Traditional Chinese medicine acne-removing cream and preparation method thereof

Abstract

This invention discloses a traditional Chinese medicine acne-removing ointment and its preparation method. By weight, it comprises the following components: 40-70 parts water, 2-8 parts butylene glycol, 1-5 parts propylene glycol, 0.5-3 parts Astragalus membranaceus extract, 0.1-1 parts 1,2-hexanediol, 0.5-4 parts Sophora flavescens extract, 0.2-2 parts Bombyx mori extract, 0.1-0.5 parts p-hydroxyacetophenone, 0.5-3 parts Paeonia lactiflora root extract, and 0.5-3 parts Poria cocos extract. This invention creatively encapsulates extracts of loquat leaf, Phellodendron amurense, Artemisia capillaris, mulberry root bark, and Glycyrrhiza glabra root in nano-olite bodies with an average particle size of 80-120 nm. This flexible nanocarrier can efficiently penetrate the skin's stratum corneum barrier, targeting and delivering the active ingredients deep into the hair follicle sebaceous gland, achieving a 5α-reductase inhibition rate as high as 93.2%. At the same time, the coating technology completely isolates oxygen and light, solving the technical problem that traditional Chinese medicine ointments are prone to oxidation, discoloration, and degradation of activity during long-term storage.

Description

Technical Field

[0001] This invention relates to the fields of cosmetics and daily chemical technology, and in particular to a traditional Chinese medicine acne-removing ointment and its preparation method. Background Technology

[0002] Acne is a common chronic inflammatory skin disease of the pilosebaceous unit, which is prevalent among adolescents and young adults. Its pathogenesis is complex and mainly includes abnormal keratinization of the pilosebaceous duct, excessive sebum secretion, excessive proliferation of microorganisms such as Propionibacterium acnes, and the resulting local immune and inflammatory responses.

[0003] Most chemical acne treatments on the market currently use salicylic acid, fruit acids, benzoyl peroxide, or antibiotics. While these ingredients are effective quickly, long-term use can easily damage the skin barrier, leading to dry skin, peeling, redness, itching, and even causing pathogens to develop drug resistance, resulting in a high recurrence rate after discontinuation.

[0004] In contrast, traditional Chinese medicine (TCM) acne treatment, due to its multi-target synergistic mechanism of "oil control, anti-inflammation, and repair," and its gentle nature, is gradually becoming a research hotspot. However, existing TCM acne creams generally suffer from the following technical bottlenecks: Traditional decoction and extraction processes are crude, resulting in low extraction rates of active ingredients from Chinese medicine. Furthermore, the extracts often contain large amounts of macromolecular proteins, polysaccharides, and tannins, leading to products that feel sticky on the skin and are prone to oxidation and discoloration.

[0005] The large differences in molecular weight and polarity of active ingredients in traditional Chinese medicine make it difficult for them to effectively penetrate the stratum corneum barrier and reach the deep hair follicles and sebaceous glands, resulting in low bioavailability and significantly reduced clinical efficacy when used topically.

[0006] The existing formulas often simply combine multiple Chinese herbs to create a functional combination, and the active ingredients fail to form a non-linear synergistic effect on specific targets, resulting in slow onset of action and long treatment courses. Summary of the Invention

[0007] The purpose of this invention is to solve the problems in the background art by proposing a traditional Chinese medicine acne-removing ointment and its preparation method.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: A traditional Chinese medicine acne treatment ointment, by weight, comprises the following components: Water 40-70 parts, Butylene glycol 2-8 parts, Propylene glycol 1-5 parts, Astragalus membranaceus extract 0.5-3 parts, 1,2-hexanediol 0.1-1 part, Sophora flavescens extract 0.5-4 parts, Bombyx mori extract 0.2-2 parts, p-hydroxyacetophenone 0.1-0.5 parts, Paeonia lactiflora root extract 0.5-3 parts, Poria cocos extract 0.5-3 parts, Lonicera japonica flower extract 0.5-2 parts, Sophora japonica flower extract 0.2-2 parts, hydrolyzed pearl 0.1-1.5 parts, phenoxyethanol 0.1-0.8 parts, Rheum palmatum root extract 0.5-2.5 parts, Carbomer 0.1-1 part, Triethanolamine 0.1-1 part, Dipotassium glycyrrhizate 0.05-0.5 parts; And 0.1-2 parts of a trace component composition, wherein the trace component composition comprises the following components: disodium EDTA, ichthammol, ethylhexylglycerin, loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract, licorice root extract, glycerin, capryloyl hydroxamic acid, and hexanediol.

[0009] Preferably, it includes the following core components: Water 55-65 parts, Butylene glycol 4-6 parts, Propylene glycol 2-4 parts, Astragalus membranaceus extract 1-2 parts, 1,2-hexanediol 0.3-0.6 parts, Sophora flavescens extract 1.5-2.5 parts, Bombyx mori extract 0.5-1.2 parts, p-hydroxyacetophenone 0.2-0.4 parts, Paeonia lactiflora root extract 1-2 parts, Poria cocos extract 1-2 parts, Lonicera japonica flower extract 0.8-1.5 parts, Sophora japonica flower extract 0.5-1.2 parts, hydrolyzed pearl 0.5-1 part, phenoxyethanol 0.3-0.5 parts, Rheum palmatum root extract 1-1.8 parts, Carbomer 0.3-0.6 parts, Triethanolamine 0.3-0.6 parts, Dipotassium glycyrrhizate 0.1-0.3 parts; The amount of the trace component composition added is 0.5-1.5 parts, wherein the proportions of each component in the trace component composition by weight percentage are: 2-5% disodium EDTA, 1-3% ichthammol, 5-10% ethylhexylglycerin, 10-20% loquat leaf extract, 10-20% phellodendron bark extract, 5-15% artemisia capillaris extract, 5-15% mulberry root bark extract, 5-10% licorice root extract, 10-20% glycerin, 2-5% capryloyl hydroxamic acid, and 2-5% hexanediol.

[0010] Preferably, the extracts of Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica, and Rheum palmatum root are prepared using an ultrasonic-assisted enzymatic hydrolysis-subcritical water step extraction process. The specific steps include: S11, raw material pretreatment: Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica, and Rheum palmatum root are selected, washed, and air-dried, then pulverized in an ultra-micro pulverizer and passed through a 120-150 mesh sieve to obtain ultra-micro powder of each Chinese medicinal material. S12. Compound enzymatic hydrolysis and cell wall breaking treatment: Mix the above ultrafine powder evenly according to the formula ratio, add 5-8 times the total weight of Chinese medicinal materials in purified water, adjust the pH value of the system to 4.5-5.5, and add 1.5-2.5% of the total weight of Chinese medicinal materials in compound enzyme preparation. The compound enzyme preparation is composed of cellulase, pectinase and papain in a mass ratio of 3:2:1. The enzyme is hydrolyzed by stirring in a constant temperature water bath at 45-50℃ for 2-3 hours. After the hydrolysis is completed, the system temperature is rapidly raised to 90-95℃ and maintained for 10-15 minutes to inactivate the enzyme preparation. The mixture is then cooled to room temperature to obtain the hydrolysate. S13. Ultrasonic-assisted subcritical water extraction: The above enzymatic hydrolysis mixture is transferred into a subcritical water extraction vessel, the reaction vessel is sealed, nitrogen gas is introduced to replace the air in the vessel, and then subcritical water is pumped in. Control the extraction temperature to 120-135℃, the extraction pressure to 2.5-3.5MPa, and simultaneously turn on the ultrasonic generator, setting the ultrasonic power to 400-600W and the ultrasonic frequency to 35-45kHz, and perform dynamic cyclic extraction for 40-60 minutes. S14. Purification and Concentration: After cooling the extract to room temperature, remove it from the pressure and centrifuge it at 4000-5000 r / min for 15-20 minutes, then collect the supernatant; The supernatant was ultrafiltered through a ceramic membrane with a molecular weight cutoff of 500-1000 Dalton to remove large molecular weight polysaccharides and protein impurities; The ultrafiltration solution was concentrated under reduced pressure at -0.08 to -0.1 MPa and 50 to 55°C to obtain an extract with a relative density of 1.15 to 1.20. S15. Freeze-drying and reconstitution: Pre-freeze the concentrated extract at -40℃ for 4-6 hours, and then dry it in a freeze dryer with a vacuum degree of less than 10Pa for 20-24 hours to obtain a light yellow to brownish-yellow multi-effect traditional Chinese medicine extract freeze-dried powder. When using, it should be redissolved in a mixed solvent of water, butanediol, and propylene glycol in proportion.

[0011] Preferably, the loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract, and licorice root extract in the trace component composition are encapsulated in nano-ol bodies. The preparation method of the nano-liposomes is as follows: S21, Prescription amount: Weigh soybean lecithin, cholesterol, and sodium deoxycholate as liposome membrane materials, with a mass ratio of 5:1:0.5; S22. Preparation of organic phase: The above membrane material is dissolved in anhydrous ethanol, and then loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract and licorice root extract mixed in the proportions described in claim 2 are added. The mixture is then ultrasonically dissolved to form a mixed organic phase. S23. Preparation of aqueous phase: Glycerol, capryloyl hydroxamic acid, hexanediol and water are mixed in proportion and heated to 45-50℃ to obtain the aqueous phase; S24. Dynamic injection film formation: Under high-speed shearing and constant temperature of 45-50°C, the mixed organic phase is injected into the aqueous phase at a rate of 1-3 mL / min using a microporous injection pump, and shearing is continued for 10-15 minutes to form a primary alcohol suspension; S25. High-pressure homogenization and particle size reduction: The primary alcohol body suspension is passed through a high-pressure homogenizer and homogenized 4-6 times under a pressure of 60-80 MPa to uniformly refine the alcohol body particle size, ultimately obtaining a Chinese herbal active microparticle nano-alcohol body suspension with an average particle size between 80-120 nm and a polydispersity index of less than 0.2; S26. Sterilization and sealing: Add the prescribed amounts of disodium EDTA, ichthammol and ethylhexylglycerin, mix evenly, and filter through a 0.22μm microporous membrane for sterilization to obtain the trace component composition.

[0012] Preferably, the preparation method of the hydrolyzed pearl is modified to enhance its synergistic anti-inflammatory and tissue repair effects with the traditional Chinese medicine extract; the specific steps are as follows: Take freshwater pearls, wash them with purified water, crush them into micron-sized pearl powder, add purified water at 10 times the weight of the pearl powder, and add 0.5-1% lactic acid for preliminary decalcification treatment. Adjust the pH to 7.5-8.0 with sodium hydroxide solution, add 2-4% alkaline protease by weight of pearl powder, and enzymatically hydrolyze at 50-55℃ for 4-6 hours; After enzymatic hydrolysis, the enzyme is inactivated by boiling, and the supernatant is collected by centrifugation. After purification and decolorization by macroporous adsorption resin, the hydrolyzed pearl powder rich in active small peptides and free amino acids is obtained by spray drying. The content of free polypeptides with a molecular weight of less than 1000 Dalton in the hydrolyzed pearl powder is not less than 85%.

[0013] Preferably, in the Sophora flavescens extract, Rheum palmatum root extract and Phellodendron chinense bark extract, the molar ratio of matrine, emodin and berberine is strictly controlled at (1.5-2.0):(1.0-1.2):(0.8-1.5).

[0014] Preferably, the gel skeleton system is composed of carbomer, triethanolamine, butylene glycol, propylene glycol and water; the carbomer is at least one of carbomer 940, carbomer 980 or carbomer U20, and its crosslinking density can provide a stable three-dimensional network suspension space for the above-mentioned macromolecular Chinese herbal extracts, preventing the active ingredients from flocculating or precipitating during long-term storage.

[0015] The preparation method of traditional Chinese medicine acne cream includes the following specific steps: Step 1, Preparation of Aqueous Phase A: Add 60-70% of the amount of water in the formulation to the aqueous phase emulsification pot, turn on the heating, and when the temperature rises to 80-85℃, slowly sprinkle in carbomer and p-hydroxyacetophenone in sequence. Turn on the bottom homogenizer and homogenize at a speed of 2000-3000 rpm for 15-20 minutes to ensure that the carbomer is completely swollen and free of lumps. Then keep warm for 30 minutes and perform vacuum degassing treatment. Step 2: Preparation of mixed polyol phase B: Mix the prescribed amounts of butanediol, propylene glycol, 1,2-hexanediol, and phenoxyethanol evenly. Add the freeze-dried powder of the multi-effect traditional Chinese medicine extract prepared according to claim 3 and the hydrolyzed pearl powder prepared according to claim 5 to the mixture. Use an ultrasonic cell disruptor to ultrasonically disperse the mixture for 20-30 minutes under ice bath conditions until it is completely dissolved to form a uniform and transparent amber solution for later use. Step 3, Neutralization and gel formation: Cool the aqueous phase A to 45-50℃, add the prescribed amount of triethanolamine for neutralization reaction, and start stirring at a speed of 40-60 rpm to bring the pH value of the system to between 5.5 and 6.5. At this time, the system changes from an aqueous solution to a transparent or translucent gel matrix. Step 4, active ingredient compounding and low-temperature emulsification: Slowly pump the mixed polyol phase B prepared in step 2 and the remaining amount of water into the gel matrix formed in step 3, turn on the variable frequency stirring system, control the temperature at 40-45℃, and stir for 20-30 minutes. Step 5, Addition of heat-sensitive trace components: When the system temperature drops below 35°C, add the nano-alcohol suspension containing trace component composition prepared according to claim 4, and dipotassium glycyrrhizate; turn on the vacuum system, control the vacuum degree between -0.06 and -0.08 MPa, and stir slowly (20-30 rpm) for 15-20 minutes until the paste has a delicate appearance, no bubbles and uniform color; Step Six: Discharging and Settling: Stop stirring, release the vacuum, and pump the prepared herbal acne cream into a clean storage tank. Settle and mature in a clean room at 20-25℃ for 24-48 hours to allow the internal polymer network structure of the cream to fully recover its stress balance. Then, perform aseptic filling (preferably). Preferably, in the process of compounding the effective ingredients in step four, programmed cooling control technology is used: After the mixed polyol phase B is added to the gel matrix, instead of using conventional natural cooling, cooling circulating water is introduced through the jacket, and the cooling rate is set to 1.5-2.0℃ / min. When the system temperature drops to 38℃, maintain the constant temperature for 10 minutes, and then slowly cool it down to below 35℃ at a rate of 0.5-1.0℃ / min.

[0016] Preferably, the traditional Chinese medicine acne-removing ointment is used in the preparation of external cosmetics or topical skin medications for treating and / or improving acne vulgaris caused by excessive sebum secretion and Propionibacterium acnes infection.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention defines the molar ratio of key active substances in the core components. When the molar ratio of matrine, emodin, and berberine in Sophora flavescens extract, Rheum palmatum root extract, and Phellodendron amurense bark extract is strictly locked at 1.8:1.1:1.2, a nonlinear synergistic amplification effect is triggered. Experiments show that this specific combination reduces the minimum inhibitory concentration (MIC) against Propionibacterium acnes to 3.91 μg / mL, which is 8 times more effective than the non-synergistic ratio formulation, effectively cutting off the inflammatory infection pathway of acne at its source.

[0018] This invention targets traditional Chinese medicinal components such as Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica flower, and Rheum palmatum root. It abandons the crude methods of boiling in water or extracting with alcohol, employing an ultrasonic-assisted, compound enzymatic hydrolysis, and subcritical water stepwise extraction process, combined with ceramic membrane ultrafiltration technology. This process thoroughly removes large molecular weight proteins, polysaccharides, and tannins that easily cause stickiness and dullness in acne creams. This not only greatly improves the purity of the extracted active ingredients but also gives the acne cream a refreshing, thin, and non-sticky feel.

[0019] This invention creatively encapsulates extracts of loquat leaf, phellodendron bark, artemisia capillaris, mulberry root bark, and licorice root in a trace component composition within nano-sized liposomes with an average particle size of 80-120 nm. This flexible nanocarrier can efficiently penetrate the skin's stratum corneum barrier, targeting and delivering the active ingredients deep into the hair follicle sebaceous glands, achieving a 5α-reductase inhibition rate as high as 93.2%. Simultaneously, the encapsulation technology completely isolates the ingredients from oxygen and light, solving the persistent technical problem of traditional Chinese medicine ointments being prone to oxidation, discoloration, and degradation of active ingredients during long-term storage.

[0020] This invention utilizes a specific lactic acid decalcification and alkaline protease hydrolysis process to treat micron-sized pearl powder, resulting in modified hydrolyzed pearl powder rich in free amino acids and highly active small peptides with a molecular weight of less than 1000 Daltons. This component exhibits excellent synergistic repair effects with traditional Chinese medicine extracts, effectively promoting the healing of damaged hair follicle epithelial tissue, accelerating the fading of acne scars, and reducing the recurrence rate. Detailed Implementation

[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0022] The formulations of the traditional Chinese medicine acne-removing ointments of Examples 1 to 5 of this invention are shown in Table 1 (by weight): Table 1: Formulas of Traditional Chinese Medicine Acne-Clearing Creams in Examples 1-5 (parts by weight) water 40 60 60 60 60 Butylene glycol 2 5 5 5 5 Propylene glycol 5 3 3 3 3 Astragalus membranaceus extract 3 1.5 1.5 1.5 1.5 1,2-Hexanediol 1 0.4 0.4 0.4 0.4 Sophora flavescens extract 0.5 2 2 2 0.6 Silkworm extract 2 0.8 0.8 0.8 0.8 p-Hydroxyacetophenone 0.5 0.3 0.3 0.3 0.3 Peony root extract 0.5 1.5 1.5 1.5 1.5 Poria cocos extract 3 1.5 1.5 1.5 1.5 Honeysuckle flower extract 0.5 1.2 1.2 1.2 1.2 Sophora japonica extract 2 0.8 0.8 0.8 0.8 Hydrolyzed Pearl 0.1 0.8 0.8 0.8 0.8 Phenoxyethanol 0.8 0.4 0.4 0.4 0.4 Rhubarb root extract 0.5 1.4 1.4 1.4 2.5 Carbomer 1 0.4 0.4 0.4 0.4 Triethanolamine 1 0.4 0.4 0.4 0.4 Dipotassium glycyrrhizate 0.05 0.2 0.2 0.2 0.2 Trace component composition 2 1 1 1 1 Note: In Examples 2, 3, 4, and 5, the weight percentages of each component in the trace component composition strictly correspond: disodium EDTA 3%, ichthammol 2%, ethylhexylglycerin 7%, loquat leaf extract 15%, phellodendron bark extract 15%, artemisia capillaris extract 10%, mulberry root bark extract 10%, licorice root extract 8%, glycerin 15%, capryloyl hydroxamic acid 6%, hexanediol 6%.

[0023] Example 1 Preparation of Traditional Chinese Medicine Extracts: The traditional decoction method was used. The prescribed amounts of Astragalus membranaceus, Sophora flavescens, Bombyx batryticatus, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica flower, and Rheum palmatum root were crushed and mixed. Ten times the total weight of the herbs were added to deionized water, and the mixture was decocted twice, 1.5 hours each time. The filtrates were combined, concentrated under normal and reduced pressure, and dried into powder. The powder was then dissolved in water before use. The herbal extracts containing trace components were also prepared using the same method.

[0024] Hydrolyzed pearl: Commercially available micron-sized ordinary pearl powder (mechanically pulverized) is directly added to the system.

[0025] Ointment preparation: Carbomer and p-hydroxyacetophenone were dissolved in the prescribed amount of water at 80℃, and triethanolamine was added to neutralize and form a transparent gel network. The system was then cooled to 50℃, and butylene glycol, propylene glycol, various free Chinese herbal extracts, micronized pearl powder, dipotassium glycyrrhizate and other trace components were directly added. After stirring evenly with frequency converter, the mixture was allowed to cool naturally to room temperature.

[0026] Example 2 Preparation of Chinese herbal extracts: The conventional decoction method is the same as in Example 1.

[0027] Hydrolyzed pearl: Made with standard commercial hydrolyzed pearl solution.

[0028] Ointment preparation: The procedure was followed according to a pre-defined schedule. First, carbomer and p-hydroxyacetophenone were swollen in water at 82°C and neutralized with triethanolamine. When the system cooled to 45°C, a polyol phase containing a mixture of traditional Chinese medicine extracts and hydrolyzed pearl liquid was added. The plant extracts in the trace components were added directly in free form along with ichthammol and other components without encapsulation. Finally, the system was allowed to cool naturally at atmospheric pressure.

[0029] Example 2 Preparation of core extracts from traditional Chinese medicine: Strictly employing an ultrasonic-assisted, compound enzymatic hydrolysis, and subcritical water step extraction process.

[0030] Raw material pretreatment: Wash and air-dry the Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica, and Rheum palmatum root, then pulverize them using an ultra-fine pulverizer and pass them through a 120-mesh sieve.

[0031] Compound enzymatic hydrolysis to break down cell walls: Mix the above powders, add purified water at 6 times the total weight of the medicinal materials, adjust the pH to 5.0, and add a compound enzyme (cellulase: pectinase: papain = 3:2:1) at 2.0% of the total weight of the medicinal materials. Hydrolyze the mixture in a constant temperature water bath at 48℃ for 2.5 hours with stirring, then rapidly raise the temperature to 92℃ and hold for 12 minutes to inactivate the enzyme, followed by cooling.

[0032] Ultrasonic-assisted subcritical water extraction: Transfer the sample to a subcritical extraction vessel and purge with nitrogen. Pump in subcritical water, controlling the extraction temperature at 128°C and the extraction pressure at 3.0 MPa. Turn on the ultrasonic waves, setting the power to 500W and the frequency to 40kHz, and perform dynamic circulation extraction for 50 minutes.

[0033] Purification and concentration: The extract was centrifuged (4500 r / min, 18 min) and the supernatant was collected. Ultrafiltration was performed using a ceramic membrane with a molecular weight cutoff of 800 Dalton. The ultrafiltrate was concentrated under reduced pressure at -0.09 MPa and 53°C to a paste with a relative density of 1.18.

[0034] Freeze-drying: The extract was pre-frozen at -40℃ for 5 hours and then freeze-dried under vacuum for 22 hours to obtain high-purity freeze-dried powder of the core extract of traditional Chinese medicine.

[0035] Nanoparticles encapsulate trace components: Weigh out soybean lecithin, cholesterol, and sodium deoxycholate in a mass ratio of 5:1:0.5.

[0036] The above-mentioned membrane material was dissolved in anhydrous ethanol, and then a mixture of loquat leaf, phellodendron bark, artemisia capillaris, mulberry root bark, and licorice root extracts were added in proportion, and the mixture was ultrasonically prepared into a mixed organic phase.

[0037] Glycerin, capryloyl hydroxamic acid, hexanediol and water were mixed and heated to 48°C to form the aqueous phase.

[0038] Under high-speed shearing (9000 rpm) and 48°C conditions, the organic phase was injected into the aqueous phase at a rate of 2 mL / min using a microporous injection pump, and the primary suspension was obtained after shearing for 12 minutes.

[0039] A suspension of active microparticles of traditional Chinese medicine with an average particle size of 92 nm and a PDI of 0.15 was obtained by homogenizing five times under a high pressure homogenizer at 70 MPa.

[0040] Add disodium EDTA, ichthammol, and ethylhexylglycerin, mix, and sterilize and seal using a 0.22μm filter membrane.

[0041] Preparation of modified hydrolyzed pearl powder: Freshwater pearls were pulverized to micron size, and 10 times the volume of water and 0.8% lactic acid were added for decalcification. The pH was adjusted to 7.8 with sodium hydroxide, and 3% alkaline protease was added. Enzymatic hydrolysis was carried out at 52°C for 5 hours. The enzyme was inactivated by boiling, and the supernatant was collected by centrifugation. The supernatant was purified and decolorized by macroporous adsorption resin, and spray-dried to obtain modified hydrolyzed pearl powder rich in active small peptides (free peptides with a molecular weight <1000 Dalton accounted for 88%).

[0042] Molar ratio control of active ingredients: By analyzing and quantifying the components of the extract, the ratio is adjusted to ensure that the molar ratio of matrine, emodin and berberine in the preparation is strictly locked at 1.8:1.1:1.2.

[0043] ointment preparation: Step 1, Aqueous Phase A: Add 65% of the formula amount of water to the emulsifying pot, heat to 82°C, add carbomer and hydroxyacetophenone, homogenize at 2500 rpm for 18 minutes, and keep warm to remove bubbles.

[0044] Step 2, Mixing polyol phase B: Mix butanediol, propanediol, 1,2-hexanediol and phenoxyethanol, add the freeze-dried powder of the core extract of traditional Chinese medicine obtained in step 1 and the modified hydrolyzed pearl powder obtained in step 3, and ultrasonically disperse under ice bath for 25 minutes to form a uniform amber solution.

[0045] Step 3: Cool aqueous phase A to 48°C, add triethanolamine, and stir slowly at 50 rpm to neutralize. The system is transformed into a uniform and thickened gel skeleton.

[0046] Step 4: Pump polyol phase B and the remaining water into the gel matrix and start the variable frequency stirring. Circulate cooling water through the jacket, strictly controlling the cooling rate to 1.8°C / min. When the temperature drops to 38°C, stop cooling for 10 minutes, then slowly cool down to 35°C at a rate of 0.8°C / min.

[0047] Step 5: When the temperature drops to 32℃, add the nano-alcohol suspension obtained in Step 2 and dipotassium glycyrrhizate. Vacuum the mixture to -0.07MPa, stir slowly at 25rpm for 18 minutes, discharge the mixture, let it stand and mature for 36 hours, and then aseptically fill it.

[0048] Example 4 The molar ratio of the herbal extract, hydrolyzed pearl, and components (matrine:emodin:berberine = 1.8:1.1:1.2) was completely consistent with that in Example 3.

[0049] Process deviation: The plant extracts in the trace components are not encapsulated in nano-alcohol bodies, but are directly added in free form along with ichthammol at low temperature. Furthermore, in step four of the ointment preparation, programmed step cooling is not used; instead, conventional rapid cooling is achieved by circulating a large amount of cold water through a jacket.

[0050] Example 5 Process technology: The ultrasonic-enzymatic hydrolysis-subcritical stepwise extraction, nano-olite encapsulation, modified hydrolyzed pearl, and programmed cooling emulsification process are exactly the same as in Example 3.

[0051] Proportioning deviation: By manually adjusting the feeding ratio of Sophora flavescens extract and Rheum palmatum root extract in the core Chinese medicine, the molar ratio of matrine, emodin and berberine in the preparation deviated from the highly efficient synergistic range and became 0.5:2.5:0.4.

[0052] In order to scientifically verify the inventiveness, substantial technological progress, and nonlinear synergistic effect between various process features of Embodiment 3 of the present invention as the optimal embodiment, the present invention conducted rigorous in vitro and clinical evaluation comparison tests.

[0053] Test methods Experiment A: In vitro antibacterial test against Propionibacterium acnes (C. acnes) was conducted using the standard plate microdilution method to determine the minimum inhibitory concentration (MIC, μg / mL) of each sample against Propionibacterium acnes. The lower the value, the stronger the antibacterial ability. At the same time, the diameter of the inhibition zone (mm) was determined using the Oxford cup agar diffusion method.

[0054] Experiment B: Human sebaceous gland cell 5α-reductase inhibition test Human sebaceous gland cells (SZ95) were cultured in vitro and incubated with samples from each example at equal dilution. The inhibition rate (%) of 5α-reductase activity in each group was determined by fluorescence substrate assay to evaluate its ability to block excessive sebum secretion at its source.

[0055] Experiment C: Clinical efficacy and skin irritation safety evaluation for acne treatment 150 participants with mild to moderate acne vulgaris were recruited and randomly divided into 5 groups of 30 each. Participants applied the corresponding product from the example formulation to the affected skin twice daily (morning and evening) for 28 consecutive days. Dermatologists counted the number of inflammatory lesions (papules and pustules) on day 0 and day 28, calculating the lesion reduction rate (i.e., the clinically effective acne treatment rate, %). Simultaneously, skin irritation scores (0-10 points, with higher scores indicating greater irritation) were assessed based on subjective feedback and the objective incidence of erythema and desquamation.

[0056] Test results The test data of the core technical indicators of the samples in each embodiment are shown in Table 2: Table 2: Comparison of physicochemical activity, in vitro and clinical trial data for each embodiment. MIC (μg / mL) of Propionibacterium acnes 62.5 31.25 3.91 15.63 31.25 Diameter of the inhibition zone (mm) 12.1 15.4 26.8 19.5 14.8 5α-Reductase Inhibition Rate (%) 45.00% 62.00% 93.20% 75.00% 58.00% 28-day clinically effective acne treatment rate (%) 58.30% 71.40% 96.50% 82.10% 68.70% Skin irritation rating (0-10 points) 1.5 0.8 0.1 0.4 0.2

[0057] Based on the complete experimental data shown in Table 2, we can conclude that: Experimental data show that when the molar ratio of matrine, emodin, and berberine in the system is strictly controlled within the synergistic range of Example 3, the minimum inhibitory concentration (MIC) against Propionibacterium acnes in Example 3 drops sharply to 3.91 μg / mL, and the diameter of the inhibition zone expands to 26.80 mm. However, in Example 5, with the same process but a different molar ratio, the MIC degrades to 31.25 μg / mL.

[0058] Although Example 4 has the same preferred ratio and stepwise extraction powder as Example 3, due to the lack of efficient follicle-targeting penetration of nano-olive bodies and the failure to use programmed stepwise speed control during cooling emulsification, some active ingredients were precipitated as microcrystals. As a result, its 5α-reductase inhibition rate dropped significantly from 93.2% to 75.0%, and the clinical acne treatment rate also dropped from 96.5% to 82.1%.

[0059] Example 3 uses ultrasound-assisted compound enzymatic hydrolysis, subcritical water step extraction, and ceramic membrane ultrafiltration to completely remove large molecular stickiness and easily oxidized impurities. Combined with modified hydrolyzed pearl powder rich in small peptides, it achieves an astonishing 96.5% clinical acne treatment rate, and the skin irritation score is reduced to a near-zero perfect state (0.10 points).

[0060] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine acne-removing ointment, characterized in that, By weight, it includes the following components: Water 40-70 parts, Butylene glycol 2-8 parts, Propylene glycol 1-5 parts, Astragalus membranaceus extract 0.5-3 parts, 1,2-hexanediol 0.1-1 part, Sophora flavescens extract 0.5-4 parts, Bombyx mori extract 0.2-2 parts, p-hydroxyacetophenone 0.1-0.5 parts, Paeonia lactiflora root extract 0.5-3 parts, Poria cocos extract 0.5-3 parts, Lonicera japonica flower extract 0.5-2 parts, Sophora japonica flower extract 0.2-2 parts, hydrolyzed pearl 0.1-1.5 parts, phenoxyethanol 0.1-0.8 parts, Rheum palmatum root extract 0.5-2.5 parts, Carbomer 0.1-1 part, Triethanolamine 0.1-1 part, Dipotassium glycyrrhizate 0.05-0.5 parts; And 0.1-2 parts of a trace component composition, wherein the trace component composition comprises the following components: disodium EDTA, ichthammol, ethylhexylglycerin, loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract, licorice root extract, glycerin, capryloyl hydroxamic acid, and hexanediol.

2. The traditional Chinese medicine acne-removing ointment according to claim 1, characterized in that: By weight, it includes the following core components: Water 55-65 parts, Butylene glycol 4-6 parts, Propylene glycol 2-4 parts, Astragalus membranaceus extract 1-2 parts, 1,2-hexanediol 0.3-0.6 parts, Sophora flavescens extract 1.5-2.5 parts, Bombyx mori extract 0.5-1.2 parts, p-hydroxyacetophenone 0.2-0.4 parts, Paeonia lactiflora root extract 1-2 parts, Poria cocos extract 1-2 parts, Lonicera japonica flower extract 0.8-1.5 parts, Sophora japonica flower extract 0.5-1.2 parts, hydrolyzed pearl 0.5-1 part, phenoxyethanol 0.3-0.5 parts, Rheum palmatum root extract 1-1.8 parts, Carbomer 0.3-0.6 parts, Triethanolamine 0.3-0.6 parts, Dipotassium glycyrrhizate 0.1-0.3 parts; The amount of the trace component composition added is 0.5-1.5 parts, wherein the proportions of each component in the trace component composition by weight percentage are: 2-5% disodium EDTA, 1-3% ichthammol, 5-10% ethylhexylglycerin, 10-20% loquat leaf extract, 10-20% phellodendron bark extract, 5-15% artemisia capillaris extract, 5-15% mulberry root bark extract, 5-10% licorice root extract, 10-20% glycerin, 2-5% capryloyl hydroxamic acid, and 2-5% hexanediol.

3. A traditional Chinese medicine acne-removing ointment according to claim 1 or 2, characterized in that, The extracts of Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica, and Rheum palmatum root were prepared using an ultrasonic-assisted enzymatic hydrolysis-subcritical water step extraction process. The specific steps include: S11, raw material pretreatment: Astragalus membranaceus, Sophora flavescens, Bombyx mori, Paeonia lactiflora root, Poria cocos, Lonicera japonica, Sophora japonica, and Rheum palmatum root were selected, washed, and air-dried, then pulverized in an ultra-micro pulverizer and passed through a 120-150 mesh sieve to obtain ultra-micro powder of each Chinese medicinal material. S12. Compound enzymatic hydrolysis and cell wall breaking treatment: Mix the above ultrafine powder evenly according to the formula ratio, add 5-8 times the total weight of Chinese medicinal materials in purified water, adjust the pH value of the system to 4.5-5.5, and add 1.5-2.5% of the total weight of Chinese medicinal materials in compound enzyme preparation. The compound enzyme preparation is composed of cellulase, pectinase and papain in a mass ratio of 3:2:

1. The enzyme is hydrolyzed by stirring in a constant temperature water bath at 45-50℃ for 2-3 hours. After the hydrolysis is completed, the system temperature is rapidly raised to 90-95℃ and maintained for 10-15 minutes to inactivate the enzyme preparation. The mixture is then cooled to room temperature to obtain the hydrolysate. S13. Ultrasonic-assisted subcritical water extraction: The above enzymatic hydrolysis mixture is transferred into a subcritical water extraction vessel, the reaction vessel is sealed, nitrogen gas is introduced to replace the air in the vessel, and then subcritical water is pumped in. Control the extraction temperature to 120-135℃, the extraction pressure to 2.5-3.5MPa, and simultaneously turn on the ultrasonic generator, setting the ultrasonic power to 400-600W and the ultrasonic frequency to 35-45kHz, and perform dynamic cyclic extraction for 40-60 minutes. S14. Purification and Concentration: After cooling the extract to room temperature, remove it from the pressure and centrifuge it at 4000-5000 r / min for 15-20 minutes, then collect the supernatant; The supernatant was ultrafiltered through a ceramic membrane with a molecular weight cutoff of 500-1000 Dalton to remove large molecular weight polysaccharides and protein impurities; The ultrafiltration solution was concentrated under reduced pressure at -0.08 to -0.1 MPa and 50 to 55°C to obtain an extract with a relative density of 1.15 to 1.

20. S15. Freeze-drying and reconstitution: Pre-freeze the concentrated extract at -40℃ for 4-6 hours, and then dry it in a freeze dryer with a vacuum degree of less than 10Pa for 20-24 hours to obtain a light yellow to brownish-yellow multi-effect traditional Chinese medicine extract freeze-dried powder. When using, it should be redissolved in a mixed solvent of water, butanediol, and propylene glycol in proportion.

4. The traditional Chinese medicine acne-removing ointment according to claim 3, characterized in that: The loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract, and licorice root extract in the trace component composition are encapsulated in nano-olites. The preparation method of the nano-liposomes is as follows: S21, Prescription amount: Weigh soybean lecithin, cholesterol, and sodium deoxycholate as liposome membrane materials, with a mass ratio of 5:1:0.5; S22. Preparation of organic phase: The above membrane material is dissolved in anhydrous ethanol, and then loquat leaf extract, phellodendron bark extract, artemisia capillaris extract, mulberry root bark extract and licorice root extract mixed in the proportions described in claim 2 are added. The mixture is then ultrasonically dissolved to form a mixed organic phase. S23. Preparation of aqueous phase: Glycerol, capryloyl hydroxamic acid, hexanediol and water are mixed in proportion and heated to 45-50℃ to obtain the aqueous phase; S24. Dynamic injection film formation: Under high-speed shearing and constant temperature of 45-50°C, the mixed organic phase is injected into the aqueous phase at a rate of 1-3 mL / min using a microporous injection pump, and shearing is continued for 10-15 minutes to form a primary alcohol suspension; S25. High-pressure homogenization and particle size reduction: The primary alcohol body suspension is passed through a high-pressure homogenizer and homogenized 4-6 times under a pressure of 60-80 MPa to make the alcohol body particle size uniform and refined, finally obtaining a Chinese herbal active microparticle nano-alcohol body suspension with an average particle size between 80-120 nm and a polydispersity index of less than 0.2; S26. Sterilization and sealing: Add the prescribed amounts of disodium EDTA, ichthammol and ethylhexylglycerin, mix evenly, and filter through a 0.22μm microporous membrane for sterilization to obtain the trace component composition.

5. The traditional Chinese medicine acne-removing ointment according to claim 4, characterized in that: The preparation method of the hydrolyzed pearl has been improved to enhance its synergistic anti-inflammatory and tissue repair effects with traditional Chinese medicine extracts; the specific steps are as follows: Take freshwater pearls, wash them with purified water, crush them into micron-sized pearl powder, add purified water at 10 times the weight of the pearl powder, and add 0.5-1% lactic acid for preliminary decalcification treatment. Adjust the pH to 7.5-8.0 with sodium hydroxide solution, add 2-4% alkaline protease by weight of pearl powder, and enzymatically hydrolyze at 50-55℃ for 4-6 hours; After enzymatic hydrolysis, the enzyme is inactivated by boiling, and the supernatant is collected by centrifugation. After purification and decolorization by macroporous adsorption resin, the hydrolyzed pearl powder rich in active small peptides and free amino acids is obtained by spray drying. The content of free polypeptides with a molecular weight of less than 1000 Dalton in the hydrolyzed pearl powder is not less than 85%.

6. A traditional Chinese medicine acne-removing ointment according to any one of claims 1 to 5, characterized in that: In the extracts of Sophora flavescens, Rheum palmatum root extract, and Phellodendron chinense bark, the molar ratio of matrine, emodin, and berberine was strictly controlled at (1.5-2.0):(1.0-1.2):(0.8-1.5).

7. The traditional Chinese medicine acne-removing ointment according to claim 5, characterized in that: The gel skeleton system is composed of carbomer, triethanolamine, butylene glycol, propylene glycol and water; the carbomer is at least one of carbomer 940, carbomer 980 or carbomer U20, and its crosslinking density can provide a stable three-dimensional network suspension space for the above-mentioned macromolecular Chinese herbal extracts, preventing the active ingredients from flocculating or precipitating during long-term storage.

8. A method for preparing a traditional Chinese medicine acne-removing ointment as described in any one of claims 1 to 7, characterized in that, It includes the following specific steps: Step 1, Preparation of Aqueous Phase A: Add 60-70% of the amount of water in the formulation to the aqueous phase emulsification pot, turn on the heating, and when the temperature rises to 80-85℃, slowly sprinkle in carbomer and p-hydroxyacetophenone in sequence. Turn on the bottom homogenizer and homogenize at a speed of 2000-3000 rpm for 15-20 minutes to ensure that the carbomer is completely swollen and free of lumps. Then keep warm for 30 minutes and perform vacuum degassing treatment. Step 2: Preparation of mixed polyol phase B: Mix the prescribed amounts of butanediol, propylene glycol, 1,2-hexanediol, and phenoxyethanol evenly. Add the freeze-dried powder of the multi-effect traditional Chinese medicine extract prepared according to claim 3 and the hydrolyzed pearl powder prepared according to claim 5 to the mixture. Use an ultrasonic cell disruptor to ultrasonically disperse the mixture for 20-30 minutes under ice bath conditions until it is completely dissolved to form a uniform and transparent amber solution for later use. Step 3, Neutralization and gel formation: Cool the aqueous phase A to 45-50℃, add the prescribed amount of triethanolamine for neutralization reaction, and start stirring at a speed of 40-60 rpm to bring the pH value of the system to between 5.5 and 6.

5. At this time, the system changes from an aqueous solution to a transparent or translucent gel matrix. Step 4, active ingredient compounding and low-temperature emulsification: Slowly pump the mixed polyol phase B prepared in step 2 and the remaining amount of water into the gel matrix formed in step 3, turn on the variable frequency stirring system, control the temperature at 40-45℃, and stir for 20-30 minutes. Step 5, Addition of heat-sensitive trace components: When the system temperature drops below 35°C, add the nano-alcohol suspension containing trace component composition prepared according to claim 4, and dipotassium glycyrrhizate; turn on the vacuum system, control the vacuum degree between -0.06 and -0.08 MPa, and stir slowly (20-30 rpm) for 15-20 minutes until the paste has a delicate appearance, no bubbles and uniform color; Step 6, Discharging and Settling: Stop stirring, release the vacuum, pump the prepared Chinese herbal acne cream into a clean storage tank, and let it stand and mature in a dust-free room at 20-25℃ for 24-48 hours to allow the high molecular network structure inside the cream to fully restore stress balance, and then perform aseptic filling.

9. The method for preparing a traditional Chinese medicine acne-removing ointment according to claim 8, characterized in that, In the process of compounding the effective ingredients in step four, programmed cooling control technology is adopted: After the mixed polyol phase B is added to the gel matrix, instead of using conventional natural cooling, cooling circulating water is introduced through the jacket, and the cooling rate is set to 1.5-2.0℃ / min. When the system temperature drops to 38℃, maintain the constant temperature for 10 minutes, and then slowly cool it down to below 35℃ at a rate of 0.5-1.0℃ / min.

10. The use of a traditional Chinese medicine acne-removing ointment as described in any one of claims 1 to 7 in the preparation of a topical cosmetic or skin medication for treating and / or improving acne vulgaris caused by excessive sebum secretion and Propionibacterium acnes infection.