An anti-dandruff, anti-inflammatory, anti-itching composition, its preparation method and use

Abstract

The application discloses a dandruff-removing, anti-inflammatory and itching-relieving composition and a preparation method and application thereof, and belongs to the technical field of biological active material preparation. Cacumen platycladi powder, radix falconiae powder and lycium fruit powder are ultrasonically extracted by using a eutectic solvent A, and mother liquor A is obtained by filtration; white willow bark powder and acacia cortex peel powder are pre-swelled by using a eutectic solvent B, and white willow bark extract and acacia extract are obtained by enzymolysis; the acacia extract is synchronously treated with an immobilized tannase column and a first nanofiltration membrane, and low-molecular enzymolysis liquid and concentrated tannin material are obtained; the white willow bark extract and the low-molecular enzymolysis liquid are mixed, enriched by a second nanofiltration membrane, and subjected to association treatment in the presence of betaine, glycerol and deionized water, so that an active association system B1 is obtained; the active association system B1 is mixed with the concentrated tannin material and homogenized, so that mother liquor B is obtained; the mother liquor B is added into the mother liquor A, stirred and homogenized, and thus the dandruff-removing, anti-inflammatory and itching-relieving composition is obtained.

Description

Technical Field

[0001] This invention belongs to the field of bioactive raw material preparation technology, specifically relating to an anti-dandruff, anti-inflammatory, and antipruritic composition, its preparation method, and its application. Background Technology

[0002] The scalp is one of the most sebaceous areas of the human body. Excessive sebum secretion, damage to the stratum corneum barrier, and the overgrowth of opportunistic pathogens such as Malassezia constitute the core links in the imbalance of the scalp's microecology, leading to a series of problems such as increased dandruff, scalp inflammation, and itching. These three factors often interact and perpetuate each other: fungal metabolites (such as oleic acid) penetrate the stratum corneum, inducing an inflammatory response; inflammation accelerates the abnormal proliferation and shedding of keratinocytes, forming dandruff; inflammatory mediators stimulate nerve endings in the scalp, causing itching; and scratching further damages the barrier and aggravates inflammation, creating a vicious cycle. Therefore, an ideal scalp care plan should address three aspects: antibacterial and dandruff-removing, anti-inflammatory and soothing, and anti-itch and repairing, synergistically intervening in the aforementioned vicious cycle from multiple targets.

[0003] Currently, commercially available anti-dandruff and anti-itch shampoos mainly rely on chemical anti-dandruff agents and anti-inflammatory and anti-itch agents, such as zinc pyrithione (ZPT), ketoconazole, clomiphene citrate, piroctone olamine, salicylic acid, and glucocorticoids. While these chemical ingredients are relatively fast-acting, they generally have problems such as high irritation, long-term use leading to scalp dryness and barrier damage, increased Malassezia drug resistance, and easy relapse after discontinuation. Some ingredients (such as ZPT) are also controversial regarding environmental friendliness and regulatory restrictions. Therefore, developing gentle, safe, long-term usable natural plant-derived compositions with multiple functions including anti-dandruff, anti-inflammatory, and anti-itch has become an important research direction in the field of scalp care.

[0004] Traditional Chinese medicine has accumulated rich experience in scalp care, and various plant extracts have been proven to have antibacterial, anti-inflammatory, antioxidant, or oil-controlling activities. For example, arborvitae leaves are rich in flavonoids and are traditionally used to cool the blood and relieve itching; when applied externally, they can inhibit scalp fungi and relieve dandruff and itching. Ligustrum lucidum contains ligustrazine, rhodioloside, and other components, which have yin-nourishing, antioxidant, and immunomodulatory effects. Polygonum multiflorum contains stilbene glycosides and anthraquinones and is traditionally used to nourish the blood and darken the hair, while also having anti-inflammatory and antioxidant activities. Terminalia chebula is rich in tannins (chebulic acid, chebulic acid, etc.), which have astringent, antibacterial, and anti-inflammatory effects. White willow bark is a natural source of salicin, which has mild keratin conditioning, anti-inflammatory, and soothing effects. Based on the above understanding, existing technologies have attempted to incorporate some medicinal herbs into shampoos and conditioners, but all have significant shortcomings. For example, Chinese patent application CN114010566A discloses a hair conditioner with hair growth function, in which the herbal extract is a compound extract of Polygonum multiflorum, Platycladus orientalis leaves, and Ligustrum lucidum. Ionic liquids are used to increase the extraction rate, thereby enhancing antioxidant properties and 5α-reductase inhibition rate to achieve hair loss prevention and hair growth. This solution only focuses on hair growth efficacy and does not address dandruff removal, anti-inflammation, or anti-itch needs. Furthermore, the formula does not contain Terminalia chebula or Salix babylonica bark, failing to recognize the beneficial effects of Terminalia chebula's astringent and antibacterial properties, and Salix babylonica bark's keratin conditioning and soothing anti-inflammatory effects on improving dandruff and scalp itching. Chinese patent application CN118384053A discloses a hair loss prevention and nourishing essence containing hirudin. Its plant extracts are prepared from ginseng, Polygonum multiflorum, Platycladus orientalis leaves, and ginger through fermentation and deep eutectic solvent enzymatic hydrolysis, focusing on promoting scalp blood circulation, stimulating hair follicle growth, and preventing hair loss. Furthermore, its dandruff-reducing and anti-itch effects rely solely on the topical effect of Platycladus orientalis leaves, lacking a systematic formulation design targeting multiple objectives related to dandruff reduction, anti-inflammation, and anti-itch relief. Chinese patent application CN121550250A discloses a composition beneficial to bone and joint health, with low molecular weight chondroitin sulfate sodium and N-acetylglucosamine as its core ingredients, and vaguely lists dozens of active ingredients such as Terminalia chebula extract and white willow bark extract in the optional excipient list. This document belongs to the field of oral health foods / pharmaceuticals, addressing the anti-inflammatory and analgesic issues of osteoarthritis. Terminalia chebula and white willow bark are only mentioned as parallel optional ingredients, neither combined with Platycladus orientalis leaves, Ligustrum lucidum, or Polygonum multiflorum, nor addressing scalp topical care scenarios, and further failing to suggest that this five-ingredient combination can be used for dandruff reduction, anti-inflammation, and anti-itch relief. Chinese patent application CN113332220A discloses a traditional Chinese medicine shampoo for strengthening roots, promoting hair growth, darkening hair, and nourishing hair. The herbal extract is made by boiling 21 medicinal materials, including dried ginger, arborvitae leaves, Polygonum multiflorum, Gleditsia sinensis, Sapindus mukorossi, Eclipta prostrata, Gallnut, Terminalia chebula, rhubarb, Phellodendron chinense, Scutellaria baicalensis, Salvia miltiorrhiza, Angelica sinensis, tea bran, aloe vera, Angelica dahurica, mulberry leaves, Artemisia argyi, Astragalus membranaceus, Ligustrum lucidum, and Cuscuta chinensis, with water. The main purpose is to strengthen roots, promote hair growth, darken hair, and nourish hair.This scheme is a comprehensive empirical formula with many kinds of medicinal materials and no distinction between primary and secondary ingredients. It does not conduct targeted compatibility research for the specific technical problems of dandruff removal, anti-inflammation, and itch relief. The coexistence of a large number of irrelevant medicinal materials dilutes the concentration of effective ingredients and increases the difficulty of process and quality control. Based on the above existing technologies, it can be seen that: (1) Existing hair care products containing Chinese medicine are mostly oriented towards hair growth, hair loss prevention, and hair darkening, and there are few targeted formula studies for the triple needs of dandruff removal, anti-inflammation, and itch relief; (2) Existing literature at most discloses simple compounding of some of the three medicinal materials of arborvitae leaves, privet fruit, and fleeceflower root, or only mentions Terminalia chebula and white willow bark in isolation in irrelevant fields. No existing literature discloses the combination of all five of them at the same time; (3) Existing technologies generally treat Chinese medicine as a general-purpose additive and simply pile it up. They do not conduct compatibility design from the perspective of multi-target synergy, so they cannot solve the scalp problems of dandruff, inflammation, and itching at the same time and efficiently.

[0005] It is evident that there is a lack of existing technologies for shampoos containing traditional Chinese medicine compositions that are simple in ingredients, scientifically formulated, and capable of synergistically exerting the effects of dandruff removal, anti-inflammation, and anti-itch, in order to overcome the shortcomings of existing chemical dandruff removers, which are highly irritating and prone to recurrence, as well as the single efficacy and insufficient targeted formulation of existing traditional Chinese medicine shampoos and conditioners. Summary of the Invention

[0006] The purpose of this invention is to provide a dandruff-removing, anti-inflammatory, and antipruritic composition, its preparation method, and its application. This invention overcomes the shortcomings of existing chemical dandruff removers, such as high irritation and easy recurrence, as well as the single efficacy and insufficient targeted compatibility of existing traditional Chinese medicine shampoos and conditioners. It also solves the technical problem that existing plant-derived scalp care compositions lack targeted treatment of active ingredients of different properties, resulting in insufficient utilization and synergistic effects of effective ingredients, making it difficult to simultaneously achieve antibacterial, dandruff-removing, anti-inflammatory, and antipruritic effects.

[0007] The objective of this invention can be achieved through the following technical solutions: A method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition includes the following steps: S1. The powders of Platycladus orientalis leaves, Polygonum multiflorum, and Ligustrum lucidum were extracted by ultrasonic extraction using a eutectic solvent A composed of betaine, lactic acid, and deionized water, and the mother liquor A was obtained by filtration. S2. The white willow bark powder and Terminalia chebula pericarp powder were pre-swollen using eutectic solvent B, respectively. After enzymatic hydrolysis with cellulase and pectinase, enzyme inactivation, filtration, centrifugation and ultrafiltration, white willow bark extract and Terminalia chebula extract were obtained. S3. The Terminalia chebula extract is simultaneously treated with an immobilized tannin enzyme column and a first nanofiltration membrane to obtain a low-molecular-weight enzymatic hydrolysate and a concentrated tannin material, respectively. The white willow bark extract is mixed with the low-molecular-weight enzymatic hydrolysate, enriched by a second nanofiltration membrane, and then associated with betaine, glycerol, and deionized water to obtain an active associative system B1. The active associative system B1 is mixed with the concentrated tannin material and homogenized to obtain mother liquor B. S4. Add 7-9 parts by weight of the mother liquor B to 11-13 parts by weight of the mother liquor A, stir, homogenize and degas to obtain the final product.

[0008] As a preferred technical solution of the present invention, in step S1, the mass ratio of the arborvitae leaf powder, Polygonum multiflorum powder and Ligustrum lucidum powder is 6-8:5-7:6-8; the molar ratio of betaine to lactic acid in the eutectic solvent A is 1:0.7-0.9, and the total water content is 20-30wt%.

[0009] This invention is based on the differences in polarity, molecular weight, cell wall binding state and oxidative stability of the active ingredients in Platycladus orientalis leaves, Polygonum multiflorum, Ligustrum lucidum, Salix babylonica bark and Terminalia chebula. It adopts a technical route of extraction by different routes, directional enzymatic hydrolysis, simultaneous enzymatic hydrolysis-membrane separation, graded enrichment and recombination, and orderly compounding, rather than simply mixing the extracts of the five Chinese herbal medicines.

[0010] In step S1, eutectic solvent A, composed of betaine and lactic acid, is used to extract powders of Platycladus orientalis leaves, Polygonum multiflorum, and Ligustrum lucidum. A hydrogen bond network forms between betaine and lactic acid, exhibiting good solubilizing effects on flavonoid glycosides, stilbene glycosides, and iridoid glycosides. An appropriate amount of deionized water reduces the viscosity of the eutectic solvent, improving its penetration and mass transfer properties in plant tissues. Cavitation generated by ultrasonic treatment further disrupts plant tissues, promoting the release of quercetin, stilbene glycosides, and ligustrazine. Low-temperature, light-protected treatment helps reduce the oxidation of phenolic components and unnecessary transformations of anthraquinone components, keeping the main active ingredients and free emodin components in mother liquor A within controlled ranges.

[0011] As a preferred embodiment of the present invention, the eutectic solvent B is selected from any one of the following: choline chloride / 1,2-hexanediol molar ratio 1:2-4, betaine / glycerol molar ratio 1:1.3-1.7, choline chloride / ethylhexylglycerol molar ratio 1:2-3, choline chloride / 1,4-butanediol molar ratio 1:2-4, betaine / 1,2-hexanediol molar ratio 1:2-3, and betaine / ethylhexylglycerol molar ratio 1:2-4; the ratio of white willow bark powder to eutectic solvent B is 1:9-11 g / mL, and the ratio of Terminalia chebula pericarp powder to eutectic solvent B is 1:9-11 g / mL.

[0012] As a preferred embodiment of the present invention, the molar ratio of betaine to glycerol in the eutectic solvent B is 1:1.3-1.7, and the total water content is 20-30 wt%.

[0013] In step S2, the white willow bark powder and Terminalia chebula pericarp powder are pre-swollen using a eutectic solvent B composed of betaine and glycerol. This eutectic solvent wets the plant cell walls and weakens the hydrogen bonding between cellulose, pectin, and plant active ingredients. Subsequently, cellulase and pectinase are used to hydrolyze the cell wall skeletons of the two plant materials, releasing salicin from the white willow bark and hydrolyzable tannins from the Terminalia chebula. Separate enzymatic hydrolysis of the white willow bark and Terminalia chebula allows for control of the degree of hydrolysis based on the tissue structure and component release characteristics of the two materials, reducing mutual interference caused by co-hydrolysis. After enzymatic hydrolysis, enzyme inactivation, filtration, centrifugation, and 10 kDa ultrafiltration remove plant residues, inactivated enzyme proteins, and some macromolecular impurities, yielding a clear extract suitable for subsequent membrane separation.

[0014] In step S3, the immobilized tanninase selectively hydrolyzes the ester bonds and phenolic acid bonds in tannins from Terminalia chebula, converting some high-molecular-weight tannins into gallic acid and low-molecular-weight tannin fragments. The immobilized tanninase column operates synchronously with a first nanofiltration membrane with a nominal molecular weight cutoff of 500 Da, ensuring that low-molecular-weight enzymatic hydrolysis products enter the permeate side of the membrane in a timely manner, while unhydrolyzed or partially hydrolyzed high-molecular-weight tannins remain on the circulation side, achieving coupling of tannin-directed enzymatic hydrolysis and molecular weight fractionation. The immobilization method also reduces the amount of free enzyme entering the product and improves the controllability of the enzymatic hydrolysis process. After cutting out the immobilized tanninase column, constant-volume washing and filtration are performed to further transfer the low-molecular-weight enzymatic hydrolysis products and some small-molecule process media to the permeate, while the high-molecular-weight tannins on the membrane cutoff side are purified and concentrated, thereby obtaining low-molecular-weight enzymatic hydrolysate and concentrated tannin material, respectively.

[0015] The extract of white willow bark was mixed with a low-molecular-weight enzymatic hydrolysate and then processed through a negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da. This process utilizes size sieving and charge repulsion to enrich plant active ingredients such as salicin and gallic acid, and constant-volume washing filtration reduces the residues of buffer salts, eutectic solvent components, and other small-molecule process media. Low-temperature vacuum concentration can increase the concentration of plant active ingredients while minimizing thermal oxidation.

[0016] Betaine, glycerol, and deionized water were quantitatively added to the obtained low-molecular-weight plant active concentrate to induce multi-point hydrogen bonding and solvation between betaine, glycerol, and active ingredients containing hydroxyl or carboxyl groups, such as salicin and gallic acid. After nitrogen protection, isothermal stirring, and programmed cooling, a non-covalent active association system B1 with controlled composition was obtained. This association system does not generate new compounds through covalent reactions, but rather improves the dispersion state of the low-molecular-weight active ingredients and reduces their tendency to crystallize, aggregate, and oxidize through hydrogen bonding and solvation.

[0017] The active associative system B1 was remixed with the concentrated tannin material, so that the mother liquor B contained both low-molecular-weight active ingredients such as salicin and gallic acid, and higher-molecular-weight tannins such as chebulic tannic acid, chebulic tannin acid, and corilagin. The low-molecular-weight components have good aqueous dispersion and diffusion capabilities, while the higher-molecular-weight tannins have strong surface adsorption, astringency, and retention properties, thus forming a plant polyphenol system with complementary molecular weight levels.

[0018] Finally, mother liquor B is added to mother liquor A. By controlling the order of addition, stirring, nitrogen protection for homogenization, and vacuum degassing, the two types of mother liquors are evenly dispersed, reducing the aggregation or precipitation caused by excessively high local tannin concentrations. At the same time, the dissolved oxygen and bubble content in the system are reduced, resulting in a homogeneous five-component traditional Chinese medicine composition.

[0019] As a preferred technical solution of the present invention, in step S1, the ratio of the crude medicinal powder A composed of the arborvitae leaf powder, Polygonum multiflorum powder and Ligustrum lucidum powder to the eutectic solvent A is 1:16-20 g / mL, and the mixture is treated in the dark at 40-44℃ and ultrasonic power density of 70-90 W / L for 30-40 min; the mass fractions of quercetin, stilbene glycoside, privetin, free emodin and free emodin methyl ether in the resulting mother liquor A are 0.0033-0.0038%, 0.0248-0.0277%, 0.0278-0.0310%, 0.00010-0.00012% and 0.00013-0.00015%, respectively.

[0020] As a preferred embodiment of the present invention, in step S2, the ratio of the white willow bark powder to the eutectic solvent B is 1:9-11 g / mL, and the ratio of the Terminalia chebula peel powder to the eutectic solvent B is 1:9-11 g / mL.

[0021] As a preferred embodiment of the present invention, in step S2, the pH of the enzymatic hydrolysis systems of white willow bark powder and Terminalia chebula peel powder is adjusted to 4.6-5.0 using a citrate-sodium citrate buffer solution with a concentration of 0.08-0.12 mol / L. 1.0-2.0 g of cellulase and 0.5-1.3 g of pectinase are added per 100 g of white willow bark powder for enzymatic hydrolysis; 1.0-2.0 g of cellulase and 0.5-1.3 g of pectinase are added per 100 g of Terminalia chebula peel powder for enzymatic hydrolysis. After enzymatic hydrolysis, the enzymatic hydrolysis systems of white willow bark powder and Terminalia chebula peel powder are heated to 78-84°C under nitrogen protection and maintained for 8-10 min, and then treated with 100-mesh filtration, centrifugation at 3000×g for 10 min, and ultrafiltration membrane with a molecular weight cutoff of 10 kDa, respectively.

[0022] In a preferred embodiment of the present invention, in step S3, the immobilized tanninase column has an inner diameter of 50 mm and an effective column length of 260-340 mm, and is filled with immobilized tanninase microspheres obtained by immobilizing 90-120 g of tanninase preparation; the Terminalia chebula extract is adjusted to 36-40℃ and pH 5.0-5.4, and circulated through the immobilized tanninase column at a rate of 300-400 mL / min, while simultaneously passing through a membrane with a nominal molecular weight cutoff of 500 Da and an effective membrane area of ​​0.45-0.55 m². 2 The first nanofiltration membrane has a transmembrane pressure of 0.9-1.1 MPa, a permeate collection flow rate of 25-40 g / min, and a synchronous treatment time of 30-48 min. After the synchronous treatment, the immobilized tannin enzyme column is cut out from the circulation pipeline, and deionized water is used as the washing medium. The first nanofiltration membrane retentate is washed with a constant volume for 120-192 min at the same water replenishment flow rate as the permeate collection flow rate. The permeates from the first nanofiltration membrane obtained from the synchronous treatment and constant volume washing are combined to obtain the low molecular weight enzymatic hydrolysate. The first nanofiltration membrane retentate after constant volume washing is concentrated under reduced pressure at 43-47℃ and an absolute pressure of 8-12 kPa to obtain the concentrated tannin material.

[0023] In a preferred embodiment of the present invention, in step S3, the mass ratio of the white willow bark extract to the low-molecular-weight enzymatic hydrolysate is 1-1.3:1; the second nanofiltration membrane is a negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da, a nanofiltration temperature of 28-32℃, and an effective membrane area of ​​0.45-0.55 m². 2 The transmembrane pressure is 1.8-2.2 MPa. First, concentrate the retentate from the second nanofiltration membrane to 1.40-1.60 L. Then, while keeping the volume of the retentate constant, add deionized water at a flow rate of 27-33 g / min and perform constant volume washing filtration for 150 min.

[0024] As a preferred embodiment of the present invention, the second nanofiltration membrane retentate is concentrated under reduced pressure at 43-47℃ and 8-12kPa absolute pressure; betaine, glycerol, and deionized water are added to the obtained low-molecular-weight plant active concentrate, with the mass ratio of added betaine to glycerol being 1:5.3-5.5, and the mass of added deionized water being 6.0-7.7 times the mass of added betaine; the mixture is stirred for 40-50 minutes at 52-58℃ and 280-320r / min under nitrogen protection, and then cooled to 28-32℃ at 1℃ / min to obtain active association system B1; the mass ratio of active association system B1 to concentrated tannin material is 4:1, and the mixture is homogenized at 6000-7000r / min for 5-7 minutes.

[0025] As a preferred embodiment of the present invention, the mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin, and free salicylic acid in the obtained mother liquor B are 3.6000-5.6000%, 2.5429-2.6741%, 3.5000-3.8000%, 2.7200-3.0000%, 1.3400-1.5000%, and 0.00050-0.00070%, respectively. In step S4, the mass ratio of mother liquor A to mother liquor B is 11-13:7-9. Mother liquor B is added to mother liquor A, stirred for 12-18 minutes, and then homogenized at 6000-7000 r / min for 5-7 minutes under nitrogen protection, and the mixture is then subjected to a pressure of [insert pressure here]. 0.09~ Degas for 4-6 minutes at 0.07 MPa.

[0026] Another object of the present invention is to provide an anti-dandruff, anti-inflammatory and antipruritic composition.

[0027] Another object of the present invention is to provide an anti-dandruff, anti-inflammatory and antipruritic composition for use in the preparation of scalp cleansing or care products for inhibiting Malassezia, reducing dandruff, relieving scalp itching and / or reducing scalp inflammation.

[0028] The beneficial effects of this invention are: (1) Based on the differences in the properties of the active ingredients in the five plant raw materials, the present invention uses betaine-lactic acid eutectic solvent for differential extraction, and combines ultrasonic treatment, cell wall enzymatic hydrolysis, ultrafiltration clarification and low temperature concentration to promote the release of flavonoid glycosides, stilbene glycosides, iridoid glycosides, salicin and tannins, reduce the insufficient extraction selectivity caused by the common water extraction or simple mixing of the five Chinese medicines, and improve the utilization rate of plant active ingredients.

[0029] (2) In this invention, an immobilized tannin enzyme column is simultaneously treated with a first nanofiltration membrane to convert some of the higher molecular weight hydrolyzable tannins in Terminalia chebula into low molecular weight phenols such as gallic acid, and low molecular weight enzymatic hydrolysate and concentrated tannin material are obtained simultaneously. Then, a second nanofiltration membrane is used to enrich active ingredients such as salicin and gallic acid, and their solubilization and dispersion are improved in the presence of betaine, glycerol and deionized water. Finally, they are recombined with the concentrated tannin material in proportion. This forms a graded plant polyphenol system in which low molecular weight active ingredients and higher molecular weight tannins coexist. This avoids the loss of function of higher molecular weight tannins due to complete enzymatic hydrolysis of tannins, and also avoids the insufficient content of low molecular weight phenols when not enzymatically hydrolyzed. It is beneficial to take into account both the aqueous diffusion of low molecular weight components and the adsorption, astringency and retention of higher molecular weight tannins on the scalp surface.

[0030] (3) This invention reduces the oxidation, local aggregation, and residual bubbles of phenolic active ingredients during the preparation process by using nitrogen protection, low-temperature vacuum concentration, controlled feeding, homogenization, and vacuum degassing, which helps improve the uniformity and storage stability of the composition. While retaining salicin, flavonoid glycosides, stilbene glycosides, and tannins, it reduces the risk of scalp irritation that may be caused by excessively high levels of free salicylic acid and free anthraquinones. Betaine and glycerin also provide moisturizing and solubilizing effects, allowing the composition to provide dandruff removal while also ensuring scalp comfort.

[0031] (4) The five synergistic effects of Platycladus orientalis leaves, Polygonum multiflorum, Ligustrum lucidum, Salix babylonica bark, and Terminalia chebula used in this invention target the dandruff formation process: the flavonoids in Platycladus orientalis leaves mainly inhibit Malassezia and reduce inflammation; the stilbene glycosides in Polygonum multiflorum mainly exert antioxidant, anti-inflammatory, and scalp-care effects; the iridoid glycosides such as ligustrazine in Ligustrum lucidum mainly exert antioxidant and anti-inflammatory effects; the salicin in Salix babylonica bark mainly exerts mild keratin conditioning, anti-inflammatory, and soothing effects; and the gallic acid and higher molecular weight tannins obtained from Terminalia chebula through directional enzymatic hydrolysis and fractionation respectively exert antibacterial, anti-inflammatory, astringent, adsorbent, and scalp-surface retention effects. These five plant active ingredients thus form a chain of action: inhibiting Malassezia - regulating abnormal keratin shedding - reducing inflammation - relieving itching - maintaining scalp condition. This helps to block the cycle of excessive Malassezia proliferation, inflammation, dandruff formation, and itching / scratching, thereby achieving synergistic improvement in dandruff removal, anti-inflammation, and itch relief.

[0032] (5) The anti-dandruff, anti-inflammatory and antipruritic composition obtained in this invention also exhibits an inhibitory effect on type I 5α-reductase activity. The use of differential extraction with low eutectic solvent, nanofiltration fractional enrichment and compounding of mother liquor A and mother liquor B are beneficial to improving the inhibitory ability of the obtained composition on type I 5α-reductase activity. This allows the obtained composition to not only exert anti-dandruff, anti-inflammatory and antipruritic effects, but also to further assist in regulating scalp sebum secretion. Detailed Implementation

[0033] The materials used in the following specific embodiments are sourced as follows: Cellulase was purchased from Shanghai Yuanye Biotechnology Co., Ltd., CAS No. 9012-54-8, catalog number S10041, with a nominal enzyme activity of 50 U / mg; pectinase was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., CAS No. 9032-75-1, catalog number P816736, with a nominal enzyme activity of 30000 U / g; tanninase was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., CAS No. 9025-71-2, catalog number T861423, with a nominal enzyme activity of 200 U / g. Unless otherwise stated, the amounts of cellulase, pectinase, and tanninase are based on the mass of the commercial enzyme preparation, and the enzyme activity is determined according to the method specified in the respective product instructions.

[0034] Immobilized tanninase was achieved using calcium alginate-chitosan composite microspheres as a carrier, cross-linked and immobilized with glutaraldehyde. The specific method is as follows: A 3% sodium alginate solution was prepared using a 0.05 mol / L citrate-sodium citrate buffer solution with a pH of 5.2. At 4°C, the tanninase preparation was mixed with the sodium alginate solution at a mass ratio of 1:4, and the mixture was slowly stirred for 20 min, avoiding the introduction of air bubbles. The resulting mixture was then dropped into a 2% calcium chloride solution at 4°C using a dropper with an inner diameter of 1.2 mm, forming calcium alginate microspheres with a particle size of 3 ± 0.5 mm. The mixture was then further solidified at 4°C for 2 h. After washing the microspheres three times with the aforementioned buffer solution, the microspheres were immersed in a 0.5% chitosan solution at a wet mass to treatment solution volume ratio of 1 g: 5 mL. The chitosan solution was prepared with a 1% aqueous acetic acid solution and adjusted to pH 5.5. After coating at 4°C for 30 min, the microspheres were transferred to a 0.2% glutaraldehyde solution prepared with the aforementioned buffer at the same solid-liquid ratio and crosslinked at 4°C for 30 min. The microspheres were repeatedly washed with the buffer solution until no free protein, free tanninase activity, or residual glutaraldehyde was detected in the washings, yielding immobilized tanninase microspheres. In the following examples, the immobilized enzyme activity recovery rate was 75.0%. The immobilized tanninase microspheres were stored at 4°C and used within 24 hours of preparation.

[0035] Example 1 Powdered arborvitae leaves, Polygonum multiflorum, and Ligustrum lucidum were mixed evenly in a mass ratio of 7:6:7 to obtain 600g of crude medicinal powder A. Betaine and lactic acid were mixed in a molar ratio of 1:0.8 and stirred at 60℃ and 300r / min for 40min. Deionized water was added to prepare a eutectic solvent A with a total water content of 25wt%. At a material-to-liquid ratio of 1:18g / mL, 10.8L of eutectic solvent A was added to 600g of crude medicinal powder A. The mixture was stirred at 25℃ for 10min, then heated to 42℃ and treated in the dark at an ultrasonic power density of 80W / L for 35min. After treatment, the mixture was filtered through a 100-mesh sieve. The filter residue was washed with 0.54L of eutectic solvent A. The filtrates were combined to obtain 11.4kg of mother liquor A containing eutectic solvent A. According to high performance liquid chromatography, the mass fractions of quercetin, stilbene glycoside, privetin, free emodin, and free emodin methyl ether in the mother liquor A were 0.0037%, 0.0273%, 0.0308%, 0.00012%, and 0.00015%, respectively.

[0036] Betaine and glycerol were mixed at a molar ratio of 1:1.5 and stirred at 65℃ and 300 rpm for 35 min. Deionized water was added to prepare a eutectic solvent B with a total water content of 25 wt%. 650 g of white willow bark powder was added to 6.5 L of eutectic solvent B and pre-swelled at 40℃ and an ultrasonic power density of 80 W / L for 15 min. The pH of the system was adjusted to 4.8 ± 0.1 by adding 650 mL of 0.1 mol / L citrate-sodium citrate buffer solution (pH 4.8). 10 g of cellulase and 7.5 g of pectinase were added, and the mixture was enzymatically hydrolyzed at 43℃ and 150 rpm for 60 min. After enzymatic hydrolysis, the system was transferred to a sealed reactor equipped with a stirrer, reflux condenser, and pressure balancing device. Nitrogen gas was introduced for 3 minutes to replace the air at the top of the reactor. The temperature was increased at 100 r / min, and the enzyme was inactivated by maintaining the temperature at the center of the system at 80±2℃ for 8 minutes. Then, the temperature was reduced to 37℃ over 15 minutes. The enzyme-inactivated system was filtered through a 100-mesh sieve and centrifuged at 3000×g for 10 minutes. The supernatant was then passed through an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. The filter residue and ultrafiltration membrane system were washed with a 0.1 mol / L citrate-sodium citrate buffer solution at pH 4.8. The wash solution and ultrafiltration permeate were combined and quantified to 6900 g to obtain the white willow bark extract. 350 g of dried mature Terminalia chebula pericarp was crushed and passed through a 30-mesh sieve. 3.5 L of eutectic solvent B was added, and the mixture was pre-swelled at 40℃ and ultrasonic power density of 80 W / L for 15 minutes. Add 350 mL of the above-mentioned citrate-sodium citrate buffer (pH 4.8) to the system to adjust the pH to 4.8 ± 0.1. Add 5 g of cellulase and 2.5 g of pectinase, and incubate at 43℃ and 150 r / min for 80 min. After enzymatic hydrolysis, process the system using the same closed-loop enzyme inactivation, filtration, centrifugation, and 10 kDa ultrafiltration method as the white willow bark system. Wash the filter residue and ultrafiltration membrane system with the above-mentioned citrate-sodium citrate buffer (pH 4.8). Combine the washing liquid and the ultrafiltration permeate and measure to 3450 g to obtain the Terminalia chebula extract.

[0037] An immobilized tanninase column with an inner diameter of 50 mm and an effective column length of 300 mm was used. Following the immobilization method described above, 105 g of tanninase preparation was mixed with 420 g of 3% sodium alginate solution. The nominal total enzyme activity of the added tanninase preparation before immobilization was 21000 U. The enzyme activity recovery rate of the resulting immobilized tanninase microspheres was 75.0%, and the measured total enzyme activity after immobilization was 15750 U. All the obtained immobilized tanninase microspheres were loaded into the immobilized tanninase column. The Terminalia chebula extract was heated to 38℃, and under stirring at 150 r / min, the pH of the system was adjusted to 5.2 ± 0.1 using a 0.1 mol / L citrate-sodium citrate buffer solution with a pH of 5.2. The pH-adjusted Terminalia chebula extract was circulated through the immobilized tanninase column at a flow rate of 350 mL / min, while simultaneously ensuring that the circulating liquid passed through an effective membrane area of ​​0.50 m². 2 A tubular ceramic nanofiltration membrane with a molecular weight cutoff of 500 Da was used as the first nanofiltration membrane for tangential flow separation, with the transmembrane pressure controlled at 1.0 ± 0.1 MPa. The permeate from the first nanofiltration membrane was continuously collected at a mass flow rate of 30 g / min, and deionized water was added at the same mass flow rate to maintain the mass of the circulating system within ±2% of the initial mass. An immobilized tannin enzyme column was then used in synergistic treatment with the first nanofiltration membrane for 40 min, accumulating 1200 g of initial low-molecular-weight enzymatic hydrolysis permeate.

[0038] After the co-processing was completed, the immobilized tanninase column was cut out of the circulation tubing, and the first nanofiltration membrane retentate was washed with constant volume. Deionized water was added at a flow rate of 30 g / min, and the washing permeate was collected at the same flow rate. The washing process was repeated for 160 min, with a total of 4800 g of deionized water added and 4800 g of washing permeate collected. At the end of the washing process, the mass fractions of betaine and glycerol from the extraction medium in the first nanofiltration membrane retentate relative to the plant-derived dry solids were 0.141% and 0.353%, respectively. The initial low-molecular-weight enzymatic hydrolysis permeate and the washing permeate were combined to obtain 6000 g of low-molecular-weight enzymatic hydrolysate. The low-molecular-weight enzymatic hydrolysate had gallic acid as the main plant-derived marker component, and also contained chebulic acid, ellagic acid, protocatechuic acid, a small amount of methyl gallate, monosaccharides and oligosaccharides, as well as betaine and glycerol introduced by the eutectic solvent B and citrate introduced by the buffer solution. The retentate from the first nanofiltration membrane was collected and placed in a vacuum concentrator equipped with a stirrer. Concentration was carried out under reduced pressure at 45±2℃, 10±2 kPa absolute pressure, and 100 r / min to obtain 80 g of concentrated tannin material. High-performance liquid chromatography (HPLC) analysis revealed that the concentrated tannin material contained 15.2 g of chebulic tannic acid, 12 g of chebulic tanninic acid, 6 g of corilagin, 0.08 g of betaine, 0.2 g of glycerol, and 20 g of water (from the extraction medium), 23.5 g of other plant-derived dry solids, and 3.02 g of residual solids from non-plant-derived process media such as citric acid-sodium citrate buffer and enzyme excipients.

[0039] White willow bark extract and low-molecular-weight enzymatic hydrolysate were mixed at a mass ratio of 23:20 to obtain a mixed low-molecular-weight extract. The pH of the mixed low-molecular-weight extract was adjusted to 4.8 ± 0.1 using a 0.1 mol / L citrate-sodium citrate buffer solution with a pH of 4.8. The extract was then subjected to a 0.50 m² / g membrane at 30°C. 2 A negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da was used as the second nanofiltration membrane for concentration, with the transmembrane pressure controlled at 2.0 ± 0.1 MPa. The retentate was first concentrated to 1.50 ± 0.05 L. Then, while maintaining the retentate volume at 1.50 ± 0.05 L, deionized water was added at a mass flow rate of 30 g / min, and the permeate was collected at the same flow rate. This washing process was repeated for 150 min, with a cumulative addition of 4500 g of deionized water. The second nanofiltration membrane retentate was then placed in a vacuum concentrator and concentrated under reduced pressure at 45 ± 2 °C and an absolute pressure of 10 ± 2 kPa to obtain 125.9683 g of low-molecular-weight plant bioactive concentrate. The Karl Fischer method determined that the water content of the low-molecular-weight plant bioactive concentrate was 12 g, and the total dry solids were 113.9683 g. The total solids contained 18g of salicin, 10.6964g of gallic acid, 0.2g of betaine from the extraction medium, and 0.5g of glycerol; the residual solids from the non-plant-derived process medium were 4.5719g, which mainly included citrate-sodium citrate buffer, enzyme-soluble excipients, and other non-plant-derived non-volatile substances remaining from the membrane treatment process. 14.5317g of betaine, 79.5g of glycerol, and 100g of deionized water were added to the low-molecular-weight plant-active concentrate. The mixture was stirred for 45min at 55℃ and 300r / min under nitrogen protection, and then cooled to 30℃ at a rate of 1℃ / min to obtain the active association system B1.

[0040] The active associative system B1 was mixed with concentrated tannin material at a mass ratio of 4:1, stirred for 20 min at 30±2℃ and 300 r / min, and then homogenized for 6 min at 6500 r / min under nitrogen protection to obtain mother liquor B. High performance liquid chromatography (HPLC) analysis showed that the mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin, and free salicylic acid in mother liquor B were 4.5000%, 2.6741%, 3.8000%, 3.0000%, 1.5000%, and 0.00050%, respectively. 600 g of mother liquor A was added to a sealed homogenizing tank equipped with a jacket, stirring device, and nitrogen protection device, and stirred at 30±2℃ and 300 r / min. 400 g of mother liquor B was added to mother liquor A at a uniform rate over 12 min, and stirring was continued at 300 r / min for 15 min to obtain a premix. The resulting premixed solution was homogenized at 6500 r / min for 6 min under nitrogen protection, and then homogenized at 100 r / min under vacuum. Degassing at 0.08 MPa for 5 min yielded an anti-dandruff, anti-inflammatory, and antipruritic composition.

[0041] Example 2 The difference from Example 1 is that 550g of crude herbal powder A was obtained by mixing arborvitae leaf powder, Polygonum multiflorum powder, and Ligustrum lucidum powder in a mass ratio of 6:5:6. Betaine and lactic acid were mixed in a molar ratio of 1:0.7 and stirred at 55°C and 300 rpm for 35 min. Deionized water was added to prepare a eutectic solvent A with a total water content of 20 wt%. 8.8 L of eutectic solvent A was added to 550g of crude herbal powder A at a material-to-liquid ratio of 1:16 g / mL. The mixture was stirred at 23°C for 8 min, then heated to 40°C and treated in the dark at an ultrasonic power density of 70 W / L for 30 min. After treatment, the mixture was filtered through a 100-mesh sieve. The filter residue was washed with 0.44 L of eutectic solvent A. The filtrates were combined and weighed to 9.24 kg using eutectic solvent A to obtain mother liquor A. According to high performance liquid chromatography, the mass fractions of quercetin, stilbene glycoside, privetin, free emodin, and free emodin methyl ether in the mother liquor A were 0.0038%, 0.0277%, 0.0310%, 0.00011%, and 0.00014%, respectively.

[0042] Betaine and glycerol were mixed at a molar ratio of 1:1.3 and stirred at 60℃ and 300 rpm for 30 min. Deionized water was added to prepare a eutectic solvent B with a total water content of 20 wt%. 600 g of white willow bark powder was added to 5.4 L of eutectic solvent B and pre-swelled at 38℃ and an ultrasonic power density of 70 W / L for 10 min. 600 mL of a 0.08 mol / L citrate-sodium citrate buffer solution (pH 4.6) was added to the system to adjust the pH to 4.6 ± 0.1. 8 g of cellulase and 6 g of pectinase were added, and enzymatic hydrolysis was performed at 41℃ and 130 rpm for 50 min. After enzymatic hydrolysis, the system was transferred to a sealed reactor equipped with a stirrer, reflux condenser, and pressure balancing device. Nitrogen gas was introduced for 3 minutes to replace the air at the top of the reactor. The temperature was increased at 100 rpm, and the enzyme was inactivated by maintaining the temperature at the center of the system at 80±2℃ for 8 minutes. Then, the temperature was reduced to 35℃ over 12 minutes. The enzyme-inactivated system was filtered through a 100-mesh sieve and centrifuged at 3000×g for 10 minutes. The supernatant was then passed through an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. The filter residue and ultrafiltration membrane system were washed with a 0.08 mol / L citrate-sodium citrate buffer solution at pH 4.6. The washing liquid and ultrafiltration permeate were combined and quantified to 6000g to obtain the white willow bark extract. 400g of dried mature Terminalia chebula pericarp was crushed and passed through a 30-mesh sieve. 3.6L of eutectic solvent B was added, and the mixture was pre-swelled at 38℃ and an ultrasonic power density of 70W / L for 10 minutes. Add 400 mL of 0.08 mol / L citrate-sodium citrate buffer (pH 4.6) to the system to adjust the pH to 4.6 ± 0.1. Add 4 g of cellulase and 2 g of pectinase, and incubate at 41 °C and 130 rpm for 70 min. After incubation, process the extract using the same closed-loop enzyme inactivation, filtration, centrifugation, and 10 kDa ultrafiltration method as the white willow bark system. Wash the filter residue and ultrafiltration membrane system with the aforementioned buffer solution. Combine the washing liquid and ultrafiltration permeate and dilute to 4000 g to obtain the Terminalia chebula extract. Use an immobilized tanninase column with an inner diameter of 50 mm and an effective column length of 260 mm. Following the immobilization method described above, 90g of tannin enzyme preparation was mixed with 360g of 3% sodium alginate solution. The nominal total enzyme activity of the added tannin enzyme preparation before immobilization was 18000U. The enzyme activity recovery rate of the resulting immobilized tannin enzyme microspheres was 75.0%, and the measured total enzyme activity after immobilization was 13500U. All the resulting immobilized tannin enzyme microspheres were loaded into the immobilized tannin enzyme column. The Terminalia chebula extract was heated to 36℃, and the pH of the system was adjusted to 5.0±0.1 using a 0.08mol / L citrate-sodium citrate buffer solution with a pH of 5.0 under stirring at 150r / min.The pH-adjusted Terminalia chebula extract was passed through the immobilized tannin enzyme column at a circulation flow rate of 300 mL / min, while the circulating liquid passed through an effective membrane area of ​​0.45 m². 2 A tubular ceramic nanofiltration membrane with a nominal molecular weight cutoff of 500 Da was used as the first nanofiltration membrane for tangential flow separation, with the transmembrane pressure controlled at 0.9 ± 0.1 MPa. The permeate from the first nanofiltration membrane was continuously collected at a mass flow rate of 25 g / min, and deionized water was added at the same mass flow rate to maintain the circulating system mass within ±2% of the initial mass. An immobilized tanninase column was co-treated with the first nanofiltration membrane for 48 min, accumulating 1200 g of initial low-molecular-weight enzymatic hydrolysis permeate. After co-treatment, the immobilized tanninase column was removed from the circulation tubing, and the first nanofiltration membrane retentate was continuously washed with constant volume. Deionized water was added at a mass flow rate of 25 g / min, and the washing permeate was collected at the same mass flow rate. This washing process was repeated for 192 min, accumulating 4800 g of deionized water added and 4800 g of washing permeate collected. The initial low-molecular-weight enzymatic hydrolysis permeate and the washing permeate were combined to obtain 6000 g of low-molecular-weight enzymatic hydrolysate. The low-molecular-weight enzymatic hydrolysate contains gallic acid as the main plant-derived marker component, along with chebulic acid, ellagic acid, protocatechuic acid, a small amount of methyl gallate, monosaccharides, and oligosaccharides. It also contains betaine and glycerol introduced by the eutectic solvent B, and citrate introduced by the buffer solution. At the end of washing and filtration, the mass fractions of betaine and glycerol from the extraction medium in the first nanofiltration membrane retentate relative to the plant-derived dry solids were 0.170% and 0.425%, respectively. The first nanofiltration membrane retentate was collected and placed in a vacuum concentrator equipped with a stirrer. Concentration was carried out under reduced pressure at 43±2℃, 12±2 kPa, and 100 r / min to obtain 90 g of concentrated tannin material. Analytical analysis using high-performance liquid chromatography revealed that the concentrated tannin material contained 15.75g of chebulic tannic acid, 12.24g of chebulic tanninic acid, and 6.03g of corilagin. Analysis of residual process media and moisture content showed that the concentrated tannin material also contained 0.135g of betaine, 0.3375g of glycerol, 24.75g of water, 24.0075g of other plant-derived dry solids, and 6.75g of non-plant-derived process media residual solids such as citric acid-sodium citrate buffer and enzyme excipients.

[0043] The bark extract of white willow was mixed with a low-molecular-weight enzymatic hydrolysate at a mass ratio of 20:20 to obtain a mixed low-molecular-weight extract. The pH of the mixed low-molecular-weight extract was adjusted to 4.6 ± 0.1 using a 0.08 mol / L citrate-sodium citrate buffer solution with a pH of 4.6. The extract was then subjected to a membrane with an effective membrane area of ​​0.45 m² at 28℃. 2A negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da was used as the second nanofiltration membrane for concentration, and the transmembrane pressure was controlled at 1.8 ± 0.1 MPa. The retentate was first concentrated to 1.40 ± 0.05 L. Then, while maintaining the retentate volume at 1.40 ± 0.05 L, deionized water was added at a mass flow rate of 27 g / min, and the permeate was collected at the same mass flow rate. The washing process was repeated for 150 min, with a cumulative addition of 4050 g of deionized water.

[0044] The retentate from the second nanofiltration membrane was placed in a vacuum concentrator and concentrated under reduced pressure at 43±2℃ and 12±2 kPa to obtain 140.40 g of low-molecular-weight plant active concentrate. The water content was determined to be 14.0625 g and the total dry solids to be 126.3375 g by Karl Fischer titration. The low-molecular-weight plant active concentrate contained 16.20 g of salicin, 11.80 g of gallic acid, 0.2925 g of betaine, 0.6975 g of glycerol, 5.6813 g of non-plant-derived process media residue solids, and 91.6662 g of other plant-derived dry solids. 15.6375 g of betaine, 83.6775 g of glycerol, and 120.285 g of deionized water were added to the low-molecular-weight plant active concentrate. The mixture was stirred for 40 min at 52 °C and 280 r / min under nitrogen protection, and then cooled to 28 °C at a rate of 1 °C / min to obtain 360 g of active association system B1. 360 g of active association system B1 was mixed with 90 g of concentrated tannin material and stirred for 15 min at 28 ± 2 °C and 280 r / min. The mixture was then homogenized for 5 min at 6000 r / min under nitrogen protection to obtain 450 g of mother liquor B. According to high performance liquid chromatography, the mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin and free salicylic acid in the mother liquor B were 3.6000%, 2.6222%, 3.5000%, 2.7200%, 1.3400% and 0.00060%, respectively.

[0045] Add 550g of mother liquor A to a sealed homogenizer equipped with a jacket, stirring device, and nitrogen protection device, and stir at 28±2℃ and 280r / min. Add 450g of mother liquor B to mother liquor A at a uniform rate over 15min, and continue stirring at 280r / min for 12min to obtain a premix. Homogenize the obtained premix at 6000r / min for 5min under nitrogen protection, and then homogenize at 100r / min and a vacuum degree of [missing value]. Degassing at 0.07 MPa for 4 minutes yielded an anti-dandruff, anti-inflammatory, and antipruritic composition.

[0046] Example 3 The difference from Example 1 is that 650g of crude herbal powder A was obtained by uniformly mixing arborvitae leaf powder, Polygonum multiflorum powder, and Ligustrum lucidum powder in a mass ratio of 8:7:8. Betaine and lactic acid were mixed in a molar ratio of 1:0.9 and stirred at 65°C and 300 rpm for 45 min. Deionized water was added to prepare a eutectic solvent A with a total water content of 30 wt%. 13.0 L of eutectic solvent A was added to 650g of crude herbal powder A at a material-to-liquid ratio of 1:20 g / mL. The mixture was stirred at 27°C for 12 min, then heated to 44°C and treated in the dark at an ultrasonic power density of 90 W / L for 40 min. After treatment, the mixture was filtered through a 100-mesh sieve. The filter residue was washed with 0.65 L of eutectic solvent A. The filtrates were combined and weighed to 13.65 kg using eutectic solvent A to obtain mother liquor A. According to high performance liquid chromatography, the mass fractions of quercetin, stilbene glycoside, privetin, free emodin, and free emodin methyl ether in the mother liquor A were 0.0033%, 0.0248%, 0.0278%, 0.00010%, and 0.00013%, respectively.

[0047] Betaine and glycerol were mixed at a molar ratio of 1:1.7 and stirred at 70℃ and 300 rpm for 40 min. Deionized water was added to prepare a eutectic solvent B with a total water content of 30 wt%. 700 g of white willow bark powder was added to 7.7 L of eutectic solvent B and pre-swelled at 42℃ and an ultrasonic power density of 90 W / L for 20 min. 700 mL of a 0.12 mol / L citrate-sodium citrate buffer solution (pH 5.0) was added to the system to adjust the pH to 5.0 ± 0.1. 12 g of cellulase and 9 g of pectinase were added, and enzymatic hydrolysis was performed at 45℃ and 170 rpm for 70 min. After enzymatic hydrolysis, the system was transferred to a sealed reactor equipped with a stirrer, reflux condenser, and pressure balancing device. Nitrogen gas was introduced for 3 minutes to replace the air at the top of the reactor. The temperature was increased at 100 r / min, and the enzyme was inactivated after the center temperature of the system reached 82±2℃ for 10 minutes. Then, the temperature was reduced to 39℃ over 18 minutes. The enzyme-inactivated system was filtered through a 100-mesh sieve and centrifuged at 3000×g for 10 minutes. The supernatant was then passed through an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. The filter residue and ultrafiltration membrane system were washed with a 0.12 mol / L citrate-sodium citrate buffer solution at pH 5.0. The wash solution and ultrafiltration permeate were combined and quantified to 7800 g to obtain the white willow bark extract. 300 g of dried mature Terminalia chebula pericarp was crushed and passed through a 30-mesh sieve. 3.3 L of eutectic solvent B was added, and the mixture was pre-swelled at 42℃ and ultrasonic power density of 90 W / L for 20 minutes. Add 300 mL of 0.12 mol / L citrate-sodium citrate buffer (pH 5.0) to the system to adjust the pH to 5.0 ± 0.1. Add 6 g of cellulase and 3 g of pectinase, and incubate at 45 °C and 170 rpm for 90 min. After incubation, process the extract using the same closed-loop enzyme inactivation, filtration, centrifugation, and 10 kDa ultrafiltration method as the white willow bark system. Wash the filter residue and ultrafiltration membrane system with the aforementioned buffer solution. Combine the washing liquid and ultrafiltration permeate and dilute to 3000 g to obtain the Terminalia chebula extract. Use an immobilized tanninase column with an inner diameter of 50 mm and an effective column length of 340 mm. Following the immobilization method described above, 120g of tannin enzyme preparation was mixed with 480g of 3% sodium alginate solution. The nominal total enzyme activity of the tannin enzyme preparation added before immobilization was 24000U. The enzyme activity recovery rate of the resulting immobilized tannin enzyme microspheres was 75.0%, and the measured total enzyme activity after immobilization was 18000U. All the resulting immobilized tannin enzyme microspheres were loaded into the immobilized tannin enzyme column. The Terminalia chebula extract was heated to 40℃, and the pH of the system was adjusted to 5.4±0.1 using a 0.12mol / L citrate-sodium citrate buffer solution with a pH of 5.4 under stirring at 150r / min.The pH-adjusted Terminalia chebula extract was passed through the immobilized tannin enzyme column at a circulation flow rate of 400 mL / min, while the circulating liquid passed through an effective membrane area of ​​0.55 m². 2 A tubular ceramic nanofiltration membrane with a nominal molecular weight cutoff of 500 Da was used as the first nanofiltration membrane for tangential flow separation, with the transmembrane pressure controlled at 1.1 ± 0.1 MPa. The permeate from the first nanofiltration membrane was continuously collected at a mass flow rate of 40 g / min, and deionized water was added at the same mass flow rate to maintain the circulating system mass within ±2% of the initial mass. An immobilized tanninase column was co-treated with the first nanofiltration membrane for 30 min, accumulating 1200 g of initial low-molecular-weight enzymatic hydrolysis permeate. After co-treatment, the immobilized tanninase column was removed from the circulation tubing, and the first nanofiltration membrane retentate was continuously washed with constant volume. Deionized water was added at a mass flow rate of 40 g / min, and the washing permeate was collected at the same mass flow rate. This washing process was repeated for 120 min, accumulating 4800 g of deionized water added and 4800 g of washing permeate collected. The initial low-molecular-weight enzymatic hydrolysis permeate and the washing permeate were combined to obtain 6000 g of low-molecular-weight enzymatic hydrolysate. The low-molecular-weight enzymatic hydrolysate contains gallic acid as the main plant-derived marker component, along with chebulic acid, ellagic acid, protocatechuic acid, a small amount of methyl gallate, monosaccharides, and oligosaccharides. It also contains betaine and glycerol introduced by the eutectic solvent B, and citrate introduced by the buffer solution. At the end of washing and filtration, the mass fractions of betaine and glycerol from the extraction medium in the first nanofiltration membrane retentate relative to the plant-derived dry solids were 0.118% and 0.295%, respectively. The first nanofiltration membrane retentate was collected and placed in a vacuum concentrator equipped with a stirrer. Concentration was carried out under reduced pressure at 47±2℃, 8±2 kPa, and 100 r / min to obtain 70 g of concentrated tannin material. Analytical analysis using high-performance liquid chromatography (HPLC) revealed that the concentrated tannin material contained 12.67 g of chebulic tannic acid, 10.01 g of chebulic tanninic acid, and 4.935 g of corilagin. The concentrated tannin material also contained 0.0525 g of betaine, 0.1313 g of glycerol, 16.1875 g of water, 24.50 g of other plant-derived dry solids, and 1.5137 g of non-plant-derived process media residues. 7800 g of white willow bark extract was mixed with 6000 g of low-molecular-weight enzymatic hydrolysate at a mass ratio of 26:20 to obtain a mixed low-molecular-weight extract. The pH of the mixed low-molecular-weight extract was adjusted to 5.0 ± 0.1 using a 0.12 mol / L citrate-sodium citrate buffer solution with a pH of 5.0. The extract was then subjected to chromatography at 32℃ using a membrane with an effective membrane area of ​​0.55 m². 2A negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da was used as the second nanofiltration membrane for concentration, with the transmembrane pressure controlled at 2.2 ± 0.1 MPa. The retentate was first concentrated to 1.60 ± 0.05 L. Then, while maintaining the retentate volume at 1.60 ± 0.05 L, deionized water was added at a flow rate of 33 g / min, and the permeate was collected at the same flow rate. This washing process was repeated for 150 min, with a cumulative addition of 4950 g of deionized water. The second nanofiltration membrane retentate was then placed in a vacuum concentrator and concentrated under reduced pressure at 47 ± 2 °C and an absolute pressure of 8 ± 2 kPa to obtain 111.30 g of low-molecular-weight plant bioactive concentrate. The Karl Fischer method determined that the water content was 10.0625 g and the total dry solids were 101.2375 g. The low-molecular-weight plant active concentrate contains 19.60g of salicin, 8.90g of gallic acid, 0.175g of betaine, 0.630g of glycerol, 3.675g of residual solids from non-plant-derived process media, and 68.2575g of other plant-derived dry solids. 13.475g of betaine, 73.745g of glycerol, and 81.48g of deionized water were added to the low-molecular-weight plant active concentrate. The mixture was stirred for 50min at 58℃ and 320r / min under nitrogen protection, and then cooled to 32℃ at a rate of 1℃ / min to obtain 280g of active association system B1. 280g of active association system B1 was mixed with 70g of concentrated tannin material and stirred for 25min at 32±2℃ and 320r / min, then homogenized for 7min at 7000r / min under nitrogen protection to obtain 350g of mother liquor B. According to high performance liquid chromatography, the mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin and free salicylic acid in the mother liquor B were 5.6000%, 2.5429%, 3.6200%, 2.8600%, 1.4100% and 0.00070%, respectively.

[0048] Add 650g of mother liquor A to a sealed homogenizer equipped with a jacket, stirring device, and nitrogen protection device, and stir at 32±2℃ and 320r / min. Add 350g of mother liquor B to mother liquor A at a uniform rate over 9min, and continue stirring at 320r / min for 18min to obtain a premix. Homogenize the obtained premix at 7000r / min for 7min under nitrogen protection, and then homogenize at 100r / min and a vacuum degree of [missing value]. Degassing at 0.09 MPa for 6 minutes yielded an anti-dandruff, anti-inflammatory, and antipruritic composition.

[0049] Comparative Example 1 The composition was prepared according to the method of Example 1, except that: when preparing mother liquor A, betaine-lactic acid eutectic solvent A was not prepared, but an equal volume of deionized water was used as the extraction medium; when preparing white willow bark extract and Terminalia chebula extract, betaine-glycerol eutectic solvent B was not prepared, but an equal volume of deionized water was used as the extraction medium. The dosage of medicinal materials, material-to-liquid ratio, ultrasonic treatment conditions, dosage of compound enzyme, enzymatic hydrolysis conditions, immobilized tannin enzyme column treatment, and treatment conditions of the first and second nanofiltration membranes were all the same as in Example 1. After the low molecular weight plant active concentrate was formed, betaine, glycerol, and deionized water were added according to the dosage in Example 1, and the homogenization, compounding, and degassing conditions were followed in Example 1 to make the final composition weigh 1000g.

[0050] Comparative Example 2 The composition was prepared according to the method of Example 1, except that: after the white willow bark powder and Terminalia chebula pericarp powder were pre-swollen in eutectic solvent B and the pH was adjusted, cellulase and pectinase were not added; instead, the mixtures were stirred at 43°C and 150 r / min for 60 min and 80 min, respectively. After stirring, the mixtures were processed according to the same closed-loop heating, filtration, centrifugation, 10 kDa ultrafiltration, immobilized tannin enzyme column treatment, first nanofiltration membrane fractionation, second nanofiltration membrane concentration, activity association, and final compounding method as in Example 1. To eliminate the influence of different enzyme preparation excipient quality, after omitting the enzyme preparation, an equal mass of pH 4.8 citrate-sodium citrate buffer was added to each system to ensure that the initial mass of each treatment system was consistent.

[0051] Comparative Example 3 Terminalia chebula extract was prepared according to the method in Example 1. The extract was heated to 38°C, the pH was adjusted to 5.2±0.1, and 78.75g of free tanninase was added directly instead of passing it through an immobilized tanninase column. Enzymatic hydrolysis was then carried out at 38°C and 150 rpm for 40 min. After hydrolysis, the system was heated to 80±2°C and held for 8 min to inactivate the enzyme, then cooled to 38°C within 15 min, and subsequently passed through a first nanofiltration membrane with a nominal molecular weight cutoff of 500 Da. The effective membrane area, transmembrane pressure, permeate collection flow rate, initial permeate collection volume, and constant volume washing conditions of the first nanofiltration membrane were the same as in Example 1. The resulting low-molecular-weight enzymatic hydrolysate and concentrated tannins were compounded with white willow bark extract according to the method in Example 1, and then concentrated using a second nanofiltration membrane, followed by betaine-glycerol association, high-speed homogenization, and final compounding.

[0052] Comparative Example 4 The Terminalia chebula extract was prepared according to the method in Example 1 and adjusted to 38°C and pH 5.2 ± 0.1. The Terminalia chebula extract was circulated alone through an immobilized tannin enzyme column at a flow rate of 350 mL / min for 40 min. During this 40 min, the first nanofiltration membrane was not activated, and the permeate was not collected. After the enzymatic hydrolysis was completed, the immobilized tannin enzyme column was removed from the tubing, and the first nanofiltration membrane was activated to perform tangential flow separation of all the hydrolysate. The transmembrane pressure, permeate collection flow rate, initial permeate collection volume, and constant volume washing conditions of the first nanofiltration membrane were all the same as in Example 1. Subsequent preparations of concentrated tannin materials, low-molecular-weight plant active concentrate, active association system B1, mother liquor B, and the compounding of mother liquor A and mother liquor B were all the same as in Example 1.

[0053] Comparative Example 5 Following the method in Example 1, the immobilized tannin enzyme column and the first nanofiltration membrane were co-treated for 40 min, and 1200 g of the initial low-molecular-weight enzymatic hydrolysis permeate was collected. After the co-treatment, the first nanofiltration membrane retentate was not washed for 160 min at a constant volume. Instead, the initial low-molecular-weight enzymatic hydrolysis permeate was directly diluted to 6000 g with deionized water as the low-molecular-weight enzymatic hydrolysate. The first nanofiltration membrane retentate was not washed and was directly concentrated under reduced pressure to 80 g under the conditions of Example 1 to obtain concentrated tannin material. The subsequent mixing of the white willow bark extract and the low-molecular-weight enzymatic hydrolysate, the concentration using the second nanofiltration membrane, the addition of betaine and glycerol, the preparation of mother liquor B, and the final compounding were all the same as in Example 1.

[0054] Comparative Example 6 White willow bark extract and low-molecular-weight enzymatic hydrolysate were prepared according to the method in Example 1 and mixed at a mass ratio of 23:20. After mixing, the mixture was not passed through a negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da. Instead, the entire mixed low-molecular-weight extract was directly placed in a vacuum concentrator and concentrated to 125.9683 g under reduced pressure at 45±2℃ and 10±2 kPa. 14.5317 g of betaine, 79.5 g of glycerol, and 100 g of deionized water were added to the obtained direct concentrate according to the amounts used in Example 1 to form an active association system. This system was then mixed with concentrated tannins to prepare mother liquor B.

[0055] Comparative Example 7 125.9683 g of low-molecular-weight plant active concentrate was prepared according to the method of Example 1. When forming the active association system B1, instead of adding 14.5317 g of betaine and 79.5 g of glycerol, 94.0317 g of deionized water was used as a substitute, and 100 g of deionized water as described in Example 1 was added. The resulting system was stirred for 45 min at 55°C and 300 r / min under nitrogen protection, and then cooled to 30°C at a rate of 1°C / min. Subsequent mixing with 80 g of concentrated tannin material, high-speed homogenization, and compounding with mother liquor A were the same as in Example 1.

[0056] Comparative Example 8 A low-molecular-weight plant-based active concentrate was prepared according to the method of Example 1, with the addition of betaine, glycerol, and deionized water. After addition, the mixture was stirred for 45 min at 55°C and 300 rpm in air, followed by natural cooling to 30°C without nitrogen protection. The resulting system was then mixed with concentrated tannins and stirred only at 300 rpm in air for 20 min, without high-speed homogenization at 6500 rpm. For the final composition, mother liquor B was added to mother liquor A and stirred only at 300 rpm for 21 min, without a second high-speed homogenization or vacuum degassing.

[0057] Comparative Example 9 Mother liquor A was prepared according to the method of Example 1. A blank process matrix, mother liquor B, was prepared separately, with the following specific steps: Eutectic solvent B and a 0.1 mol / L citrate-sodium citrate buffer solution with a pH of 4.8 were prepared according to the composition and preparation method of Example 1, using the same batch of enzyme preparation as in Example 1; no white willow bark powder or Terminalia chebula pericarp powder was added to the blank process. 6.5 L of eutectic solvent B was taken, and the white willow bark extraction steps of Example 1 were followed sequentially: pre-swelling treatment, addition of 650 mL of the buffer solution, addition of 10 g of cellulase and 7.5 g of pectinase, enzymatic hydrolysis, enzyme inactivation by sealing, filtration, centrifugation, and 10 kDa ultrafiltration. The equipment was washed with the buffer solution, and the ultrafiltration permeate and washing solution were combined and quantified to 6900 g to obtain the white willow bark blank extract. Take another 3.5L of eutectic solvent B, and follow the steps of Terminalia chebula extraction in Example 1 to perform pre-swelling treatment, add 350mL of the buffer solution, add 5g of cellulase and 2.5g of pectinase, enzymatic hydrolysis, seal and inactivate enzymes, filter, centrifuge and ultrafilter at 10kDa, wash the equipment with the buffer solution and combine the ultrafiltration permeate and washing solution, and quantify to 3450g to obtain Terminalia chebula blank extract.

[0058] The Terminalia chebula blank extract was passed through the immobilized tanninase column described in Example 1, under the same temperature, pH, circulation flow rate, and processing time as in Example 1, and simultaneously passed through the first nanofiltration membrane. The immobilized tanninase column was then cut out, and constant-volume washing and filtration were performed under the same water replenishment flow rate and time as in Example 1. The initial permeate and the washing permeate were combined and quantified to 6000g to obtain the Terminalia chebula blank low-molecular-weight process solution. The first nanofiltration membrane retentate after washing was concentrated under reduced pressure under the conditions of Example 1 and quantified to 80g to obtain the blank concentrated retentate. 6900g of the white willow bark blank extract was mixed with 6000g of the Terminalia chebula blank low-molecular-weight process solution, and treated under the same pH adjustment, second nanofiltration membrane concentration, and constant-volume washing and filtration conditions as in Example 1. The mixture was then concentrated under reduced pressure and quantified to 125.9683g to obtain the blank low-molecular-weight process concentrate. Add 14.5317g of betaine, 79.5g of glycerol and 100g of deionized water to the blank low molecular weight process concentrate. Stir at 55°C and 300r / min for 45min under nitrogen protection. Then cool down to 30°C at 1°C / min and correct the total mass of the material to 320g with deionized water to obtain blank association system B1.

[0059] 320g of blank associative system B1 was mixed with 80g of blank concentrated retentate and stirred for 20min at 30±2℃ and 300r / min, then homogenized for 6min at 6500r / min under nitrogen protection to obtain 400g of mother liquor B blank process matrix. Mother liquor B blank process matrix did not contain plant components derived from white willow bark or Terminalia chebula; high performance liquid chromatography (HPLC) analysis showed that salicin, gallic acid, chebulic tannic acid, chebulic tannin, and corilagin were all below the limit of quantitation. 600g of mother liquor A and 400g of mother liquor B blank process matrix were taken and prepared into Comparative Example 9 composition under the same feeding, stirring, homogenizing, and degassing conditions as in Example 1.

[0060] Comparative Example 10 Mother liquor B was prepared according to the method in Example 1. A blank process matrix, mother liquor A, was prepared separately, with the following steps: 278.613 g of anhydrous betaine and 171.387 g of lactic acid were weighed according to their purity, making the molar ratio of betaine to lactic acid 1:0.8; the mixture was stirred at 60°C and 300 r / min for 40 min, and 150.000 g of deionized water was added to obtain 600 g of eutectic solvent A with a total water content of 25 wt%. When the lactic acid raw material is an aqueous solution, the amount of lactic acid raw material added should be calculated based on the measured lactic acid content, and the water introduced by the lactic acid raw material should be deducted from the amount of deionized water added. In the blank process, no arborvitae leaf powder, Polygonum multiflorum powder, or Ligustrum lucidum powder were added. The obtained eutectic solvent A was stirred at 25°C for 10 min, then heated to 42°C and treated in the dark at an ultrasonic power density of 80 W / L for 35 min. After cooling to room temperature, deionized water was used to compensate for the volatilization loss during the treatment process, and the volume was quantified to 600 g to obtain the blank process matrix of mother liquor A. Detection by high performance liquid chromatography showed that quercetin, stilbene glycoside, privetin, free emodin, and free emodin methyl ether were all below the limit of quantification. 600 g of the blank process matrix of mother liquor A and 400 g of mother liquor B were taken, and the same feeding, stirring, homogenization, and degassing conditions as in Example 1 were used to prepare the composition of Comparative Example 10.

[0061] Comparative Example 11 Mother liquor A and mother liquor B were prepared according to the method in Example 1. 500g of mother liquor A was added to a sealed homogenizing tank and stirred at 30±2℃ and 300r / min. 500g of mother liquor B was then added to mother liquor A at a uniform rate over 12min, and stirring continued for 15min. The resulting premixed solution was homogenized at 6500r / min for 6min under nitrogen protection, and then homogenized at 100r / min and a vacuum degree of [missing information]. Degassing was performed at 0.08 MPa for 5 min to obtain a composition with a mass ratio of mother liquor A to mother liquor B of 50:50.

[0062] Comparative Example 12 Mother liquor A and mother liquor B were prepared according to the method in Example 1. 700g of mother liquor A was added to a sealed homogenizing tank and stirred at 30±2℃ and 300r / min. 300g of mother liquor B was then added to mother liquor A at a uniform rate over 12min, and stirring continued for 15min. The resulting premixed solution was homogenized at 6500r / min for 6min under nitrogen protection, and then homogenized at 100r / min and a vacuum degree of [missing information]. Degassing was performed at 0.08 MPa for 5 min to obtain a composition with a mass ratio of mother liquor A to mother liquor B of 70:30.

[0063] Comparative Example 13 Mother liquor A, white willow bark extract, low-molecular-weight enzymatic hydrolysate, and concentrated tannin material were prepared according to the method in Example 1. The difference was that 5100g of white willow bark extract and 6000g of low-molecular-weight enzymatic hydrolysate were mixed at a mass ratio of 17:20 to obtain a mixed low-molecular-weight extract. The remaining portion of the white willow bark extract was not used in subsequent processing. The pH of the mixed low-molecular-weight extract was adjusted to 4.8 ± 0.1 using a 0.1 mol / L citrate-sodium citrate buffer solution with a pH of 4.8. The solution was then passed through a 0.50 m² effective membrane at 30°C. 2 A negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da was used for concentration, with the transmembrane pressure controlled at 2.0 ± 0.1 MPa. The retentate was first concentrated to 1.50 ± 0.05 L. Then, while maintaining the retentate volume at 1.50 ± 0.05 L, deionized water was added at a flow rate of 30 g / min, and the permeate was collected at the same flow rate. This washing process was repeated for 150 min, with a cumulative addition of 4500 g of deionized water. The retentate from the second nanofiltration membrane was then placed in a vacuum concentrator and concentrated under reduced pressure at 45 ± 2 °C and an absolute pressure of 10 ± 2 kPa, yielding 125.9683 g of low-molecular-weight plant bioactive concentrate. Karl Fischer titration determined that the water content was 12 g and the total dry solids were 113.9683 g. The low-molecular-weight plant active concentrate contains 13.3043g of salicin, 10.6964g of gallic acid, 0.2g of betaine, 0.5g of glycerol, 4.5719g of residual solids from non-plant-derived process media, and 84.6957g of other plant-derived dry solids. 14.5317g of betaine, 79.5g of glycerol, and 100g of deionized water were added to the low-molecular-weight plant active concentrate. The mixture was stirred for 45min at 55℃ and 300r / min under nitrogen protection, and then cooled to 30℃ at a rate of 1℃ / min to obtain 320g of active association system B1. Active association system B1 was mixed with 80g of concentrated tannin material at a mass ratio of 4:1, stirred for 20min at 30±2℃ and 300r / min, and then homogenized for 6min at 6500r / min under nitrogen protection to obtain 400g of mother liquor B. The mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin, and free salicylic acid in mother liquor B were 3.3261%, 2.6741%, 3.8000%, 3.0000%, 1.5000%, and 0.00050%, respectively, as determined by high-performance liquid chromatography. 600g of mother liquor A and 400g of mother liquor B were taken, and the composition was prepared according to the feeding, stirring, homogenization, and degassing conditions described in Example 1.

[0064] Comparative Example 14 Sufficient amounts of mother liquor A, white willow bark extract, low-molecular-weight enzymatic hydrolysate, and concentrated tannins were prepared according to the method in Example 1. The difference was that 8700g of white willow bark extract and 6000g of low-molecular-weight enzymatic hydrolysate were mixed at a mass ratio of 29:20 to obtain a mixed low-molecular-weight extract. The pH of the mixed low-molecular-weight extract was adjusted to 4.8±0.1 using a 0.1mol / L citrate-sodium citrate buffer solution with a pH of 4.8. The extract was then concentrated at 30°C through a negatively charged polyamide nanofiltration membrane with an effective membrane area of ​​0.50m² and a nominal molecular weight cutoff of 180Da, with the transmembrane pressure controlled at 2.0±0.1MPa. First, the membrane retentate was concentrated to 1.50±0.05L. Then, while maintaining the membrane retentate volume at 1.50±0.05L, deionized water was added at a flow rate of 30g / min, and the permeate was collected at the same flow rate. This process was repeated for 150min, with a cumulative addition of 4500g of deionized water. The second nanofiltration membrane retentate was placed in a vacuum concentrator and concentrated under reduced pressure at 45±2℃ and 10±2kPa to obtain 125.9683g of low-molecular-weight plant bioactive concentrate. The Karl Fischer method determined that the water content was 12g and the total dry solids were 113.9683g. The low-molecular-weight plant bioactive concentrate contained 22.6957g of salicin, 10.6964g of gallic acid, 0.2g of betaine, 0.5g of glycerol, 4.5719g of non-plant-derived process media residual solids, and 75.3043g of other plant-derived dry solids. Add 14.5317 g of betaine, 79.5 g of glycerol, and 100 g of deionized water to the low-molecular-weight plant active concentrate. Stir for 45 min at 55 °C and 300 r / min under nitrogen protection, then cool to 30 °C at a rate of 1 °C / min to obtain 320 g of active association system B1. Mix active association system B1 with 80 g of concentrated tannin material at a mass ratio of 4:1, stir for 20 min at 30 ± 2 °C and 300 r / min, then homogenize for 6 min at 6500 r / min under nitrogen protection to obtain 400 g of mother liquor B. The mass fractions of salicin, gallic acid, chebulic tannic acid, chebulic tannin, corilagin, and free salicylic acid in mother liquor B were 5.6739%, 2.6741%, 3.8000%, 3.0000%, 1.5000%, and 0.00050%, respectively, as determined by high-performance liquid chromatography. 600g of mother liquor A and 400g of mother liquor B were taken, and the composition was prepared according to the feeding, stirring, homogenization, and degassing conditions described in Example 1.

[0065] Preparation of blank process matrix: Take 600g of blank process matrix A of Comparative Example 10 and 400g of blank process matrix B of Comparative Example 9, and process them under the same feeding, stirring, homogenization and degassing conditions as in Example 1 to obtain blank process matrix, which is used as blank process matrix group in the following performance tests.

[0066] Performance testing Test Example 1: Malassezia Growth and Biofilm Formation Inhibition Test *Malassezia spheroidosa* (brand: Beina Biotechnology; product number: BNCC358073) and *Malassezia repens* (Shanghai Xuanke Biotechnology Co., Ltd.; product number: xkjz0058) were selected, respectively. Modified Leeming-Notman liquid medium contained 10g bacterial peptone, 10g glucose, 2g yeast extract, 8g dried taurine, 10mL glycerol, 0.5g glyceryl monostearate, 5mL Tween-60, and 20mL olive oil per liter, and was diluted to 1L with deionized water and the pH was adjusted to 5.6±0.2. The substrates from Examples 1-3, Comparative Examples 1-14, and the blank were prepared into double-concentration test sample solutions with a mass concentration of 0.20% using modified Leeming-Notman liquid medium. The activated *Malassezia* strains were prepared into double-concentration bacterial suspensions; after equal volumes were mixed, the final mass concentration of the test composition in the reaction system was 0.10%, and the final bacterial concentration was 5×10⁻⁶. 4 CFU / mL. Six parallel wells were set up for each group, and the experiment was independently repeated three times. 100 μL of double-concentration bacterial suspension and 100 μL of double-concentration test sample solution were added to each well of a 96-well plate, for a total volume of 200 μL per well, and incubated at 32℃ for 96 h. Subsequently, 20 μL of 0.015% resazurin solution was added to each well, and the plate was incubated in the dark for 4 h. Fluorescence intensity was measured at an excitation wavelength of 560 nm and an emission wavelength of 590 nm. The experiment included a culture medium blank group, a bacterial suspension control group, a blank process matrix group, a ketoconazole positive control group, a test sample group, and a sample background group. The final concentration of ketoconazole was 16.0 μg / mL; the final volume fraction of dimethyl sulfoxide in each bacterial group and its corresponding background group was uniformly 0.5%. The sample background group contained the test sample but no bacterial suspension, and was used to subtract sample color and autofluorescence.

[0067] The growth inhibition rate of Malassezia is calculated using the following formula: I1={1-[(Fs-Fsβ) / (Fc-Fβ)]}×100%; In the formula, I1 is the growth inhibition rate of Malassezia; Fs is the fluorescence value of the sample bacterial culture well; Fsβ is the fluorescence value of the sample background well; Fc is the fluorescence value of the bacterial culture control well; and Fβ is the fluorescence value of the culture medium blank well.

[0068] In the biofilm formation inhibition assay, the bacterial cell concentration was adjusted to 1×10⁻⁶. 6Add 200 μL of bacterial suspension (CFU / mL) to each well and incubate at 32°C for 2 h to allow bacterial cell adhesion. Discard the supernatant, wash twice gently with sterile phosphate buffer, add fresh culture medium containing 0.10% of the corresponding test composition, and incubate at 32°C for 72 h. After incubation, discard the culture medium, wash three times gently, fix with methanol for 15 min, dry, stain with 0.1% crystal violet solution for 15 min, wash away unbound dye, dissolve the bound crystal violet with 33 wt% acetic acid, and measure the absorbance at 590 nm. Each group has 6 parallel wells, and each group is independently replicated 3 times.

[0069] The biofilm formation inhibition rate is calculated using the following formula: I2={1-[(As-Asβ) / (Ac-Aβ)]}×100%; In the formula, I2 is the biofilm formation inhibition rate; As is the absorbance of the sample bacterial culture well; Asβ is the absorbance of the sample sterile background well; Ac is the absorbance of the bacterial culture control well; and Aβ is the absorbance of the culture medium blank well. The average biofilm inhibition rate in Table 1 is the arithmetic mean of the biofilm formation inhibition rates of the two Malassezia species.

[0070] The test results are shown in Table 1 below: Table 1 Results of the test on the growth and biofilm formation inhibition of Malassezia

[0071] Test Example 2: HaCaT Cell Anti-inflammatory Performance Test Human immortalized keratinocytes (HaCaT) were cultured in DMEM medium containing 10 wt% fetal bovine serum and 1 wt% penicillin-streptomycin at 37°C and 5% carbon dioxide. Examples 1-3 and Comparative Examples 1-14 were diluted with complete culture medium to a final mass concentration of 0.10% for all test compositions. After adding the samples to the culture system, the pH was maintained at 7.3 ± 0.1. Comparative Examples 9 and 10 served as controls for the individual effects of the plant-derived active component in mother solution A and mother solution B, respectively.

[0072] HaCaT cells were spaced at 1×10⁶ cells per well. 4 Cells were seeded in 96-well plates and cultured for 24 hours. The corresponding samples were then added, and the plates were cultured for another 24 hours. A background well containing an equal amount of sample and CCK-8 reagent was included for each sample to subtract the absorbance from the sample's own color and the reaction with the detection reagent. 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C for 2 hours. The absorbance was measured at 450 nm. Each group had 6 parallel wells, with 3 independent replicates.

[0073] Cell viability is calculated using the following formula: Vc=[(As-Asβ) / (Am-Aβ)]×100%; In the formula, Vc represents cell viability; As represents the absorbance of the sample cell wells; Asβ represents the absorbance of the corresponding sample wells without cell background; Am represents the absorbance of the inflammatory model group cell wells; and Aβ represents the absorbance of the culture medium blank wells.

[0074] In the anti-inflammatory assay, HaCaT cells were prepared at a ratio of 1 × 10⁶ cells per well. 5 Cells were seeded in 24-well plates and cultured for 24 hours to allow for full cell adhesion. The original culture medium was discarded, and the cells were pretreated for 2 hours with medium containing 0.10 wt% of the corresponding experimental composition. Then, TNF-α and IFN-γ were added to a final concentration of 10 ng / mL, and the cells were cultured for another 24 hours. The following groups were established: normal cell group, inflammation model group, blank substrate group, experimental sample group, and dexamethasone positive control group. The final concentration of dexamethasone was 40 μmol / L, and the final volume fraction of dimethyl sulfoxide in each group was 0.1%. Each group had three parallel wells, with three independent replicates. The culture supernatant was collected, and the IL-6 and IL-8 levels were measured according to the ELISA kit instructions.

[0075] The inhibition rate of inflammatory factors is calculated according to the following formula: Ic = [(Cm-Cs) / (Cm-Cn)] × 100%; In the formula, Ic is the inhibition rate of inflammatory factors; Cm is the content of inflammatory factors in the inflammatory model group; Cs is the content of inflammatory factors in the sample group; and Cn is the content of inflammatory factors in the normal cell group.

[0076] The test results are shown in Table 2 below: Table 2 Results of the anti-inflammatory performance test of HaCaT cells

[0077] Test Example 3: Efficacy Test of Anti-dandruff and Anti-itch Effect on Human Scalp The compositions prepared in Examples 1-3 and Comparative Examples 1-14 were added to the same blank shampoo base at an addition amount of 2.0 wt% to prepare test shampoos with similar appearance, color, fragrance, and viscosity. The blank base group used the same shampoo base without the addition of the compositions of the present invention. Subjects aged 18-55 years with mild to moderate dandruff and scalp itching were recruited. Subjects with psoriasis, tinea capitis, severe seborrheic dermatitis, scalp damage, or other scalp diseases that may affect the evaluation were excluded, as well as those who had used antifungal drugs, corticosteroids, or medicated anti-dandruff products in the 4 weeks prior to the test. After a 14-day washout period, eligible subjects were randomly divided into 18 groups, with 10 subjects in each group, for a total of 180 subjects. Subjects used the test shampoo 3 times a week, with each application being 6±1g, massaging the scalp and keeping it on for 3 minutes before rinsing with water, for 28 consecutive days. During the trial, no other anti-dandruff, antifungal, anti-itch, or strong scalp cleansing products may be used. The scoring criteria are as follows: Dandruff score: The scalp is divided into 8 fixed areas. Evaluators who are uniformly trained and unaware of the sample groupings rate the stickiness of dandruff in each area on a scale of 0-10. The scores for each area are added together to obtain the total dandruff score.

[0078] The reduction rate of dandruff score on day 14 and day 28 was calculated using the following formulas: Rd,t=[(S0-St) / S0]×100%, t=14 or 28; In the formula, Rd,t is the dandruff score reduction rate on day t; S0 is the total dandruff score before use; and St is the total dandruff score on day 14 or day 28.

[0079] Itching score: The degree of scalp itching was evaluated using a 0-10 point visual analog scale, where 0 points indicated no itching and 10 points indicated unbearable persistent itching.

[0080] The rate of decrease in pruritus score on day 28 is calculated using the following formula: Ri=[(V0-V28) / V0]×100%; In the formula, Ri is the rate of reduction in pruritus score on day 28; V0 is the pruritus score before use; and V28 is the pruritus score on day 28.

[0081] Malassezia load: Before use and on day 28, samples were collected from the same fixed 2cm × 2cm area on the top of the subject's head using a sterile swab, swabbing back and forth 20 times. Total microbial DNA was extracted, and the copy number of Malassezia was determined using real-time quantitative PCR targeting the conserved regions of Malassezia ribosomal DNA, and converted to the copy number per square centimeter of scalp. Each batch of tests was set up with 10 samples. 2 -10 8 Standards in copies / μL series, template-free control, and extraction negative control.

[0082] The decrease in Malassezia load is calculated using the following formula: ΔM = log10(N0) - log10(N28); In the formula, N0 and N28 are the Malassezia copy numbers per square centimeter of scalp before use and on day 28, respectively; ΔM is in log10 copies / cm². 2 The test results are shown in Table 3: Table 3. Results of the test on the anti-dandruff and anti-itch efficacy of human scalp

[0083] Test Example 4: Test on the inhibitory effect of type I 5α-reductase activity The IPHASE type I (SRD5A1) 5α-reductase inhibition rate assessment kit (KS0126D039, Huizhi Heyuan Biotechnology (Suzhou) Co., Ltd.) was used. This kit uses type I 5α-reductase from SD rat liver as the enzyme source, testosterone as the substrate, and NADPH as the coenzyme. The second step of colorimetric detection was performed using the kit's accompanying reaction solution. A tartrazine positive control working solution was prepared using dimethyl sulfoxide (DMSO) at a concentration of 12.5 mg / mL. Sample working solutions of the compositions obtained in Examples 1-3, Comparative Examples 1, 6, 9, and 10 were prepared using Buffer A, with a mass concentration of 2.0 wt% for each sample working solution. All samples were thoroughly mixed and used immediately.

[0084] The assay was performed using transparent 96-well microplates, with a total reaction volume of 200 μL. The final testosterone concentration for each group was 5 μmol / L; except for the background group and the blank group (without enzyme), the final protein concentration of type I 5α-reductase was 0.2 mg / mL; NADPH was added according to the dosage specified in the kit instructions. The following groups were set up: (1) Negative control group: type I 5α-reductase, testosterone, NADPH and 1 μL DMSO were added, but the test composition was not added; (2) Positive control group: type I 5α-reductase, testosterone, NADPH and 1 μL of the dutasteride working solution were added to make the final mass concentration of dutasteride 62.5 μg / mL; (3) Test group: 10 μL of each sample working solution was added to make the final mass concentration of the test composition 0.10 wt%, and type I 5α-reductase, testosterone and NADPH were added, and 1 μL DMSO was added; (4) Sample background group: the same amount of sample working solution, testosterone, NADPH and 1 μL DMSO as the corresponding test group were added, but type I 5α-reductase was not added, and the enzyme solution was replaced with an equal volume of Buffer A; (5) Positive background group: the same amount of dutasteride working solution, testosterone and NADPH as the positive control group were added, but type I 5α-reductase was not added, and the enzyme solution was replaced with an equal volume of Buffer A. A replaces the enzyme solution; (6) Reagent blank group: no test composition and type I 5α-reductase are added, 10 μL Buffer A replaces the sample working solution, an equal volume of Buffer A replaces the enzyme solution, and 1 μL DMSO is added. Each group is made up to the same total volume with Buffer A so that the pH of the enzyme reaction system is 6.0±0.1 and the final volume fraction of DMSO is 0.5%.

[0085] Besides the enzyme solution, first mix the required testosterone, NADPH, sample working solution or corresponding substitute solution, and dutasteride working solution or DMSO for each group, and make up the volume with Buffer A; finally, add type I 5α-reductase or an equal volume of Buffer A to start the reaction, and incubate at 37℃ for 30 min. Then, stop the enzymatic reaction by treating at 85℃ for 10 min, centrifuge at 10000×g for 3 min, take an equal volume of supernatant, and mix it with the colorimetric reaction solution according to the kit instructions. Immediately after mixing, read the absorbance A1 at 405 nm, and continue incubating at 37℃ for 4 min, then read the absorbance A2 at 405 nm. Calculate the absorbance change value ΔA = A2 - A1 for each well. All groups used the same operating conditions from sample addition, incubation, inactivation, centrifugation to colorimetric detection.

[0086] Analyte inhibition rate (%) = [1 - (ΔA test group - ΔA test control group) / (ΔA negative - ΔA blank)] × 100% The higher the 5α-reductase inhibition rate, the stronger the oil control ability of the sample.

[0087] The test results are shown in Table 4 below: Table 4. Inhibitory effect of samples on 5α-reductase activity 5α-Reductase Inhibition Rate % Positive control group 72.56% Example 1 48.09% Example 2 42.82% Example 3 46.57% Comparative Example 1 28.77% Comparative Example 6 29.02% Comparative Example 9 30.16% Comparative Example 10 28.59% .

Claims

1. A method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition, characterized in that, Includes the following steps: S1. The powders of Platycladus orientalis leaves, Polygonum multiflorum, and Ligustrum lucidum were extracted by ultrasonic extraction using a eutectic solvent A composed of betaine, lactic acid, and deionized water, and the mother liquor A was obtained by filtration. S2. The white willow bark powder and Terminalia chebula pericarp powder were pre-swollen using eutectic solvent B, respectively. After enzymatic hydrolysis with cellulase and pectinase, enzyme inactivation, filtration, centrifugation and ultrafiltration, white willow bark extract and Terminalia chebula extract were obtained. S3. The Terminalia chebula extract is simultaneously treated with an immobilized tannin enzyme column and a first nanofiltration membrane to obtain a low-molecular-weight enzymatic hydrolysate and a concentrated tannin material, respectively. The white willow bark extract is mixed with the low-molecular-weight enzymatic hydrolysate, enriched by a second nanofiltration membrane, and then associated with betaine, glycerol, and deionized water to obtain an active associative system B1. The active associative system B1 is mixed with the concentrated tannin material and homogenized to obtain mother liquor B. S4. Add 7-9 parts by weight of the mother liquor B to 11-13 parts by weight of the mother liquor A, stir, homogenize and degas to obtain the final product.

2. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 1, characterized in that, In step S1, the mass ratio of the arborvitae leaf powder, Polygonum multiflorum powder and Ligustrum lucidum powder is 6-8:5-7:6-8; the molar ratio of betaine to lactic acid in the eutectic solvent A is 1:0.7-0.9, and the total water content is 20-30wt%.

3. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 2, characterized in that, In step S1, the ratio of the crude medicinal powder A, composed of the arborvitae leaf powder, Polygonum multiflorum powder, and Ligustrum lucidum powder, to the eutectic solvent A is 1:16-20 g / mL.

4. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 1, characterized in that, In step S2, the eutectic solvent B is selected from any one of the following: choline chloride / 1,2-hexanediol molar ratio 1:2-4, betaine / glycerol molar ratio 1:1.3-1.7, choline chloride / ethylhexylglycerol molar ratio 1:2-3, choline chloride / 1,4-butanediol molar ratio 1:2-4, betaine / 1,2-hexanediol molar ratio 1:2-3, and betaine / ethylhexylglycerol molar ratio 1:2-4; the ratio of white willow bark powder to eutectic solvent B is 1:9-11 g / mL, and the ratio of Terminalia chebula pericarp powder to eutectic solvent B is 1:9-11 g / mL.

5. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 4, characterized in that, In step S2, the eutectic solvent B has a betaine to glycerol molar ratio of 1:1.3-1.7 and a total water content of 20-30 wt%; the pH of the enzymatic hydrolysis systems of white willow bark powder and Terminalia chebula peel powder is adjusted to 4.6-5.0 using a 0.08-0.12 mol / L citrate-sodium citrate buffer solution; and 1.0-2.0 g of cellulase and 0.5-1 g of other enzymes are added per 100 g of white willow bark powder. 3g of pectinase was used for enzymatic hydrolysis; 1.0-2.0g of cellulase and 0.5-1.3g of pectinase were added per 100g of Terminalia chebula pericarp powder for enzymatic hydrolysis; after enzymatic hydrolysis, the enzymatic hydrolysis system of white willow bark powder and the enzymatic hydrolysis system of Terminalia chebula pericarp powder were heated to 78-84℃ under nitrogen protection and held for 8-10min, and then filtered through 100 mesh, centrifuged at 3000×g for 10min and treated with an ultrafiltration membrane with a molecular weight cutoff of 10kDa, respectively.

6. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 5, characterized in that, In step S3, the immobilized tanninase column has an inner diameter of 50 mm and an effective column length of 260-340 mm, and is filled with immobilized tanninase microspheres obtained by immobilizing 90-120 g of tanninase preparation. The Terminalia chebula extract is adjusted to 36-40℃ and pH 5.0-5.4, and circulated through the immobilized tanninase column at a rate of 300-400 mL / min, while simultaneously passing through a membrane with a nominal molecular weight cutoff of 500 Da and an effective membrane area of ​​0.45-0.55 m². 2 The first nanofiltration membrane has a transmembrane pressure of 0.9-1.1 MPa, a permeate collection flow rate of 25-40 g / min, and a synchronous treatment time of 30-48 min. After the synchronous treatment, the immobilized tannin enzyme column is cut out from the circulation pipeline, and deionized water is used as the washing medium. The first nanofiltration membrane retentate is washed with a constant volume for 120-192 min at the same water replenishment flow rate as the permeate collection flow rate. The permeates from the first nanofiltration membrane obtained from the synchronous treatment and constant volume washing are combined to obtain the low molecular weight enzymatic hydrolysate. The first nanofiltration membrane retentate after constant volume washing is concentrated under reduced pressure at 43-47℃ and an absolute pressure of 8-12 kPa to obtain the concentrated tannin material.

7. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 6, characterized in that, In step S3, the mass ratio of the white willow bark extract to the low-molecular-weight enzymatic hydrolysate is 1-1.3:1; the second nanofiltration membrane is a negatively charged polyamide nanofiltration membrane with a nominal molecular weight cutoff of 180 Da, a nanofiltration temperature of 28-32℃, and an effective membrane area of ​​0.45-0.55 m². 2 The transmembrane pressure is 1.8-2.2 MPa. First, concentrate the retentate from the second nanofiltration membrane to 1.40-1.60 L. Then, while keeping the volume of the retentate constant, add deionized water at a flow rate of 27-33 g / min and perform constant volume washing filtration for 150 min.

8. The method for preparing an anti-dandruff, anti-inflammatory, and antipruritic composition according to claim 7, characterized in that, The second nanofiltration membrane retentate was concentrated under reduced pressure at 43-47℃ and 8-12 kPa to obtain a low-molecular-weight plant active concentrate. Betaine, glycerol, and deionized water were added to the obtained low-molecular-weight plant active concentrate, with the mass ratio of added betaine to glycerol being 1:5.3-5.5 and the mass of added deionized water being 6.0-7.7 times the mass of added betaine. The mixture was stirred for 40-50 min at 52-58℃ and 280-320 r / min under nitrogen protection, and then cooled to 28-32℃ at 1℃ / min to obtain the active association system B1. The mass ratio of the active association system B1 to the concentrated tannin material was 4:1, and the mixture was homogenized at 6000-7000 r / min for 5-7 min.

9. A dandruff-reducing, anti-inflammatory, and antipruritic composition, characterized in that, The composition was prepared using the method described in any one of claims 1-8 for the preparation of an anti-dandruff, anti-inflammatory, and antipruritic composition.

10. The use of the anti-dandruff, anti-inflammatory, and antipruritic composition as described in claim 9 in the preparation of a scalp cleansing or care product for inhibiting Malassezia, reducing dandruff, relieving scalp itching, and / or reducing scalp inflammation.

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