A Chinese medicine gel plaster for treating menstrual disorders and preparation method thereof

Abstract

The invention relates to the technical field of external medicines, and discloses a Chinese medicine gel patch for treating menstrual disorders and a preparation method thereof. Microcapsule technology is combined with Chinese medicine gel patch technology to prepare a microcapsule that can achieve uniform degradation and drug release at human epidermal temperature, thereby increasing the shelf life of the product and improving the drug efficacy. Essential oils are compounded with existing ingredients to enhance diffusion and improve user experience.

Description

Technical Field

[0001] The invention relates to the technical field of external medicine, in particular to a traditional Chinese medicine gel plaster for treating menstrual disorders and a preparation method thereof. Background Art

[0002] Dysmenorrhea is a common gynecological disease in women, which is manifested by abnormal menstrual cycle, excessive or insufficient menstrual blood, dysmenorrhea and other symptoms, which seriously affect women's quality of life and health. Traditional treatment methods mainly include Western medicine and Chinese medicine. Western medicine usually uses hormone drugs to regulate endocrine. Although it works quickly, long-term use may cause side effects. Chinese medicine achieves the purpose of treatment by adjusting the overall functional state of the human body, emphasizing the treatment of syndrome differentiation, with the advantages of small side effects and lasting efficacy. In recent years, with the increasing attention paid to natural medicines and non-invasive therapies, Chinese medicine external preparations have gradually received attention due to their high safety and easy acceptance. Traditional Chinese medicine gel plaster is a new type of external dosage form that combines modern pharmaceutical technology and traditional Chinese medicine theory. It is based on a specific traditional Chinese medicine formula, uses a gel carrier to directly apply the active ingredients to the skin surface, and exerts its efficacy through transdermal absorption, avoiding problems such as gastrointestinal irritation that may be caused by oral medications. However, existing traditional Chinese medicine gel plasters, such as the Yao medicine warm palace plaster and its preparation method disclosed in patent No. CN110638995A, have a plaster preparation disclosed in which the effective medicinal materials are directly in contact with the air, which can easily lead to reduced efficacy or even failure over a long period of time. At the same time, due to the characteristics of our own skin, the bioavailability of the formula is low, and the unique smell of the medicinal materials makes the odor obvious during use, resulting in a poor user experience.

[0003] The present invention aims to provide a Chinese medicine gel plaster for menstrual disorders and a preparation method thereof. The product not only inherits the advantages of traditional Chinese medicine, but also integrates modern pharmaceutical technology, aiming to overcome various limitations existing in the prior art and provide patients with a safe and effective treatment option. Summary of the invention

[0004] In order to solve the technical problems mentioned in the above background technology, such as poor drug stability, easy failure, low bioavailability, and obvious odor during use leading to poor usage experience, the present invention provides a traditional Chinese medicine gel patch for treating menstrual disorders and a preparation method thereof. By doping microcapsule technology in the traditional hydrogel plaster system, while achieving sustained and controlled release of the drug, the addition of essential oil ingredients can also promote the body's absorption of the drug and enhance the usage experience.

[0005] The specific technical scheme of the present invention is: a traditional Chinese medicine gel patch for treating menstrual disorders, comprising a backing layer, a gel layer coated on the backing layer, and an anti-sticking layer arranged on the surface of the gel layer; microcapsules are evenly distributed in the gel layer, and the microcapsules include a wall material and a core material, wherein the wall material includes a polylactic acid-hydroxybenzaldehyde polymer, a surfactant, a plasticizer and a cross-linking agent; the core material includes a red date pulp extract, a motherwort extract, a lindera extract, an argyi extract, a codonopsis extract, ginger essential oil and a rose essential oil.

[0006] The invention provides a Chinese medicine gel patch for treating menstrual disorders. The hydrogel layer in the traditional hydrogel patch is mixed with microcapsule technology containing medicinal ingredients, and the medicine is sealed in an air-tight place to extend the shelf life of the medicine. At the same time, the microcapsules are in contact with the human body when used, and the microcapsules are dissolved and the core material is released after the temperature rises, so as to achieve the effect of sustained-release medicine. Essential oil components are added to the previous formula. Due to its strong volatility, after the core material is released, the essential oil carries the drug molecules to enter the human body faster to exert their effects. At the same time, the unique fragrance of the plant essential oil can enhance the feeling of use and pleasure, stimulate the human body to positively regulate endocrine, shorten the treatment cycle, modify poly-lactic acid-glycolic acid, and combine the acid-sensitive hydrazone bond with the hydrophilic group PEG to form a wall material that is sensitive to water and acid. When used, it only needs to be slightly activated to achieve the desired effect.

[0007] Furthermore, the molecular molar ratio of lactic acid to glycolic acid in the polylactic acid-hydroxybenzaldehyde polymer is 75:25-85:15, and the molecular weight of the polylactic acid-hydroxybenzaldehyde polymer is less than 10000Da. In order to realize that after the microcapsules are applied to human epidermal cells, the drug release can be achieved only by temperature control while maintaining the speed of controlled drug release, that is, within 48 hours of medication, the speed of drug release by vitrification of the microcapsules should be maintained within a certain range. The glass transition temperature of the polylactic acid-hydroxybenzaldehyde polymer used in the present invention is generally higher than the temperature that the human epidermis can reach, so it is necessary to perform some Parameter limitation. During the research process, the researchers found that the lactic acid content in the polylactic acid-hydroxybenzaldehyde polymer can be limited. When the molecular molar ratio of lactic acid and glycolic acid is limited to the range of 75:25 to 85:15, the glass transition temperature of the polylactic acid-hydroxybenzaldehyde polymer is close to the human epidermal temperature, and its degradation rate is moderate, which can achieve slow and uniform drug release. At the same time, for a polymer compound, the larger the molecular weight, the more difficult it is to degrade, and the slower the degradation rate. Controlling the molecular weight of the polylactic acid-hydroxybenzaldehyde polymer within 10,000 and controlling the molecular molar ratio together can achieve uniform and slow release of the drug effect.

[0008] Furthermore, the components in the wall material are calculated by weight as follows: 20-25% of polylactic acid-hydroxybenzaldehyde polymer, 1-3% of surfactant, 5-7% of plasticizer, and 0.1-0.2% of cross-linking agent.

[0009] Furthermore, the surfactant is one of Tween 80 or lecithin, the plasticizer is one of glycerol or triethyl citrate, and the cross-linking agent is one of glutaraldehyde or calcium ion. In the technical scheme of the present invention provided above, although the glass transition temperature of the produced polylactic acid-hydroxybenzaldehyde polymer has reached the temperature that the human epidermis can reach, the human surface temperature is not constant, especially in the specific population used in the preparation - menstrual disorders, the proportion of body surface temperature caused by body cold lower than that of ordinary people is very high. In order to make the preparation provided by the present invention applicable to more people, it is very necessary to further reduce the glass transition temperature of the polyethylene-hydroxyacetic acid polymer; the plasticizer, as a small molecule added to the polymer, can be inserted between polymer chains to weaken the interaction between hydrogen bonds and van der Waals forces between molecules. In the process of preparing the wall material of the microcapsule, the plasticizer is added to the polyethylene-hydroxyacetic acid, which can reduce its degradation temperature and accelerate the reaction rate. The research of the present invention team shows that the effect is best when the addition amount of the plasticizer is 5-7wt%.

[0010] Furthermore, the components in the core material are calculated by weight as follows: 25-30% red date pulp extract, 20-25% motherwort extract, 15-20% lindera stolonifera extract, 20-30% wormwood extract, 7-10% codonopsis pilosula extract, 0.1%-1% ginger essential oil, and 0.1-1% rose essential oil.

[0011] A method for preparing a traditional Chinese medicine gel plaster for treating menstrual disorders, characterized in that it comprises the following steps: 1) dispersing carbomer in an appropriate amount of water, heating and stirring until completely dissolved, adding a thickener, a humectant, and a cross-linking agent in turn, cooling the solution naturally, adding dry microcapsules for treating menstrual disorders under low temperature stirring, and mixing with the aid of ultrasound to obtain a hydrogel, wherein the temperature of the solution naturally cooled is 35-40° C.; 2) evenly coating the hydrogel obtained in step 1) on a backing material to obtain a gel layer, placing an anti-adhesive layer on the gel layer, and packaging the product; 3) The product is taken out, the anti-adhesive layer is peeled off, and a layer of 0.001-0.005wt% salicylic acid solution is coated on the surface of the gel layer. The polylactic acid-hydroxybenzaldehyde polymer used in the present invention has a hydrophilic group PEG connected through an acid-sensitive hydrazone bond, so that the formed wall material is sensitive to water and weak acid. When the product is used, a layer of weak acid salicylic acid solution with no side effects on human epidermis is coated on the surface, which can further stimulate the rupture of the internal bonds of the polylactic acid-hydroxybenzaldehyde polymer and accelerate the degradation rate to produce a slow drug release effect at human surface temperature, thereby exerting the efficacy.

[0012] Furthermore, in step 1), the pH value of the hydrogel is 6.5-7.5.

[0013] Preferably, parabens are incorporated into the hydrogel as preservatives to ensure the shelf life of the product.

[0014] Furthermore, the preparation steps of microcapsules for treating menstrual disorders are as follows: a) adding polylactic acid-hydroxybenzaldehyde polymer powder to dichloromethane, stirring until completely dissolved, to obtain a wall material solution; b) dispersing red jujube pulp extract, motherwort extract, lindera stolonifera extract, wormwood extract, and codonopsis pilosula extract in order by weight in water, and after uniform dispersion, dropping ginger essential oil and rose essential oil into the water, and mixing well to obtain a core material solution; c) slowly adding the core material solution to the wall material solution in a stirring state, and after thorough mixing, obtaining a primary emulsion, and adding the primary emulsion to an aqueous solution containing a plasticizer and a cross-linking agent, and stirring to form a crude microcapsule product; d) evaporating and centrifuging the crude microcapsules, washing and drying them to obtain microcapsules for treating menstrual disorders.

[0015] Ultrasonic waves are used to assist in short-term treatment to help break up agglomerations and better disperse the microcapsules.

[0016] Furthermore, the evaporation in step d) is performed by rotary evaporation, and the evaporation temperature is 32-35°C.

[0017] Furthermore, the drying in step d) is performed by freeze drying.

[0018] Compared with the prior art, the beneficial effects of the present invention are: 1) The addition of microencapsulation technology can not only achieve sustained and controlled release of drugs, but also extend the shelf life of the product and facilitate storage.

[0019] 2) The molecular weight and composition ratio of the main component of the microcapsule wall material, polylactic acid-hydroxybenzaldehyde polymer, are limited to control the speed of controlled drug release and achieve slow and uniform drug release. At the same time, the modification of PLGA with hydrazone bonds and polyethylene glycol makes it sensitive to water and acid. It only needs to coat a layer of weakly acidic water on the surface to slowly and evenly degrade, exert the efficacy, and improve the bioavailability of the drug.

[0020] 3) Adding ginger essential oil and rose essential oil to the traditional formula for treating menstrual disorders can not only promote the entry of drugs into the human body and increase the bioavailability of medicinal materials, but the unique fragrance of herbal essential oils can enhance the user's experience. DETAILED DESCRIPTION

[0021] The present invention will be further described below in conjunction with the embodiments.

[0022] Example 1 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0023] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 75:25; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.5 wt % of ginger essential oil and 0.5 wt % of rose essential oil are dropped into the solution, and the core material solution is mixed to obtain a core material solution. The mixture was slowly added into the wall material solution under stirring, and after complete mixing, a primary emulsion was obtained. The primary emulsion was added into a solution containing 6 g of plasticizer triethyl citrate and 0.15 g of cross-linking agent calcium chloride and 100 ml of water, and stirred on a magnetic stirrer at a speed of 1200 r / min for 2 hours to form a crude microcapsule. The crude microcapsule was evaporated at 32°C for 1 hour using a rotary evaporator, and centrifuged at a speed of 3000 r / min for 10 minutes. The crude microcapsule was washed with distilled water for 3 times, pre-frozen at -50°C for 4 hours, and then dried at a vacuum degree of 50 Pascals for 24 hours to obtain microcapsules for treating menstrual disorders.

[0024] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0025] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0026] Comparative Example 1 The difference between this comparative example and Example 1 is that, in step 2), no plasticizer triethyl citrate is added to the microcapsules, and the remaining steps are the same as those in Example 1. The specific steps are: 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0027] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 75:25; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.5 wt % of ginger essential oil and 0.5 wt % of rose essential oil are dropped into the mixture, and the mixture is mixed to obtain a core material solution. , slowly add the core material solution to the wall material solution in a stirring state, and after complete mixing, obtain a primary emulsion, add the primary emulsion into a solution of 100 ml of water containing 0.15 g of a cross-linking agent, calcium chloride, and stir on a magnetic stirrer at a speed of 1200 r / min for 2 hours to form a crude microcapsule; evaporate the crude microcapsule at 32°C for 1 hour using a rotary evaporator, centrifuge at a speed of 3000 r / min for 10 minutes, wash the crude microcapsule with distilled water for 3 times, pre-freeze at -50°C for 4 hours, and dry at a vacuum degree of 50 Pascals for 24 hours to obtain microcapsules for treating menstrual disorders.

[0028] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0029] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0030] Table 1 Effect of plasticizer addition on sustained release of microcapsules According to the data in Table 1, we can conclude that when preparing the wall material of microcapsules, if the plasticizer triethyl citrate is not added, the final microcapsules are almost impossible to degrade, the core material inside cannot be released, and the effect of controlled release of drugs cannot be achieved.

[0031] Comparative Example 2 The difference between this comparative example and Example 1 is that in this comparative example, in step 2) when preparing microcapsules, the molar ratio of lactic acid (LA) to glycolic acid (GA) of the polylactic acid-hydroxybenzaldehyde polymer used is 90:10, and the rest of the process is the same as that of Example 1, and the specific steps are as follows: 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0032] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 90:10; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.5 wt % of ginger essential oil and 0.5 wt % of rose essential oil are dropped into the solution, and the core material solution is mixed to obtain a core material solution. The mixture was slowly added into the wall material solution under stirring, and after complete mixing, a primary emulsion was obtained. The primary emulsion was added into a solution containing 6 g of plasticizer triethyl citrate and 0.15 g of cross-linking agent calcium chloride and 100 ml of water, and stirred on a magnetic stirrer at a speed of 1200 r / min for 2 hours to form a crude microcapsule. The crude microcapsule was evaporated at 32°C for 1 hour using a rotary evaporator, and centrifuged at a speed of 3000 r / min for 10 minutes. The crude microcapsule was washed with distilled water for 3 times, pre-frozen at -50°C for 4 hours, and then dried at a vacuum degree of 50 Pascals for 24 hours to obtain microcapsules for treating menstrual disorders.

[0033] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0034] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0035] Comparative Example 3 The difference between this comparative example and Example 1 is that in this comparative example, in step 2) when preparing microcapsules, the molar ratio of lactic acid (LA) to glycolic acid (GA) in the polylactic acid-hydroxybenzaldehyde polymer used is 50:50, and the rest of the process is the same as that in Example 1, and the specific steps are as follows: 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0036] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 50:50; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.5 wt % of ginger essential oil and 0.5 wt % of rose essential oil are dropped into the solution, and the core material solution is mixed. The mixture was slowly added into the wall material solution under stirring, and after complete mixing, a primary emulsion was obtained. The primary emulsion was added into a solution containing 6 g of plasticizer triethyl citrate and 0.15 g of cross-linking agent calcium chloride and 100 ml of water, and stirred on a magnetic stirrer at a speed of 1200 r / min for 2 hours to form a crude microcapsule. The crude microcapsule was evaporated at 32°C for 1 hour using a rotary evaporator, and centrifuged at a speed of 3000 r / min for 10 minutes. The crude microcapsule was washed with distilled water for 3 times, pre-frozen at -50°C for 4 hours, and then dried at a vacuum degree of 50 Pascals for 24 hours to obtain microcapsules for treating menstrual disorders.

[0037] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0038] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0039] Table 2 Effect of the molar ratio of LA and GA in polylactic acid-hydroxybenzaldehyde polymer on the controlled release of microcapsules From the data in Table 2, we can see that when the GA content in the polylactic acid-hydroxybenzaldehyde polymer is too low, the synthesized microcapsules will not be able to degrade at the human epidermal temperature. The higher the GA content, the faster the degradation rate of the polylactic acid-hydroxybenzaldehyde polymer and the lower the glass transition temperature. However, if the GA content is too high, the microcapsules will not be able to achieve a relatively uniform and rapid drug release, and the drug efficacy will be released too quickly, which is not conducive to daily use.

[0040] Comparative Example 4 The difference between the comparative example and Example 1 is that in this comparative example, in step 2) when preparing microcapsules, the polylactic acid-hydroxybenzaldehyde polymer used has a Mw of 20,000, and the rest of the process is the same as in Example 1, and the specific steps are as follows: 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0041] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 20000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 75:25; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.5 wt % of ginger essential oil and 0.5 wt % of rose essential oil are dropped into the solution, and the core material solution is mixed. The liquid is slowly added to the wall material solution in a stirring state, and after complete mixing, a primary emulsion is obtained. The primary emulsion is added to a solution containing 6g of plasticizer triethyl citrate and 0.15g of cross-linking agent calcium chloride and 100ml of water, and stirred on a magnetic stirrer at a speed of 1200r / min for 2h to form a crude microcapsule. The crude microcapsule is evaporated at 32°C for 1h using a rotary evaporator and centrifuged at a speed of 3000r / min for 10min. The crude microcapsule is washed 3 times with distilled water, pre-frozen at -50°C for 4h, and then dried at a vacuum degree of 50 Pascal for 24h to obtain microcapsules for treating menstrual disorders.

[0042] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0043] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0044] Table 3 Effect of weight average molecular weight (Mw) of polylactic acid-hydroxybenzaldehyde polymer on controlled release of microcapsules From the data in Table 3, when the weight average molecular weight of the polylactic acid-hydroxybenzaldehyde polymer is too large, the microcapsules finally formed will not be able to degrade at the human epidermal temperature and will not be able to release the contents.

[0045] Comparative Example 5 The difference between this comparative example and Example 1 is that PLGA is not modified in this comparative example, and the remaining steps are the same as those in Example 1, and the specific steps are as follows: 1) Preparation of Chinese herbal medicine extracts 30 parts of red date pulp, 25 parts of Leonurus japonicus, 15 parts of Linderae strychnifolia, 20 parts of Artemisia argyi and 10 parts of Codonopsis pilosula were weighed by weight, and the mixture was ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials was 3:1. The solution after cold-soaking was concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0046] 2) Preparation of microcapsules 23g of polylactic acid-glycolic acid copolymer powder was added to 100ml of dichloromethane, 2wt% of Tween 80 was added, and the mixture was stirred at a speed of 800r / min for 30min on a magnetic stirrer until it was completely dissolved to obtain a uniform and transparent wall material solution, wherein the Mw of PLGA was 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) was 75:25; the Chinese medicine extract prepared in step 1) was dispersed in pure water, and after uniform dispersion, 0.5wt% of ginger essential oil and 0.5wt% of rose essential oil were dropped into the mixture, and the core material solution was mixed to obtain a core material solution, and the core material solution was slowly added into The crude microcapsules were added into a wall material solution under stirring and mixed completely to obtain a primary emulsion. The primary emulsion was added into a solution containing 6 g of triethyl citrate as a plasticizer and 0.15 g of calcium chloride as a cross-linking agent in 100 ml of water. The mixture was stirred on a magnetic stirrer at a speed of 1200 r / min for 2 h to form a crude microcapsule. The crude microcapsule was evaporated at 32° C. for 1 h using a rotary evaporator and centrifuged at a speed of 3000 r / min for 10 min. The crude microcapsule was washed with distilled water for 3 times, pre-frozen at -50° C. for 4 h, and dried at a vacuum degree of 50 Pascals for 24 h to obtain microcapsules for treating menstrual disorders.

[0047] 3) Preparation of Chinese medicine gel plaster Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively, and then a cross-linking agent triethanolamine is added, and then the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while being stirred, and after ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-sticking layer is placed above the gel layer, and the product is obtained after packaging.

[0048] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0049] Table 4 Effect of PLGA modification on controlled release of microcapsules From the data in Table 4, when PLGA is not chemically modified, it is insensitive to water and acid, which will cause the final microcapsules to degrade slowly or almost not degrade at the human epidermal temperature, thereby releasing the contents.

[0050] Example 2 1) Preparation of Chinese herbal medicine extracts 27 parts of red date pulp, 23 parts of Leonurus japonicus, 18 parts of Linderae strychnifolia, 25 parts of Artemisia argyi and 8 parts of Codonopsis pilosula were weighed by weight, ultrasonically crushed and mixed, and then cold-soaked twice in ethyl acetate at 10°C, each time for 48 hours, wherein the total volume ratio of ethyl acetate to medicinal materials is 3:1, and the solution after cold soaking is concentrated under reduced pressure at 40°C to obtain the Chinese medicine extract.

[0051] 2) Preparation of microcapsules 23 g of polylactic acid-hydroxybenzaldehyde polymer powder is added to 100 ml of dichloromethane, 2 wt % of Tween 80 is added, and the mixture is stirred at a speed of 800 r / min for 30 min on a magnetic stirrer until it is completely dissolved to obtain a uniform and transparent wall material solution, wherein the polylactic acid-hydroxybenzaldehyde polymer has an Mw of 7000, and the molar ratio of lactic acid (LA) to glycolic acid (GA) is 85:15; the Chinese medicine extract prepared in step 1) is dispersed in pure water, and after uniform dispersion, 0.3 wt % of ginger essential oil and 0.3 wt % of rose essential oil are dropped into the solution, and the core material is mixed to obtain a core material solution. The solution is slowly added to the wall material solution in a stirring state, and after complete mixing, a primary emulsion is obtained. The primary emulsion is added to a solution containing 6g of plasticizer glycerol and 0.15g of cross-linking agent glutaraldehyde and 100ml of water, and stirred on a magnetic stirrer at a speed of 1200r / min for 2h to form a crude microcapsule. The crude microcapsule is evaporated at 32°C for 1h using a rotary evaporator and centrifuged at a speed of 3000r / min for 10min. The crude microcapsule is washed with distilled water for 3 times, pre-frozen at -50°C for 4h, and then dried at a vacuum degree of 50 Pascals for 24h to obtain microcapsules for treating menstrual disorders.

[0052] 3) Preparation of Chinese medicine gel plaster: Carbomer is dispersed in an appropriate amount of water, heated and stirred until completely dissolved, and then a thickener xanthan gum and a moisturizer glycerin are added successively. After adding a cross-linking agent triethanolamine, the solution is naturally cooled to 35° C., and the dried microcapsules for treating menstrual disorders prepared in step 2) are added while stirring. After ultrasonic-assisted mixing, the pH of the hydrogel solution is adjusted to 7 with sodium hydroxide or hydrochloric acid to obtain a hydrogel; the hydrogel is evenly coated on a backing material to obtain a gel layer, the thickness of the gel layer is 0.3 mm, the thickness of the gel layer is kept uniform everywhere, and an anti-adhesive layer is placed above the gel layer, and the product is obtained after packaging.

[0053] 4) Detection The Chinese medicine gel patch prepared in step 3) is taken out, the anti-sticking layer is peeled off, a layer of 0.002wt% salicylic acid solution is coated on the surface of the gel layer and then placed on a 35°C uniform heating plate to conduct a simulated human body test. The gel patch is sliced ​​after heating for 1h, 3h, 7h, 20h, and 36h, respectively, and observed under a microscope to record the percentage of broken microcapsules.

[0054] The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art.

[0055] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A Chinese medicine gel plaster for treating menstrual disorders, characterized in that: The invention comprises a backing layer and a gel layer coated on the backing layer, wherein an anti-sticking layer is arranged on the surface of the gel layer; microcapsules are evenly distributed in the gel layer, wherein the wall material comprises a polylactic acid-hydroxyphenylaldehyde copolymer, a surfactant, a plasticizer and a cross-linking agent; the core material comprises a red date pulp extract, a motherwort extract, a lindera extract, an argyi leaf extract, a codonopsis extract, ginger essential oil and rose essential oil; the molar ratio of lactic acid to glycolic acid in the polylactic acid-hydroxyphenylaldehyde copolymer is 75:25-85:15, and the molecular weight of the polylactic acid-hydroxybenzaldehyde is less than 10000Da.

2. A Chinese medicine gel plaster for treating menstrual disorders according to claim 2, characterized in that: The components in the wall material are calculated by weight as follows: polylactic acid-hydroxybenzaldehyde copolymer 20-25%, surfactant 1-3%, plasticizer 5-7%, and cross-linking agent 0.1-0.2%.

3. A Chinese medicine gel plaster for treating menstrual disorders according to claim 1 or 2, characterized in that: The surfactant is one of Tween 80 or lecithin, and the cross-linking agent is one of glutaraldehyde or calcium ion.

4. A Chinese medicine gel plaster for treating menstrual disorders according to claim 1 or 2, characterized in that: The plasticizer is one of glycerol or triethyl citrate.

5. A Chinese medicine gel plaster for treating menstrual disorders according to claim 2, characterized in that: The components in the core material are calculated by weight as follows: 25-30% red date pulp extract, 20-25% motherwort extract, 15-20% lindera stolonifera extract, 20-30% wormwood extract, 7-10% codonopsis pilosula extract, 0.1%-1% ginger essential oil, and 0.1-1% rose essential oil.

6. A method for preparing a Chinese medicine gel plaster for treating menstrual disorders according to any one of claims 1 to 5, characterized in that: The following steps are involved: 1) Disperse carbomer in an appropriate amount of water, heat and stir until completely dissolved, then add a thickener, a humectant, and a cross-linking agent, and then cool the solution naturally. Add dry microcapsules for treating menstrual disorders under low-temperature stirring, and mix with the aid of ultrasound to obtain a hydrogel. The temperature at which the solution is naturally cooled is 35-40°C. 2) The hydrogel obtained in step 1) is evenly coated on a backing material to obtain a gel layer, and an anti-adhesive layer is placed on the gel layer, and the product is obtained after packaging; 3) Take out the product, peel off the anti-sticking layer, and apply a layer of 0.001~0.005wt% salicylic acid solution on the surface of the gel layer.

7. The method for preparing a Chinese medicine gel patch for treating menstrual disorders according to claim 6, characterized in that: In step 1), the pH value of the hydrogel is 6.5-7.

5.

8. A method for preparing a Chinese medicine gel patch for treating menstrual disorders according to claim 6 or 7, characterized in that: The preparation steps of microcapsules for treating menstrual disorders are as follows: a) adding polylactic acid-hydroxybenzaldehyde copolymer powder into dichloromethane and stirring until completely dissolved to obtain a wall material solution; b) dispersing the red date pulp extract, motherwort extract, lindera stolonifera extract, wormwood extract, and codonopsis pilosula extract in order by weight in water, adding ginger essential oil and rose essential oil dropwise after evenly dispersing, and mixing to obtain a core material solution; c) slowly adding the core material solution to the wall material solution in a stirring state, and after completely mixing, a primary emulsion is obtained, and the primary emulsion is added to an aqueous solution containing a plasticizer and a cross-linking agent, and stirred to form a crude microcapsule product; d) evaporating and centrifuging the crude microcapsules, washing and drying them to obtain microcapsules for treating menstrual disorders.

9. The method for preparing a Chinese medicine gel patch for treating menstrual disorders according to claim 8, characterized in that: The evaporation in step d) is performed by rotary evaporation at a temperature of 32-35°C.

10. A method for preparing a Chinese medicine gel patch for treating menstrual disorders according to claim 8 or 9, characterized in that: The drying in step d) is carried out by freeze drying.

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