Sanfu paste gel and preparation method thereof

Abstract

The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a Sanfu paste gel and a preparation method thereof. The application provides a Sanfu paste traditional Chinese medicine gel paste which can retain the medicinal components of white radish seed, stably load volatile components, and has a good gel matrix forming property. The preparation method of the Sanfu paste gel comprises the following steps: A, preparing traditional Chinese medicine volatile oil; B, preparing a traditional Chinese medicine extract; C, preparing white radish seed powder; D, preparing ginger juice and green onion juice; E, preparing a volatile oil inclusion compound; and F, preparing a gel paste. The application has the following advantages: (1) effectively solves the enzymatic hydrolysis problem of white radish seed in an aqueous gel matrix, and protects the core medicinal components; (2) solves the technical problem of destroying the stability of a gel matrix by volatile medicinal materials, and retains the medicinal effect characteristics of the original prescription; (3) endows the gel paste with excellent adhesion, and realizes quantitative control of product quality; (4) the process is stable and controllable; and the application provides a brand new option for the public.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a Sanfu Patch gel and its preparation method. Background Technology

[0002] Sanfu Patch is a unique external treatment method in Traditional Chinese Medicine (TCM) for "treating winter diseases in summer." First recorded in the Qing Dynasty's *Zhang's Medical Treatise*, it primarily uses warm and pungent herbs such as white mustard seed, corydalis rhizome, euphorbia kansui, and asarum, mixed with ginger juice. Applied to acupoints such as Dazhui (GV14) and Feishu (BL13), it has a good therapeutic effect on recurrent chronic respiratory diseases. The typical preparation method for Sanfu Patch is as follows: 1. Herb processing: After mixing the required Chinese herbs in the specified proportions, grind them into a fine powder using a mortar and pestle or grinder, ensuring a smooth texture and even application. 2. Preparation into a paste: Extract juice from an appropriate amount of fresh ginger and mix it with the herb powder in a certain ratio (e.g., 1:1), stirring to form a paste of suitable consistency. Honey or rice wine can also be used instead of ginger juice, adjusted according to individual constitution and symptoms. 3. Forming into medicated cakes or patches: Knead the prepared paste into small cakes about 2-3 cm in diameter; or directly spread it onto a non-woven fabric patch to make ready-to-use patches for easy storage and use. For standard application, after cleansing the skin, place the medicated patch on acupoints such as Feishu, Dazhui, Zhongwan, and Shenshu, and then secure it with medical tape. Adults should wear the patch for 4–6 hours each time, and children for 2–4 hours, to avoid blistering or allergic reactions.

[0003] However, traditional Sanfu Patch treatments have always faced two major technical bottlenecks. First, the formulation is outdated, making quality control difficult. Traditional Sanfu Patch treatments involve directly applying a mixture of medicinal powder and ginger juice, then fixing it to the skin with adhesive tape or non-woven fabric. This is not only inconvenient and lacks breathability, but also results in insufficient transdermal absorption of the active ingredients. Numerous adverse reactions have occurred in clinical use, exposing the safety risks of traditional Sanfu Patch treatments relying on manual preparation and lacking standardized processes. Second, the stability of key medicinal materials remains a challenge in dosage form upgrades. White mustard seed is the core ingredient in this prescription. Its active ingredient, glucosinolate, is not inherently irritating; it is hydrolyzed by myrosinase in water to produce mustard oil, which then exerts its medicinal effect. However, mustard oil is highly irritating and volatile. If white mustard seed is directly added to an aqueous gel matrix, glucosinolate will be enzymatically hydrolyzed during preparation and storage, leading not only to the loss of the active ingredient but also potentially uncontrollable skin irritation. Traditional processing techniques show that roasting white mustard seed can inactivate myrosinase, thereby inhibiting the enzymatic reaction and protecting the active ingredient. In addition, if the volatile components of the Chinese medicinal materials in the prescription are directly added to the aqueous gel matrix, it will significantly reduce the matrix adhesion and affect the cross-linking molding; even if β-cyclodextrin inclusion technology is used, there is still the problem of poor compatibility between the inclusion complex and the aqueous matrix.

[0004] Gel patches (or poultices), as a novel topical preparation, utilize a three-dimensional network structure formed by cross-linking hydrophilic polymers to carry the drug. They offer advantages such as high drug loading capacity, breathability, moisture retention, and ease of use, representing a mainstream direction for the modernization and upgrading of traditional Chinese medicine topical ointments. However, existing research often involves water extraction or direct powdering of the prescribed medicinal materials into the gel, failing to provide systematic solutions to the two core issues of enzymatic hydrolysis of white mustard seeds upon contact with water and the destruction of the matrix by volatile components. Furthermore, the safety and usability of Sanfu patches are limited. The prescription of this invention is based on traditional Chinese medicine theory and combined with long-term clinical experience, continuously optimized to achieve significant clinical efficacy without compromising usability.

[0005] Therefore, how to develop the Sanfu Patch formula into a stable, safe, easy-to-use, and quality-controllable gel patch, while effectively preserving the medicinal components of white mustard seed and avoiding the negative impact of volatile oil on the matrix, is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] The technical problem solved by this invention is to provide a Sanfu Patch gel that can retain the medicinal components of white mustard seed, stably load volatile components, and form a good gel matrix.

[0007] The Sanfu Patch gel of this invention uses white mustard seed, asarum, cinnamon, corydalis, tangerine peel, chuanxiong, ginger, and scallion as raw materials, supplemented with specific excipients. The components work together to prepare a gel patch with excellent initial adhesion and adhesion, as well as better penetration and stability.

[0008] The raw materials for the Sanfu Patch gel of this invention are composed of the following ingredients in the indicated weight ratios: 20-40 parts white mustard seed, 10-20 parts asarum, 10-20 parts cinnamon, 25-40 parts corydalis, 10-25 parts dried tangerine peel, 15-30 parts chuanxiong, 30-60 parts ginger, and 30-60 parts scallion.

[0009] More preferably, the raw materials of the Sanfu Patch gel of the present invention are composed of the following raw materials in the indicated weight ratios: 30 parts white mustard seed, 15 parts asarum, 15 parts cinnamon, 30 parts corydalis, 15 parts dried tangerine peel, 15 parts chuanxiong, 50 parts ginger, and 50 parts scallion.

[0010] The excipients of the Sanfu Patch gel of this invention are composed of the following raw materials in the following weight ratios: 1.2-3.6 parts of aluminum hydroxyacetate, 250-350 parts of glycerin, 18-48 parts of sodium polyacrylate (PAAS NP700), 1.2-3.6 parts of disodium EDTA, 4.8-18 parts of kaolin, 6-18 parts of polyvinylpyrrolidone (PVP K30), and 12-24 parts of azone; it also includes β-cyclodextrin, and the weight ratio of the volatile oil of the Chinese herbal medicine obtained from the raw material to β-cyclodextrin is 1:5-6.

[0011] Further preferably, the excipients of the Sanfu Patch gel of the present invention are composed of the following raw materials in the following weight ratio: 2.4 parts of aluminum hydroxyl, 300 parts of glycerin, 30 parts of sodium polyacrylate (PAAS NP700), 2.4 parts of disodium EDTA, 12 parts of kaolin, 12 parts of polyvinylpyrrolidone (PVP K30), 12 parts of azone, and also includes β-cyclodextrin. The weight ratio of the volatile oil of the Chinese medicine obtained from the raw material to β-cyclodextrin is 1:5.

[0012] Based on the above-mentioned components as active pharmaceutical ingredients and excipients, the present invention achieves its objective by employing the following preparation method, which includes the following steps:

[0013] A. Preparation of volatile oils from traditional Chinese medicine:

[0014] A1. Take the raw materials Asarum, Cinnamon, Corydalis, Tangerine Peel, and Ligusticum chuanxiong, pulverize them, and pass them through a 20-60 mesh sieve;

[0015] A2. Extraction by steam distillation: Place the raw medicinal materials described in step A1 in the extraction equipment, add 10-20 times the amount of water to soak, connect the volatile oil extraction equipment and the condensation equipment, heat and collect the distillate;

[0016] A3. Separation of volatile oil: The distillate from step A2 is allowed to stand and separate into layers. The oil layer is separated, anhydrous sodium sulfate is added for dehydration, and the mixture is filtered to obtain the volatile oil.

[0017] In the preparation of the volatile oil from the traditional Chinese medicine described in step A, at least one of the following conditions must be met:

[0018] The sieving mentioned in step A1 is sieving through a 20-60 mesh sieve.

[0019] Preferably, the sieving in step A1 is sieving through a 40-mesh sieve.

[0020] The soaking conditions described in step A2 are: add 10-20 times the amount of water;

[0021] Preferably, the soaking in water step A2 is performed by adding 10 times the amount of water;

[0022] The soaking conditions described in step A2 are as follows: the water is purified water;

[0023] The soaking conditions described in step A2 are: soaking for 1-2 hours;

[0024] Preferably, the soaking in water in step A2 is: soaking for 1 hour.

[0025] The volatile oil extraction equipment mentioned in step A2 is a volatile oil extractor.

[0026] The condensing device mentioned in step A2 is a condenser tube.

[0027] The heating and collection of distillate in step A2 is carried out by the following method: heating to boiling, controlling the distillation rate to 2-3 drops per second, controlling the condensate temperature to less than or equal to 20°C, distilling until the oil droplets no longer increase, stopping heating and collecting the distillate.

[0028] Preferably, the heating and collection of distillate in step A2 is carried out by the following method: heating to boiling, controlling the distillate rate to 1-2 drops per second, controlling the condensate temperature at 15-20°C or lower, distilling until the oil droplets no longer increase, stopping heating and collecting the distillate.

[0029] Preferably, the distillation time in step A2 is 3-8 hours.

[0030] Alternatively, the distillation time is 5 hours.

[0031] The volatile oil obtained in step A3 should be stored in a cool, dark place for later use.

[0032] The yield of volatile oil in step A shall not be less than 2.5%.

[0033] B. Preparation of extracts from traditional Chinese medicine:

[0034] B1. After collecting the volatile oil in step A, take the raw material extract extracted by the extraction equipment, filter it to obtain the residue and filtrate, and keep the filtrate for later use.

[0035] B2. Then, take the residue obtained in step B1, add water to extract it, and obtain the extract filtrate. Combine the filtrates obtained in steps B1 and B2.

[0036] B3. Concentrate the combined filtrate obtained in step B2 to obtain the extract;

[0037] B4. Drying the extract obtained in step B3;

[0038] B4. After drying, it is pulverized to obtain extract powder;

[0039] In the preparation of the traditional Chinese medicine extract described in step B, at least one of the following conditions must be met:

[0040] The conditions for water extraction described in step B2 are as follows: extract 2-3 times, each time for 1.5-2 hours, and each time add 8-10 times the amount of water.

[0041] Preferably, the conditions for water extraction in step B2 are: extraction twice, 1.5 hours each time, and the amount of water added each time is 8 times the volume of water.

[0042] The water mentioned in step B2 is purified water.

[0043] The concentration described in step B3 is achieved by rotary evaporation.

[0044] The relative density of the concentrated extract obtained in step B3 is 1.2 + 0.5.

[0045] Preferably, the relative density of the concentrated extract obtained in step B3 is 1.2.

[0046] The drying process described in step B4 is freeze drying.

[0047] Preferably, the freeze-drying conditions in step B4 are as follows: the extract is first frozen at -40°C to -20°C for at least 12 hours, and then freeze-dried in a freeze-drying apparatus.

[0048] The most preferred method is to freeze-dry the extract at -20°C for at least 12 hours.

[0049] Preferably, the freeze-drying conditions in the freeze-drying equipment described in step B4 are: partition temperature -20°C to -80°C, vacuum degree 10Pa to 50Pa, drying time not less than 12 hours, until the moisture content is less than 6%.

[0050] Most preferably, the freeze-drying conditions in the freeze-drying equipment described in step B4 are: partition temperature -40°C to -50°C, vacuum degree 10-30Pa, drying time not less than 12 hours, until the moisture content is less than 5%.

[0051] The material described in step B4 is pulverized to pass through an 80-100 mesh sieve.

[0052] Preferably, step B4 involves pulverizing the material to pass through a 100-mesh sieve.

[0053] The yield of the aqueous extract powder of traditional Chinese medicine obtained by the above preparation method is about 20-30%.

[0054] C. Preparation of white mustard powder

[0055] C1. Grind white mustard seeds into coarse powder;

[0056] C2, Crispy white mustard powder;

[0057] C3. Grind the brittle white mustard seeds into coarse powder, and sieve to obtain ultrafine powder;

[0058] In step C, the preparation of white mustard powder, at least one of the following conditions must be met:

[0059] The pulverization in step C1 is prepared using the following method:

[0060] C1-1. Before grinding, freeze the white mustard seeds at a temperature of -18℃ to -28℃ for at least 4 hours;

[0061] C1-2. Crush the frozen white mustard seeds to pass through an 80-100 mesh sieve.

[0062] Preferably, before crushing in step C1-1, the white mustard seeds are frozen at a temperature of -18℃ to -28℃ for 4-6 hours.

[0063] Preferably, the pulverization condition in step C1-2 is to pulverize immediately after freezing.

[0064] Preferably, the pulverizing conditions in step C1-2 are as follows: the pulverizer is used to grind the powder, the grinding time is controlled within 15-30 seconds, and the operation is intermittent.

[0065] The embrittlement process described in step C2 involves placing coarse white mustard powder into a low-temperature resistant container, slowly adding liquid nitrogen for immersion, and pre-cooling for 5-15 minutes to obtain embrittled coarse white mustard powder.

[0066] The pulverization conditions described in step C3 are as follows: the brittle white mustard coarse powder is added together with the liquid nitrogen in the container to a liquid nitrogen pulverizer and pulverized at 4000-6000 rpm for 15-30 minutes.

[0067] The sieving described in step C3 refers to sieving through a sieve of at least 200-300 mesh.

[0068] Preferably, the sieving in step C3 is sieving through a 300-mesh sieve.

[0069] D. Preparation of ginger juice and scallion juice:

[0070] D1. Preparation of ginger juice: Take fresh ginger, wash it, slice it, put it into a juicing device to extract the juice, collect the juice, filter it and set it aside.

[0071] D2. Preparation of scallion juice: Take fresh scallion whites, wash them, cut them into small sections, put them into a juicing device to extract the juice, collect the juice, filter it and set it aside.

[0072] In step D, the preparation of ginger and scallion juice, at least one of the following conditions must be met:

[0073] The ginger juice in step D1 and the scallion juice in step D2 are filtered through an 80-500 mesh sieve.

[0074] Preferably, the ginger juice in step D1 and the scallion juice in step D2 are filtered through a 100-300 mesh sieve;

[0075] Furthermore, because ginger juice will produce sediment after filtration and standing, possibly due to the precipitation of certain substances during this process, a finer mesh is used for filtration. Therefore, the following filtration parameters can also be used:

[0076] In step D1, the filtration process for preparing ginger juice involves first coarse filtration using an 80-100 mesh sieve, followed by fine filtration using a 200-500 mesh filter cloth.

[0077] Preferably, the filtration in step D1 is to first use a 100-mesh sieve for coarse filtration, and then use a 300-mesh filter cloth for fine filtration;

[0078] Step D2: Preparation of scallion juice; filtration is performed using a 100-300 mesh filter cloth.

[0079] Preferably, the filtration in step D2 is performed using a 200-mesh filter cloth.

[0080] E. Preparation of volatile oil inclusion complexes:

[0081] E1. Take the volatile oil of the Chinese medicine obtained in step A, add anhydrous ethanol to dissolve it completely, and obtain a volatile oil ethanol solution;

[0082] E2. Add the volatile oil ethanol solution obtained in step E1 dropwise to the β-cyclodextrin solution to encapsulate and obtain the reaction solution;

[0083] E3. The inclusion reaction solution obtained in step E2 is allowed to stand, filtered, and the resulting precipitate is dried to obtain the volatile oil inclusion complex.

[0084] In step E, the preparation of the volatile oil inclusion complex must satisfy at least one of the following conditions:

[0085] The weight ratio of volatile oil to anhydrous ethanol in step E1 is 1:1.5-1:3.

[0086] Preferably, the weight ratio of volatile oil to anhydrous ethanol in step E1 is 1:2.5.

[0087] The β-cyclodextrin solution in step E2 is prepared by the following method: based on the weight of the volatile oil of the Chinese herbal medicine obtained in step A, take 5-6 times the amount of β-cyclodextrin, add water and heat to dissolve.

[0088] Preferably, the β-cyclodextrin solution in step E2 is prepared by the following method: taking 5 times the weight of the volatile oil of the Chinese herbal medicine obtained in step A, adding water and heating to dissolve.

[0089] Preferably, the amount of water added to β-cyclodextrin is 3-6 times, and most preferably, the amount of water added to β-cyclodextrin is 4 times. That is, 5 times the amount of β-cyclodextrin requires 20 times the amount of water.

[0090] Preferably, step E2 heating is performed in a water bath at 40℃-70℃.

[0091] The preferred method is to heat in a 55°C water bath during step E2.

[0092] The inclusion reaction conditions described in step E2 are constant temperature stirring at 40℃-55℃ for 0.5-2 hours.

[0093] Preferably, the inclusion reaction conditions in step E2 are: constant temperature stirring at 55°C for 0.5-1 hour.

[0094] Step E3 involves allowing the inclusion reaction solution to stand at 0°C-10°C for 6-24 hours.

[0095] Preferably, step E3 involves allowing the inclusion reaction solution to stand at 5°C for 8-12 hours.

[0096] The filtration described in step E3 uses methods such as vacuum filtration, centrifugation, and pressure filtration to separate the precipitate.

[0097] The drying process described in step E3 involves drying at a temperature of 40℃-65℃.

[0098] Preferably, the drying in step E3 is performed at a temperature of 55°C.

[0099] The drying oven described in step E3 is used for drying.

[0100] F. Preparation of gel patches

[0101] F1. Preparation of the first phase: The white mustard ultrafine powder obtained in step C is mixed with glycerol and PAAS NP700 and stirred until evenly dispersed to obtain white mustard glycerol premix, which is an oil phase mixture;

[0102] F2. Preparation of the second phase: Take the extract powder obtained in step B, the scallion juice and ginger juice obtained in step D, and the volatile oil inclusion complex obtained in step E, add water and aqueous phase excipients, stir and mix evenly to obtain an aqueous phase mixture;

[0103] F3. Mixing and Crosslinking: Add the first phase oil mixture to the second phase aqueous mixture, stir evenly, add the crosslinking agent aluminum hydroxide, then coat it onto the backing layer, let it stand to form, and cut it to obtain the Sanfu gel patch.

[0104] In the preparation of the gel patch in step F, at least one of the following conditions must be met:

[0105] After adding the crosslinking agent aluminum hydroxyl as described in step F3, stir rapidly and then coat it onto the backing layer.

[0106] Preferably, after adding the crosslinking agent aluminum hydroxide in step F3, the mixture is stirred rapidly for 1-2 minutes and then coated onto the backing layer.

[0107] The backing layer described in step F3 is made of non-woven fabric, polyethylene (PE), polypropylene (PP), composite aluminum foil, polyurethane film, and polyester (PET).

[0108] Preferably, the backing layer in step F3 is a non-woven fabric backing layer.

[0109] The coating thickness described in step F3 is 1-2 mm.

[0110] The standing conditions described in step F3 are: stand at room temperature for 10-20 minutes for cross-linking until the paste is formed.

[0111] Preferably, the standing conditions in step F3 are as follows: stand at room temperature for 15-20 minutes for crosslinking until the paste is formed.

[0112] The Sanfu Patch gel of the present invention has the following advantages:

[0113] (1) This invention effectively solves the problem of enzymatic hydrolysis of white mustard seeds in aqueous gel matrix and protects the core active ingredients;

[0114] (2) This invention solves the technical problem of volatile medicinal materials destroying the stability of the gel matrix, and preserves the efficacy characteristics of the original formula;

[0115] (3) This invention endows the gel patch with excellent adhesive properties, and realizes quantitative control of product quality;

[0116] (4) The process is stable and controllable, providing a practical and feasible method for the modern production of traditional Sanfu Patch. Attached Figure Description

[0117] Figure 1 Photographs of guinea pig skin irritation test.

[0118] in, Figure 1 A: Single dose; Figure 1 B: Continuous administration.

[0119] Figure 2 HE staining pathological images of guinea pig skin tissue.

[0120] Among them, a, b, and c are the single-dose blank group, the single-dose powder group, and the single-dose Sanfu patch group, respectively; d, e, and f are guinea pig skin tissue sections of the continuous-dose blank group, the continuous-dose powder group, and the continuous-dose Sanfu patch group, respectively.

[0121] Figure 3 The in vitro release curves of the gel patch of this invention and traditional powder. Detailed Implementation

[0122] The present invention will be explained and described below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0123] This invention addresses the following shortcomings of existing Sanfu Patch treatments:

[0124] (1) Traditional Sanfu Patch preparations are outdated and their quality is uncontrollable. The safety and usability of traditional Sanfu Patch prescriptions are limited. They are made by temporarily mixing raw medicinal powder with a suitable medium, which relies on manual mixing. There are large batch-to-batch differences, making them inconvenient to use. Furthermore, the skin irritation is uncontrollable, posing safety risks.

[0125] (2) White mustard seeds are enzymatically hydrolyzed by water, making it difficult to retain the active ingredients. The glucosinolates in white mustard seeds are hydrolyzed by myrosinase to produce mustard oil after encountering water. If they are directly added to an aqueous gel matrix, the enzymatic reaction will continue to occur during preparation and storage, resulting in the loss of active ingredients and making it difficult to control skin irritation.

[0126] (3) Volatile medicinal materials disrupt the stability of the gel matrix. Current research on traditional Chinese medicine gel plasters often involves water extraction or direct powdering of the prescription medicinal materials into the gel, lacking a process design that "separates and treats" white mustard seed and volatile components, thus failing to simultaneously achieve the protection of effective ingredients and matrix stability.

[0127] In this application context, the inventors provide the traditional Chinese medicine gel patch of the present invention and its preparation method.

[0128] This invention is a gel patch containing traditional Chinese medicine ingredients, comprising: traditional Chinese medicine ingredients and excipient composition;

[0129] The traditional Chinese medicine composition, by weight, includes the following components: 30-60 parts ginger, 30-60 parts scallion, 20-40 parts white mustard seed, 10-20 parts asarum, 10-20 parts cinnamon, 25-40 parts corydalis, 10-25 parts dried tangerine peel, and 15-30 parts chuanxiong.

[0130] The excipient composition, by weight, includes the following components: 1.2-3.6 parts of aluminum hydroxyacetate, 250-350 parts of glycerin, 18-48 parts of sodium polyacrylate (PAAS NP700), 1.2-3.6 parts of disodium ethylenediaminetetraacetate, 4.8-18 parts of kaolin, 6-18 parts of polyvinylpyrrolidone (PVP K30), 12-24 parts of azone, and β-cyclodextrin added in an amount according to a weight ratio of volatile oil to β-cyclodextrin of 1:5 to 1:6.

[0131] Preferably, the traditional Chinese medicine composition consists of the following parts by weight: 50 parts ginger, 50 parts scallion, 30 parts white mustard seed, 15 parts asarum, 15 parts cinnamon, 30 parts corydalis, 15 parts dried tangerine peel, and 15 parts chuanxiong.

[0132] Preferably, the excipient composition comprises the following parts by weight: 2.4 parts of aluminum hydroxyl, 300 parts of glycerol, 30 parts of sodium polyacrylate (PAAS NP700), 2.4 parts of disodium ethylenediaminetetraacetate, 12 parts of kaolin, 12 parts of polyvinylpyrrolidone (PVP K30), 12 parts of azone, and β-cyclodextrin added in a weight ratio of volatile oil to β-cyclodextrin of 1:5.

[0133] The following examples use the following raw materials in the following weight parts: 50 parts ginger, 50 parts scallion, 30 parts white mustard seed, 15 parts asarum, 15 parts cinnamon, 30 parts corydalis, 15 parts dried tangerine peel, and 15 parts chuanxiong; and the following excipient composition in the following weight parts: 2.4 parts aluminum hydroxyacetate, 300 parts glycerin, 30 parts sodium polyacrylate (PAAS NP700), 2.4 parts disodium EDTA, 12 parts kaolin, 12 parts polyvinylpyrrolidone (PVP K30), 12 parts azone, and β-cyclodextrin is added at a weight ratio of volatile oil to β-cyclodextrin of 1:5.

[0134] Example 1: Preparation of volatile oils from traditional Chinese medicine

[0135] Take the remaining medicinal materials (excluding white mustard seed, ginger, and scallion) in the prescribed amounts (Asarum heterotropoides, cinnamon, Corydalis yanhusuo, tangerine peel, and Ligusticum chuanxiong), grind them, and pass them through a 40-mesh sieve. Extract using steam distillation: Place the medicinal materials in the extraction equipment, add 10 times the amount of purified water, soak for 1-2 hours, connect the volatile oil extractor to the condenser, heat to boiling, control the distillation rate at 1-2 drops per second, and control the condensate temperature at 15-20℃ or lower. Distill for 5 hours until the oil droplets no longer increase, then stop heating. Collect the distillate, allow it to stand and separate into layers, separate the oil layer, add anhydrous sodium sulfate for dehydration, filter, and obtain the volatile oil. Store in a cool, dark place for later use. The yield of volatile oil was determined to be no less than 2.5%.

[0136] Example 2 Preparation of Traditional Chinese Medicine Extracts

[0137] Filter the herbal liquid from the extraction tank in Example 1 and set aside. Then extract the residue twice more, 1.5 hours each time, adding 8 times the amount of purified water each time, filter, collect the three filtrates, and concentrate by rotary evaporation until the relative density of the extract is about 1.2. Place the extract in a -20°C freezer for at least 12 hours, then transfer it to a freeze dryer for freeze drying. Set the freeze dryer parameters as follows: baffle temperature -40°C to -50°C, vacuum degree 10-30 Pa, drying time not less than 12 hours, until the moisture content is less than 5%. Grind and pass through a 100-mesh sieve to obtain the herbal water extract powder with a yield of 20-30%, and set aside.

[0138] Example 3 Preparation of white mustard powder

[0139] Weigh out white mustard seeds and freeze them in the freezer (-18℃ to -28℃) for 4-6 hours. Immediately after freezing, grind them into powder using a grinder for 15-30 seconds intermittently. Pass the powder through an 80-100 mesh sieve to obtain coarse powder. Place the coarse powder in a low-temperature resistant container and slowly add liquid nitrogen to soak it. Pre-cool for 5-15 minutes to make the material completely brittle. Pour the pre-cooled material along with the excess liquid nitrogen into a liquid nitrogen grinder and grind it at 4000-6000 rpm for 15-30 minutes. After grinding, wait for the equipment to return to room temperature, collect the ultrafine powder, and pass it through a 300 mesh sieve to obtain the final product.

[0140] Example 4: Preparation of ginger and scallion juice

[0141] Take fresh ginger, wash it, slice it, and juice it in a juicer. Collect the juice, first coarsely filter it through a 100-mesh sieve, then finely filter it through a 300-mesh filter cloth. Reserve the filtrate to obtain ginger juice. Separately, take fresh scallion whites, wash them, cut them into small sections, and juice them in a juicer. Filter the juice through a 200-mesh filter cloth. Reserve the filtrate to obtain scallion white juice. The ginger juice and scallion white juice can be collected separately for later use, or they can be mixed together for later use. In this embodiment of the invention, the ginger juice and scallion white juice are mixed evenly for later use.

[0142] Example 5 Preparation of volatile oil inclusion complexes

[0143] Accurately weigh the compound volatile oil obtained in Example 1 and dissolve it completely in 2.5 times its weight of anhydrous ethanol. Separately, place 5 times its weight (based on the weight of the volatile oil) of β-cyclodextrin in a beaker, add 20 times its weight of distilled water, and heat to dissolve in a 55°C water bath. While stirring, slowly add the volatile oil ethanol solution dropwise to the β-cyclodextrin solution, and maintain the mixture at a constant temperature of 55°C with stirring for 0.5-1 hour to achieve inclusion. After inclusion is complete, transfer the reaction solution to 5°C and allow it to stand for 8-12 hours. Separate the precipitate by vacuum filtration, and dry the precipitate in a 55°C oven to obtain the compound volatile oil inclusion complex powder.

[0144] Example 6 Preparation of Gel Patch (Stepwise Drug Loading Process)

[0145] (1) Preparation of the first phase (oil phase / premix): 30 parts of white mustard ultrafine powder, 300 parts of glycerol and 30 parts of PAAS NP700 prepared in Example 3 were mixed and stirred to disperse evenly to obtain white mustard glycerol premix.

[0146] (2) Preparation of the second phase (aqueous phase): Take the ginger and scallion juice obtained in Example 4, the volatile oil inclusion compound powder obtained in Example 5, and the Chinese herbal water extract powder obtained in Example 2, add an appropriate amount of purified water, and then add 2.4 parts of EDTA-2Na, 12 parts of kaolin, 12 parts of PVP K30, and 12 parts of azone, and stir to dissolve evenly.

[0147] (3) Mixing and cross-linking: Add the first phase (white mustard glycerol premix) to the second phase and stir evenly. Finally, add 2.4 parts of cross-linking agent aluminum hydroxyl, stir quickly for 1-2 minutes, and immediately apply it to the non-woven fabric backing layer, controlling the coating thickness to be 1-2 mm. Let it stand at room temperature for cross-linking for 15-20 minutes until the paste is formed, then cut and package to obtain the Sanfu gel patch.

[0148] The following experimental examples use the Sanfu Patch gel prepared in Example 6 to illustrate the beneficial effects of the present invention.

[0149] Experimental Example 1: Evaluation of the initial tack of gel patches

[0150] The initial tack of the Sanfu gel patch was determined using the rolling ball ramp stop method. Referring to the Adhesion Determination Method 0952 in Part IV of the 2025 edition of the Chinese Pharmacopoeia, a No. 7 steel ball (5.556 mm in diameter) was selected as the test ball, with a ramp angle of 30°. The maximum distance L (cm) that the steel ball slid across the test patch was measured, and the measurement was repeated three times. The results are shown in Table 1.

[0151] Table 1. Initial tack of gel patch (based on maximum sliding distance L (cm))

[0152]

[0153] The experimental results are shown in Table 1. The average initial adhesion of the gel patch prepared according to the method of the present invention is 52.33 mm, which has excellent initial adhesion performance and can ensure close adhesion to the skin when applied.

[0154] Experimental Example 2: Evaluation of Gel Patch Adhesion

[0155] The gel patch sample was fixed on the test platform of the texture analyzer, ensuring its surface was flat. A standard probe was used to compress and stretch the sample at a constant speed and pressure to simulate the adhesion process in actual use. The force (N·s) required for the probe to detach from the sample was recorded, and this was repeated three times. The results are shown in Table 2.

[0156] Table 2 Results of gel bond adhesion

[0157]

[0158] The experimental results are shown in Table 2. The average stickiness of the gel patch prepared according to the method of the present invention is about 49.64 N·S, indicating that it has good long-term application stability.

[0159] Experimental Example 3: Skin Irritation Test of Gel Patch

[0160] Thirty male guinea pigs were randomly divided into five groups of six each: a blank control group, a single-dose positive control group, a continuous-dose positive control group, a single-dose experimental group, and a continuous-dose experimental group. The experiment used a self-control method with left and right sides of the guinea pigs. Twenty-four hours before administration, the guinea pigs' backs were shaved on both sides, with a shaving area of ​​5 cm × 5 cm on each side. An appropriate amount of depilatory cream was evenly applied to the exposed areas, and after standing, the skin was gently wiped clean with cotton balls soaked in PBS buffer to thoroughly remove any residue, ensuring full skin exposure. Subsequent procedures are shown in Table 3.

[0161] Table 3. Results of skin irritation tests on different groups of gel patches

[0162]

[0163] Visual observation was performed at 30 min, 24 h, and 48 h after the last application and removal of the patch to check for erythema and edema at the application site. After 48 h, three randomly selected animals from each group were dissected to obtain skin tissue for HE staining and pathological examination. Photos of the skin irritation test and HE-stained images are attached. Figure 1-2 .

[0164] The results showed that after single and multiple administrations of the gel patch of the present invention, no erythema or edema occurred on the skin of guinea pigs, and histopathological examination revealed no obvious inflammatory cell infiltration or tissue destruction. In contrast, the positive control group (traditional herbal powder) developed mild to moderate erythema and edema after continuous administration. These results indicate that the skin irritation of the gel patch of the present invention is significantly lower than that of traditional Sanfu herbal powder, demonstrating good safety in clinical application.

[0165] Experiment Example 4: In vitro release experiment

[0166] The Franz in vitro transdermal diffusion method was used to compare the in vitro release of Sanfu gel patches and clinical powder. 1.5g of laboratory-made Sanfu gel patches and 1g of powder were weighed. A Franz vertical diffusion cell was used as the diffusion apparatus, with PBS as the receiving medium. A 1µm FES biomembrane was used, cut into circular pieces approximately 2 cm in diameter, and fixed between the diffusion cell and the sample cell. The receiving cell contained a magnetic stirring bead, and 15.5mL of the receiving medium was injected, with air bubbles removed. The slanted opening of the receiving cell was sealed with aluminum foil to prevent leakage of the test solution. The water bath temperature was maintained at 33.0±0.5℃, and the mixture was stirred at a constant speed (300rpm). After the transdermal test stabilized for 30 min, 1 mL samples were taken from the slanted opening of the receiving cell at 1, 2, 4, 6, 8, and 10 h, and an equal volume of blank receiving medium at the same temperature was added. Each test was performed in triplicate. The sample solution was pretreated, and 20 µL was automatically injected for HPLC analysis of the sinapicin concentration in the sample solution. The peak area was measured, and the cumulative release rate was calculated by substituting it into the linear regression equation. The formula is as follows:

[0167]

[0168] Parameter description:

[0169] Qn%: Cumulative release rate (%) at time point n

[0170] V: Total volume of the receiving liquid in the receiving chamber (mL)

[0171] Cn: Drug concentration (ug / mL) measured at the nth time point

[0172] Vs: Volume of each sample taken (mL, 1 mL in the text).

[0173] Ci: Drug concentration at time point i (ug / mL)

[0174] W: Total mass of medication contained in the patch (ug)

[0175] The in vitro release curve (cumulative release rate of sinigrin thiocyanate - time curve) is attached. Figure 3 The results showed that the cumulative permeability of sinigrin thiocyanate in the gel patch of the present invention reached 97.68% after 10 hours, while the cumulative release of traditional powder administration was only 7.59%. The results indicate that the gel patch of the present invention significantly improves the transdermal release efficiency of the active ingredient.

[0176] The gel patch of this invention can retain the medicinal components of white mustard seed, stably load volatile components, and has good gel matrix formation. It has excellent initial adhesion and adhesion, and also brings better penetration and stability. It has the advantages of significant therapeutic effect and higher safety. The preparation process of this invention is stable and controllable, providing a practical and feasible method for the modern production of traditional Sanfu patch.

Claims

1. A method for preparing Sanfu Patch gel, characterized in that: The raw materials for the Sanfu Patch gel are composed of the following ingredients in the indicated weight ratios: 20-40 parts white mustard seed, 10-20 parts asarum, 10-20 parts cinnamon, 25-40 parts corydalis, 10-25 parts dried tangerine peel, 15-30 parts chuanxiong, 30-60 parts fresh ginger, and 30-60 parts scallion. The excipients of the Sanfu Patch gel are composed of the following raw materials in the indicated weight ratios: 1.2-3.6 parts aluminum hydroxyacetate, 250-350 parts glycerin, 18-48 parts sodium polyacrylate (PAAS NP700), 1.2-3.6 parts disodium EDTA, 4.8-18 parts kaolin, 6-18 parts polyvinylpyrrolidone (PVP K30), and 12-24 parts azone; it also includes β-cyclodextrin, and the weight ratio of the volatile oil from the raw material to β-cyclodextrin is 1:5-6. The preparation method includes the following steps: A. Preparation of volatile oils from traditional Chinese medicine: A1. Take the raw materials Asarum, Cinnamon, Corydalis, Tangerine Peel, and Ligusticum chuanxiong, pulverize them, and pass them through a 20-60 mesh sieve; A2. Extraction by steam distillation: Place the raw medicinal materials described in step A1 in the extraction equipment, add 10-20 times the amount of water to soak, connect the volatile oil extraction equipment and the condensation equipment, heat and collect the distillate; A3. Separation of volatile oil: The distillate from step A2 is allowed to stand and separate into layers. The oil layer is separated, anhydrous sodium sulfate is added for dehydration, and the mixture is filtered to obtain the volatile oil. B. Preparation of extracts from traditional Chinese medicine: B1. After collecting the volatile oil in step A, take the raw material extract extracted by the extraction equipment, filter it to obtain the residue and filtrate, and keep the filtrate for later use. B2. Then, take the residue obtained in step B1, add water to extract it, and obtain the extract filtrate. Combine the filtrates obtained in steps B1 and B2. B3. Concentrate the combined filtrate obtained in step B2 to obtain the extract; B4. Drying the extract obtained in step B3; B4. After drying, it is pulverized to obtain extract powder; C. Preparation of white mustard powder C1. Grind white mustard seeds into coarse powder; C2, Crispy white mustard powder; C3. Grind the brittle white mustard seeds into coarse powder, and sieve to obtain ultrafine powder; D. Preparation of ginger juice and scallion juice: D1. Preparation of ginger juice: Take fresh ginger, wash it, slice it, put it into a juicing device to extract the juice, collect the juice, filter it and set it aside. D2. Preparation of scallion juice: Take fresh scallion whites, wash them, cut them into small sections, put them into a juicing device to extract the juice, collect the juice, filter it and set it aside. E. Preparation of volatile oil inclusion complexes: E1. Take the volatile oil of the Chinese medicine obtained in step A, add anhydrous ethanol to dissolve it completely, and obtain a volatile oil ethanol solution; E2. Add the volatile oil ethanol solution obtained in step E1 dropwise to the β-cyclodextrin solution to encapsulate and obtain the reaction solution; E3. The inclusion reaction solution obtained in step E2 is allowed to stand, filtered, and the resulting precipitate is dried to obtain the volatile oil inclusion complex. F. Preparation of the gel patch: F1. Preparation of the first phase: The white mustard ultrafine powder obtained in step C is mixed with glycerol and PAAS NP700 and stirred until evenly dispersed to obtain white mustard glycerol premix, which is an oil phase mixture; F2. Preparation of the second phase: Take the extract powder obtained in step B, the scallion juice and ginger juice obtained in step D, and the volatile oil inclusion complex obtained in step E, add water and aqueous phase excipients, stir and mix evenly to obtain an aqueous phase mixture; F3. Mixing and Crosslinking: Add the first phase oil mixture to the second phase aqueous mixture, stir evenly, add the crosslinking agent aluminum hydroxide, then coat it onto the backing layer, let it stand to form, and cut it to obtain the Sanfu gel patch.

2. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In the preparation of the volatile oil from the traditional Chinese medicine described in step A, at least one of the following conditions must be met: The sieving mentioned in step A1 refers to passing the material through a 20-60 mesh sieve; Preferably, the sieving in step A1 is sieving through a 40-mesh sieve; The soaking conditions described in step A2 are: add 10-20 times the amount of water; Preferably, the soaking in water step A2 is performed by adding 10 times the amount of water; The soaking conditions described in step A2 are as follows: the water is purified water; The soaking conditions described in step A2 are: soaking for 1-2 hours; Preferably, the soaking in water in step A2 is: soaking for 1 hour; The volatile oil extraction equipment mentioned in step A2 is a volatile oil extractor; The condensing device mentioned in step A2 is a condenser tube; The heating and collection of distillate in step A2 is carried out by the following method: heating to boiling, controlling the distillation rate to 2-3 drops per second, controlling the condensate temperature to less than or equal to 20°C, distilling until the oil droplets no longer increase, stopping heating and collecting the distillate; Preferably, the heating and collection of distillate in step A2 is carried out by the following method: heating to boiling, controlling the distillation rate to 1-2 drops per second, controlling the condensate temperature at 15-20°C or lower, distilling until the oil droplets no longer increase, stopping heating and collecting the distillate; Preferably, the distillation time in step A2 is 3-8 hours; Alternatively, the distillation time is 5 hours; The volatile oil obtained in step A3 should be stored in a cool, dark place for later use. The yield of volatile oil in step A shall not be less than 2.5%.

3. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In the preparation of the traditional Chinese medicine extract described in step B, at least one of the following conditions must be met: The conditions for water extraction described in step B2 are as follows: extract 2-3 times, each time for 1.5-2 hours, and each time add 8-10 times the amount of water; Preferably, the conditions for water extraction in step B2 are: extraction twice, 1.5 hours each time, and 8 times the amount of water added each time; The water mentioned in step B2 is purified water; The concentration described in step B3 is achieved by rotary evaporation. The relative density of the concentrated extract obtained in step B3 is 1.2 ± 0.5; Preferably, the relative density of the concentrated extract obtained in step B3 is 1.2; The drying process described in step B4 is freeze drying; Preferably, the freeze-drying conditions in step B4 are as follows: the extract is first frozen at -40°C to -20°C for at least 12 hours, and then freeze-dried in a freeze-drying apparatus; The most preferred method is to freeze-dry the extract at -20°C for at least 12 hours. Preferably, the freeze-drying conditions in the freeze-drying equipment described in step B4 are: partition temperature -20°C to -80°C, vacuum degree 10Pa to 50Pa, drying time not less than 12 hours, until the moisture content is less than 6%; Most preferably, the freeze-drying conditions in the freeze-drying equipment described in step B4 are: partition temperature -40°C to -50°C, vacuum degree 10-30 Pa, drying time not less than 12 hours, until the moisture content is less than 5%; The process described in step B4 involves pulverizing the material until it passes through an 80-100 mesh sieve. Preferably, the pulverization process described in step B4 involves passing the material through a 100-mesh sieve. The yield of the aqueous extract powder of traditional Chinese medicine obtained by the above preparation method is about 20-30%.

4. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In step C, the preparation of white mustard powder, at least one of the following conditions must be met: The pulverization in step C1 is prepared using the following method: C1-1. Before grinding, freeze the white mustard seeds at a temperature of -18℃ to -28℃ for at least 4 hours; C1-2. Crush the frozen white mustard seeds into powder that passes through an 80-100 mesh sieve; Preferably, before pulverizing in step C1-1, the white mustard seeds are frozen at a temperature of -18℃ to -28℃ for 4-6 hours; Preferably, the pulverization condition in step C1-2 is pulverization immediately after freezing; Preferably, the pulverizing conditions in step C1-2 are as follows: the pulverizer is used to grind the powder, the grinding time is controlled within 15-30 seconds, and the operation is intermittent. The embrittlement process described in step C2 involves placing coarse white mustard powder into a low-temperature resistant container, slowly adding liquid nitrogen for immersion, and pre-cooling for 5-15 minutes to obtain embrittled coarse white mustard powder. The pulverization conditions described in step C3 are as follows: the brittle white mustard powder and the liquid nitrogen in the container are added to a liquid nitrogen pulverizer and pulverized at 4000-6000 rpm for 15-30 minutes. The sieving described in step C3 refers to sieving through a sieve of at least 200-300 mesh. Preferably, the sieving in step C3 is sieving through a 300-mesh sieve.

5. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In step D, the preparation of ginger and scallion juice, at least one of the following conditions must be met: The ginger juice in step D1 and the scallion juice in step D2 are filtered through an 80-500 mesh sieve. Preferably, the ginger juice in step D1 and the scallion juice in step D2 are filtered through a 100-300 mesh sieve; Furthermore, since ginger juice will produce sediment after filtration and standing, possibly due to the precipitation of certain substances during the process, a finer mesh is used for filtration; therefore, the following filtration parameters can also be used: In step D1, the filtration process for preparing ginger juice involves first coarse filtration using an 80-100 mesh sieve, followed by fine filtration using a 200-500 mesh filter cloth. Preferably, the filtration in step D1 is to first use a 100-mesh sieve for coarse filtration, and then use a 300-mesh filter cloth for fine filtration; Step D2: Preparation of scallion juice; filtration is performed using a 100-300 mesh filter cloth. Preferably, the filtration in step D2 is performed using a 200-mesh filter cloth.

6. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In step E, the preparation of the volatile oil inclusion complex must satisfy at least one of the following conditions: The weight ratio of volatile oil to anhydrous ethanol in step E1 is 1:1.5-1:3; Preferably, the weight ratio of volatile oil to anhydrous ethanol in step E1 is 1:2.5; The β-cyclodextrin solution in step E2 is prepared by the following method: based on the weight of the volatile oil of the Chinese herbal medicine obtained in step A, take 5-6 times the amount of β-cyclodextrin, add water and heat to dissolve; Preferably, the β-cyclodextrin solution in step E2 is prepared by the following method: based on the weight of the volatile oil of the Chinese herbal medicine obtained in step A, take 5 times the amount of β-cyclodextrin, add water and heat to dissolve; Preferably, the amount of water added to β-cyclodextrin is 3-6 times the amount of water, and most preferably, the amount of water added to β-cyclodextrin is 4 times the amount of water; that is, 5 times the amount of β-cyclodextrin requires 20 times the amount of water. Preferably, step E2 heating is performed in a water bath at 40℃-70℃; Most preferably, step E2 heating is performed in a 55°C water bath; The inclusion reaction conditions described in step E2 are: constant temperature stirring at 40℃-55℃ for 0.5-2 hours; Preferably, the inclusion reaction conditions in step E2 are: constant temperature stirring at 55°C for 0.5-1 hour; The standing time mentioned in step E3 is to place the inclusion reaction solution at 0℃-10℃ for 6-24 hours; Preferably, the standing in step E3 is to place the inclusion reaction solution at 5°C for 8-12 hours; The filtration described in step E3 uses methods such as vacuum filtration, centrifugation, and pressure filtration to separate the precipitate; The drying process described in step E3 is performed at a temperature of 40℃-65℃. Preferably, the drying in step E3 is performed at a temperature of 55°C. The drying oven described in step E3 is used for drying.

7. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: In the preparation of the gel patch in step F, at least one of the following conditions must be met: After adding the crosslinking agent aluminum hydroxide as described in step F3, stir rapidly and then coat it onto the backing layer; Preferably, after adding the crosslinking agent aluminum hydroxide in step F3, the mixture is stirred rapidly for 1-2 minutes and then coated onto the backing layer; The backing layer described in step F3 is made of non-woven fabric, polyethylene (PE), polypropylene (PP), composite aluminum foil, polyurethane film, and polyester (PET). Preferably, the backing layer in step F3 is a non-woven fabric backing layer; The coating thickness described in step F3 is 1-2 mm; The standing conditions described in step F3 are: standing at room temperature for 10-20 minutes for cross-linking until the paste is formed; Preferably, the standing conditions in step F3 are as follows: stand at room temperature for 15-20 minutes for crosslinking until the paste is formed.

8. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: The raw materials for the Sanfu Patch gel are composed of the following ingredients in the indicated weight ratios: 30 parts white mustard seed, 15 parts asarum, 15 parts cinnamon, 30 parts corydalis, 15 parts dried tangerine peel, 15 parts chuanxiong, 50 parts ginger, and 50 parts scallion.

9. The method for preparing the Sanfu Patch gel according to claim 1, characterized in that: The excipients of the Sanfu Patch gel are composed of the following raw materials in the following weight ratio: 2.4 parts aluminum hydroxyacetate, 300 parts glycerin, 30 parts sodium polyacrylate (PAASNP700), 2.4 parts disodium EDTA, 12 parts kaolin, 12 parts polyvinylpyrrolidone (PVP K30), 12 parts azone, and also include β-cyclodextrin. The weight ratio of the volatile oil of the Chinese medicine obtained from the raw material to β-cyclodextrin is 1:

5.

10. The Sanfu Patch gel prepared by the preparation method according to any one of claims 1-9.

Images