A traditional Chinese medicine gel, a preparation method thereof and application of the traditional Chinese medicine gel in treatment of acne with internal retention of dampness

Abstract

This invention relates to the field of pharmaceutical technology. The invention provides a traditional Chinese medicine gel, comprising, by weight percentage: 0.5-5% traditional Chinese medicine exosomes, 5-15% traditional Chinese medicine extracts, 10-25% gel matrix, 1-5% transdermal penetration enhancer, 2-8% moisturizer, 0.1-0.5% preservative, 0.05-0.3% pH adjuster, and the balance deionized water. The traditional Chinese medicine gel prepared using the technical solution of this invention uses traditional Chinese medicine exosomes as the core active ingredient, combined with traditional Chinese medicine extracts, and leverages the advantages of a gel formulation to achieve highly efficient transdermal absorption of the active ingredients. It can specifically treat acne caused by internal dampness, and is highly safe, stable, and easy to use.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a traditional Chinese medicine gel, its preparation method, and its application in treating acne caused by internal dampness. Background Technology

[0002] Acne is a common chronic inflammatory disease of the hair follicles and sebaceous glands, mainly affecting adolescents. Clinically, it is characterized by polymorphic skin lesions, primarily on the face, including comedones, papules, pustules, and nodules. In severe cases, it can lead to acute suppurative lesions, scarring, and even affect the patient's mental health, causing psychological problems such as low self-esteem and anxiety. Traditional Chinese medicine (TCM) classifies acne into various syndromes, among which the dampness-heat syndrome is a common clinical pattern. This is often caused by a habitual consumption of spicy and stimulating foods that damage the spleen and stomach, leading to impaired spleen function and the generation of dampness, or by kidney yang deficiency, which fails to warm and nourish the spleen yang, resulting in the accumulation of dampness, which transforms into heat, causing tissue decay and acne formation. Typical symptoms include excessive facial oiliness, rashes mainly consisting of red papules and comedones, accompanied by itching and pain, a pale tongue with teeth marks on the edges, a thin white coating, and a slippery pulse. Some patients also experience loose stools.

[0003] Currently, there are many types of products available for the clinical treatment of acne, including Western medicine topical preparations and traditional Chinese medicine topical preparations. While Western medicine topical preparations have a faster onset of action, they suffer from problems such as strong irritation, easy development of drug resistance, and high recurrence rate, and are not very effective against acne caused by internal dampness. Traditional Chinese medicine topical preparations are mostly ointments and lotions, which have drawbacks such as poor transdermal absorption of active ingredients, unsatisfactory efficacy, and inconvenience of use.

[0004] In recent years, research on exosomes of traditional Chinese medicine has gradually increased. These exosomes not only possess the pharmacological activity of traditional Chinese medicine but also improve the bioavailability of active ingredients and reduce adverse reactions. Based on this, and considering the pathogenesis of acne caused by internal dampness, this study screens traditional Chinese medicines with spleen-strengthening, dampness-eliminating, heat-clearing, detoxifying, nodule-dispersing, and acne-reducing effects. The exosomes and active ingredients are then extracted from these herbs to prepare a gel product with good transdermal properties, significant efficacy, and high safety, which is key to overcoming the shortcomings of existing technologies. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine gel, which uses traditional Chinese medicine exosomes as the core active ingredient, combined with traditional Chinese medicine extracts, and combines the advantages of gel formulation to achieve targeted treatment of acne caused by internal dampness.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a traditional Chinese medicine gel, comprising the following raw materials: 0.5-5% traditional Chinese medicine exosomes, 5-15% traditional Chinese medicine extracts, 10-25% gel matrix, 1-5% transdermal penetration enhancer, 2-8% moisturizer, 0.1-0.5% preservative, 0.05-0.3% pH adjuster, and the balance being deionized water.

[0007] Preferably, the components of the herbal exosomes include any two or more of the following: Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica; and the components of the herbal extracts include any two or more of the following: Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea.

[0008] Preferably, when the components of the Chinese herbal medicine exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica, the mass ratio of Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica is (2-3):(1-2):(1-1.5):0.5.

[0009] Preferably, when the components of the herbal extract are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea, the mass ratio of Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea is (2.5-3.5):(1-2):(0.5-1.5):1:1:(2.5-3.5).

[0010] Preferably, the gel matrix includes any one or more of carbomer 940, hydroxypropyl methylcellulose, and xanthan gum; the transdermal penetration enhancer includes any one or more of menthol, borneol, and azone; the moisturizer includes any one or more of glycerin, propylene glycol, and sodium hyaluronate; the preservative is phenoxyethanol or ethylparaben; and the pH adjuster is triethanolamine or citric acid.

[0011] The present invention also provides a method for preparing the traditional Chinese medicine gel, comprising the following steps: (1) Mix the gel matrix with 1 / 3 volume of deionized water to swell and obtain a gel matrix solution; (2) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, moisturizers and preservatives in sequence, and mix to obtain a mixed active solution; (3) Add the mixed active liquid and transdermal accelerator to the gel matrix solution in sequence, and stir to obtain system 1; (4) Add pH adjuster and remaining deionized water to system 1, stir and degas to obtain the final product.

[0012] Preferably, the method for preparing the Chinese herbal exosomes includes the following steps: pulverizing the components of the Chinese herbal exosomes, adding water and decocting to obtain extract A, then collecting the supernatant by differential centrifugation; filtering the supernatant through a filter membrane and then centrifuging at high speed to collect the precipitate; resuspending the precipitate with PBS buffer, extracting with a gradient sucrose solution medium, centrifuging and collecting the precipitate; resuspending the precipitate again with PBS buffer and freeze-drying to obtain the final product.

[0013] Preferably, the differential centrifugation method involves centrifuging extract A sequentially at 2500-3500 r / min for 10-18 min, 5000-6000 r / min for 25-30 min, and 10000-12000 r / min for 40-55 min.

[0014] Preferably, the concentration range of the gradient sucrose solution is 8wt%-60wt%.

[0015] Preferably, the swelling time in step (1) is 20-25 h; the stirring speed in step (3) is 300-500 r / min, and the stirring time is 5-10 min.

[0016] This invention also provides the application of the traditional Chinese medicine gel in the treatment of acne caused by internal dampness.

[0017] By adopting the above technical solution, the present invention has the following beneficial effects: This invention combines the TCM pathogenesis of acne caused by internal dampness with the extraction of exosomes from herbs such as Smilax glabra, Plantago asiatica, and Alisma plantago-aquatica. These exosomes are then combined with extracts from herbs such as Viola yedoensis, Fritillaria thunbergii, and Portulaca oleracea, which are known for their heat-clearing, dampness-eliminating, detoxifying, and nodule-dispersing properties. This combination of herbs precisely addresses the pathogenesis of "excessive dampness, excessive heat, and blood stasis," providing targeted treatment for acne caused by internal dampness and improving symptoms such as oily skin, papules, and pustules, with significant therapeutic effects.

[0018] With exosomes of traditional Chinese medicine as the core active ingredient, combined with extracts of traditional Chinese medicine and the advantages of gel formulation, it can effectively penetrate the skin's stratum corneum barrier, promote transdermal absorption and targeted delivery of active ingredients, improve bioavailability, and solve the problems of poor transdermal absorption and unsatisfactory efficacy of traditional topical Chinese medicine preparations.

[0019] The traditional Chinese medicine gel prepared by the technical solution of this invention has high safety. Safety tests have verified that it is non-irritating to the skin, non-sensitizing, and has few adverse reactions. It also has good stability. Accelerated stability and long-term stability tests have verified that after 12 months of storage at room temperature, its properties, content, and pH value do not change significantly. It has a long shelf life and is easy to store and use. Detailed Implementation

[0020] This invention provides a traditional Chinese medicine gel, comprising, by weight percentage, the following raw materials: 0.5-5% traditional Chinese medicine exosomes, 5-15% traditional Chinese medicine extract, 10-25% gel matrix, 1-5% transdermal penetration enhancer, 2-8% humectant, 0.1-0.5% preservative, 0.05-0.3% pH adjuster, and the balance deionized water; a further preferred formulation comprises: 0.8-4.5% traditional Chinese medicine exosomes, 8-14% traditional Chinese medicine extract, 12-23% gel matrix, 1.5-4.5% transdermal penetration enhancer, 3-7% humectant, 0.2-0.4% preservative, 0.08-0.25% pH adjuster, and the balance deionized water; an even more preferred formulation comprises: 3.5% traditional Chinese medicine exosomes, 12% traditional Chinese medicine extract, 20% gel matrix, 4.2% transdermal penetration enhancer, 6% humectant, 0.3% preservative, 0.15% pH adjuster, and the balance deionized water.

[0021] In this invention, the components of the herbal exosomes include any two or more of the following: Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica.

[0022] In this invention, the Smilax glabra has the effects of detoxification, dampness removal and joint mobility promotion. Its active ingredients (such as astilbin and flavonoids) may improve acne symptoms through mechanisms such as anti-inflammation, inhibition of Propionibacterium acnes growth and regulation of sebum metabolism.

[0023] In this invention, the white hyacinth bean strengthens the spleen and eliminates dampness, harmonizes the stomach and relieves summer heat. It is also rich in zinc, vitamin E and amino acids, which help skin repair, anti-oxidation and collagen synthesis, and have a certain lightening effect on post-acne pigmentation. The phytohemagglutinin and flavonoids it contains can inhibit common skin pathogens such as Staphylococcus aureus.

[0024] In this invention, the Alisma plantago-aquatica has the functions of promoting diuresis and eliminating dampness, clearing heat and promoting urination. It also contains saponin compounds that have anti-inflammatory effects, which can reduce local redness and inflammation caused by allergies and may have a mild sedative effect on mild skin allergies. It can also be used to promote diuresis and eliminate dampness, and to treat edema.

[0025] In this invention, the Plantago seed promotes urination, eliminates dampness, and stops diarrhea; it contains flavonoids, polysaccharides, and other active ingredients, possessing anti-inflammatory, antibacterial, and antioxidant properties, which help alleviate skin sensitivity, acne, and other problems; its mucilage can form a protective film, locking in moisture and improving dry skin. The four herbs mentioned in this invention—Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago seed—are all high-quality traditional Chinese medicines for regulating internal dampness. Their exosomes not only carry the active ingredients of these herbs but also enhance transdermal absorption, synergistically exerting the effects of promoting diuresis, resolving lumps, detoxifying, and reducing swelling, specifically improving symptoms such as facial oiliness and papules in acne caused by internal dampness.

[0026] In this invention, the components of the traditional Chinese medicine extract include any two or more of the following: Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea.

[0027] In this invention, the Viola yedoensis contains active ingredients such as flavonoids, organic acids, and volatile oils, possessing antibacterial, anti-inflammatory, antiviral, and immunomodulatory effects. It is suitable for the adjunctive treatment of mild skin infections, folliculitis, boils, and other problems, and also has the effects of clearing heat and detoxifying, cooling blood and dispersing blood stasis. The combination of Viola yedoensis, dandelion, and purslane in this invention enhances the heat-clearing and detoxifying effects, better addressing the redness and infection problems of acne.

[0028] In this invention, the Sophora flavescens contains matrine, oxymatrine, etc., which have antibacterial and anti-inflammatory effects on common pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, and Candida albicans. It also helps to shrink pores, regulate sebum secretion, and improve oily skin and acne problems.

[0029] In this invention, Fritillaria thunbergii has the effects of clearing heat and resolving phlegm, dispersing nodules and reducing swelling, and antibacterial and anti-inflammatory properties. When combined with other herbs, it aligns with the pathogenesis of acne caused by internal dampness, characterized by "excessive dampness, excessive heat, and blood stasis." Furthermore, its synergistic effect with exosomes enhances the efficacy of clearing heat and detoxifying, promoting diuresis and dispersing nodules, and relieving acne and itching, thereby improving the therapeutic effect.

[0030] In this invention, when the components of the Chinese herbal medicine exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica, the preferred mass ratio of Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica is (2-3):(1-2):(1-1.5):0.5, further preferably (2.2-2.8):(1.2-1.8):(1.1-1.4):0.5, and even more preferably 2.5:1.5:1.2:0.5.

[0031] In this invention, when the components of the traditional Chinese medicine extract are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea, the preferred mass ratio of Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea is (2.5-3.5):(1-2):(0.5-1.5):1:1:(2.5-3.5), further preferably (2.8-3.2):(1.2-1.8):(0.8-1.3):1:1:(2.8-3.2), and even more preferably 3:1.6:1.2:1:1:3.

[0032] In this invention, the gel matrix includes any one or more of carbomer 940, hydroxypropyl methylcellulose, and xanthan gum; more preferably, it is hydroxypropyl methylcellulose. The gel matrix of this invention has good water solubility and film-forming properties, and can enhance the moisturizing and adhesion properties of the gel.

[0033] In this invention, the transdermal penetration enhancer includes any one or more of menthol, borneol, and azone; more preferably, azone. The transdermal penetration enhancer of this invention can reduce the barrier function of the stratum corneum, significantly increase the transdermal penetration rate and cumulative transdermal amount of active ingredients, and ensure that the exosomes and extracts of traditional Chinese medicine can effectively penetrate into the hair follicle sebaceous glands to exert their therapeutic effects.

[0034] In this invention, the moisturizer includes any one or more of glycerin, propylene glycol, and sodium hyaluronate; more preferably, propylene glycol. The moisturizer of this invention has excellent moisturizing properties, replenishes skin moisture, improves dry skin, and reduces pigmentation after acne healing.

[0035] In this invention, the preservative is phenoxyethanol or ethylparaben, and more preferably phenoxyethanol.

[0036] In this invention, the pH adjuster is triethanolamine or citric acid.

[0037] The present invention also provides a method for preparing the traditional Chinese medicine gel, comprising the following steps: (1) Mix the gel matrix with 1 / 3 volume of deionized water to swell and obtain a gel matrix solution; (2) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, moisturizers and preservatives in sequence, and mix to obtain a mixed active solution; (3) Add the mixed active liquid and transdermal accelerator to the gel matrix solution in sequence, and stir to obtain system 1; (4) Add pH adjuster and remaining deionized water to system 1, stir and degas to obtain the final product.

[0038] In this invention, the gel matrix is ​​mixed with 1 / 3 volume of deionized water to swell, and the swelling time is preferably 20-25h, more preferably 21-24h, and even more preferably 22h.

[0039] In this invention, the preparation method of the Chinese herbal exosomes includes the following steps: the components of the Chinese herbal exosomes are crushed and decocted with water to obtain extract A, and then the supernatant is collected by differential centrifugation; the supernatant is filtered through a filter membrane and then centrifuged at high speed, and the precipitate is collected; the precipitate is resuspended with PBS buffer, and extracted with a gradient sucrose solution medium, centrifuged and the precipitate is collected; the precipitate is resuspended with PBS buffer again and freeze-dried to obtain the final product.

[0040] In this invention, the components of the exosomes of traditional Chinese medicine are pulverized and then decocted with water to obtain extract A. The amount of deionized water added is preferably sufficient to cover the surface of the medicinal materials, allowing for thorough soaking and meeting the requirements of decoction, ensuring the full dissolution of the effective components of the medicinal materials. In this invention, after adding water, it is preferable to first soak the herbs before decocting. The soaking time is preferably 1-2 hours, more preferably 1.2-1.8 hours, and even more preferably 1.5 hours. The decoction time is preferably 1-1.5 hours per decoction, more preferably 1.1-1.4 hours per decoction, and even more preferably 1.3 hours per decoction. The number of decoctions is preferably 2-3 times.

[0041] In this invention, the above-mentioned extract A is subjected to differential centrifugation to remove precipitates (impurities, cell debris, etc.) and the supernatant is collected. The differential centrifugation method of the present invention preferably involves centrifuging extract A sequentially at 2500-3500 r / min for 10-18 min, at 5000-6000 r / min for 25-30 min, and at 10000-12000 r / min for 40-55 min. Specifically, the first centrifugation speed is further preferably 2800-3200 r / min, and even more preferably 3000 r / min; the first centrifugation time is further preferably 10-18 min, and even more preferably 15 min; the second centrifugation speed is further preferably 5200-5800 r / min, and even more preferably 5500 r / min; the second centrifugation time is further preferably 26-28 min, and even more preferably 27 min; the third centrifugation speed is further preferably 10500-11500 r / min, and even more preferably 11000 r / min; the third centrifugation time is further preferably 45-52 min, and even more preferably 50 min.

[0042] In this invention, the supernatant is filtered through a membrane to further remove impurities, then ultracentrifuged, and the precipitate is collected. The filter membrane of this invention preferably has a micrometer diameter of 0.22 μm. The ultracentrifugation speed is preferably 110,000-130,000 g, more preferably 115,000-125,000 g, and even more preferably 120,000 g; the ultracentrifugation time is preferably 9-12 h, more preferably 9.5-11 h, and even more preferably 10 h.

[0043] In this invention, the precipitate is resuspended in PBS buffer and extracted and centrifuged using a gradient sucrose solution medium. The concentration range of the gradient sucrose solution is preferably 8wt%-60wt%, more preferably 8wt%, 30wt%, 45wt%, and 60wt%; the centrifugation speed is preferably 110,000-130,000g, more preferably 115,000-125,000g, and even more preferably 120,000g; the centrifugation time is preferably 12-15h, more preferably 13-14.5h, and even more preferably 14h.

[0044] In this invention, after centrifugation, preferably, a 30%-40% volumetric layer solution is centrifuged to wash away the sucrose, and the precipitate is collected. The centrifugation speed is preferably 120,000-180,000 g, more preferably 130,000-170,000 g, and even more preferably 150,000 g; the centrifugation time is preferably 12-15 h, more preferably 13-14 h, and even more preferably 13.5 h.

[0045] In this invention, the preparation method of the traditional Chinese medicine extract includes the following steps: the components of the pulverized traditional Chinese medicine extract are mixed with ethanol at a material-to-liquid ratio of 1g:(10-15)mL, then refluxed for extraction, concentrated under reduced pressure, vacuum dried, and pulverized to obtain the traditional Chinese medicine extract.

[0046] In this invention, the volume concentration of ethanol is preferably 70-80%, more preferably 72-78%, and even more preferably 75%.

[0047] In this invention, the preferred ratio of the components of the herbal extract to ethanol is 1g:(10-15)mL, more preferably 1g:(11-14)mL, and even more preferably 1g:12mL; the preferred reflux extraction time is 1.5-2h / time, more preferably 1.6-1.9h / time, and even more preferably 1.8h / time; the preferred number of reflux extractions is 2-3 times.

[0048] In this invention, a mixed active liquid and a transdermal penetration enhancer are added sequentially to a gel matrix solution and stirred to obtain system 1. The stirring speed is preferably 300-500 r / min, more preferably 350-450 r / min, and even more preferably 400 r / min. The stirring time is preferably 5-10 min, more preferably 6-9 min, and even more preferably 8 min.

[0049] In this invention, the pH is preferably adjusted to 6.0-7.0.

[0050] This invention also provides the application of the traditional Chinese medicine gel in the treatment of acne caused by internal dampness.

[0051] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0052] Example 1

[0053] A traditional Chinese medicine gel for treating acne caused by internal dampness, comprising the following ingredients by weight percentage: The composition includes 3.5% exosomes of traditional Chinese medicine, 12% extracts of traditional Chinese medicine, 20% hydroxypropyl methylcellulose, 4.2% azone, 6% propylene glycol, 0.3% phenoxyethanol, 0.15% pH adjuster, and the remainder deionized water. The components of the herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica in a mass ratio of 2.5:1.5:1.2:0.5; the components of the herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea in a mass ratio of 3:1.6:1.2:1:1:3.

[0054] Example 2

[0055] A traditional Chinese medicine gel for treating acne caused by internal dampness, comprising the following ingredients by weight percentage: The composition includes: 4.5% exosomes of traditional Chinese medicine, 10% extract of traditional Chinese medicine, 22% hydroxypropyl methylcellulose, 4% azone, 5% propylene glycol, 0.2% phenoxyethanol, 0.12% pH adjuster, and the remainder deionized water; The components of the herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica in a mass ratio of 2.5:1.5:1.2:0.5; the components of the herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea in a mass ratio of 3:1.6:1.2:1:1:3.

[0056] Example 3

[0057] A traditional Chinese medicine gel for treating acne caused by internal dampness, comprising the following ingredients by weight percentage: The composition includes 3% exosomes of traditional Chinese medicine, 13% extracts of traditional Chinese medicine, 18% hydroxypropyl methylcellulose, 3.5% azone, 4% propylene glycol, 0.3% phenoxyethanol, 0.16% pH adjuster, and the remainder deionized water. The components of the herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica in a mass ratio of 2.5:1.5:1.2:0.5; the components of the herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea in a mass ratio of 3:1.6:1.2:1:1:3.

[0058] Example 4

[0059] A traditional Chinese medicine gel for treating acne caused by internal dampness, comprising the following ingredients by weight percentage: The composition includes 3.5% exosomes of traditional Chinese medicine, 12% extracts of traditional Chinese medicine, 20% hydroxypropyl methylcellulose, 4.2% azone, 6% propylene glycol, 0.3% phenoxyethanol, 0.15% pH adjuster, and the remainder deionized water. The components of the herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica in a mass ratio of 2:1.5:1:0.5; the components of the herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea in a mass ratio of 3.5:1.6:1.5:1:1:2.5.

[0060] Example 4

[0061] The preparation method of the traditional Chinese medicine gel described in Example 1 includes the following steps: (1) Preparation of exosomes from traditional Chinese medicine: Take the components of the exosomes from traditional Chinese medicine, wash and crush them, add deionized water, enough to cover the surface of the medicinal materials, fully soak them and meet the requirements for decoction, soak at room temperature for 1.5 h, decoct twice, 1.3 h each time, combine the decoctions, filter to obtain extract A; centrifuge extract A sequentially at 3000 r / min for 15 min, 5500 r / min for 27 min, and 11000 r / min for 50 min to remove the precipitate and collect the supernatant; sift the supernatant through a 0.22 The sample was filtered through a μm filter membrane to further remove impurities. Then, it was centrifuged at 120,000g for 10 hours using ultracentrifugation, and the precipitate was collected. The precipitate was resuspended in PBS buffer and then extracted sequentially with a gradient of 8wt%, 30wt%, 45wt%, and 60wt% sucrose solutions. After centrifugation at 120,000g for 14 hours, 30%-40% of the volumetric layer solution was centrifuged at 150,000g for 13.5 hours to wash away the sucrose. Finally, the precipitate was resuspended in PBS buffer to obtain a suspension of traditional Chinese medicine exosomes, which was then freeze-dried to obtain the final product. (2) Preparation of Chinese herbal extract: Mix the components of the Chinese herbal extract, pulverize them and add 75% ethanol solution at a material-to-liquid ratio of 1g:12mL. Reflux and extract twice, 1.8h each time. Combine the extracts, concentrate under reduced pressure until there is no alcohol taste, dry under vacuum, and pulverize into fine powder to obtain the Chinese herbal extract. (3) Mix hydroxypropyl methylcellulose with 1 / 3 volume of deionized water and let it swell for 22 hours. Stir until homogeneous to obtain a hydroxypropyl methylcellulose solution. (4) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, propylene glycol and phenoxyethanol in sequence, mix and stir to dissolve, and obtain a mixed active solution; (5) Slowly add the mixed active solution to the hydroxypropyl methylcellulose solution while stirring. Stir at 400 r / min for 8 min, then add azone and continue stirring until the system is uniform and fine to obtain system 1. (6) Add pH adjuster to system 1 to adjust pH value to 6.0-7.0, add the remaining deionized water, stir evenly, degas, and the product is obtained.

[0062] Example 5

[0063] The preparation method of the traditional Chinese medicine gel described in Example 1 includes the following steps: (1) Preparation of exosomes from traditional Chinese medicine: Take the components of the exosomes from traditional Chinese medicine, wash and crush them, add deionized water, enough to cover the surface of the medicinal materials, fully soak them and meet the requirements for decoction, soak at room temperature for 1 hour, then decoct twice, 1.5 hours each time, combine the decoctions, filter, and obtain extract A; centrifuge extract A sequentially at 3500 r / min for 10 min, 6000 r / min for 25 min, and 10000 r / min for 55 min to remove the precipitate and collect the supernatant; sift the supernatant through 0.2 The mixture was filtered through a 2μm filter membrane to further remove impurities. Then, it was centrifuged at 110,000g for 9 hours using ultracentrifugation, and the precipitate was collected. The precipitate was resuspended in PBS buffer and then extracted sequentially with a gradient of 8wt%, 30wt%, 45wt%, and 60wt% sucrose solutions. After centrifugation at 110,000g for 12 hours, 30%-40% of the volumetric layer solution was centrifuged at 120,000g for 12 hours to wash away the sucrose. Finally, the precipitate was resuspended in PBS buffer to obtain a suspension of exosomes from traditional Chinese medicine. The suspension was then freeze-dried to obtain the final product. (2) Preparation of Chinese herbal extract: Mix the components of the Chinese herbal extract, pulverize them and add 70% ethanol solution at a material-to-liquid ratio of 1g:10mL. Reflux and extract twice, 1.5h each time. Combine the extracts, concentrate under reduced pressure until there is no alcohol taste, dry under vacuum, and pulverize into fine powder to obtain the Chinese herbal extract. (3) Mix hydroxypropyl methylcellulose with 1 / 3 volume of deionized water and let it swell for 24 hours. Stir until homogeneous to obtain a hydroxypropyl methylcellulose solution. (4) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, propylene glycol and phenoxyethanol in sequence, mix and stir to dissolve, and obtain a mixed active solution; (5) Slowly add the mixed active solution to the hydroxypropyl methylcellulose solution while stirring. Stir at 500 r / min for 10 min, then add azone and continue stirring until the system is uniform and fine to obtain system 1. (6) Add pH adjuster to system 1 to adjust pH value to 6.0-7.0, add the remaining deionized water, stir evenly, degas, and the product is obtained.

[0064] Example 6

[0065] The preparation method of the traditional Chinese medicine gel described in Example 2 is as follows: (1) Preparation of exosomes from traditional Chinese medicine: Take the components of the exosomes from traditional Chinese medicine, wash and crush them, add deionized water, enough to cover the surface of the medicinal materials, fully soak them and meet the requirements for decoction, soak at room temperature for 1.5 h, decoct twice, 1.3 h each time, combine the decoctions, filter to obtain extract A; centrifuge extract A sequentially at 3000 r / min for 15 min, 5500 r / min for 27 min, and 11000 r / min for 50 min to remove the precipitate and collect the supernatant; sift the supernatant through a 0.22 The sample was filtered through a μm filter membrane to further remove impurities. Then, it was centrifuged at 120,000g for 10 hours using ultracentrifugation, and the precipitate was collected. The precipitate was resuspended in PBS buffer and then extracted sequentially with a gradient of 8wt%, 30wt%, 45wt%, and 60wt% sucrose solutions. After centrifugation at 120,000g for 14 hours, 30%-40% of the volumetric layer solution was centrifuged at 150,000g for 13.5 hours to wash away the sucrose. Finally, the precipitate was resuspended in PBS buffer to obtain a suspension of traditional Chinese medicine exosomes, which was then freeze-dried to obtain the final product. (2) Preparation of Chinese herbal extract: Mix the components of the Chinese herbal extract, pulverize them and add 75% ethanol solution at a material-to-liquid ratio of 1g:12mL. Reflux and extract twice, 1.8h each time. Combine the extracts, concentrate under reduced pressure until there is no alcohol taste, dry under vacuum, and pulverize into fine powder to obtain the Chinese herbal extract. (3) Mix hydroxypropyl methylcellulose with 1 / 3 volume of deionized water and let it swell for 22 hours. Stir until homogeneous to obtain a hydroxypropyl methylcellulose solution. (4) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, propylene glycol and phenoxyethanol in sequence, mix and stir to dissolve, and obtain a mixed active solution; (5) Slowly add the mixed active solution to the hydroxypropyl methylcellulose solution while stirring. Stir at 400 r / min for 8 min, then add azone and continue stirring until the system is uniform and fine to obtain system 1. (6) Add pH adjuster to system 1 to adjust pH value to 6.0-7.0, add the remaining deionized water, stir evenly, degas, and the product is obtained.

[0066] Example 7

[0067] The preparation method of the traditional Chinese medicine gel described in Example 3 is as follows: (1) Preparation of exosomes from traditional Chinese medicine: Take the components of the exosomes from traditional Chinese medicine, wash and crush them, add deionized water, enough to cover the surface of the medicinal materials, fully soak them and meet the requirements for decoction, soak at room temperature for 1.5 h, decoct twice, 1.3 h each time, combine the decoctions, filter to obtain extract A; centrifuge extract A sequentially at 3000 r / min for 15 min, 5500 r / min for 27 min, and 11000 r / min for 50 min to remove the precipitate and collect the supernatant; sift the supernatant through a 0.22 The sample was filtered through a μm filter membrane to further remove impurities. Then, it was centrifuged at 120,000g for 10 hours using ultracentrifugation, and the precipitate was collected. The precipitate was resuspended in PBS buffer and then extracted sequentially with a gradient of 8wt%, 30wt%, 45wt%, and 60wt% sucrose solutions. After centrifugation at 120,000g for 14 hours, 30%-40% of the volumetric layer solution was centrifuged at 150,000g for 13.5 hours to wash away the sucrose. Finally, the precipitate was resuspended in PBS buffer to obtain a suspension of traditional Chinese medicine exosomes, which was then freeze-dried to obtain the final product. (2) Preparation of Chinese herbal extract: Mix the components of the Chinese herbal extract, pulverize them and add 75% ethanol solution at a material-to-liquid ratio of 1g:12mL. Reflux and extract twice, 1.8h each time. Combine the extracts, concentrate under reduced pressure until there is no alcohol taste, dry under vacuum, and pulverize into fine powder to obtain the Chinese herbal extract. (3) Mix hydroxypropyl methylcellulose with 1 / 3 volume of deionized water and let it swell for 22 hours. Stir until homogeneous to obtain a hydroxypropyl methylcellulose solution. (4) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, propylene glycol and phenoxyethanol in sequence, mix and stir to dissolve, and obtain a mixed active solution; (5) Slowly add the mixed active solution to the hydroxypropyl methylcellulose solution while stirring. Stir at 400 r / min for 8 min, then add azone and continue stirring until the system is uniform and fine to obtain system 1. (6) Add pH adjuster to system 1 to adjust pH value to 6.0-7.0, add the remaining deionized water, stir evenly, degas, and the product is obtained.

[0068] Example 8

[0069] The preparation method of the traditional Chinese medicine gel described in Example 4 is as follows: (1) Preparation of exosomes from traditional Chinese medicine: Take the components of the exosomes from traditional Chinese medicine, wash and crush them, add deionized water, enough to cover the surface of the medicinal materials, fully soak them and meet the requirements for decoction, soak at room temperature for 1.5 h, decoct twice, 1.3 h each time, combine the decoctions, filter to obtain extract A; centrifuge extract A sequentially at 3000 r / min for 15 min, 5500 r / min for 27 min, and 11000 r / min for 50 min to remove the precipitate and collect the supernatant; sift the supernatant through a 0.22 The sample was filtered through a μm filter membrane to further remove impurities. Then, it was centrifuged at 120,000g for 10 hours using ultracentrifugation, and the precipitate was collected. The precipitate was resuspended in PBS buffer and then extracted sequentially with a gradient of 8wt%, 30wt%, 45wt%, and 60wt% sucrose solutions. After centrifugation at 120,000g for 14 hours, 30%-40% of the volumetric layer solution was centrifuged at 150,000g for 13.5 hours to wash away the sucrose. Finally, the precipitate was resuspended in PBS buffer to obtain a suspension of traditional Chinese medicine exosomes, which was then freeze-dried to obtain the final product. (2) Preparation of Chinese herbal extract: Mix the components of the Chinese herbal extract, pulverize them and add 75% ethanol solution at a material-to-liquid ratio of 1g:12mL. Reflux and extract twice, 1.8h each time. Combine the extracts, concentrate under reduced pressure until there is no alcohol taste, dry under vacuum, and pulverize into fine powder to obtain the Chinese herbal extract. (3) Mix hydroxypropyl methylcellulose with 1 / 3 volume of deionized water and let it swell for 22 hours. Stir until homogeneous to obtain a hydroxypropyl methylcellulose solution. (4) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, propylene glycol and phenoxyethanol in sequence, mix and stir to dissolve, and obtain a mixed active solution; (5) Slowly add the mixed active solution to the hydroxypropyl methylcellulose solution while stirring. Stir at 400 r / min for 8 min, then add azone and continue stirring until the system is uniform and fine to obtain system 1. (6) Add pH adjuster to system 1 to adjust pH value to 6.0-7.0, add the remaining deionized water, stir evenly, degas, and the product is obtained.

[0070] Comparative Example 1

[0071] Similar to Example 5, only the Chinese medicine exosomes and the process of preparing Chinese medicine exosomes in step (1) are removed.

[0072] Comparative Example 2

[0073] Similar to Example 5, only the Chinese herbal extract and the process of preparing the Chinese herbal extract in step (2) are removed.

[0074] Comparative Example 3

[0075] Similar to Example 5, only the following is changed: "The components of the Chinese herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica in a mass ratio of 2.5:1.5:1.2:0.5; the components of the Chinese herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea in a mass ratio of 3:1.6:1.2:1:1:3" to "The components of the Chinese herbal exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica, and Plantago asiatica in a mass ratio of 1:1:1:0.5; the components of the Chinese herbal extracts are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea in a mass ratio of 1:1:1:1:1:1".

[0076] Experimental Example 1

[0077] The following tests were conducted on the gel products prepared in Examples 5-8 and Comparative Examples 1-3.

[0078] (a) Safety test

[0079] Ninety Kunming mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into nine groups: Example 5, Example 6, Example 7, Example 8, Comparative Example 1, Comparative Example 2, Comparative Example 3, Negative Control Group (physiological saline), and Positive Control Group (2,4-dinitrochlorobenzene), with ten mice in each group.

[0080] The backs of mice were shaved (approximately 2cm × 2cm area). Each example group and comparative group was coated with 0.2g of the prepared gel product per mouse. The negative control group was coated with an equal volume of physiological saline, and the positive control group was coated with 0.1% 2,4-dinitrochlorobenzene solution. The mice were sensitized three times, with each exposure lasting 24 hours and an interval of 2 days. 24 hours after the last sensitization exposure, the mice were observed for sensitization reactions such as erythema, edema, and papules, and the sensitization rate was calculated.

[0081] Sensitization rate (%) = (Number of mice exhibiting sensitized skin reaction / Initial number of mice) × 100%

[0082] The results showed that the mice in each of the example groups and the comparative group had no skin sensitization reaction, with a sensitization rate of 0%. The negative control group had no sensitization reaction, while the positive control group had a sensitization rate of 100%, indicating that the gel products prepared in each example and the comparative group had no skin sensitization.

[0083] (ii) Stability test

[0084] Accelerated stability testing and long-term stability testing were used to conduct product stability tests.

[0085] Accelerated stability test: The gel products prepared in Examples 5-8 and Comparative Examples 1-3 were placed in a constant temperature and humidity chamber at 40±2℃ and 75%±5% relative humidity for 6 months. Samples were taken at 0, 1, 2, 3 and 6 months to observe the properties (color, uniformity, consistency) of the test samples and to determine the pH value.

[0086] Long-term stability test: The gel products prepared in Examples 5-8 and Comparative Examples 1-3 were placed in a constant temperature and humidity chamber at 25±2℃ and 60%±5% relative humidity for 12 months. Samples were taken at 0, 3, 6, 9 and 12 months respectively to test the above indicators.

[0087] The results showed that after 6 months of accelerated stability testing, the gel products in each group had uniform color, no stratification, no precipitation, and the pH value remained between 6.0 and 7.0. After 12 months of long-term stability testing, the gel products in each group showed no significant changes in properties, the pH value met the requirements, and there was no significant degradation. This indicates that the gel product described in this invention has good stability and can maintain its performance and efficacy for a long time under specified storage conditions, with a shelf life of more than 12 months, meeting the stability requirements of topical preparations.

[0088] Experimental Example 2

[0089] Mouse model experiments were conducted based on the gel products prepared in Examples 5-8 and Comparative Examples 1-3.

[0090] A mouse acne model was induced using Propionibacterium acnes (ATCC6919, purchased from the ATCC website). Mice were placed in an environment with a temperature of 35±1℃ and a relative humidity of 85±5% for 6 hours daily for 14 consecutive days. Starting from day 12, 0.1 mL of P. acnes suspension was injected intradermally into the right ear of each mouse (Kunming mice), while an equal volume of physiological saline was injected into the left ear as a blank control. This injection was repeated for 3 consecutive days to establish a mouse inflammatory acne model. After successful modeling, the right ear of the mice showed obvious swelling, redness, and erythema. Microscopic examination revealed infiltration of inflammatory cells such as macrophages and neutrophils, similar to human acne lesions, which can simulate the inflammatory response and skin lesions of acne with internal dampness.

[0091] Mice that successfully modeled the disease were randomly divided into a model control group, a positive control group, groups 5-8, and groups 1-3, with 10 mice in each group. The model control group was treated with saline solution, while groups 5-8 and groups 1-3 were treated with 0.2g / mouse of the corresponding prepared gel product. The positive control group was treated with 0.2g / mouse of adapalene gel. Treatment was administered once daily for 14 consecutive days. After 14 days of treatment, ear patches of the same area from the same location on both sides of the auricle were taken using a punch, and the degree of ear swelling was calculated. The serum levels of the inflammatory factors IL-1β and IL-8 in each group of mice were detected using ELISA.

[0092] Ear swelling degree = Right ear slice quality - Left ear slice quality

[0093] Table 1. Serum levels of inflammatory factors IL-1β and IL-8 in mice of each group.

[0094] The results showed that compared with the model control group, the swelling of the right ear of mice in Examples 5-8 and Comparative Examples 1-3 was significantly reduced, and the serum levels of IL-1β and IL-8 were significantly reduced. The effects of Examples 5-8 were comparable to those of the positive control group, with no significant adverse reactions (some mice in the positive control group experienced dry skin and desquamation). This indicates that the gel product of this invention can significantly reduce the inflammatory response of acne in mice, lower the levels of inflammatory factors, and has good anti-inflammatory and acne-reducing effects, with a safety profile superior to the positive control drug.

[0095] Experimental Example 3

[0096] Seventy patients clinically diagnosed with acne due to internal dampness were selected, including 42 males and 28 females, aged 15-30 years, with a disease course of 1-6 months. The main skin lesions were oily face, papules, and pustules; some patients also had nodules, accompanied by itching and pain. The tongue was pale or had teeth marks on the edges, with a thin white coating, and the pulse was slippery. Patients allergic to the ingredients of this invention, those with other skin diseases, or those who had recently used other acne treatments were excluded.

[0097] All patients used the gel products prepared in Examples 5-8 topically, twice a day (once in the morning and once in the evening). Before application, cleanse the face, apply the gel evenly to the acne area, and gently massage until absorbed. One course of treatment lasted for 4 weeks, and a total of 2 courses of treatment were performed.

[0098] The efficacy evaluation criteria for this trial were formulated based on the "Chinese Expert Consensus on Clinical Severity Grading and Efficacy Evaluation of Acne Vulgaris (2025 Edition)" and the acne lesion condition, as shown in Table 2.

[0099] Overall effective rate = (number of cured cases + number of cases with significant improvement + number of cases with improvement) / total number of cases × 100%.

[0100] Table 2. Evaluation Criteria for Therapeutic Effect

[0101] The results showed that after two courses of treatment, among the 70 patients, 35 (50%) were cured, 21 (30%) showed significant improvement, 7 (10%) showed improvement, and 7 (10%) showed no improvement, with a total effective rate of 90%. During the treatment, only one patient experienced mild skin redness, with no other adverse reactions; the symptoms subsided spontaneously after discontinuation of the medication. During a 3-month follow-up, 3 patients relapsed, significantly fewer than with traditional Chinese medicine gels. This indicates that the gel product of this invention is significantly effective in treating acne caused by internal dampness, with a low recurrence rate, high safety, and can effectively improve patients' clinical symptoms and skin condition.

[0102] In summary, the technical solution of this invention uses Chinese herbal exosomes as the core active ingredient, combined with Chinese herbal extracts, and combines the advantages of gel formulation to produce a gel with good transdermal properties, significant efficacy, high safety, and good stability. It can specifically treat acne caused by internal dampness and improve symptoms such as facial oiliness, papules, and pustules, with significant efficacy.

[0103] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine gel, characterized in that, By weight percentage, it includes the following ingredients: 0.5-5% exosomes of traditional Chinese medicine, 5-15% extracts of traditional Chinese medicine, 10-25% gel matrix, 1-5% transdermal penetration enhancer, 2-8% moisturizer, 0.1-0.5% preservative, 0.05-0.3% pH adjuster, and the balance deionized water.

2. The traditional Chinese medicine gel according to claim 1, characterized in that, The components of the Chinese herbal exosomes include any two or more of the following: Smilax glabra, white hyacinth bean, Alisma plantago-aquatica, and Plantago asiatica. The components of the herbal extract include any two or more of the following: Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea, and Portulaca oleracea.

3. The traditional Chinese medicine gel of claim 1, characterized in that, When the components of the Chinese herbal medicine exosomes are Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica, the mass ratio of Smilax glabra, Dolichos lablab, Alisma plantago-aquatica and Plantago asiatica is (2-3):(1-2):(1-1.5):0.5; When the components of the traditional Chinese medicine extract are Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea, the mass ratio of Viola yedoensis, Sophora flavescens, Fritillaria thunbergii, Taraxacum mongolicum, Atractylodes lancea and Portulaca oleracea is (2.5-3.5):(1-2):(0.5-1.5):1:1:(2.5-3.5).

4. The traditional Chinese medicine gel of claim 1, characterized in that, The gel matrix includes any one or more of carbomer 940, hydroxypropyl methylcellulose, and xanthan gum; The transdermal penetration enhancer includes any one or more of menthol, borneol, and azone. The moisturizing agent includes any one or more of glycerin, propylene glycol, and sodium hyaluronate; The preservative is phenoxyethanol or ethylparaben; The pH adjuster is triethanolamine or citric acid.

5. The preparation method of the traditional Chinese medicine gel according to any one of claims 1-4, characterized in that, Includes the following steps: (1) Mix the gel matrix with 1 / 3 volume of deionized water to swell and obtain a gel matrix solution; (2) Take 1 / 3 volume of deionized water, add Chinese herbal exosomes, Chinese herbal extracts, moisturizers and preservatives in sequence, and mix to obtain a mixed active solution; (3) Add the mixed active liquid and transdermal accelerator to the gel matrix solution in sequence, and stir to obtain system 1; (4) Add pH adjuster and remaining deionized water to system 1, stir and degas to obtain the final product.

6. The production method according to claim 5, wherein The preparation method of the Chinese herbal exosomes includes the following steps: the components of the Chinese herbal exosomes are crushed and decocted with water to obtain extract A, and then the supernatant is collected by differential centrifugation; the supernatant is filtered through a filter membrane and then centrifuged at high speed, and the precipitate is collected; the precipitate is resuspended with PBS buffer, and extracted with a gradient sucrose solution medium, centrifuged and the precipitate is collected; the precipitate is resuspended with PBS buffer again and freeze-dried to obtain the extract.

7. The preparation method according to claim 6, characterized in that, The differential centrifugation method involves sequentially centrifuging extract A at 2500-3500 r / min for 10-18 min, at 5000-6000 r / min for 25-30 min, and at 10000-12000 r / min for 40-55 min.

8. The preparation method according to claim 6, characterized in that, The concentration range of the gradient sucrose solution is 8wt%-60wt%.

9. The preparation method according to claim 5, characterized in that, The swelling time in step (1) is 20-25 hours; The stirring speed in step (3) is 300-500 r / min, and the stirring time is 5-10 min.

10. The use of the traditional Chinese medicine gel according to any one of claims 1-4, or the traditional Chinese medicine gel prepared by the preparation method according to any one of claims 5-9, in the treatment of acne caused by internal dampness.

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