Industrialized preparation method of emplastrum composition capable of improving safety

Abstract

The invention relates to the technical field of traditional Chinese medicine external preparations, in particular to an industrialized preparation method of an emplastrum composition capable of improving safety. The preparation method comprises the following steps: partially dissolving rubber by using gasoline A, then adding rosin, and stirring for dissolving; adding activated zinc oxide, mixing, adding lanolin, vaseline, musk wind-dispelling and pain-relieving liquid extract, belladonna liquid extract, rutin extract, menthol, borneol, camphor, methyl salicylate and a gasoline B part, and performing pH regulation to obtain musk wind-dispelling and pain-relieving paste mucilage; the activated zinc oxide is obtained by the following steps: mixing zinc oxide and liquid paraffin, and standing for 2-4 hours in an environment of 120-140 DEG C, so as to obtain the activated zinc oxide. According to the technical scheme, on the basis of keeping the treatment effect of the original medicinal components, the technical problem that the musk wind-dispelling and pain-relieving ointment contains viscous matrix components such as rosin and rubber, so that the skin is easily stimulated, and adverse reactions such as skin erythema are generated is solved, and the musk wind-dispelling and pain-relieving ointment has good market prospects and social benefits.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine external preparations, and in particular to an industrialized preparation method of a patch composition with improved safety. Background Art

[0002] Musk Wind-Chasing Pain-Relieving Ointment is a traditional Chinese medicine topical patch widely used to treat joint pain, muscle aches, sprains, swelling, and pain caused by rheumatic arthritis. Its main ingredients are Musk Wind-Chasing Pain-Relieving Fluid Extract (containing raw Aconitum kusnezoffii, raw Chuanwu, frankincense, myrrh, raw Strychnos nux vomica, cloves, cinnamon bark, schizonepeta tenuifolia, siler, geranium, cyperus rotundus, Centella asiatica, Drynaria fortunei, Angelica dahurica, Kaempferia galanga, dried ginger, and artificial musk), camphor, menthol, borneol, methyl salicylate, rue extract, and belladonna extract. The general preparation process is as follows: Mix Musk Wind-Chasing Pain-Relieving Fluid Extract and belladonna fluid extract and set aside. The remaining five ingredients, including camphor, are mixed thoroughly, and the fluid extract is added. A 3.7-4.0-fold amount of a matrix consisting of rubber, rosin, zinc oxide, petrolatum, lanolin, and liquid paraffin is added. The mixture is then mixed to form a coating, which is then applied to the ointment. The ointment is then cut into sections, covered with a backing, and then cut into pieces. Musk Wind-Chasing and Analgesic Ointment has good anti-inflammatory, analgesic and blood circulation-activating and collateral-unblocking effects and is widely used clinically.

[0003] However, during long-term clinical use, it was found that some patients experienced varying degrees of skin irritation reactions such as itching, erythema, and swelling after using the patch preparation, affecting the patient's medication compliance and treatment effect. Studies have shown that these adverse reactions are mainly caused by the natural plant-derived materials used in the patch matrix, such as rosin, rubber and other sticky matrix components. These natural materials are usually directly collected and dried from plant slurries without deep purification. Various foreign protein allergens may remain in them, becoming one of the main causes of skin irritation reactions.

[0004] At present, for the allergen components contained in such natural plant-derived materials, there is still a lack of effective removal methods, resulting in the widespread presence of certain skin irritation risks in traditional plaster preparations represented by rubber matrix. Therefore, how to reduce the negative impact of potential sensitizers in plaster preparations while retaining active pharmaceutical ingredients and therapeutic effects, improve the safety and patient tolerance of products, has become the key issues and technical difficulties in the research and development of such external-use plasters. Therefore, this area is in urgent need of providing an improved plaster composition and preparation method thereof, to overcome the above-mentioned defects present in the prior art, to enhance the safety and comfort of drug use. Summary of the Invention

[0005] The present invention aims to provide an industrial preparation method for a patch composition with improved safety, so as to solve the technical problem that musk wind-chasing and analgesic plaster contains sticky matrix components such as rosin and rubber, which easily irritates the skin and causes adverse reactions such as skin erythema.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for industrially preparing a patch composition with improved safety comprises using gasoline (part A) to dissolve rubber, then adding rosin and stirring to dissolve; then adding activated zinc oxide and mixing; then adding lanolin, vaseline, musk wind-chasing and analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate, and gasoline (part B); and finally adjusting the pH to obtain musk wind-chasing and analgesic plaster.

[0008] Activated zinc oxide is obtained by mixing zinc oxide and liquid paraffin, and placing the mixture in an environment of 120°C to 140°C for 2 to 4 hours.

[0009] Furthermore, the raw materials of the patch composition include, in parts by weight: 50-60 parts of musk analgesic fluid extract, 25-35 parts of rue extract, 30-40 parts of belladonna fluid extract, 20-30 parts of menthol, 8-15 parts of camphor, 20-30 parts of borneol, 10-20 parts of methyl salicylate, 400-600 parts of gasoline, 150-200 parts of rubber, 150-200 parts of rosin, 10-20 parts of liquid paraffin, 10-20 parts of lanolin, 10-20 parts of vaseline, and 200-300 parts of zinc oxide.

[0010] Furthermore, the zinc oxide and the liquid paraffin are mixed in a manner of placing the zinc oxide and the liquid paraffin in an environment of a rotation speed of 20 to 30 rpm and stirring for 20 to 30 minutes.

[0011] Furthermore, the usage ratio of gasoline part A to gasoline part B is 15:85 to 25:75.

[0012] Furthermore, the method of using gasoline part A to dissolve the rubber is as follows: the rubber and gasoline part A are placed in a closed environment and soaked for 18 to 30 hours.

[0013] Furthermore, the stirring method after adding the rosin is: stirring at a speed of 20 to 30 rpm for 2 to 3 hours to dissolve the material; the method of adding activated zinc oxide and mixing is: stirring at a speed of 20 to 30 rpm for 2 to 3 hours.

[0014] Further, after adding lanolin, vaseline, musk wind-chasing and analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate and gasoline part B, stirring at a speed of 20 to 30 rpm for 5 to 8 hours; then adjusting the pH value to 5.5 to 6.5, and stirring at a speed of 20 to 30 rpm for 5 to 8 hours to obtain musk wind-chasing and analgesic ointment syrup.

[0015] Furthermore, the musk wind-chasing analgesic plaster is coated on a carrier, and the musk wind-chasing analgesic plaster is obtained after cutting; preferably, the carrier is a stretch fabric; the musk wind-chasing analgesic plaster contains ≥1.65g / 100cm 2 .

[0016] Furthermore, the musk wind-chasing and analgesic fluid extract is prepared by the following method: taking raw kusnezoffii, raw Chuanwu, frankincense, myrrh, raw strychnine, cloves, cinnamon, schizonepeta, siler, geranium, cyperus rotundus, Centella asiatica, drynaria, angelica dahurica, galangal, and dried ginger, and crushing them to obtain coarse powder; using ethanol as a solvent to perform percolation extraction on the coarse powder, and collecting the percolation liquid; filtering and concentrating the percolation liquid to obtain a thick paste; adding ethanol to the thick paste, mixing and letting it stand, and then taking the supernatant; concentrating the supernatant to obtain an extract, and adding musk to the extract to obtain the musk wind-chasing and analgesic fluid extract.

[0017] Furthermore, the raw materials of musk wind-chasing and analgesic fluid extract include, by weight: 20-30 parts of raw aconiti kusnezoffii, 20-30 parts of raw aconiti kusnezoffii, 20-30 parts of frankincense, 20-30 parts of myrrh, 20-30 parts of raw strychnine seeds, 20-30 parts of cloves, 40-60 parts of cinnamon, 40-60 parts of schizonepeta tenuifolia, 40-60 parts of siler, 40-60 parts of geranium, 40-60 parts of angelica dahurica bark, 40-60 parts of centella asiatica, 40-60 parts of drynaria, 70-80 parts of angelica dahurica, 70-80 parts of galangal, 70-80 parts of dried ginger, and 0.5-2 parts of musk.

[0018] The technical principle of this technical solution is:

[0019] The present invention provides an innovative method for preparing a patch composition, which is specifically used to solve the potential skin irritation problem in traditional Chinese medicine external preparations such as Musk Chasing Wind and Pain Relief Plaster. The core of this method is to use zinc oxide treated under specific conditions to significantly improve the safety of the patch. During the preparation process, zinc oxide and liquid paraffin are mixed and heated at a temperature range of 120°C to 140°C for 2 to 4 hours to complete the activation treatment. The use of zinc oxide after the above treatment to prepare Musk Chasing Wind and Pain Relief Plaster can effectively reduce the risk of sensitization caused by the use of the patch.

[0020] The inventors believe this may be due to the activation effect, which affects the crystal structure of zinc oxide to a certain extent, increasing the number and reactivity of its surface active sites, resulting in stronger adsorption capacity and higher chemical stability. Activated zinc oxide effectively denatures or degrades the plant proteins in rosin and rubber, reducing their immunogenicity and allergenicity. Furthermore, zinc oxide inherently possesses certain antioxidant properties, which are enhanced after activation, helping to neutralize free radicals that can cause skin irritation.

[0021] The beneficial effects of this technical solution are:

[0022] The patch prepared using the method described herein not only maintains the therapeutic effects of the original drug ingredients but also significantly reduces skin irritation caused by the matrix material. Compared to unactivated zinc oxide, activated zinc oxide has a more significant effect on the aging or passivation of plant proteins in rosin and rubber, effectively reducing the presence of allergens.

[0023] Furthermore, animal studies have shown that the incidence of adverse reactions such as skin redness and swelling is significantly reduced with activated zinc oxide-treated patches, significantly improving the safety and comfort of medication use. This approach not only addresses the potential skin irritation associated with traditional rubber-based patches but also improves overall product quality through process optimization.

[0024] Furthermore, the technical solution proposed in this invention is easy to implement for industrial production and has good market prospects and social benefits. It provides a scientific basis and technical support for the modernization of traditional Chinese medicine external-use preparations, and in particular, demonstrates great potential for improving product safety. Through this innovative improvement, the effectiveness of traditional Chinese medicine preparations is guaranteed while their safety is enhanced, which is of great significance for promoting the modernization of traditional Chinese medicine. At the same time, this method also provides a reference model for improving the safety of other types of external-use preparations, promoting the progress and development of the entire pharmaceutical industry. DETAILED DESCRIPTION

[0025] The following examples are intended only to more clearly illustrate the technical solutions of the present invention and are therefore provided as examples only and are not intended to limit the scope of protection of the present invention. The specific embodiments listed herein are merely exemplary of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, any equivalent modifications and substitutions made to the embodiments described below are also within the scope of the present invention. Therefore, equivalent transformations and modifications made without departing from the spirit and scope of the present invention should be encompassed within the scope of the present invention. To better illustrate the present invention, numerous specific details are provided in the following specific embodiments. Those skilled in the art should understand that the present invention can be implemented without certain specific details. In other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. Unless otherwise specified, the units used in this specification are international standard units, and the numerical values and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0026] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Materials, reagents, or instruments used, for which the manufacturer is not indicated, are commercially available. For any unspecified conditions in the examples, conventional conditions or those recommended by the manufacturer were followed. The present invention does not limit the sources of the raw materials used; unless otherwise specified, the raw materials used in the present invention are commercially available products in the art. Unless otherwise specified, "ratios" in the following examples are by mass.

[0027] The existing Musk Wind-Chasing Pain-Relieving Ointment can be found in the National Drug Standard WS-11370 (ZD-1370)-2002-2012Z-2019 issued by the State Food and Drug Administration. This technical solution further improves upon the existing technology and aims to address the skin irritation problem of the existing Musk Wind-Chasing Pain-Relieving Ointment.

[0028] The formula of Musk Wind-Chasing Pain-Relieving Ointment is shown in the following table (Table 1):

[0029] Table 1: The formula of Musk Wind-Chasing Pain-Relieving Ointment

[0030]

[0031]

[0032] Musk Wind-Chasing Pain-Relieving Fluid Extract is an intermediate used in the preparation of Musk Wind-Chasing Pain-Relieving Plaster. It is also a standardized Chinese patent medicine raw material (intermediate) approved and recognized by the State Food and Drug Administration and is recorded in the Musk Wind-Chasing Pain-Relieving Plaster Quality Standard (WS-11370(ZD-1370)-2002-2012Z-2019). Its preparation method is generally as follows:

[0033] Raw kusnezoffii root, raw Chuanwu root, frankincense, myrrh, raw strychnine seeds, cloves, cinnamon bark, schizonepeta tenuifolia, siler, geranium, cyperus rotundus, Centella asiatica, drynaria root, angelica dahurica, galangal, and dried ginger are ground into coarse powder; the coarse powder is subjected to conventional percolation extraction using ethanol as a solvent, and the percolation liquid is collected; the percolation liquid is filtered and concentrated to obtain a thick paste; ethanol is added to the thick paste, mixed and allowed to stand, and then the supernatant is collected; the supernatant is concentrated to obtain a fluid extract, and musk is added to the fluid extract to obtain a musk wind-chasing and analgesic fluid extract.

[0034] The more specific process is as follows:

[0035] Take 20-30 parts by weight of raw aconite root, 20-30 parts of raw Chuanwu root, 20-30 parts of frankincense, 20-30 parts of myrrh, 20-30 parts of raw strychnine seeds, 20-30 parts of cloves, 40-60 parts of cinnamon bark, 40-60 parts of schizonepeta, 40-60 parts of siler, 40-60 parts of geranium, 40-60 parts of perilla bark, 40-60 parts of centella asiatica, 40-60 parts of drynaria, 70-80 parts of angelica dahurica, 70-80 parts of kaempferia galanga and 70-80 parts of dried ginger, grind them into coarse powder with a mesh size of 24-65; and prepare musk wind-chasing and analgesic fluid extract by percolation.

[0036] The percolation method is as follows: the crushed medicinal materials are mixed uniformly, ethanol with a concentration of 75% to 95% by weight is used as a solvent, the medicinal materials are moistened with the solvent for 2 to 4 hours, the medicinal materials are placed in a percolator, the solvent is added until the medicinal materials are immersed, and after immersion for 40 to 50 hours, percolation is started at a flow rate of 1 to 3 ml / min, and the initial percolation liquid of 1 to 2 times the amount of the medicinal materials is collected in another container; the percolation is continued to collect the subsequent percolation liquid of 5 to 8 times the amount of the medicinal materials, the subsequent percolation liquid is combined with the initial percolation liquid, and the percolation liquid is heated to -0. The method comprises the following steps: recovering ethanol under reduced pressure at 0.08 to -0.1 MPa, filtering, and concentrating the filtrate to a thick paste at a temperature of 60 to 70°C; adding 8 to 12 times the amount of ethanol after the concentrated thick paste, stirring evenly, standing for 2 to 4 hours, absorbing the supernatant, recovering ethanol under reduced pressure at -0.08 to -0.1 MPa, and concentrating the mixture to a fluid extract with a relative density of 1.03 to 1.08; adding 0.5 to 2 parts of musk to the fluid extract, and mixing evenly to obtain a musk wind-chasing and analgesic fluid extract.

[0037] Preferably, the musk wind-chasing and analgesic fluid extract is prepared as follows: take 25 parts each of raw aconite, raw Chuanwu, frankincense, myrrh, raw strychnine, and cloves, 50 parts each of cinnamon, schizonepeta, siler, geranium, fragrant bark, centella asiatica, and drynaria, 75 parts each of angelica, kaempferia, and dried ginger, grind them into coarse powder, use 90% ethanol as a solvent, soak for 48 hours, slowly filter at a rate of 1 to 3 ml per minute, collect about 800 ml of the initial filter liquid, store it in another container, continue to filter, collect 5000 ml of the subsequent filter liquid, combine it with the initial filter liquid to recover ethanol under reduced pressure, filter, and concentrate the filtrate at 60 to 70 ° C to a thick paste, add 10 times the amount of ethanol, stir evenly, let it stand, absorb the supernatant, and after reducing pressure to recover ethanol, concentrate it to a fluid extract with a relative density of 1.05 (60 ° C), add 1 part of musk, mix well, and obtain. For the convenience of comparison, the Musk Wind-Chasing and Analgesic Fluid Extract used in subsequent experiments was prepared according to this optimized method.

[0038] A method for industrial preparation of a patch composition with improved safety is as follows:

[0039] Preparation of S1 activated zinc oxide:

[0040] Zinc oxide: liquid paraffin is added into a mixer at a ratio of 100:5-7 and mixed at a speed of 20-30 rpm (preferably 25 rpm) for 20-30 minutes (preferably 25 minutes). The mixture is then transferred to an activation tank and activated at a temperature of 120°C-140°C (preferably 130°C) for 2-4 hours (preferably 3 hours) to obtain activated zinc oxide (zinc oxide + liquid paraffin).

[0041] Preparation of S2 plaster composition paste:

[0042] Take the prescribed amount of rubber, add 15% to 25% (preferably 20%) of gasoline, and soak it in a sealed stainless steel barrel for 18 to 30 hours (preferably 25 hours). Then transfer it to a double-shaft horizontal stirring filter, add the prescribed amount of rosin, stir (20 to 30 rpm, preferably 25 rpm) and dissolve it for 2 to 3 hours (preferably 2.5 hours). Then, add the activated zinc oxide prepared in step S1, continue stirring at a speed of 20 to 30 rpm (preferably 25 rpm) for 2 to 3 hours, then add lanolin, vaseline, musk analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate and the remainder of gasoline, stir (20 to 30 rpm, preferably 25 rpm) for 5 to 8 hours (preferably 7 hours) to form a paste (mucilage), adjust the pH value of the mucilage to 5.5 to 6.5 (preferably 6.0) with an appropriate amount of phosphoric acid, continue stirring (20 to 30 rpm, preferably 25 rpm) for 3 to 5 hours (preferably 4 hours) to mix evenly.

[0043] S3 coating, cutting and packaging: Open the steam valves of each drying section of the hot air circulation coating unit, adjust the temperature of drying section 1 and drying section 5 to 35-45℃, adjust the temperature of drying sections 2, 3 and 4 to 60-70℃, and adjust the temperature of the cooling section to 8-20℃. Turn on the hot air circulation coating unit to start coating, and apply the musk chasing wind and pain-relieving ointment paste on the stretch fabric. Adjust the coating speed to 8-10 meters / minute, corresponding to the frequency of the hot air circulation coating unit speed inverter of 15-25Hz. Adjust the coating thickness so that the paste content is not less than 1.65g / 100cm 2 Lay the dried elastic band on the dimethicone paper. Cut the laminated elastic band into 7cm x 10cm pieces. Place the cut plaster pieces into aluminum-plastic composite bags to obtain the finished Musk Wind-Chasing Pain-Relieving Plaster.

[0044] Example 1

[0045] The formula of the Musk Wind-Chasing Pain-Relief Ointment of the present embodiment is:

[0046] 55 parts of musk wind-chasing and analgesic fluid extract, 30 parts of rue extract, 35 parts of belladonna fluid extract, 25 parts of menthol, 11 parts of camphor, 25 parts of borneol, 15 parts of methyl salicylate, 500 parts of gasoline, 180 parts of rubber, 180 parts of rosin, 15 parts of liquid paraffin, 15 parts of lanolin, 15 parts of vaseline, and 250 parts of zinc oxide. The mass ratio of zinc oxide to liquid paraffin is 250:15 (i.e., 100:6).

[0047] The preparation process specifically employed the optimized parameters of the aforementioned process (see "A Method for Industrialized Preparation of a Patch Composition with Enhanced Safety"), except that in S1, the ratio of zinc oxide to liquid paraffin was 100:6, and the activation conditions were 130°C for 3 hours. The patch prepared in this example is designated Patch 1.

[0048] Example 2

[0049] The formula of the Musk Wind-Chasing Pain-Relief Ointment of the present embodiment is:

[0050] Musk wind-chasing and analgesic fluid extract 60 parts, Rutaecarpa extract 35 parts, belladonna fluid extract 40 parts, menthol 30 parts, camphor 15 parts, borneol 30 parts, methyl salicylate 20 parts, gasoline 600 parts, rubber 200 parts, rosin 200 parts, liquid paraffin 20 parts, lanolin 20 parts, vaseline 20 parts, zinc oxide 300 parts. The mass ratio of zinc oxide to liquid paraffin is 300:20 (i.e., 100:6.7).

[0051] The preparation process was carried out using the optimized parameters of the aforementioned process, except that in S1, the ratio of zinc oxide to liquid paraffin was 100:6.7, and after the zinc oxide and liquid paraffin were mixed, the activation temperature in the activation tank was 140°C and the activation time was 2 hours. The patch prepared in this example is named: Patch 2.

[0052] Example 3

[0053] The formula of the Musk Wind-Chasing Pain-Relief Ointment of the present embodiment is:

[0054] 50 parts of Musk Wind-Removing and Pain-Relief Fluid Extract, 25 parts of Rutaecarpa Extract, 30 parts of Belladonna Fluid Extract, 20 parts of menthol, 8 parts of camphor, 20 parts of borneol, 10 parts of methyl salicylate, 400 parts of gasoline, 150 parts of rubber, 150 parts of rosin, 10 parts of liquid paraffin, 10 parts of lanolin, 10 parts of vaseline, and 200 parts of zinc oxide. The mass ratio of zinc oxide to liquid paraffin is 200:10 (i.e., 100:5).

[0055] The preparation process was carried out using the optimized parameters of the aforementioned process, except that in S1, the ratio of zinc oxide to liquid paraffin was 100:5, and after the zinc oxide and liquid paraffin were mixed, the activation temperature in the activation tank was 120°C and the activation time was 4 hours. The patch prepared in this example was named: Patch 3.

[0056] Comparative Example 1

[0057] The formula of this comparative example is basically the same as that of Example 1, except that step S1 of Example 1 is not performed in this comparative example. The specific preparation process of the patch is as follows:

[0058] Operation method 1:

[0059] Get the rubber of recipe quantity, add the gasoline of recipe quantity 20%, airtight soak 25 hours in stainless steel barrel, then proceed in biaxial horizontal stirred filter, add the rosin of recipe quantity, 25 rev / mins of stirring and dissolving 2.5 hours.Then, add the zinc oxide without activation, continue to stir 2.5 hours with the rotating speed of 25 rev / mins, then add liquid paraffin, lanolin, vaseline, musk wind-chasing analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate and surplus gasoline, stir and make paste (mucilage) for 7 hours, with appropriate phosphoric acid, the pH value of mucilage is adjusted 6.0, continue to stir and mix in 4 hours.Remaining operation process is with embodiment 1, and the plaster prepared by this comparative example operating mode one is named after: contrast plaster 1-1.

[0060] Operation method 2:

[0061] Zinc oxide: liquid paraffin in a ratio of 100:6 was added to a mixer at 25 rpm for 25 minutes (preferably 25 minutes). The mixture was then added to step S2, replacing the activated zinc oxide described in Example 1. The remaining procedures were the same as in Example 1. The patch prepared in this comparative example, operating method 2, is designated Comparative Patch 1-2.

[0062] Comparative Example 2

[0063] The formula of this comparative example is basically the same as that of Example 2, except that the activation treatment method of zinc oxide is different, as follows:

[0064] The prescribed amount of zinc oxide and liquid paraffin was placed in a mixer and mixed at 25 rpm for 25 minutes. The mixture was then transferred to an activation tank and activated at 150°C for 3 hours to obtain activated zinc oxide. The patch prepared in this comparative example was designated Comparative Patch 2.

[0065] Comparative Example 3

[0066] The formula of this comparative example is basically the same as that of Example 3, except that the activation treatment method of zinc oxide is different, as follows:

[0067] The prescribed amount of zinc oxide and liquid paraffin was placed in a mixer and mixed at 25 rpm for 25 minutes. The mixture was then transferred to an activation tank and activated at 110°C for 3 hours to obtain activated zinc oxide. The patch prepared in this comparative example was designated Comparative Patch 3.

[0068] Comparative Example 4

[0069] The formula of this comparative example is basically the same as that of Example 1, except that this comparative example uses a different method to treat zinc oxide, as follows:

[0070] Zinc oxide is added to an activation tank and activated at a temperature of 130° C. (preferably 130° C.) for 3 hours to obtain activated zinc oxide. The subsequent preparation process is substantially the same as in Example 1. Since liquid paraffin is not added in the zinc oxide activation step, liquid paraffin is added together with lanolin, vaseline, etc. after adding zinc oxide to prepare a plaster. That is, this comparative example directly heat-treats zinc oxide without mixing it with liquid paraffin, and liquid paraffin is not used to activate zinc oxide. The plaster prepared in this comparative example is named: Comparative Plaster 4.

[0071] Comparative Example 5

[0072] The formula of this comparative example is basically the same as that of Example 1, except that this comparative example uses a different method to treat zinc oxide, as follows:

[0073] Zinc oxide: liquid paraffin: lanolin is put into a mixer at a ratio of 100:6:6, and mixed at a speed of 25 rpm for 25 minutes (preferably 25 minutes). The mixture is then transferred to an activation tank and activated at a temperature of 120°C to 140°C (preferably 130°C) for 2 to 4 hours (preferably 3 hours) to obtain activated zinc oxide. The subsequent preparation process is basically the same as in Example 1. Since lanolin is added in the zinc oxide activation step, lanolin is no longer added in the subsequent operation steps, and the plaster is then prepared. The plaster prepared in this comparative example is named: Comparative Plaster 5.

[0074] Comparative Example 6

[0075] The formula of this comparative example is basically the same as that of Example 1, except that this comparative example uses a different method to treat zinc oxide, as follows:

[0076] Zinc oxide: liquid paraffin: vaseline is put into a mixer at a ratio of 100:6:6 and mixed at a speed of 25 rpm for 25 minutes (preferably 25 minutes). The mixture is then transferred to an activation tank and activated at a temperature of 120°C to 140°C (preferably 130°C) for 2 to 4 hours (preferably 3 hours) to obtain activated zinc oxide. The subsequent preparation process is basically the same as in Example 1. Since vaseline is added in the zinc oxide activation step, vaseline is no longer added in the subsequent operation steps to prepare a patch. The patch obtained in this comparative example is named: Comparative Patch 6.

[0077] Experimental Example 1: Plaster Quality Inspection

[0078] The specific testing standards are as follows (refer to Musk Wind-Chasing Pain-Relieving Ointment Quality Standard WS-11370(2D-1370)-2002-2012Z-2019):

[0079] [Properties] This product is a light yellow or light yellow-green sheet of adhesive tape with a fragrant smell.

[0080] [Identification] (1) Take 12 tablets of this product, cut them into strips, remove the cover and liner, place them in a 250ml round-bottom flask, add 150ml of 1% hydrochloric acid ethanol solution, heat and reflux for 1 hour, filter, evaporate the ethanol, add 30ml of 1% hydrochloric acid solution, ultrasonicate for 15 minutes, filter, add ammonia test solution to the filtrate to make it alkaline (pH 10-11), add chloroform and shake to extract twice, 25ml each time, take the chloroform solution, evaporate to dryness, and dissolve the residue in 5ml of anhydrous ethanol to prepare the test solution. Separately, take atropine sulfate, strychnine and strychnine reference standards, add anhydrous ethanol to make a mixed solution containing 1mg of each per 1ml, and use it as the reference solution. According to the thin layer chromatography method (Appendix VI B of Part I of the Chinese Pharmacopoeia 2000 Edition), 30 μl of the test solution and 5 μl of the reference solution were spotted separately onto the same silica gel G thin layer plate with sodium carboxymethylcellulose as the adhesive. The plate was developed using a lower layer solution of chloroform-acetone-methanol-concentrated ammonia solution (14:2:3:0.8). The plate was removed, air-dried, and sprayed with dilute potassium bismuth iodide test solution. In the chromatogram of the test sample, a spot of the same color appeared at the corresponding position in the chromatogram of the reference sample.

[0081] (2) Take one tablet of this product, cut it into strips, remove the cap and liner, place it in a stoppered conical flask, add 50 ml of ethyl acetate, ultrasonically treat for 15 minutes, let it stand, filter the supernatant, and use the filtrate as the test solution. Separately, take camphor, menthol, borneol, methyl salicylate, and eugenol reference substances, add ethyl acetate to prepare mixed solutions containing 0.5 mg, 0.3 mg, 0.1 mg, 0.5 mg, and 0.5 mg of each per ml, and use them as the reference solution. Test according to the gas chromatography method (Appendix VI E of Part I of the Chinese Pharmacopoeia 2000 Edition), using polyethylene glycol (PEG)-20M as the stationary phase and a coating concentration of 10%. Program temperature rise: 130-195°C, hold the initial temperature for 20 minutes, then increase by 7.5°C per minute, and hold the final temperature for 20 minutes. Take 2 μl of each reference solution and test solution, inject them into the gas chromatograph, and measure. The test sample chromatogram should show a chromatographic peak with the same retention time as the reference sample.

[0082]

Inspection

[0083] Aconitine: Take 12 tablets of this product in limited quantity, cut into strips, remove the cover and lining, place in a 250ml round-bottom flask, add 150ml of 1% hydrochloric acid ethanol solution, heat and reflux for 1 hour, filter, evaporate the filtrate to dryness, add 20ml of 1% hydrochloric acid solution to the residue, dissolve it in batches, filter, add ammonia test solution to the filtrate to adjust the pH value to 10-11, shake and extract with chloroform twice, 20ml each time, combine the chloroform solution, evaporate to dryness, add 5ml of anhydrous ethanol to dissolve the residue, concentrate and make up to volume in a 2ml volumetric flask, shake well, and use as the test solution. Separately, take aconitine reference substance and add anhydrous ethanol to prepare a solution containing 0.805 mg per 1 ml. This solution is used as the reference solution and tested according to the thin layer chromatography method (Appendix VI B of Part I of the Chinese Pharmacopoeia 2000). 30 μl of the test solution and 2 μl of the reference solution are spotted separately on the same silica gel G thin layer plate with sodium carboxymethyl cellulose as the adhesive. The plate is developed using a lower layer solution of chloroform-acetone-methanol-concentrated ammonia solution (14:2:3:0.8). The plate is then removed, air-dried, and sprayed with dilute potassium bismuth iodide test solution. The spot in the test sample chromatogram corresponding to the reference sample chromatogram should be smaller than the reference sample spot or absent.

[0084] Others should comply with the relevant provisions under rubber plasters (Appendix IQ of Part I of the Chinese Pharmacopoeia 2000 Edition).

[0085] [Content Determination] Determined by gas chromatography (Appendix VI E of Part I of the Chinese Pharmacopoeia 2000 edition).

[0086] Chromatographic conditions and system suitability tests were conducted using polyethylene glycol (PEG)-20M as the stationary phase with a coating concentration of 10% and a column temperature of 130°C. The theoretical plate number calculated based on the camphor peak should be no less than 2000.

[0087] Preparation of internal standard solution: Accurately weigh an appropriate amount of n-tetradecane, place it in a brown volumetric flask, and add anhydrous ethanol to make a solution containing 0.25 mg per 1 ml.

[0088] Determination Method: Accurately weigh an appropriate amount of camphor reference substance and add ethyl acetate to prepare a solution containing 5 mg per 1 ml. Accurately measure 2 ml each of this solution and the internal standard solution and place them in a 25 ml volumetric flask. Add ethyl acetate to the mark, shake well, aspirate 2 μl, inject into the gas chromatograph, and record the chromatogram. Separately, cut one tablet of this product into strips, remove the cap and liner, place in a stoppered conical flask, accurately add 50 ml of ethyl acetate, stopper tightly, weigh, sonicate for 15 minutes, remove, cool to room temperature, weigh again, and make up the lost weight with ethyl acetate to prepare the test solution. In another 25 ml volumetric flask, accurately add 2 ml of the internal standard solution, dilute to the mark with the test solution, shake well, aspirate 2 μl, inject into the gas chromatograph, and calculate according to the internal standard method.

[0089] Each tablet of this product contains camphor (C 10 H 16O) shall not be less than 7.0 mg.

[0090] The experimental results are detailed in Tables 2 and 3.

[0091] Table 2: Plaster quality test results

[0092]

[0093] Table 3: Test results of aconitine, camphor content and paste content

[0094]

[0095]

[0096] The test results show that the patches prepared in the examples all meet the quality standards of Musk Wind-Removing Pain-Relieving Plaster. In particular, regarding the content of the active ingredient, the products of the examples of this solution meet the requirements. Ensuring that the active ingredient content meets the standard requirements is the basis for ensuring its therapeutic effect.

[0097] Experimental Example 2: Skin repeated administration irritation test

[0098] (1) Grouping and administration of repeated skin irritation test

[0099] Get 42 rabbits, before administration 24h, first both sides of the back administration area are depilated, the depilated area is 6cm × 6cm, check after 24h whether the depilated skin is injured, and the injured skin can not be tested for irritation.Depilated rabbits are randomly divided into comparative example 1~6 test group (comparison patch 1-1, comparison patch 2~6), embodiment 1 test group (patch 1, dosage is the patch sheet of 4cm × 4cm), 6 in every group, apply once a day, each application is removed after 8h or 16h, for 14 consecutive days.After each administration, uncover the patch, observe whether the irritation reactions such as erythema, edema occur in the applied skin local skin, carry out skin irritation experiment reaction scoring and stimulus intensity evaluation.

[0100] (2) Scoring criteria

[0101] According to the technical guidelines for the study of irritation and hemolysis of traditional Chinese medicine and natural medicine, scores are calculated according to the scoring criteria in Table 4.

[0102] Table 4: Skin irritation scoring criteria

[0103]

[0104] According to the above method, the experimental observation of each group of animals was carried out, and the average response value was calculated. The average response value was used to determine the stimulation intensity (Table 5). The calculation method was:

[0105] The average response value of the skin irritation test = (total erythema score + total edema score) / number of animals. The total erythema score is the sum of the erythema scores of all experimental animals in the group, and the total edema score is the sum of the edema scores of all experimental animals in the group.

[0106] Table 5: Skin irritation intensity evaluation

[0107] evaluate Score Non-irritating 0.00～0.49 Mild irritant 0.50～2.99 Moderate irritation 3.00～5.99 Severe irritant 6.00～8.00

[0108] (3) Results of repeated skin irritation test

[0109] After 14 consecutive days of topical administration, the rabbits showed no significant abnormalities in their mental state, activity, respiration, food intake, body weight, appearance, urine and stool characteristics and color, or fur skin color. There were no abnormal secretions from the nose, pharynx, or mouth. The experimental results are detailed in Tables 6, 7, 8, and 9.

[0110] Table 6: Results of repeated skin irritation test of Musk Wind-Chasing Pain-Relieving Ointment (n=6; unit: minutes; Example 1, Comparative Example 1, Comparative Example 2; single administration time 8 hours)

[0111]

[0112] Table 7: Results of repeated skin irritation test of Musk Wind-Chasing Pain-Relieving Ointment (n=6, unit: minutes; Comparative Examples 3-6; single administration time 8 hours)

[0113]

[0114] Table 8: Results of repeated skin administration irritation test of Musk Wind-Removing Pain-Relieving Ointment (n=6; unit: minutes; Example 1, Comparative Example 1, Comparative Example 2; single administration time 16 h)

[0115]

[0116] Table 9: Results of repeated skin irritation test of Musk Wind-Chasing Pain-Relieving Ointment (n=6, unit: minutes; Comparative Examples 3-6; single administration time 16 hours)

[0117]

[0118] The experimental results in Tables 6-9 show that the patch prepared using this protocol (Example 1, Patch 1) exhibited minimal skin irritation, with skin erythema occurring only after 11 days of repeated administration (8-hour dosing) or 10 days of repeated administration (16-hour dosing). Furthermore, in subsequent experiments, the average response value did not exceed 0.33, demonstrating that the patch of Example 1 is non-irritating and has minimal side effects.

[0119] The experimental data explanation (relative to the patch 1 of embodiment 1) of the contrast patch 1-1 of comparative example 1: the activation of zinc oxide (zinc oxide and liquid paraffin mix and heat treated) can reduce the irritation of patch for skin, specifically act on: delay the time that skin erythema or edema occur in continuous administration, reduce the severity of patch to skin irritation (reduce erythema and edema quantity and reduce skin irritation reaction score value).Contrast patch 1-1 in 8h administration test and 16h administration test, all demonstrated mild irritation.Contrast patch 1-1 is the patch prepared by prior art conventional means, short time (within 9 days) medication and each 8h with the situation of interior administration time, patch demonstrates non-irritation.But administration time prolongs, and can cause patch to produce certain irritating side effect of skin.Therefore, for the user who needs to prolong medication time or prolong single administration time, it is necessary to further reduce the patch side effect.

[0120] The experimental data from Comparative Patches 1-2 in Comparative Example 1 demonstrates that simply mixing zinc oxide and liquid paraffin (pre-exposing them) does not resolve the skin irritation issue with the patch; the post-mixing heating process is crucial. Comparative Patches 1-2 exhibited mild irritation in both the 8-hour and 16-hour dosing tests.

[0121] In addition, the temperature range of the heat treatment after zinc oxide and liquid paraffin are mixed is very critical for reducing the skin irritation of the patch. Through experimental research, the patch of this scheme adopts a heat treatment temperature of 120-140 ℃ during the activation of zinc oxide, and the effect is the most excellent. The contrast patch 2 of comparative example 2 adopts a higher zinc oxide activation temperature, and the contrast patch 3 of comparative example 3 adopts a lower zinc oxide activation temperature, and other conditions are the same as the patch 1 of embodiment 1. Experimental results find that: contrast patch 2 begins to cause rabbit skin erythema on the 4th day (8h administration) or the 2nd day (16h administration) of continuous administration, and in subsequent experiments, contrast patch 2 will cause skin erythema or edema phenomenon, and the skin irritation reaction score score can reach up to 1.67 (8h administration) or 3.17 (16h administration). It can be seen that contrast patch 2 has mild irritation under the 8h administration condition, and the administration time increases, and it has moderate irritation, and its irritation is higher than patch 1. Comparative Patch 3 began to cause skin erythema in rabbits on the 5th day (8-hour administration) or the 4th day (16-hour administration) of continuous administration, and in subsequent experiments, Comparative Patch 3 also caused skin erythema or edema, and the skin irritation reaction score was as high as 1.50 (8-hour administration) or 2.83 (16-hour administration). It can be seen that Comparative Patch 3 is mildly irritating, and its irritation is higher than that of Patch 1.

[0122] The above experimental results illustrate that appropriate mixed heating temperature is very critical for reducing the irritation of the patch. After zinc oxide and paraffin are mixed, the heating temperature is inappropriate and is also difficult to effectively reduce the skin irritation of the patch. In addition, relative to contrast patch 1-1 and contrast patch 1-2, the effect of the reduction irritation of the patch of contrast patch 2 and contrast patch 3 is slightly poor, and its skin irritation even increases slightly. This illustrates improper heat activation mode, which can result in further improving the irritation of the patch than inactivated operating mode.

[0123] It should be noted that this program selects liquid paraffin and zinc oxide mixed heating activation, produces the effect of good reduction irritation.Except liquid paraffin, the inventor has also attempted zinc oxide direct heating activation, and then prepares contrast plaster 4 (comparative example 4).Experimental result finds: contrast plaster 4 just starts to cause rabbit skin erythema on the 4th day (8h administration) or the 3rd day (16h administration) of continuous administration, and in subsequent experiments, contrast plaster 4 all can cause skin erythema or edema phenomenon, and skin irritation reaction score value is up to 2.00 (8h administration) or 3.33 (16h administration), it is seen that contrast plaster 4 has mild irritation or moderate irritation, and its irritation is higher than plaster 1.This also illustrates the criticality of using liquid paraffin for zinc oxide activation, zinc oxide can not be heated and activated separately.

[0124] In Comparative Examples 5 and 6, the inventors attempted to add lanolin or vaseline to an activation system consisting of zinc oxide and liquid paraffin, thereby preparing Comparative Patches 5 and 6. The experimental results showed that Comparative Patches 5 began to cause skin erythema in rabbits on the fourth day (8-hour dosing) or the third day (16-hour dosing) of continuous administration. In subsequent experiments, Comparative Patches 5 also caused skin erythema or edema, and the skin irritation reaction score was as high as 2.33 (8-hour dosing) or 4.00 (16-hour dosing). It can be seen that Comparative Patches 5 are mildly irritating or moderately irritating, and its irritation is higher than that of Patches 1. Comparative Patch 6 began to cause skin erythema in rabbits on the third day (8-hour dosing) or the second day (16-hour dosing) of continuous dosing. In subsequent experiments, Comparative Patch 6 also caused skin erythema or edema, with skin irritation scores reaching as high as 2.50 (8-hour dosing) or 4.83 (16-hour dosing), indicating that Comparative Patch 6 is mildly or moderately irritating. This indicates that the activation system composed of zinc oxide and liquid paraffin should not be supplemented with other substances such as lanolin or petrolatum, as this would affect the activation effect of zinc oxide.

[0125] Test Example 3: Skin allergy test

[0126] (1) Animal Grouping and Dosing (Based on the results of the repetitive stimulation test, Example 1, which has less irritation, was selected for the experiment, and the patch 1-1 of Comparative Example 1 was also selected to compare the effects)

[0127] Thirty guinea pigs, half male and half female, were provided by the Laboratory Animals Committee of a medical university. Twenty-four hours before dosing, the 30 guinea pigs were depilated from the dosing area on both sides of their backs. The depilated area was 6 cm x 6 cm. After 24 hours, the depilated skin was inspected for damage. Injured skin could not be used for allergy testing. The depilated guinea pigs were randomly divided into the following groups:

[0128] Comparative Example 1 Musk Wind-Chasing Pain-Relieving Plaster Group (Patch 1-1, dosage: 4 cm × 4 cm patch);

[0129] Positive control group (2,4-dinitrochlorobenzene, sensitizing concentration 5 mg / mL, challenging concentration 2.5 mg / mL);

[0130] Example 1 Musk Wind-Chasing Pain-Relieving Plaster Group (dosage is a 4 cm×4 cm plaster sheet).

[0131] Ten mice were included in each group. The drug patch was applied to the right depilated area. On day 0 of the experiment, the patch was removed after 6 hours of contact with the skin. Skin allergy was observed and scored 1 hour and 24 hours later. For the positive control group, 0.1 mL of 5 mg / mL 2,4-dinitrochlorobenzene (prepared in acetone) was applied to the right depilated area. The drug-applied area was then covered with a 4 cm x 4 cm stretch fabric, and the edges of the fabric were secured with hypoallergenic medical tape.

[0132] On the 7th and 14th days, apply the drug or apply it to induce sensitization once each, and observe and score the skin allergy 1 hour and 24 hours later respectively.

[0133] On day 28, the corresponding drug was applied to the left depilated area of the back of each group of animals using the same method. The positive control group was challenged with 0.1 mL of 2,4-dinitrochlorobenzene at 2.5 mg / mL. The drug-applied area was then covered with a 4 cm × 4 cm stretch cloth, secured in the same manner. The other groups were treated as before. Six hours later, the drug was removed and the animals were immediately observed. Skin allergic reactions were observed and scored 24, 48, and 72 hours after the final removal of the drug patch. Animals were also closely observed for severe systemic allergic reactions such as asthma, instability, or shock.

[0134] (2) Scoring criteria

[0135] According to the technical guidelines for the study of immunotoxicity (allergic and photoallergic reactions) of traditional Chinese medicine and natural medicine, scores are calculated according to the scoring criteria in Table 10:

[0136] Table 10: Scoring criteria for skin allergic reactions

[0137]

[0138]

[0139] Based on the above-mentioned scoring criteria, the skin allergy test results of each group of guinea pigs were observed, and the average score of the skin allergy test was recorded. The calculation method is:

[0140] The average score of skin allergic reaction test = (total score of erythema formation + total score of edema formation) / total number of animals, the incidence rate of allergic reaction (%) = (number of animals with allergic reaction / total number of animals) × 100%, and the degree of allergy is determined.

[0141] The results of the skin allergy test are shown in Table 11. The average scores of the skin allergy test reactions and the incidence of allergic reactions were measured and recorded.

[0142] Table 11: Results of the allergy test on Musk Wind-Removing Pain-Removing Ointment (n=10)

[0143]

[0144] The positive control group had varying degrees of erythema and edema within 72 hours of drug removal, with an average reaction score of 1.10-3.50 and a sensitization rate of 100%. The Musk Wind-Chasing Pain-Relieving Ointment Group of Example 1 and the Musk Wind-Chasing Pain-Relieving Ointment Group of Comparative Example 1 had an average skin allergy reaction score of 0 during the three-dose sensitization process. After re-exposure to the drug on the 28th day, no erythema or edema reaction occurred immediately after observation for 72 hours, nor did any systemic allergic reactions such as asthma and unsteady standing. The average reaction score was 0 and the sensitization rate was 0. The results are shown in Table 10. The experimental results show that although the patch prepared in this scheme has a certain skin irritation, it does not have a significant sensitization effect.

[0145] The experimental data of experimental examples 1-3 show that the skin irritation reaction score of the plaster prepared using the activated zinc oxide process (Example 1) is significantly lower than that of the control group during the 14-day continuous administration process. In the experiment of single-dose 8h, the process plaster showed no irritation, while the other comparative example plasters only showed a clinically acceptable mild irritation. It is worth noting that when the single application time was extended to 16 hours, the skin irritation difference of each group of plasters was significantly enlarged. This discovery has important clinical significance: although Musk Wind-Chasing Pain Relief Plaster has a significant effect, patients often extend the single use time due to insufficient pain relief, resulting in a significant increase in the risk of skin irritation of traditional plasters, and even causing treatment interruption. This solution significantly reduces adverse reactions by optimizing the process, so that patients with chronic pain (especially sensitive skin, allergic people and those who need to apply for a long time) can use medication regularly for a long time and ensure the persistence of efficacy.

[0146] At the same time, process innovation improves safety through strict paste content (≥1.65g / 100cm 2 ) and active ingredients (such as camphor, aconitine) detection to ensure that the stability of the core drug ingredients is consistent with the pharmacopoeia standards, thereby maintaining the original therapeutic effect of the plaster. This improvement not only solves the clinical pain points of traditional plasters, but also provides patients with a safe and reliable treatment option. At the same time, the inventors creatively adjusted the preparation process to further ensure that the finished product prepared by the improved process has the same content and active ingredients as the standard. The activation process does not affect the content and stability of the core ingredients of the drug (such as camphor, aconitine), and the paste content (≥1.65g / 100cm 2 ) and active ingredients are in compliance with pharmacopoeia standards, ensuring their therapeutic effects.

[0147] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. A method for industrializing the preparation of a patch composition with improved safety, characterized in that: Part A of gasoline is used to dissolve the rubber, and then rosin is added and stirred to dissolve; activated zinc oxide is then added and mixed, followed by lanolin, vaseline, musk wind-chasing and analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate, and part B of gasoline, and the pH is adjusted to obtain musk wind-chasing and analgesic paste; Activated zinc oxide is obtained by mixing zinc oxide and liquid paraffin, and placing the mixture in an environment of 120°C to 140°C for 2 to 4 hours.

2. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 1, wherein: The raw materials of the patch composition include, in parts by weight: 50-60 parts of musk wind-chasing and analgesic fluid extract, 25-35 parts of rue extract, 30-40 parts of belladonna fluid extract, 20-30 parts of menthol, 8-15 parts of camphor, 20-30 parts of borneol, 10-20 parts of methyl salicylate, 400-600 parts of gasoline, 150-200 parts of rubber, 150-200 parts of rosin, 10-20 parts of liquid paraffin, 10-20 parts of lanolin, 10-20 parts of vaseline, and 200-300 parts of zinc oxide.

3. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 1, wherein: The zinc oxide and the liquid paraffin are mixed in the following manner: the zinc oxide and the liquid paraffin are placed in a rotation speed environment of 20 to 30 revolutions per minute and stirred for 20 to 30 minutes.

4. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 1, wherein: The usage ratio of gasoline part A and gasoline part B is 15:85 to 25:

75.

5. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 4, wherein: The method of using gasoline part A to dissolve rubber is: placing the rubber and gasoline part A in a closed environment and soaking them for 18 to 30 hours.

6. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 5, wherein: After the rosin is added, the stirring method is: stirring at a speed of 20 to 30 rpm for 2 to 3 hours to dissolve the material; the activated zinc oxide is added and mixed: stirring at a speed of 20 to 30 rpm for 2 to 3 hours.

7. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 6, wherein: After adding lanolin, vaseline, musk wind-chasing and analgesic fluid extract, belladonna fluid extract, rue extract, menthol, borneol, camphor, methyl salicylate and gasoline part B, stirring at a speed of 20 to 30 rpm for 5 to 8 hours; then adjusting the pH value to 5.5 to 6.5, and stirring at a speed of 20 to 30 rpm for another 5 to 8 hours to obtain musk wind-chasing and analgesic ointment syrup.

8. The industrialized preparation method of a patch composition with improved safety according to any one of claims 1 to 7, characterized in that: The musk wind-chasing analgesic plaster is coated on a carrier, and the musk wind-chasing analgesic plaster is obtained after cutting; preferably, the carrier is a stretch fabric; the musk wind-chasing analgesic plaster contains ≥1.65g / 100cm 2 .

9. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 8, wherein: The musk wind-chasing and analgesic fluid extract is prepared by the following method: taking raw kusnezoffii, raw Chuanwu, frankincense, myrrh, raw strychnine seeds, cloves, cinnamon bark, schizonepeta, siler, geranium, cyperus rotundus, centella asiatica, drynaria, angelica dahurica, galangal, and dried ginger, and crushing them to obtain coarse powder; using ethanol as a solvent to perform percolation extraction on the coarse powder, and collecting the percolation liquid; filtering and concentrating the percolation liquid to obtain a thick paste; adding ethanol to the thick paste, mixing and letting it stand, and then collecting the supernatant; concentrating the supernatant to obtain an extract, and adding musk to the extract to obtain the musk wind-chasing and analgesic fluid extract.

10. The method for industrializing the preparation of a safety-enhancing patch composition according to claim 9, wherein: Calculated by weight, the raw materials of musk wind-chasing and analgesic fluid extract include: 20-30 parts of raw aconite, 20-30 parts of raw Chuanwu, 20-30 parts of frankincense, 20-30 parts of myrrh, 20-30 parts of raw strychnine seeds, 20-30 parts of cloves, 40-60 parts of cinnamon, 40-60 parts of schizonepeta, 40-60 parts of siler, 40-60 parts of geranium, 40-60 parts of angelica root, 40-60 parts of centella asiatica, 40-60 parts of drynaria, 70-80 parts of angelica dahurica, 70-80 parts of galangal, 70-80 parts of dried ginger, and 0.5-2 parts of musk.

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