A composition containing sea cucumber peptide, matrine and inositol and a preparation method thereof

Abstract

The present application relates to a kind of moisturizing, soothing, soothing cream of relieving itching, the cream includes sea cucumber peptide, matrine, inositol, humectant, emulsifier, antioxidant, preservative, emollient and flavouring agent and solvent, the humectant is selected from one or more of glycerol, dimethicone, lecithin, ceramide EOP and sodium hyaluronate, the emulsifier is selected from one or more of stearic acid, cetyl alcohol and sorbitan oleate.The cream of the present application will sea cucumber peptide, matrine, inositol as active substance, synergistic effect of moisturizing, soothing, soothing effect of relieving itching.The cream of the present application cream body is uniform, no layering, texture is delicate, no sand grain feeling, cream preparation process is suitable for industrialized mass production.

Description

Technical Field

[0001] This invention relates to the field of pharmaceuticals, specifically to a pharmaceutical composition with moisturizing, antipruritic, soothing, and repairing effects. Background Technology

[0002] Sea cucumbers belong to the class Holothuroidea of ​​the phylum Echinodermata and possess high nutritional and medicinal value. Modern pharmacological studies have shown that sea cucumber peptides are marine bioactive peptides with a molecular weight range of 800-2200 Da. Sea cucumber peptides contain 17 amino acids, with a total amino acid content as high as 221.105 μg / mg. The most abundant amino acids are arginine (approximately 50 μg / mg) and glycine (approximately 30 μg / mg), followed by proline, glutamic acid, alanine, and valine. Sea cucumber peptides exhibit various biological activities, including anti-inflammatory, anti-fatigue, anti-tumor, immunomodulatory, and antihypertensive effects. Research on the skin physiological activities of sea cucumber peptides is limited. Previous pharmacodynamic studies have shown that sea cucumber peptides have wound-repairing and antioxidant activities.

[0003] Sophora flavescens is the dried root of the legume Sophora flavescens. It contains various active ingredients, including alkaloids, flavonoids, and volatile oils, with alkaloids and flavonoids and their derivatives being the main active components. Matrine, a bioactive substance isolated from the root, is one of the two most abundant alkaloids. Modern pharmacological studies have confirmed that matrine possesses antitumor, antiviral, anti-inflammatory, hepatoprotective, antiarrhythmic, analgesic, anti-allergic, and antiasthmatic effects. In the field of dermatology, matrine has anti-inflammatory, immunomodulatory, anti-allergic, and anti-fibrotic effects, and is clinically used to treat acute, subacute, or chronic inflammatory skin diseases characterized by allergic reactions, such as dermatitis and eczema, with minimal adverse reactions similar to glucocorticoids.

[0004] Pruritus is one of the most common clinical symptoms of various skin diseases such as dermatitis, psoriasis, infections, xerosis, and eczema. It is also a clinical manifestation of systemic diseases such as diabetes, kidney failure, and AIDS. Pruritus is often characterized by recurring symptoms and difficulty in curing. Severe itching can lead to skin inflammation, roughness, dryness, scaling, and ulceration. In addition to disease factors, environmental degradation and the overuse of various additives are also contributing to the increasing number of people with allergies and sensitive skin. When sensitive skin is stimulated by external factors, it is prone to erythema, papules, and telangiectasia, accompanied by symptoms such as itching, stinging, burning, and tightness. Pruritus is characterized by its tendency to relapse and its persistent nature, and long-term drug treatment also poses safety risks. Therefore, there is an urgent need to develop drugs or functional cosmetics that are reliable in efficacy, have stable and controllable quality, and are gentle and safe. Summary of the Invention

[0005] To solve the above-mentioned technical problems, the present invention includes the following aspects: A first aspect of the present invention provides a moisturizing, antipruritic, soothing, and repairing cream, the cream comprising sea cucumber peptide, matrine, inositol, a moisturizer, an emulsifier, and a solvent.

[0006] Preferably, the sea cucumber peptide accounts for 0.01-0.5% of the weight in the cream. More preferably, the sea cucumber peptide accounts for 0.05-0.15% of the weight in the cream. Even more preferably, the sea cucumber peptide accounts for 0.1% of the weight in the cream.

[0007] Preferably, the matrine accounts for 0.1-0.5% of the weight in the cream. More preferably, the matrine accounts for 0.3-0.5% of the weight in the cream. Even more preferably, the matrine accounts for 0.5% of the weight in the cream. Preferably, the inositol accounts for 0.01-0.5% of the weight in the cream. More preferably, the inositol accounts for 0.05-0.15% of the weight in the cream. Even more preferably, the inositol accounts for 0.1% of the weight in the cream.

[0008] Preferably, the weight ratio of sea cucumber peptides to inositol in the cream is (1:3) to (3:1). More preferably, the weight ratio of sea cucumber peptides to inositol in the cream is (1:2) to (2:1). Even more preferably, the weight ratio of sea cucumber peptides to inositol in the cream is 1:1.

[0009] Preferably, the average molecular weight of the sea cucumber peptides in the cream is 200-3000 Da. More preferably, the average molecular weight of the sea cucumber peptides in the cream is 300-2000 Da. Even more preferably, the average molecular weight of the sea cucumber peptides in the cream is 500-1000 Da.

[0010] Preferably, more than 90% of the sea cucumber peptides in the cream have a molecular weight of less than 2000 Da.

[0011] Preferably, the moisturizer is selected from one or more of glycerin, polydimethylsiloxane, lecithin, ceramide EOP, and sodium hyaluronate. More preferably, the moisturizer is a combination of (a) one or more of glycerin, polydimethylsiloxane, and sodium hyaluronate, and (b) one or more of lecithin and ceramide EOP. Even more preferably, the moisturizer is a combination of glycerin, polydimethylsiloxane, lecithin, ceramide EOP, and sodium hyaluronate.

[0012] Preferably, the moisturizer comprises an aqueous phase moisturizer and an oil phase moisturizer, wherein the aqueous phase moisturizer is selected from one or more of glycerin and sodium hyaluronate, and the oil phase moisturizer is selected from one or more of polydimethylsiloxane, lecithin, and ceramide EOP. More preferably, the aqueous phase moisturizer is a combination of glycerin and sodium hyaluronate, and the oil phase moisturizer is a combination of polydimethylsiloxane, lecithin, and ceramide EOP.

[0013] Preferably, the moisturizer accounts for 20-40% by weight in the cream. More preferably, the moisturizer accounts for 25-35% by weight in the cream. Even more preferably, the moisturizer accounts for 28-32% by weight in the cream.

[0014] Preferably, the glycerin accounts for 20-30% by weight in the cream. More preferably, the glycerin accounts for 22-28% by weight in the cream. Even more preferably, the glycerin accounts for 25% by weight in the cream.

[0015] Preferably, the polydimethylsiloxane comprises 1-10% by weight in the cream. More preferably, the polydimethylsiloxane comprises 2-6% by weight in the cream. Even more preferably, the polydimethylsiloxane comprises 4% by weight in the cream.

[0016] Preferably, the lecithin accounts for 0.01-0.1% of the weight in the cream. More preferably, the lecithin accounts for 0.02-0.08% of the weight in the cream. Even more preferably, the lecithin accounts for 0.05% of the weight in the cream.

[0017] Preferably, the ceramide EOP in the cream is 0.01-0.1% by weight. More preferably, the ceramide EOP in the cream is 0.02-0.08% by weight. Even more preferably, the ceramide EOP in the cream is 0.05% by weight.

[0018] Preferably, the sodium hyaluronate in the cream accounts for 0.005-0.05% by weight. More preferably, the sodium hyaluronate in the cream accounts for 0.01-0.02% by weight. Even more preferably, the sodium hyaluronate in the cream accounts for 0.01% by weight.

[0019] Preferably, the emulsifier is selected from one or more of stearic acid, cetyl alcohol, and sorbitan oleate. More preferably, the emulsifier is a combination of stearic acid, cetyl alcohol, and sorbitan oleate.

[0020] Preferably, the stearic acid accounts for 1-10% of the weight percentage in the cream. More preferably, the stearic acid accounts for 2-6% of the weight percentage in the cream. Even more preferably, the stearic acid accounts for 4% of the weight percentage in the cream.

[0021] Preferably, the cetyl alcohol comprises 0.5-5% by weight in the cream. More preferably, the cetyl alcohol comprises 1-2% by weight in the cream. Even more preferably, the cetyl alcohol comprises 1.5% by weight in the cream.

[0022] Preferably, the weight percentage of sorbitan oleate in the cream is 0.1-2%. More preferably, the weight percentage of sorbitan oleate in the cream is 0.2-1%. Even more preferably, the weight percentage of sorbitan oleate in the cream is 0.5%.

[0023] Preferably, the cream further comprises one or more of antioxidants, preservatives, emollients, and flavoring agents. More preferably, the cream further comprises antioxidants, preservatives, emollients, and flavoring agents.

[0024] Preferably, the antioxidant is selected from one or more of tocopherol, ascorbate glucoside, and ascorbic acid. More preferably, the antioxidant is selected from one or more of tocopherol and ascorbate glucoside. Even more preferably, the antioxidant is a combination of tocopherol and ascorbate glucoside.

[0025] Preferably, the antioxidant accounts for 1-8% of the weight percentage of the cream. More preferably, the antioxidant accounts for 1-5% of the weight percentage of the cream. Even more preferably, the antioxidant accounts for 3% of the weight percentage of the cream.

[0026] Preferably, the tocopherol content in the cream is 1-5% by weight. More preferably, the tocopherol content in the cream is 1-3% by weight. Even more preferably, the tocopherol content in the cream is 2% by weight.

[0027] Preferably, the ascorbate glucoside accounts for 0.001-0.05% by weight in the cream. More preferably, the ascorbate glucoside accounts for 0.005-0.02% by weight in the cream. Even more preferably, the ascorbate glucoside accounts for 0.01% by weight in the cream.

[0028] Preferably, the preservative is selected from one or more of phenoxyethanol, methylparaben, and ethylparaben. More preferably, the preservative is selected from one or more of phenoxyethanol and methylparaben. Even more preferably, the preservative is a combination of phenoxyethanol and methylparaben.

[0029] Preferably, the preservative accounts for 0.2-2% of the weight percentage in the cream. More preferably, the preservative accounts for 0.5-1.5% of the weight percentage in the cream. Even more preferably, the preservative accounts for 0.8-1% of the weight percentage in the cream.

[0030] Preferably, the phenoxyethanol content in the cream is 0.1-2% by weight. More preferably, the phenoxyethanol content in the cream is 0.5-1% by weight. Even more preferably, the phenoxyethanol content in the cream is 0.8% by weight.

[0031] Preferably, the methylparaben contains 0.1-1% by weight in the cream. More preferably, the methylparaben contains 0.2-0.5% by weight in the cream. Even more preferably, the methylparaben contains 0.1% by weight in the cream.

[0032] Preferably, the emollient is selected from allantoin.

[0033] Preferably, the emollient accounts for 0.1-1% of the weight percentage of the cream. More preferably, the emollient accounts for 0.1-0.5% of the weight percentage of the cream. Even more preferably, the emollient accounts for 0.2% of the weight percentage of the cream.

[0034] Preferably, the allantoin contains 0.1-1% by weight in the cream. More preferably, the allantoin contains 0.1-0.5% by weight in the cream. Even more preferably, the allantoin contains 0.2% by weight in the cream.

[0035] Preferably, the flavoring agent is selected from one or more of ginger flower flavoring, peppermint flavoring, orange flavoring, and strawberry flavoring. More preferably, the flavoring agent is selected from one or more of ginger flower flavoring and peppermint flavoring. Even more preferably, the flavoring agent is ginger flower flavoring.

[0036] Preferably, the flavoring agent accounts for 0.01-0.1% of the weight of the cream. More preferably, the flavoring agent accounts for 0.02-0.08% of the weight of the cream. Even more preferably, the flavoring agent accounts for 0.05% of the weight of the cream.

[0037] Preferably, the ginger flower fragrance accounts for 0.01-0.1% of the weight of the cream. More preferably, the ginger flower fragrance accounts for 0.02-0.08% of the weight of the cream. Even more preferably, the ginger flower fragrance accounts for 0.05% of the weight of the cream.

[0038] Preferably, the solvent is purified water.

[0039] Preferably, the solvent accounts for 50-70% by weight in the cream. More preferably, the solvent accounts for 50-65% by weight. Even more preferably, the solvent accounts for 55-62% by weight in the cream.

[0040] Preferably, the cream contains sea cucumber peptide, matrine, inositol, glycerin, dimethicone, lecithin, ceramide EOP, sodium hyaluronate, stearic acid, cetyl alcohol, sorbitan oleate, tocopherol, ascorbyl glucoside, phenoxyethanol, methylparaben, allantoin, ginger flower fragrance, and purified water.

[0041] Preferably, the cream comprises the following components by weight percentage: 0.02-0.5% sea cucumber peptide, 0.1-1% matrine, 0.02-0.5% inositol, 15-35% glycerin, 1-8% polydimethylsiloxane, 0.01-0.2% lecithin, 0.01-0.2% ceramide EOP, 0.002-0.05% sodium hyaluronate, 1-8% stearic acid, 1-5% cetyl alcohol, 0.1-1% sorbitan oleate, 1-5% tocopherol, 0.001-0.05% ascorbyl glucoside, 0.2-2% phenoxyethanol, 0.05-0.5% methylparaben, 0.05-1% allantoin, 0.01-0.1% ginger flower fragrance, and 50-65% purified water, wherein the total weight percentage of the above components is 100%.

[0042] More preferably, the cream comprises the following components by weight percentage: 0.05-0.2% sea cucumber peptide, 0.2-0.5% matrine, 0.05-0.2% inositol, 20-30% glycerin, 3-5% polydimethylsiloxane, 0.02-0.1% lecithin, 0.02-0.1% ceramide EOP, 0.005-0.02% sodium hyaluronate, 2-6% stearic acid, 1-2% cetyl alcohol, 0.2-0.5% sorbitan oleate, 1-3% tocopherol, 0.005-0.02% ascorbyl glucoside, 0.5-1% phenoxyethanol, 0.1-0.2% methylparaben, 0.1-0.5% allantoin, 0.02-0.08% ginger flower fragrance, and 55-62% purified water, wherein the total weight percentage of the above components is 100%.

[0043] More preferably, the cream comprises the following components in weight percentage: 0.1% sea cucumber peptide, 0.5% matrine, 0.1% inositol, 25% glycerin, 4% dimethicone, 0.05% lecithin, 0.05% ceramide EOP, 0.01% sodium hyaluronate, 4% stearic acid, 1.5% cetyl alcohol, 0.5% sorbitan oleate, 2% tocopherol, 0.01% ascorbyl glucoside, 0.8% phenoxyethanol, 0.1% methylparaben, 0.2% allantoin, 0.05% ginger flower fragrance, and 61.03% purified water.

[0044] A second aspect of the present invention provides a method for preparing the above-mentioned cream, the method comprising the following steps: (1) Weigh out the prescribed amounts of antioxidant, emulsifier and oil phase humectant, and heat and stir the above oil phase excipients until dissolved; (2) Weigh out the prescribed amount of solvent, add the prescribed amounts of sea cucumber peptide, matrine, inositol, aqueous moisturizer, preservative and emollient, stir until completely dissolved, and mix well; (3) Under stirring conditions, slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) for emulsification and homogenization, add the prescribed amount of flavoring agent, stir evenly, and the product is obtained.

[0045] Preferably, the method includes the following steps: (1) Weigh out the prescribed amounts of tocopherol, polydimethylsiloxane, sorbitan oleate, stearic acid, cetyl alcohol, lecithin and ceramide EOP, and heat and stir the above oil phase excipients until dissolved; (2) Weigh the prescribed amount of purified water, add the prescribed amounts of methylparaben, glycerin, ascorbyl glucoside, phenoxyethanol, allantoin, inositol, sodium hyaluronate, sea cucumber peptide and matrine, stir until completely dissolved, and mix well. (3) Under stirring conditions, slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) for emulsification and homogenization, add the prescribed amount of ginger flower essence, stir evenly, and you will get the product.

[0046] Preferably, in step (1), the oil phase auxiliary material is heated to 70-85°C. More preferably, in step (1), the oil phase auxiliary material is heated to 70-80°C. Even more preferably, in step (1), the oil phase auxiliary material is heated to 75°C.

[0047] Preferably, the temperature of the oil-water two-phase mixture in step (3) is controlled at 75℃-80℃.

[0048] Preferably, the homogenization in step (3) is carried out in a homogenizer at a homogenization speed of 8000 rpm and a stirring speed of 800 rpm. After 2 minutes, the homogenization is stopped and the stirring speed is reduced to 500 rpm.

[0049] Preferably, the step (3) before adding ginger flower flavoring includes the following steps: turn on the cooling water, fill the outer layer of the emulsification tank, turn off the water, start timing for 15 minutes, then turn on the circulating water and continue stirring until 65°C.

[0050] Preferably, after adding ginger flower flavoring in step (3), the following steps are further included: turn on the vacuum pump and stir continuously; when the temperature drops to about 40°C, turn off the cooling water and stop stirring; open the pressure reducing valve and dispense.

[0051] A third aspect of the present invention provides the use of the above-described cream in the preparation of a medicament for treating pruritus or a functional cosmetic.

[0052] A fourth aspect of the invention provides the use of a moisturizer in improving the chemical stability of matrine in the above-mentioned cream, said moisturizer comprising lecithin and ceramide EOP.

[0053] Preferably, the lecithin accounts for 0.01-0.1% of the weight in the cream. More preferably, the lecithin accounts for 0.02-0.08% of the weight in the cream. Even more preferably, the lecithin accounts for 0.05% of the weight in the cream.

[0054] Preferably, the ceramide EOP in the cream is 0.01-0.1% by weight. More preferably, the ceramide EOP in the cream is 0.02-0.08% by weight. Even more preferably, the ceramide EOP in the cream is 0.05% by weight.

[0055] Preferably, the moisturizer is a combination of glycerin, polydimethylsiloxane, lecithin, ceramide EOP and sodium hyaluronate.

[0056] Preferably, the moisturizer is 25% glycerin, 4% polydimethylsiloxane, 0.05% lecithin, 0.05% ceramide EOP and 0.01% sodium hyaluronate, the weight percentages being based on the total weight of the cream.

[0057] Preferably, the cream comprises the following components in weight percentage: 0.1% sea cucumber peptide, 0.5% matrine, 0.1% inositol, 25% glycerin, 4% dimethicone, 0.05% lecithin, 0.05% ceramide EOP, 0.01% sodium hyaluronate, 4% stearic acid, 1.5% cetyl alcohol, 0.5% sorbitan oleate, 2% tocopherol, 0.01% ascorbyl glucoside, 0.8% phenoxyethanol, 0.1% methylparaben, 0.2% allantoin, 0.05% ginger flower fragrance, and 61.03% purified water.

[0058] The technical effects of this invention are as follows: 1. This invention unexpectedly discovered that the combination of sea cucumber peptides, matrine, and inositol as active ingredients in a cream can synergistically exert a therapeutic effect on pruritus. In vitro animal experiments have confirmed that, compared to creams containing only matrine and sea cucumber peptides or only matrine and inositol, the cream of this invention has a more significant inhibitory effect on 4-aminopyridine-induced pruritus response in mice.

[0059] 2. This invention, by optimizing the cream formulation (e.g., sodium hyaluronate concentration, matrine content, etc.) and its preparation process parameters (e.g., oil-water phase mixture temperature, discharge temperature, cooling rate, etc.), has obtained a high-quality cream formulation suitable for large-scale industrial production. The cream prepared by this invention has a uniform color, no layering, a fine texture without any gritty feel, and a pH value of 7-7.5.

[0060] 3. This invention selects glycerin, polydimethylsiloxane, lecithin, ceramide EOP, and sodium hyaluronate as a composite moisturizer, which significantly improves the moisturizing effect of the cream. Surprisingly, in addition to its moisturizing effect, the moisturizer of this invention can also significantly improve the chemical stability of matrine, the active ingredient in the cream. In particular, the combination of lecithin and ceramide EOP inhibits the formation of matrine impurities, significantly improving the stability of the cream during production and storage. Detailed Implementation

[0061] The present invention will be further described below with reference to embodiments and experimental examples, but the implementation of the present invention is not limited thereto. The sea cucumber peptides in the embodiments and experimental examples of the present invention were purchased from Xi'an Huipu Biotechnology Co., Ltd. (more than 90% of the sea cucumber peptides have a molecular weight of less than 2000 Da), matrine was purchased from Qiyuan Pharmaceutical Co., Ltd., and polydimethylsiloxane was purchased from Zigong Honghe Pharmaceutical Co., Ltd. (viscosity 970 mm). 2 Sodium hyaluronate was purchased from Bloomage Biotechnology Co., Ltd. (J100240048, molecular weight 1450 kDa). Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0062] Example 1: Moisturizing and antipruritic drug cream of the present invention 1 1. Prescription (each batch is packaged in 1500g containers, with a specification of 50g / bottle) 2. Preparation method Step (1): Weigh out the prescribed amounts of tocopherol, polydimethylsiloxane, sorbitan oleate, stearic acid, cetyl alcohol, lecithin and ceramide EOP respectively, place the above oil phase excipients in a stainless steel bucket, heat and stir until dissolved, and control the oil phase temperature at 75℃. Step (2): Add the prescribed amount of purified water to another stainless steel bucket, add the prescribed amount of methylparaben, heat and stir until the methylparaben is completely dissolved, then add the prescribed amounts of glycerin, ascorbyl glucoside, phenoxyethanol, allantoin, inositol, sodium hyaluronate, matrine and sea cucumber peptide, stir until completely dissolved, and mix well. Step (3): Under stirring conditions, slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) for emulsification, transfer to a small emulsification tank, and prepare the cream on the machine. Before the cream is prepared, the temperature of the oil-water mixture is controlled at 75℃-80℃. Step (4): Turn on the homogenizer at 8000 rpm and simultaneously start the mixer at 800 rpm. Stop homogenizing after 2 minutes. Reduce the mixer speed to 500 rpm, turn on the cooling water, fill the outer layer of the emulsification tank, then turn off the water and start timing. After 15 minutes, turn on the circulating water and continue mixing until the temperature reaches 65°C. Add the prescribed amount of ginger flower essence, turn on the vacuum pump, and continue mixing. When the temperature drops to 40°C, turn off the cooling water and stop mixing. Open the pressure reducing valve to end the cream preparation process. Dispense the product to obtain the moisturizing, antipruritic, soothing, and repairing drug cream 1 of this invention.

[0063] The cream prepared using the above method in Example 1 has a uniform color, no layering, a fine texture, no gritty feel, and a pH value of 7.2.

[0064] Example 2 In Example 1, 0.1% sea cucumber peptide and 0.1% inositol were replaced with 0.15% sea cucumber peptide and 0.05% inositol, while the remaining components, contents, and preparation methods were the same as in Example 1, to prepare the cream of Example 2.

[0065] Example 3 In Example 1, 0.1% sea cucumber peptide and 0.1% inositol were replaced with 0.05% sea cucumber peptide and 0.15% inositol, while the remaining components, contents, and preparation methods were the same as in Example 1, to prepare the cream of Example 3.

[0066] Example 4 In Example 1, 0.05% lecithin and 0.05% ceramide EOP were replaced with 0.1% lecithin (i.e., ceramide EOP was omitted), while the remaining components, contents, and preparation methods were the same as in Example 1, to prepare the cream of Example 4.

[0067] Example 5 In Example 1, 0.05% lecithin and 0.05% ceramide EOP were replaced with 0.1% ceramide EOP (i.e., lecithin was omitted), while the remaining components, contents, and preparation methods were the same as in Example 1, to prepare the cream of Example 5.

[0068] Comparative Examples 1-3 (Creams with different sodium hyaluronate contents) The sodium hyaluronate content in the formulation of Example 1 was replaced by 0.5%, 0.1%, and 0.0% respectively (i.e., no addition), and the other components and contents, as well as the preparation method, were the same as in Example 1 (purified water was added to make the total weight of the formulation 1500g). Comparative Examples 1-3 creams were prepared respectively.

[0069] Comparative Examples 4-6 (Creams with different processing parameters) Replace the temperature of the oil-water phase mixture before loading into the machine in step (3) of the preparation method in Example 1 with 91°C. The remaining components and preparation methods are the same as in Example 1. Prepare the cream of Comparative Example 4.

[0070] The ointment temperature in step (4) of the preparation method in Example 1 was replaced with 25°C instead of 40°C. The remaining components and preparation methods were the same as in Example 1. Comparative Example 5 ointment was prepared.

[0071] Replace the cooling method in step (4) of the preparation method in Example 1, which is "turn on the condenser, fill the outer layer of the emulsification tank and then turn off the water, start timing and turn on the circulating water after 15 minutes", with "turn on the condenser and circulate directly". The remaining components and preparation methods are the same as in Example 1. Prepare the cream of Comparative Example 6.

[0072] Comparative Examples 7-8 (Creams with different matrine contents) The matrine content in the formulation of Example 1 was replaced from 0.5% to 0.8% and 1.0% respectively. The other components and contents, as well as the preparation method, were the same as in Example 1 (purified water was added to make the total weight of the formulation 1500g) to prepare Comparative Example 7-8 cream.

[0073] Comparative Examples 9-10 (Creams with Different Active Ingredients) In Example 1, 0.1% sea cucumber peptide and 0.1% inositol were replaced with 0.2% sea cucumber peptide (i.e., inositol was omitted). The other components and contents, as well as the preparation method, were the same as in Example 1 (purified water was added to make the total weight of the prescription 1500g) to prepare Comparative Example 9 cream.

[0074] In Example 1, 0.1% sea cucumber peptide and 0.1% inositol were replaced with 0.2% inositol (i.e., sea cucumber peptide was omitted). The other components and contents, as well as the preparation method, were the same as in Example 1 (purified water was added to make the total weight of the prescription 1500g) to prepare Comparative Example 10 cream.

[0075] Experimental Example 1: Screening Experiment of the Formulation and Process of the Drug Cream of the Present Invention 1. Screening test for sodium hyaluronate dosage Typically, sodium hyaluronate at appropriate concentrations forms a moisturizing film on the skin surface, locking in moisture and reducing water evaporation, maintaining skin hydration for several hours. Screening tests for hyaluronic acid dosage showed that in Comparative Examples 1 and 2, adding 0.5% and 0.1% sodium hyaluronate resulted in a thinner consistency and a film-like texture, inconsistent with a cream formulation. Further reducing the concentration to 0.01% (Example 1) resulted in a lightweight cream with optimal appearance and feel. Further reducing the sodium hyaluronate concentration to none (Comparative Example 3) resulted in a highly fluid consistency again. Therefore, a sodium hyaluronate content of 0.01% was ultimately determined. Creams made with this concentration exhibited suitable viscosity, uniformity, and a glossy finish, meeting the requirements for a cream.

[0076] 2. Screening test of preparation process parameters The quality of a cream is closely related to its preparation method and process parameters. Screening tests of process parameters showed that the preparation method of Comparative Example 4 prolonged the time from loading the oil-water mixture to cream output, resulting in excessively thick cream. The preparation method of Comparative Example 5 prolonged the cream output time; although the cream was fine and uniform with increased viscosity, the excessive time resulted in low production efficiency and was unsuitable for large-scale production. The preparation method of Comparative Example 6 resulted in a cream with high fluidity. In conclusion, only the process parameters of the formulation in Example 1 can yield a cream that meets the requirements of large-scale production and has good performance.

[0077] 3. Screening test of matrine dosage The pH value of facial cosmetics (such as emulsions and serums) is mostly between 6 and 7.5. Test results show that the pH values ​​of creams in comparative examples 7 and 8 are 7.9 and 8.0, respectively, exceeding the suitable range for facial cosmetics and making them unsuitable for facial use. Therefore, the content of matrine needs to be controlled below 0.5% of the total amount in the cream.

[0078] Experimental Example 2: Effect of the cream of the present invention on a 4-aminopyridine-induced pruritus model mouse. 1. Test Methods Sixty SPF-grade KM mice, half male and half female, were randomly divided into six groups: a blank matrix group, the drug cream groups 1-3 of this invention, and the comparative drug cream groups 1-2, with ten mice in each group. Before the experiment, approximately 2cm × 2cm of hair was removed from the back of the neck of each mouse, and mice with intact skin were selected for the experiment. Mice in the blank matrix group were given 0.1g of a blank matrix (the matrix formulation is the same as in Example 1, but without the active ingredients sea cucumber peptide, matrine, and inositol) in the hair-removed area. Mice in the drug cream groups 1-3 and the comparative drug cream groups 1-2 were given 0.1g of the drug creams prepared in Examples 1-3 and 9-10 of this invention, respectively, in the hair-removed area. All mice in each experimental group were administered the drugs twice daily for 10 consecutive days, once in the morning and once in the evening. One hour after the last administration, 4-aminopyridine was subcutaneously injected into the neck and back of mice at a dose of 1 mg / kg body weight. The licking response of the mice was immediately observed within 15 minutes. One lick was counted as a mouse repeatedly turning its head and licking both sides of its back until a brief pause occurred. The latency time and the number of licks were recorded.

[0079] 2. Test Results A mouse pruritus model was established using 4-aminopyridine to study the effect of the drug cream of the present invention on the pruritus response in mice. The experimental results are shown in Table 1.

[0080] Table 1. Effects of the drug cream of the present invention on 4-aminopyridine-induced pruritus in mice. As shown in Table 1 above, compared with the blank matrix group and the creams of Comparative Examples 9-10 (without inositol or sea cucumber peptide), the drug creams of the present invention in groups 1-3 significantly prolonged the pruritus latency time in mice and significantly reduced the number of pruritus episodes (both statistically significant), indicating that the drug creams of the present invention have a significant inhibitory effect on 4-aminopyridine-induced pruritus response in mice, suggesting that the drug creams have a significant effect in improving skin pruritus in patients. It is noteworthy that, with the same total amount of active ingredients sea cucumber peptide and inositol, the drug cream prepared in Example 1 was significantly superior to that in Examples 2-3 in improving pruritus response in mice, producing an unexpectedly excellent effect.

[0081] Example 3: Chemical stability test of the cream of the present invention 1. Test Methods The pharmaceutical creams prepared in Examples 1 and 4-5 of this invention were stored at 60°C, with three samples repeated for each experimental group. On days 0, 5, and 10, 10g of each cream was accurately weighed, added to 50mL of water, and stirred thoroughly. The filtrate was extracted twice with chloroform (30mL each time), the extracts were combined, evaporated to dryness, and the residue was dissolved in 1mL of acetonitrile-anhydrous ethanol (8:1) to obtain the test solution. The content of matrine in the creams of each example at different storage times was determined using HPLC, and the average content of matrine in each experimental group after storage was calculated. The chromatographic conditions used were as follows: an Agilent ZORBAX NH2 column (250mm × 4.6mm, 5μm), a mobile phase of acetonitrile-anhydrous ethanol-3% phosphoric acid aqueous solution (80:10:10), a detection wavelength of 220nm, a flow rate of 0.8mL / min, and a column temperature of 35°C.

[0082] 2. Test Results The average matrine content in each experimental group is shown in Table 2 below.

[0083] Table 2. Results of the stability test of the pharmaceutical cream of the present invention at high temperature. As shown in Table 2 above, the matrine content of the pharmaceutical creams in Examples 1 and 4-5 did not decrease significantly after storage under high temperature conditions, and the content of active ingredients remained above 90%. In particular, the matrine content in the pharmaceutical cream of Example 1 was still as high as 97.79% after 10 days of storage, indicating that compared with formulations using 0.1% lecithin (Example 4) or 0.1% ceramide EOP (Example 5) alone as moisturizers, the cream of this invention (Example 1), using 0.05% lecithin and 0.05% ceramide EOP as a composite moisturizer, had the best effect on improving the chemical stability of matrine. The above experimental results show that the moisturizer selected in the cream of this invention can effectively inhibit the formation of impurities from matrine, and the cream of this invention is expected to have good stability during production and storage.

[0084] Although specific embodiments of the invention have been described, those skilled in the art will recognize that various changes and modifications can be made to the invention without departing from its scope or spirit. Therefore, the invention is intended to cover all such changes and modifications falling within the scope of the appended claims and their equivalents.

Claims

1. The application of humectants in improving the chemical stability of matrine in creams, characterized in that, The cream comprises the following components by weight percentage: 0.1% sea cucumber peptide, 0.5% matrine, 0.1% inositol, 25% glycerin, 4% dimethicone, 0.05% lecithin, 0.05% ceramide EOP, 0.01% sodium hyaluronate, 4% stearic acid, 1.5% cetyl alcohol, 0.5% sorbitan oleate, 2% tocopherol, 0.01% ascorbyl glucoside, 0.8% phenoxyethanol, 0.1% methylparaben, 0.2% allantoin, 0.05% ginger flower fragrance, and 61.03% purified water.

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