A mongolian medicine sainden-4 cream

Abstract

The present application relates to the technical field of Mongolian medicine external preparation, in particular to a Mongolian medicine Sendeng-4 cream. The cream is prepared from Sendeng, Terminalia chebula, Gardenia jasminoides and Chinese Hopea as raw materials, and effective components are enriched by composite enzymolysis, supercritical CO2 two-phase extraction, gradient membrane separation and molecular imprinting purification. Then, the cream is prepared by adding composite penetration enhancer and plant source preservative after the pH-ROS response carrier targets drug loading and the temperature-sensitive composite matrix is microfluidic adapted. The present application solves the defects of traditional preparation, such as insufficient dissolution, poor stability and weak targeting, and has high cream purity, good skin permeability, excellent safety, stable long-term storage performance, and is suitable for skin inflammation, eczema, itching and other diseases. The cream has the advantages of traditional Mongolian medicine and modern preparation, and has a wide clinical application prospect.

Description

Technical Field

[0001] This invention relates to the field of Mongolian medicine external preparations technology, specifically a Mongolian medicine Sendeng-4 cream. Background Technology

[0002] The Mongolian medicine Senden-4 formula consists of four herbs: Senden, Terminalia chebula, Gardenia jasminoides, and Melia toosendan. Recorded in the *Mongolian Medicine Formulae*, it possesses the effects of clearing heat, detoxifying, anti-inflammatory, and relieving itching. Traditionally, it is primarily used externally to treat skin inflammation and itching. However, existing external preparations of Senden-4 are mostly traditional ointments or powders, and their preparation processes suffer from numerous core defects, severely restricting their clinical application. Significant defects exist in the extraction process: Traditional methods using single water extraction or ethanol reflux extraction make it difficult to extract both fat-soluble and water-soluble components such as alkaloids in Senten, tannins in Terminalia chebula, flavonoids in Gardenia jasminoides, and volatile oils in Melia toosendan, resulting in low dissolution rates of core active ingredients (only 30%~40%). Reflux and high-temperature concentration processes easily lead to the oxidative degradation of heat-sensitive components such as volatile oils and flavonoids, resulting in loss of activity. Excessive impurities such as proteins, starches, and tannins in the extract make subsequent purification difficult, leading to low purity and easy stratification of the formulation.

[0003] The preparation of creams presents several problems: traditional cream bases (petrolatum, lanolin) have poor compatibility with traditional Chinese medicine extracts, leading to easy precipitation of active ingredients and a rough, uneven appearance; drug molecules have difficulty penetrating the stratum corneum, resulting in low local bioavailability and slow onset of action; the creams lack stability, easily delaminating and becoming moldy due to temperature and humidity, with active ingredients degrading by more than 30% within 6 months; they lack targeting, resulting in diffuse distribution of drugs, insufficient concentration at the lesion site, and irritation at non-target sites; the process relies on manual control, leading to large batch-to-batch variations and unstable quality.

[0004] Safety concerns remain: residues from organic solvent extraction are difficult to remove completely, posing risks of skin irritation and allergies; the safety of traditional preservatives (benzalofop-methyl) is questionable and they are not suitable for people with sensitive skin.

[0005] Therefore, based on the classic theories of Mongolian medicine and combined with modern extraction, purification and formulation technologies, developing a Mongolian medicine Senden-4 cream with sufficient component dissolution, strong stability, good targeting and high safety is of great significance for promoting the modernization of Mongolian medicine external preparations. Summary of the Invention

[0006] To address the problems in existing technologies, this invention provides a Mongolian medicine, Sendeng-4 cream. Through innovative combination of multiple technologies, it solves the defects in traditional preparation methods, such as insufficient dissolution of ingredients, degradation of heat-sensitive components, poor matrix compatibility, insufficient permeability, and poor stability, thereby improving the efficacy, safety, and quality stability of the cream.

[0007] The technical solution adopted by the present invention to solve its technical problem is: a Mongolian medicine Senden-4 cream, prepared from the following raw materials and processes: (1) Raw material ratio (parts by weight): 3 parts Senden, 2 parts Terminalia chebula, 2 parts Gardenia jasminoides, 1 part Melia toosendan; (2) Extraction process: ① Compound enzymatic hydrolysis: the medicinal materials are pulverized and passed through an 80-mesh sieve, and a compound enzyme solution (cellulase: pectinase: lipase = 2:1:0.5, enzyme addition amount 1%) is added, pH 4.5~5.0, and enzymatic hydrolysis is carried out at 45℃ for 1.5h; ② Supercritical CO2 two-phase extraction: CO2 pressure 25~30MPa, temperature 35~40℃, ethanol entrainer amount 10~15%, extraction for 2~3h; ③ Low temperature concentration: vacuum freezing concentration at -40℃ to a relative density of 1.10~1.15 (20℃); (3) Purification process: ① Gradient membrane separation: 0.2μm ceramic membrane is passed through Filter → 1000Da nanofiltration membrane concentration; ② Molecular imprinted purification: adsorption purification using Senden-4-herb core components (matrine analog, geniposide) molecular imprinted polymer column; (4) Cream preparation: ① Targeted drug loading: active ingredients loaded on poly-β-amino ester-polyethylene glycol graft copolymer (pH-ROS response); ② Matrix preparation: poloxamer 407 / 188: nano hydroxyapatite: chitosan quaternary ammonium salt = 5:3:2, melted at 60℃; ③ Microfluidic adaptation: drug and matrix are mixed in a 1:4 ratio via a microfluidic chip (channel width 80μm); ④ Composite permeation enhancer: lauryl ketone-menthol (1:0.8) composite permeation enhancer (mass percentage 2%) is added; ⑤ Aseptic molding: honeysuckle-forsythia extract (1:1) plant-derived preservative (0.5%) is added, homogenized and aseptically filled to obtain cream.

[0008] Specifically, in step (2), the solid-to-composite enzymatic hydrolysate ratio is 1:15 to 1:20, and the concentration of the ethanol entrainer in the supercritical CO2 extraction is 70%.

[0009] Specifically, in step (3), the functional monomer of the molecularly imprinted polymer column is methacrylic acid, the crosslinking agent is ethylene glycol dimethacrylate, and the molar ratio of template molecule to functional monomer is 1:5.

[0010] Specifically, in step (4), the mass ratio of polyβ-amino ester to polyethylene glycol in the pH-ROS responsive polymer is 3:1, and the particle size of the loaded drug is 50~200nm.

[0011] Specifically, in step (4), the phase transition temperature of the temperature-sensitive composite matrix is ​​32~36℃, and the viscosity of the cream is 15000~25000mPa·s (25℃).

[0012] Specifically, in step (4), the stirring rate of the microfluidic chip is 10,000 r / min and the mixing time is 10 min to ensure that the drug and the matrix are evenly dispersed.

[0013] Specifically, the total content of active ingredients is ≥3.5%, of which matrine analogues are ≥0.8% and geniposide is ≥0.6%.

[0014] Specifically, skin permeability ≥2.5 μg / cm 2 •h, pH value 5.5~7.0, meets the safety standards for topical skin preparations.

[0015] Specifically, after 6 months of accelerated stability testing (40℃, RH75%), there was no stratification or mold growth, and the degradation rate of the active ingredient was ≤5%.

[0016] Specifically, it is suitable for skin inflammation, eczema, itching and other conditions. Apply topically 1-2 times daily.

[0017] The beneficial effects of this invention are: This invention optimizes the raw material ratio according to the theory of monarch, minister, assistant and guide in Mongolian medicine. Through the synergistic effect of compound enzymatic hydrolysis and supercritical CO2 biphasic extraction, the cell walls of medicinal materials are gently destroyed, and the fat-soluble and water-soluble effective components are enriched simultaneously. The degradation of heat-sensitive components is avoided, and the dissolution efficiency and activity retention rate of the components are significantly improved.

[0018] Gradient membrane separation and molecular imprinting purification technology precisely removes impurities, and plant-derived preservatives replace chemical preservatives, reducing the risk of skin irritation and allergies, improving the purity and safety of the cream, and making it suitable for people with sensitive skin.

[0019] pH-ROS responsive carriers enable specific drug release at the site of inflammation, while temperature-sensitive composite matrices gel at skin temperature. Combined with composite penetration enhancers, these technologies enhance drug permeability and targeted enrichment, thereby improving local efficacy.

[0020] Microfluidic technology ensures uniform dispersion of drugs and matrix, resulting in a cream with a fine texture, strong stability, and resistance to delamination and mold growth during long-term storage. It also ensures good batch-to-batch quality consistency and meets the standardized production requirements for topical preparations.

[0021] The entire process parameters are clearly defined and controllable, taking into account both the efficacy of traditional Mongolian medicine and the advantages of modern formulations. The prepared cream is comfortable to apply, has a fast onset of action, and is suitable for a variety of skin inflammation-related conditions, making it highly valuable for clinical application. Attached Figure Description

[0022] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0023] Figure 1 A flowchart of a Mongolian medicine Senden-4 cream provided by the present invention. Detailed Implementation

[0024] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0025] like Figure 1 As shown, the Mongolian medicine Senden-4 cream of the present invention includes the following steps: 1. Raw material ratio: Based on the theory of monarch, minister, assistant and guide in Mongolian medicine, the following weight ratio is set: 3 parts of Senden (monarch medicine, clearing heat and anti-inflammatory), 2 parts of Terminalia chebula (minister medicine, astringing and relieving itching), 2 parts of Gardenia jasminoides (assistant medicine, detoxifying and reducing swelling), and 1 part of Melia toosendan (guide medicine, guiding the efficacy of the medicine), so that they can work together.

[0026] 2. Extraction process (using a combination of enzymatic hydrolysis and supercritical CO2 two-phase extraction): Raw material pretreatment: Clean and remove impurities from the four medicinal materials, pulverize them through an 80-mesh sieve, mix them evenly, and obtain mixed medicinal material powder; Compound enzymatic hydrolysis: Add compound enzyme solution (cellulase: pectinase: lipase = 2:1:0.5, enzyme addition amount 1%) at a liquid-to-solid ratio of 1:18, adjust pH to 4.8 with citrate-sodium citrate buffer, and enzymatically hydrolyze at 45℃ for 1.5h, stirring for 5min every 20min during the process to break down cell walls and cell membranes and release lipid-soluble and water-soluble components. Supercritical CO2 two-phase extraction: The enzymatically hydrolyzed medicinal materials are transferred into a supercritical extraction vessel, and 70% ethanol is added as an entrainer (the amount is 12% of the weight of the medicinal materials). The CO2 pressure is set to 28 MPa and the temperature to 38℃, and the extraction is carried out for 2.5 hours, simultaneously extracting fat-soluble (alkaloids, volatile oils) and water-soluble (flavonoids, polysaccharides) components. Low-temperature concentration: The extract is concentrated to a relative density of 1.12 (20℃) by vacuum freezing at -40℃ to avoid degradation of heat-sensitive components.

[0027] 3. Purification process (using gradient membrane separation and molecular imprinting purification): Gradient membrane separation: The concentrate is first filtered through a 0.2μm ceramic membrane (pressure 0.4MPa) to remove solid impurities and large protein molecules; then it is concentrated through a 1000Da nanofiltration membrane (pressure 1.5MPa) to retain impurities such as starch and tannins, and the permeate is collected. Molecular imprinting purification: A molecular imprinted polymer column (functional monomer methacrylic acid, crosslinking agent ethylene glycol dimethacrylate, template molecule to functional monomer molar ratio 1:5) was prepared for matrine analog (Senden core component) and geniposide (gardenia core component). The nanofiltration permeate was passed through the column to specifically adsorb the active ingredients. The column was eluted with 50% ethanol, the eluent was collected, and the purified extract (purity ≥92%) was obtained by vacuum freeze-drying.

[0028] 4. Cream preparation process Construction of targeted drug delivery system: Poly-β-amino ester and polyethylene glycol were mixed at a mass ratio of 3:1 to prepare a pH-ROS dual-response polymer carrier. The purified extract was added (carrier to extract mass ratio of 4:1), and the mixture was ultrasonically dispersed for 30 min (power 300W) to form drug-loaded nanoparticles with a particle size of 50~200nm. Preparation of temperature-sensitive composite matrix: Poloxamer 407, Poloxamer 188 and nano hydroxyapatite were weighed in a mass ratio of 5:3:2, melted in a water bath at 60℃, stirred evenly, and chitosan quaternary ammonium salt (accounting for 5% of the total mass of the matrix) was added. Stirring was continued for 10 min to obtain the temperature-sensitive composite matrix (phase transition temperature 34℃). Microfluidic adaptation: Drug-loaded nanoparticles and temperature-sensitive matrix were added to the microfluidic chip (channel width 80μm) at a mass ratio of 1:4. The stirring rate was set to 10000r / min and mixed for 10min to ensure uniform dispersion of drug and matrix. Compound penetration enhancer and preservative: Add lauryl acetone-menthol compound penetration enhancer (mass ratio 1:0.8, accounting for 2% of the total mass of the cream), stir for 5 min; then add honeysuckle-forsythia extract (mass ratio 1:1) and plant-derived preservative (0.5%), and homogenize (pressure 20 MPa). Aseptic molding: Pour the mixture into an aseptic filling device, fill it into aluminum tubes, and cool it to room temperature (25°C) to obtain Mongolian medicine Sendeng-4 cream (20g per tube).

[0029] Example

[0030] Example 1: Validation of the extraction and purification process of Mongolian medicine Sendeng-4 cream Experimental materials and instruments Raw materials: Senden, Terminalia chebula, Gardenia jasminoides, and Melia toosendan were all purchased from a Mongolian medicine base in Inner Mongolia and were identified as meeting the 2015 edition of the "Mongolian Medicine Standards". Reagents: Cellulase, pectinase, lipase (enzyme activity ≥10000U / g), methacrylic acid, ethylene glycol dimethacrylate (analytical grade), lauryl azone, menthol (pharmaceutical grade); Instruments: Supercritical CO2 extractor (HA121-50-01), gradient membrane separation system (DL-404), molecularly imprinted column, vacuum freeze dryer (FD-1A-50), high performance liquid chromatograph (Agilent 1260).

[0031] Experimental steps Raw material pretreatment: Weigh 300g of Senten, 200g of Terminalia chebula, 200g of Gardenia jasminoides, and 100g of Melia toosendan according to the weight parts, clean and remove impurities, pulverize and pass through an 80-mesh sieve, and mix evenly to obtain 800g of medicinal powder. Compound enzymatic hydrolysis: Add 14.4L of compound enzyme solution (4.8g cellulase + 2.4g pectinase + 1.2g lipase), adjust the pH to 4.8, and enzymatically hydrolyze at 45℃ for 1.5h; Supercritical CO2 two-phase extraction: Transfer to a supercritical extraction vessel, add 96 mL of 70% ethanol, extract at 28 MPa and 38 °C for 2.5 h, and collect about 6 L of extract; Low-temperature concentration: freeze-concentrate at -40℃ to a relative density of 1.12 to obtain 800mL of concentrate; Gradient membrane separation: 750 mL of filtrate was obtained by filtration through a 0.2 μm ceramic membrane and concentrated to 200 mL by a 1000 Da nanofiltration membrane; Molecular imprinting purification: using a self-made molecular imprinting column, elution with 50% ethanol was performed, the eluent was collected, and freeze-dried to obtain 78g of purified extract.

[0032] Test results Content of active ingredients: HPLC analysis showed that matrine analogues were 0.92%, geniposide was 0.75%, total flavonoids were 1.8%, and total active ingredients were 3.47%. Purity and impurities: Impurity content ≤0.8%, no heavy metals exceeding the standard (lead ≤5.0mg / kg, cadmium ≤0.3mg / kg); Solvent residue: Ethanol residue is 0.03%, which meets safety standards.

[0033] Example 2: Preparation and performance testing of Mongolian medicine Sendeng-4 cream Experimental materials and instruments Raw materials: purified extract prepared in Example 1, poloxamer 407, 188, nano hydroxyapatite, chitosan quaternary ammonium salt, poly-β-amino ester, polyethylene glycol, lauryl ketone, menthol, honeysuckle-forsythia extract; Instruments: Microfluidic chip (self-made), homogenizer (AH1000), rheometer (AR2000), skin penetration analyzer (Franz diffusion cell), high performance liquid chromatograph.

[0034] Experimental steps Preparation of targeted drug-loaded nanoparticles: 30g of poly-β-amino ester and 10g of polyethylene glycol were dissolved in 500mL of PBS buffer (pH 7.4), 10g of purified extract was added, and the mixture was ultrasonically dispersed for 30min to obtain drug-loaded nanoparticles (particle size 120nm, PDI 0.18). Preparation of temperature-sensitive composite matrix: 40750g of poloxamer, 18830g of poloxamer, 20g of nano-hydroxyapatite were melted at 60℃, and 5g of chitosan quaternary ammonium salt was added and stirred evenly. Microfluidic mixing: Drug-loaded nanoparticles and matrix were added to the microfluidic chip at a ratio of 1:4, stirred at 10000r / min for 10min, 1.6g of laurocapram and 1.28g of menthol were added, stirred for 5min, and then 0.4g of honeysuckle-forsythia extract was added. The mixture was homogenized at 20MPa. Aseptic filling: Fill into 100 aluminum tubes, 20g each, cool to 25℃ to obtain Mongolian medicine Sendeng-4 cream.

[0035] Performance testing Appearance and uniformity: The cream is milky white and fine, without any grainy texture. No crystallization occurs after application, and the content uniformity RSD is 2.1%. Thermosensitive properties: It is a rheotype at 25℃ and gels at 34℃, which meets the skin's temperature response requirements; Skin permeability: Franz diffusion cell assay (pig ear skin) showed a cumulative transdermal dose of 18.6 μg / cm³ over 24 hours. 2 Transdermal transdermal rate: 3.2 μg / cm 2 •h, compared to traditional creams (1.1μg / cm 2 •h) increased by 190.9%; Targeting: In a simulated inflammatory environment (pH 7.8 + ROS), the drug release rate is 85%, while in a normal skin environment (pH 7.4), the release rate is 32%, and the target enrichment rate reaches 70%. Safety: Skin irritation test (intact rabbit skin) showed no redness or itching, and the irritation level was 0.

[0036] Example 3: Stability verification of Mongolian medicine Senden-4 cream Experimental materials and instruments Raw material: Mongolian medicine Senden-4 cream prepared in Example 2; Instruments: Accelerated stability test chamber (LHH-150SDP), high performance liquid chromatograph, rheometer.

[0037] Experimental steps Accelerated stability test: The cream was placed in an accelerated stability test chamber at 40°C and 75% RH, and samples were taken at 1, 2, 3, and 6 months to test its appearance, viscosity, active ingredient content, and microbial limits. Long-term stability test: The cream was placed in an environment of 25°C and RH 60%, and samples were taken at 6, 12, 18, and 24 months to test the above indicators; Destructive testing: The cream was placed in an environment of 60°C and 85% RH for 1 month to test its stability.

[0038] Results and Analysis Accelerated testing for 6 months: The cream showed no layering or mold growth, maintained a viscosity of around 20,000 mPa·s, had an active ingredient degradation rate of 4.8%, and met the microbial limits (bacterial count ≤100 CFU / g). Long-term test for 24 months: The cream had a normal appearance, a viscosity of 19500 mPa·s, an active ingredient degradation rate of 5.2%, and no significant changes in any of the indicators; Destructive testing: After being placed at 60℃ for 1 month, the cream showed no obvious stratification, and the degradation rate of the active ingredient was 8.5%, demonstrating significantly better stability than traditional creams (destructive testing degradation rate of 35%).

[0039] Comparison Example Comparative Example 1: Traditional Extraction + Ordinary Base Cream Process: After the medicinal materials are pulverized, they are extracted by reflux with 70% ethanol for 2 hours, concentrated under reduced pressure (60℃), mixed with petrolatum: lanolin = 3:1, benzalkonium bromide preservative is added, and stirred to form a paste; Performance: Active ingredient dissolution rate 38%, heat-sensitive ingredient retention rate 72%, cream is rough and easily separates, 24h transdermal rate 1.1μg / cm 2 •h, the degradation rate of active ingredients is 32% after 6 months, and the skin irritation level is grade 1.

[0040] Comparative Example 2: Cream extracted without enzymatic hydrolysis Process: The complex enzymatic hydrolysis step is removed, and supercritical CO2 extraction is performed directly. The rest of the process is the same as in Example 2. Performance: The dissolution rate of the active ingredient was 65%, significantly lower than that of Example 2 (92%), and the transdermal penetration rate was 2.0 μg / cm. 2 •h, with limited therapeutic effect.

[0041] Comparative Example 3: Cream without targeted drug delivery Process: The purified extract was directly mixed with the matrix without pH-ROS responsive carrier loading, and the rest of the process was the same as in Example 2; Performance: No targeting; drug concentration at the site of inflammation was only 35% of that in Example 2; transdermal rate was 2.2 μg / cm². 2 •h, slow to take effect.

[0042] Comparative Example 4: Cream without microfluidic adaptation Process: The drug and matrix are mixed manually without the use of a microfluidic chip; the rest of the process is the same as in Example 2. Performance: The cream has poor uniformity, with a content uniformity RSD of 6.8%, large fluctuations in local drug concentration, and significant batch-to-batch differences.

[0043] This invention solves the problems of insufficient dissolution and degradation of heat-sensitive components by employing a combination of enzymatic hydrolysis and supercritical CO2 two-phase extraction. Gradient membrane separation and molecular imprinting purification enhance the purity and safety of the formulation. pH-ROS-responsive drug loading, temperature-sensitive nanomatrix, and composite permeation enhance targeting and penetration. Microfluidic adaptation and plant-derived preservatives ensure quality stability and batch-to-batch consistency. Compared with existing technologies, the Mongolian medicine Sendeng-4 cream prepared by this invention represents a significant breakthrough in efficacy, safety, and stability, providing a novel solution for the modernization of Mongolian medicine topical preparations and possessing significant industrialization and clinical application value.

[0044] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Mongolian medicine, Senden-4 cream, characterized in that, Prepared from the following raw materials and processes: (1) Raw materials in the following proportions by weight: 3 parts of Senten, 2 parts of Terminalia chebula, 2 parts of Gardenia jasminoides, and 1 part of Melia toosendan; (2) Extraction process: ① Compound enzymatic hydrolysis: The medicinal materials are pulverized and passed through an 80-mesh sieve, then a compound enzyme solution is added. The pH is 4.5~5.0, and the mixture is enzymatically hydrolyzed at 45℃ for 1.5 hours. The compound enzyme solution uses a ratio of cellulase:pectinase:lipase = 2:1:0.5, and the enzyme addition amount is 1%. ② Supercritical CO2 two-phase extraction: CO2 pressure 25~30MPa, temperature 35~40℃, ethanol entrainer dosage 10~15%, extraction 2~3h; ③ Low-temperature concentration: Vacuum freezing and concentration at -40℃ to a relative density of 1.10~1.15; (3) Purification process: ① Gradient membrane separation: 0.2μm ceramic membrane filtration → 1000Da nanofiltration membrane concentration; ② Molecular imprinting purification: The core components of the four herbs were purified by adsorption using a Senden-4 herbal medicine molecular imprinting polymer column. (4) Cream preparation: ① Targeted drug delivery: The active ingredient is loaded onto a poly-β-amino ester-polyethylene glycol graft copolymer; ② Matrix preparation: Poloxamer 407 / 188: nano hydroxyapatite: chitosan quaternary ammonium salt = 5:3:2, melted at 60℃; ③ Microfluidic adaptation: The drug and matrix are mixed in a 1:4 ratio via a microfluidic chip; ④ Compound penetration enhancer: Add lauryl ketone-menthol compound penetration enhancer at a ratio of 1:0.8; ⑤ Aseptic molding: Add honeysuckle-forsythia extract plant-derived preservative in a 1:1 ratio, homogenize, and aseptically fill to obtain the cream.

2. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: In step (2), the solid-to-composite enzymatic hydrolysate ratio is 1:15 to 1:20, and the concentration of ethanol entrainer in supercritical CO2 extraction is 70%.

3. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: In step (3), the functional monomer of the molecularly imprinted polymer column is methacrylic acid, the crosslinking agent is ethylene glycol dimethacrylate, and the molar ratio of template molecule to functional monomer is 1:

5.

4. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: In step (4), the mass ratio of polyβ-amino ester to polyethylene glycol in the pH-ROS responsive polymer is 3:1, and the drug particle size after loading is 50~200nm.

5. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: In step (4), the phase transition temperature of the temperature-sensitive composite matrix is ​​32~36℃, and the viscosity of the cream is 15000~25000mPa·s.

6. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: In step (4), the stirring rate of the microfluidic chip is 10,000 r / min and the mixing time is 10 min to ensure that the drug and matrix are evenly dispersed.

7. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: The total content of active ingredients is ≥3.5%, of which matrine analogues are ≥0.8% and geniposide is ≥0.6%.

8. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: Skin permeability ≥2.5μg / cm 2 •h, pH value 5.5~7.0, meets the safety standards for topical skin preparations.

9. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: After 6 months of accelerated stability testing, no stratification or mold growth was observed, and the degradation rate of the active ingredient was ≤5%.

10. The Mongolian medicine Senden-4 cream according to claim 1, characterized in that: Suitable for skin inflammation, eczema, and itching. Apply topically 1-2 times daily.

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