations made by mixing medicinal extracts, drugs with suitable hydrophilic matrices and spreading them on cloth. Its English name is cataplasm, meaning plaster. Hydrophilic matrix cataplasms are less applied in the field of traditional Chinese medicine. The cataplasm varieties included in the local standards and produced in batches include Musk Strong Bone Cataplasm, Bufo Analgesic Cataplasm, Anti-inflammatory and Analgesic Cataplasm, Joint Analgesic Cataplasm, etc. There are still many traditional Chinese medicine varieties to be developed. As an external preparation, the anti-inflammatory and analgesic cataplasm can promote blood circulation, reduce inflammation and relieve pain through percutaneous absorption, has a dilating effect on local blood vessels, and is used for neuralgia, rheumatic pain, shoulder pain, sprain, joint pain, muscle pain.

[0003] The national drug standard WS-11353(ZD-1353)-2002-2012Z of the State Food and Drug Administration discloses the prescription and preparation method of the anti-inflammatory and analgesic cataplasm. Specifically, the main components in the prescription are methyl salicylate, eucalyptus oil, menthol, camphor, borneol, thymol, belladonna liquid extract and diphenhydramine hydrochloride. The preparation method is to mix the above eight herbs with the matrix, apply the paste, cover the lining, and slice to obtain the product. The above disclosed preparation method does not involve the exploration of specific process parameters, nor does it deeply study the influence of key process parameters on aspects such as the transdermal effect, appearance, viscosity, product stability, etc. of external preparations.

[0004] In order to obtain an anti-inflammatory and analgesic cataplasm with obvious drug efficacy, stable and reliable quality, and at the same time improve the many deficiencies such as easy appearance of white spots, pungent smell, long paste-making time and coating sheet weight difference during product preparation, the present invention is carried out. Summary of the Invention

[0005] The primary object of the present invention is to provide an anti-inflammatory and analgesic cataplasm for improving drug stability and a preparation method thereof.

[0006] To achieve the above object, the present invention adopts the following technical solutions: The invention provides an anti-inflammatory and analgesic plaster for improving drug stability. The anti-inflammatory and analgesic plaster comprises the following raw material components by weight: 4-6 parts of methyl salicylate; 3-5 parts of eucalyptus oil; 21-25 parts of synthetic menthol; 5-8 parts of camphor; 9-13 parts of borneol; 4-7 parts of thymol; 5-9 parts of belladonna fluid extract; 1-2 parts of diphenhydramine hydrochloride; 9-12 parts of DL-tartaric acid; 22-28 parts of gelatin; 14-18 parts of titanium dioxide; 60-74 parts of PVP; 318-388 parts of sorbitol; 96-115 parts of beta-cyclodextrin; 5-8 parts of aluminum glycolate; 13-18 parts of castor oil; 248-304 parts of partially neutralized sodium polyacrylate; 1222-1494 parts of glycerol; and 574-702 parts of purified water.

[0007] The inventors found that by encapsulating the volatile materials in the formula with β-cyclodextrin and optimizing the particle size of β-cyclodextrin, the stability of the volatile materials can be effectively guaranteed, the unpleasant odor of the drug can be concealed, and the problem of white spots in the product can be solved.

[0008] On the other hand, the present invention provides a method for preparing the anti-inflammatory and analgesic plaster with improved drug stability, comprising the following steps: (1) Preparation of preform: according to the prescribed amount, add purified water, β-cyclodextrin, and then add volatile drugs, diphenhydramine hydrochloride, and belladonna fluid extract in sequence, stir evenly, and set aside; (2) Preparation of the mixture: according to the prescribed amount and the properties of the excipients, stir glycerol, partially neutralized sodium polyacrylate, and titanium dioxide evenly and set aside; heat purified water, add gelatin, sorbitol, PVP, and DL-tartaric acid, stir and dissolve, keep warm and set aside; stir and dissolve glycerol and aluminum glycolate, set aside; (3) preparing the paste: sequentially mix and stir the materials prepared in step (2), control the paste temperature under vacuum, stir evenly, and set aside; (4) applying the ointment prepared in step (3), drying the ointment, and packaging the ointment to obtain the anti-inflammatory and analgesic ointment of the present invention; The volatile medicinal materials include methyl salicylate, synthetic menthol, camphor, borneol, thymol and eucalyptus oil.

[0009] The inventors found that the raw materials of the anti-inflammatory and analgesic bub ointment contain volatile components such as methyl salicylate, synthetic menthol, camphor, borneol, thymol and eucalyptus oil. The preparation process in the national drug standard WS-11353 (ZD-1353)-2002-2012Z of the State Food and Drug Administration adopts direct mixing to make the ointment. The stability of the volatile raw materials in this process is poor. However, after being included in the product with β-cyclodextrin, the solubility is increased, the product is not easy to produce white spots, and the stability is improved. The bioavailability of the drug can be improved, and the irritation and toxic side effects of the drug can be reduced.

[0010] Preferably, in the step (1), the particle size of β-cyclodextrin is 120 mesh to 150 mesh.

[0011] Preferably, in the step (1), the volatile medicinal materials include methyl salicylate, synthetic menthol, camphor, borneol, thymol and eucalyptus oil.

[0012] Preferably, the volatile medicinal materials are prepared by the following method: add menthol, camphor, borneol, thymol and eucalyptus oil according to the prescription amount and stir to dissolve, then add the prescription amount of methyl salicylate and castor oil, mix and stir to form a eutectic, and set aside.

[0013] Preferably, in the step (1), the weight ratio of the volatile medicinal materials to β-cyclodextrin is 1:1.5 to 1:2.5.

[0014] The inventor optimized the formulation process of the excipients, formulated the excipients according to the properties of the excipients, making the stirring and dispersion more uniform, which is beneficial to the subsequent paste preparation; and in the step (2), gelatin, sorbitol, DL-tartaric acid and polyvinylpyrrolidone K90 were dissolved and formulated together. Compared with the original process where each excipient was formulated separately, the production process was simplified, the production efficiency was improved, and the risk of errors was reduced.

[0015] Preferably, the heating temperature in the step (2) is 55°C to 65°C.

[0016] Preferably, the heat preservation temperature in the step (2) is 50°C to 60°C.

[0017] Through repeated process innovations, the inventor explored the appropriate paste mixing time, standing time and paste preparation temperature, which can not only fully mix all materials, but also reduce the damage to the effective components of the drug, and effectively control the difference in the coated tablet weight.

[0018] Preferably, in the step (3), the mixing and stirring time is 10 to 15 minutes, and the paste standing time can be omitted.

[0019] Preferably, in the step (3), the pressure controlled under vacuum is -0.03 to -0.04 MPa.

[0020] Preferably, in the step (3), the temperature of the paste controlled under vacuum is 10°C to 20°C.

[0021] Preferably, for the preparation method of the anti-inflammatory and analgesic cataplasm, the preparation steps are as follows: (1)Preparation of the prefabricate: According to the prescription amount, add purified water and β-cyclodextrin and stir until dissolved. Then, sequentially add the volatile medicinal materials and stir evenly. Diphenhydramine hydrochloride and belladonna fluid extract are stirred evenly and reserved. The volatile medicinal materials are prepared by the following method: Add menthol, camphor, borneol, thymol and eucalyptus oil according to the prescription amount and stir to dissolve. Then, add methyl salicylate and castor oil according to the prescription amount and mix and stir to obtain a eutectic product by melting; (2)Preparation of the mixture: According to the prescription amount, stir glycerol, partially neutralized sodium polyacrylate and titanium dioxide evenly according to the properties of the excipients and reserve. Heat the purified water to 55-65°C, add gelatin, sorbitol, PVP and DL-tartaric acid and stir to dissolve. Keep it at 50-60°C for standby; Stir glycerol and aluminum glycoxide to dissolve and reserve; (3)Preparation of the paste: Sequentially stir the standby materials in step (2) evenly at a temperature of 10-20°C, control the temperature of the paste at 10-20°C under a vacuum of -0.03 to -0.04 MPa, and stir evenly for standby; (4)Coat the paste prepared in step (3), air-dry the cloth, and package to obtain the anti-inflammatory and pain-relieving cataplasm of the present invention.

[0022] The preparation method of the anti-inflammatory and pain-relieving cataplasm of the present invention has the following advantages: First, the volatile materials in the formula are included by β-cyclodextrin, which can effectively improve the stability of the volatile materials, cover up the bad smell of the drug, and the inclusion complex also has high water solubility and can improve the release rate and bioavailability of the included drug in the organism. It is a good co-solvent.

[0023] Second, the inventor solves the problem of white spots in the product by optimizing the particle size of β-cyclodextrin.

[0024] Third, the present invention distributes the materials according to the properties of the excipients, dissolves and formulates gelatin, sorbitol, DL-tartaric acid and polyvinylpyrrolidone K90 together. Compared with the original process of formulating the excipients separately, the production process is simplified, the production efficiency is improved, the error risk is reduced, and the stirring and dispersion are more uniform.

[0025] Finally, through repeated process innovations, the appropriate mixing time, standing time and paste preparation temperature are explored, which can not only fully mix and dissolve all the materials, but also reduce the damage to the effective components of the drug, and effectively control the difference in coating tablet weight. The anti-inflammatory and pain-relieving cataplasm prepared by the preparation method of the present application contains significantly less impurities, has reliable quality, is not easy to produce white spots, and the drug efficacy is significantly improved, so it is safer and more effective to use. Description of the Drawings

[0026] Figure 1 is the process flow chart of the preparation method of the anti-inflammatory and pain-relieving cataplasm of the present invention.

[0027] Figure 2 This is the properties of the finished product obtained when the particle size of β-cyclodextrin is 100-120 mesh.

[0028] Figure 3 This is the properties of the finished product obtained when the particle size of β-cyclodextrin is 120-150 mesh.

[0029] Figure 4 This is a comparison chart of the in vitro release of thymol from the anti-inflammatory and analgesic papule in Example 5. DETAILED DESCRIPTION

[0030] The present application is further described in detail below through specific examples and drawings. The following examples are only used to further illustrate the present application and should not be construed as limiting the present application.

[0031] The initial viscosity of the obtained cataplasm of the present invention is checked according to the rolling ball test method under the cataplasm item of the 2000 edition of the Pharmacopoeia of the People's Republic of China. When the initial viscosity of the product is between 16 and 28, the initial viscosity of the product is good; if it is lower than the small ball of No. 16, the epidermal adhesion is poor, the adhesion to the joints is not firm enough, and it is easy to fall off; when it is higher than No. 28, the skin will feel a little pain when peeling off the patch, so No. 16 to 28 is preferred. The attachment to the joints of the body can last for many days.

[0032] The present invention adopts the third method of the release rate determination method in Appendix XD of the 2000 edition of the Pharmacopoeia of the People's Republic of China, and the release medium is a 30% ethanol physiological saline solution. The same method is used to investigate the release of each active component of the drug. The results show that the release rates of each active component are positively correlated. Since thymol can reflect the main efficacy of the drug, has stable properties, controllable ingredients in the preparation, and accurate and convenient detection, thymol is selected as the marker drug for the transdermal experiment of the present invention.

[0033] Example 1 In this embodiment, the inventors introduced in detail the process of developing the method for preparing the anti-inflammatory and analgesic Babu ointment.

[0034] 1.1 Determination of β-cyclodextrin inclusion The raw materials of the anti-inflammatory and analgesic Babu paste contain volatile components such as methyl salicylate, synthetic menthol, camphor, borneol and eucalyptus oil. The preparation process in the National Drug Standard WS-11353 (ZD-1353)-2002-2012Z of the State Food and Drug Administration adopts direct mixing to make the paste, which will produce an unpleasant odor and the stability of the volatile raw materials is poor. Therefore, in the early stage of method development, the inventors investigated whether the product effect of the anti-inflammatory and analgesic Babu paste obtained under the same conditions was obtained by adding β-cyclodextrin to encapsulate the volatile raw materials.

[0035] prescription Weigh the following raw materials in parts by weight according to the prescription: 5 parts of methyl salicylate, 3.3 parts of eucalyptus oil, 23.3 parts of synthetic menthol, 6.67 parts of camphor, 11.67 parts of borneol, 5.67 parts of thymol, 7 parts of belladonna liquid extract, and 1.2 parts of diphenhydramine hydrochloride.

[0036] Weigh the following excipients in parts by weight according to the prescription: 10.4 parts of DL-tartaric acid, 25.33 parts of gelatin, 16.7 parts of titanium dioxide, 70 parts of PVP, 353.3 parts of sorbitol, 106.7 parts of β-cyclodextrin, 6.53 parts of glycohydroxyaluminum, and 15.3 parts of castor oil.

[0037] Weigh the following matrices in parts by weight according to the prescription: 276.7 parts of partially neutralized sodium polyacrylate, 1360 parts of glycerol, and 639.9 parts of purified water.

[0038] Preparation process (1) Preparation of the prefabricate: According to the prescription, add the prescribed amount of purified water into a clean stainless steel bucket, start the stirrer, slowly add the prescribed amount of β-cyclodextrin, stir for 30 min, then slowly add the prescribed amount of menthol, camphor, borneol, thymol and eucalyptus oil and stir to dissolve. Then add the prescribed amount of methyl salicylate and castor oil, mix and stir to form a eutectic, and then stir for 10 min. Then add diphenhydramine hydrochloride and belladonna liquid extract and stir until uniform, and set aside.

[0039] (2) Preparation of the mixture: Add the prescribed amount of glycerol into a stirring kettle, start the stirrer, slowly add the prescribed amount of partially neutralized sodium polyacrylate and stir evenly, then add titanium dioxide and stir evenly, and set aside; add purified water into the stirring kettle, start the stirrer, heat to 60 °C, slowly add gelatin and stir to dissolve; then slowly add sorbitol and stir to dissolve; then slowly add polyvinylpyrrolidone and stir to dissolve, and then slowly add DL-tartaric acid and stir to dissolve, and keep it at 55 °C for standby; according to the prescription, add glycerol and glycohydroxyaluminum and stir to dissolve, and set aside.

[0040] (3) Preparation of the paste: Add the materials of each phase into a double planetary mixer in sequence, start the stirrer, pass cooling water, and stir for 15 min; open the vacuum valve, evacuate to -0.03 to -0.04 MPa, pass cooling water (control the paste temperature at 10 to 20 °C), and stir for 15 min.

[0041] (4) Coat the prepared ointment, air-dry the cloth, and package to obtain the anti-inflammatory and pain-relieving cataplasm of the present invention.

[0042] Referring to the above method, screen the mass ratio of the volatile medicinal materials to β-cyclodextrin, keep the others unchanged, and investigate the bad smell and solubility of the drug during the preparation process. The specific investigation results are shown in Table 1.

[0043] Table 1

[0044] 1.2 Determination of the particle size range of β-cyclodextrin Refer to the method in 1.1 of Example 1 to screen the particle size of β-cyclodextrin and investigate the influence on the properties of the finished product. The specific investigation results are shown in Table 2 below.

[0045] Table 2

[0046] Figure 2 It is a diagram of the properties of the finished product prepared when the particle size of β-cyclodextrin is 100 - 120 mesh. Figure 3 It is a diagram of the properties of the finished product prepared when the particle size of β-cyclodextrin is 120 - 150 mesh. As Figure 3 can be seen, when the particle size of β-cyclodextrin is selected to be 120 - 150 mesh, the prepared finished product will not produce white spots.

[0047] 1.3 Investigation of the paste-making process parameters Refer to the method in 1.1 of Example 1 to change the relevant process parameters during the paste-making process in step (3), with other conditions remaining unchanged, and investigate the effect of the preparation method. The specific investigation results are shown in Table 3 below.

[0048] Table 3

[0049] Example 2 Prescription Weigh the following raw materials in parts by weight according to the prescription amount: 4 parts of methyl salicylate, 3 parts of eucalyptus oil, 21 parts of synthetic menthol, 5 parts of camphor, 9 parts of borneol, 4 parts of thymol, 5 parts of belladonna liquid extract, and 1 part of diphenhydramine hydrochloride.

[0050] Weigh the following auxiliary materials in parts by weight according to the prescription amount: 9 parts of DL-tartaric acid, 22 parts of gelatin, 14 parts of titanium dioxide, 60 parts of PVP, 318 parts of sorbitol, 96 parts of β-cyclodextrin, 5 parts of glycohydroxyaluminum, and 13 parts of castor oil.

[0051] Weigh the following matrix materials in parts by weight according to the prescription amount: 248 parts of partially neutralized sodium polyacrylate, 1222 parts of glycerol, and 574 parts of purified water.

[0052] According to the preparation method of Example 1 of the present invention, wherein the particle size of β-cyclodextrin is 120 - 150 mesh, and the mass ratio of the volatile medicinal material to β-cyclodextrin is 1:1.5. The anti-inflammatory and analgesic cataplasm is prepared.

[0053] Example 3 Prescription Weigh the following raw materials in parts by weight according to the prescription amount: 6 parts of methyl salicylate, 5 parts of eucalyptus oil, 25 parts of synthetic menthol, 8 parts of camphor, 13 parts of borneol, 7 parts of thymol, 9 parts of belladonna liquid extract, and 2 parts of diphenhydramine hydrochloride.

[0054] Weigh the following excipients in parts by weight according to the prescription amount: 12 parts of DL-tartaric acid, 28 parts of gelatin, 18 parts of titanium dioxide, 74 parts of PVP, 388 parts of sorbitol, 115 parts of β-cyclodextrin, 8 parts of glyceryl aluminum hydroxide, and 18 parts of castor oil.

[0055] Weigh the following matrices in parts by weight according to the prescription amount: 304 parts of partially neutralized sodium polyacrylate, 1494 parts of glycerol, and 702 parts of purified water.

[0056] According to the preparation method of Example 1 of the present invention, wherein the particle size of β-cyclodextrin is 120 - 150 mesh, and the mass ratio of volatile medicinal materials to β-cyclodextrin is 1:2.5. The anti-inflammatory and pain-relieving cataplasm is prepared.

[0057] Example 4 Compare the long-term stability test of the anti-inflammatory and pain-relieving cataplasm prepared according to the preparation method of Example 1 of the present invention with that of the anti-inflammatory and pain-relieving cataplasm prepared according to the national drug standard WS-11353(ZD-1353)-2002-2012Z of the State Food and Drug Administration of China (hereinafter referred to as "the prior art"). Among them, the particle size of β-cyclodextrin is 120 - 150 mesh, and the mass ratio of volatile medicinal materials to β-cyclodextrin is 1:1.9.

[0058] The anti-inflammatory and pain-relieving cataplasm prepared by the present invention and the prior art are respectively placed for several months under long-term test conditions, and samples are regularly taken and inspected at 0, 3, 6, 9, 12, 18, and 24 months, and compared with the test results at 0 month. The results are shown in Table 4 and Table 5 below.

[0059] Table 4 Long-term stability test results of the anti-inflammatory and pain-relieving cataplasm prepared by the prior art (long-term test)

[0060] Table 5 Stability test results of the anti-inflammatory and pain-relieving cataplasm of the present invention (long-term test)

[0061] Table of stability test results of anti-inflammatory and analgesic cataplasm of the prior art (long-term test) (Table 4) and table of stability test results of anti-inflammatory and analgesic cataplasm of the present invention (long-term test) (Table 5). The test results in the above Tables 4 and 5 show that: compared with the anti-inflammatory and analgesic cataplasm of the prior art, for the anti-inflammatory and analgesic cataplasm of the present invention, no white spots appear, the initial adhesiveness is more appropriate, and the stability is significantly improved. Thus, the present invention is safer, more reliable and has higher stability than the prior art.

[0062] Example 5 Comparison of in vitro release (thymol) of the anti-inflammatory and analgesic cataplasm prepared by the preparation method of Example 1 of the present invention and the anti-inflammatory and analgesic cataplasm prepared according to the national drug standard WS-11353(ZD-1353)-2002-2012Z of the State Food and Drug Administration of China (hereinafter referred to as "the prior art"). Among them, the particle size of β-cyclodextrin is 120-150 mesh, and the mass ratio of volatile medicinal materials to β-cyclodextrin is 1:1.9.

[0063] For the anti-inflammatory and analgesic cataplasm prepared by the present invention and the prior art, the penetration rate of thymol was measured respectively according to the third method in the dissolution determination method in Appendix XD of Part I of the Chinese Pharmacopoeia (2000 Edition). The results are shown in Tables 6 and 7 below.

[0064] Table 6 In vitro release (thymol) of the anti-inflammatory and analgesic cataplasm prepared by the prior art

[0065] Table 7 In vitro release (thymol) of the anti-inflammatory and analgesic cataplasm of the present invention

[0066] Table of in vitro release (thymol) results of the anti-inflammatory and analgesic cataplasm of the prior art (Table 6) and table of in vitro release (thymol) results of the anti-inflammatory and analgesic cataplasm of the present invention (Table 7). From the test results in the above Tables 6 and 7 or ( Figure 3 ) it shows that: the anti-inflammatory and analgesic cataplasm of the present invention overcomes the stability of the product when water-soluble drugs and lip-soluble drugs are added simultaneously, and fully exerts the pharmacological effects of the active components, achieving unexpected results. Compared with the above tests, the penetration rate of thymol is 1 to 2 times that of it, far superior to the drug delivery system of the prior art.

[0067] The above content is a further detailed description of the present application in combination with specific embodiments, and it cannot be determined that the specific implementation of the present application is only limited to these descriptions. For those of ordinary skill in the technical field to which the present application belongs, without departing from the concept of the present application, several simple deductions or substitutions can be made, and all should be regarded as belonging to the protection scope of the present application.

Claims

1. An anti-inflammatory and analgesic plaster for improving drug stability, characterized in that: The raw material components are as follows by weight: 4-6 parts of methyl salicylate; 3-5 parts of eucalyptus oil; 21-25 parts of synthetic menthol; 5-8 parts of camphor; 9-13 parts of borneol; 4-7 parts of thymol; 5-9 parts of belladonna fluid extract; 1-2 parts of diphenhydramine hydrochloride; 9-12 parts of DL-tartaric acid; 22-28 parts of gelatin; 14-18 parts of titanium dioxide; 60-74 parts of PVP; 318-388 parts of sorbitol; 96-115 parts of β-cyclodextrin; 5-8 parts of aluminum glycolate; 13-18 parts of castor oil; 248-304 parts of partially neutralized sodium polyacrylate; 1222-1494 parts of glycerol; and 574-702 parts of purified water.

2. The method for preparing the anti-inflammatory and analgesic cataplasm according to claim 1, characterized in that: The following steps are involved: (1) Preparation of preform: according to the prescribed amount, add purified water, β-cyclodextrin, and then add volatile drugs, diphenhydramine hydrochloride, and belladonna fluid extract in sequence, stir evenly, and set aside; (2) Preparation of the mixture: according to the prescribed amount and the properties of the excipients, stir glycerol, partially neutralized sodium polyacrylate, and titanium dioxide evenly and set aside; heat purified water, add gelatin, sorbitol, PVP, and DL-tartaric acid, stir and dissolve, keep warm and set aside; stir and dissolve glycerol and aluminum glycolate, set aside; (3) preparing the paste: sequentially mix and stir the materials prepared in step (2), control the paste temperature under vacuum, stir evenly, and set aside; (4) applying the ointment prepared in step (3), drying the ointment, and packaging the ointment to obtain the anti-inflammatory and analgesic ointment; The volatile medicinal materials include methyl salicylate, synthetic menthol, camphor, borneol, thymol and eucalyptus oil.

3. The preparation method according to claim 2, characterized in that: The particle size of the β-cyclodextrin in step (1) is 120 mesh to 150 mesh.

4. The preparation method according to claim 2 or 3, characterized in that: The volatile drug material in step (1) is prepared by the following method: menthol, camphor, borneol, thymol and eucalyptus oil are added in the prescribed amount and stirred to dissolve, and then methyl salicylate and castor oil are added in the prescribed amount, mixed and stirred to melt, and then set aside.

5. The preparation method according to claim 2 or 3, characterized in that: In step (1), the weight ratio of the volatile drug material to β-cyclodextrin is 1:1.5 to 1:2.

5.

6. The preparation method according to claim 2 or 3, characterized in that: The heating temperature in step (2) is 55°C to 65°C; and / or the insulation temperature is 50°C to 60°C.

7. The preparation method according to claim 2 or 3, characterized in that: The pressure controlled under vacuum in step (3) is -0.03 to -0.04 MPa.

8. The preparation method according to claim 2 or 3, characterized in that: In step (3), the paste temperature is controlled at 10°C to 20°C under vacuum.

9. The preparation method according to claim 2 or 3, characterized in that: The preparation steps are as follows: (1) Preparation of preform: according to the prescribed amount, add purified water and β-cyclodextrin and stir until dissolved, then add volatile drugs in sequence and stir evenly, diphenhydramine hydrochloride and belladonna fluid extract are stirred evenly and set aside, the volatile drugs are prepared by the following method: according to the prescribed amount, add menthol, camphor, borneol, thymol and eucalyptus oil and stir to dissolve, then add methyl salicylate and castor oil in the prescribed amount, mix and stir to melt; (2) Preparation of the mixture: according to the prescribed amount and the properties of the excipients, stir glycerol, partially neutralized sodium polyacrylate, and titanium dioxide evenly and set aside; heat purified water to 55-65°C, add gelatin, sorbitol, PVP, and DL-tartaric acid, stir and dissolve, and keep warm at 50-60°C for later use; stir and dissolve glycerol and aluminum glycolate and set aside; (3) Preparation of paste: Stir the prepared materials in step (2) in turn at a temperature of 10-20°C, control the paste temperature to 10-20°C under a vacuum of -0.03-0.04 MPa, stir evenly, and set aside; (4) applying the ointment prepared in step (3), drying it, and packaging it to obtain the anti-inflammatory and analgesic papule ointment.

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