Composition containing sea cucumber peptide, sophocarpidine and inositol and preparation method thereof

Abstract

The present invention relates to a moisturizing, itching relieving, soothing and repairing cream, the cream comprises sea cucumber peptide, sophocarpidine, inositol, a moisturizing agent, an emulsifier, an antioxidant, a preservative, an emollient, a flavoring agent and a solvent, the moisturizing agent is selected from one or more of glycerol, polydimethylsiloxane, lecithin, ceramide EOP and sodium hyaluronate, and the emulsifier is selected from one or more of glycerol, polydimethylsiloxane, lecithin, ceramide EOP and sodium hyaluronate. The emulsifier is selected from one or more of stearic acid, cetyl alcohol and sorbitan oleate. The cream disclosed by the invention takes the sea cucumber peptide, the sophocarpidine and the inositol as active substances, and synergistically exerts the effects of moisturizing, relieving itching, relieving and repairing. The cream is uniform in cream body color, free of layering, fine and smooth in texture and free of sand grain feeling, and the cream preparation technology is suitable for large-scale industrial production.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a pharmaceutical composition with moisturizing, antipruritic, soothing and repairing effects. Background Art

[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 of up to 221.105 μg / mg. Arginine (approximately 50 μg / mg) and glycine (approximately 30 μg / mg) are the most abundant, followed by proline, glutamic acid, alanine, and valine. Sea cucumber peptides exhibit a variety of biological activities, including anti-inflammatory, anti-fatigue, anti-tumor, immunomodulatory, and antihypertensive activities. However, research on the physiological activities of sea cucumber peptides in the skin is limited. Previous pharmacodynamic studies have shown that sea cucumber peptides have wound tissue repair and antioxidant activities.

[0003] Sophora flavescens is the dried root of the leguminous plant Sophora flavescens. It contains a variety of effective ingredients such as alkaloids, flavonoids, and volatile oil compounds. Among them, alkaloids and flavonoids and their derivatives are the main active ingredients of Sophora flavescens. Matrine is a bioactive substance isolated from the root of Sophora flavescens and is one of the two alkaloids with the highest content. Modern pharmacological research has confirmed that matrine has anti-tumor, antiviral, anti-inflammatory, liver-protecting, anti-arrhythmic, analgesic, anti-allergic, and anti-asthmatic effects. In the field of skin diseases, matrine has anti-inflammatory, immunomodulatory, anti-allergic, and anti-skin fibrosis effects. It is clinically used to treat acute, subacute, or chronic inflammatory skin diseases characterized by allergic reactions, such as dermatitis and eczema, and is not prone to glucocorticoid-like adverse reactions.

[0004] Itch is one of the most common clinical symptoms of various skin diseases, including dermatitis, psoriasis, infections, xerosis, and eczema. It is also a clinical manifestation of systemic diseases such as diabetes, renal failure, and AIDS. Itch is often characterized by recurring symptoms and prolonged duration. Severe itching can lead to skin inflammation, roughness, dryness, scaling, and ulcers. In addition to disease-related factors, ecological degradation and the overuse of various additives contribute to the annual increase in the number of people with allergies and sensitive skin. When exposed to external stimuli, sensitive skin is prone to erythema, papules, and dilated capillaries, accompanied by symptoms such as itching, stinging, burning, and tightness. Itch is prone to recurrence and persistence, and long-term drug treatment poses safety risks. Therefore, there is an urgent need to develop pharmaceuticals or functional cosmetics with reliable efficacy, stable and controllable quality, and gentleness and safety. Summary of the Invention

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

[0006] Preferably, the weight percentage of the sea cucumber peptide in the cream is 0.01-0.5%. More preferably, the weight percentage of the sea cucumber peptide in the cream is 0.05-0.15%. Further preferably, the weight percentage of the sea cucumber peptide in the cream is 0.1%.

[0007] Preferably, the weight percentage of matrine in the cream is 0.1-0.5%. More preferably, the weight percentage of matrine in the cream is 0.3-0.5%. Further preferably, the weight percentage of matrine in the cream is 0.5%. Preferably, the weight percentage of inositol in the cream is 0.01-0.5%. More preferably, the weight percentage of inositol in the cream is 0.05-0.15%. Further preferably, the weight percentage of inositol in the cream is 0.1%.

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

[0009] Preferably, the average molecular weight of the sea cucumber peptide in the cream is 200-3000 Da. More preferably, the average molecular weight of the sea cucumber peptide in the cream is 300-2000 Da. Further preferably, the average molecular weight of the sea cucumber peptide 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 moisturizing agent is selected from one or more of glycerin, dimethicone, lecithin, ceramide EOP, and sodium hyaluronate. More preferably, the moisturizing agent is a combination of (a) one or more of glycerin, dimethicone, and sodium hyaluronate and (b) one or more of lecithin and ceramide EOP. Even more preferably, the moisturizing agent is a combination of glycerin, dimethicone, lecithin, ceramide EOP, and sodium hyaluronate.

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

[0013] Preferably, the weight percentage of the moisturizing agent in the cream is 20-40%. More preferably, the weight percentage of the moisturizing agent in the cream is 25-35%. Further preferably, the weight percentage of the moisturizing agent in the cream is 28-32%.

[0014] Preferably, the weight percentage of the glycerol in the cream is 20-30%. More preferably, the weight percentage of the glycerol in the cream is 22-28%. Further preferably, the weight percentage of the glycerol in the cream is 25%.

[0015] Preferably, the weight percentage of the polydimethylsiloxane in the cream is 1-10%. More preferably, the weight percentage of the polydimethylsiloxane in the cream is 2-6%. Further preferably, the weight percentage of the polydimethylsiloxane in the cream is 4%.

[0016] Preferably, the weight percentage of the lecithin in the cream is 0.01-0.1%. More preferably, the weight percentage of the lecithin in the cream is 0.02-0.08%. Further preferably, the weight percentage of the lecithin in the cream is 0.05%.

[0017] Preferably, the weight percentage of the ceramide EOP in the cream is 0.01-0.1%. More preferably, the weight percentage of the ceramide EOP in the cream is 0.02-0.08%. Further preferably, the weight percentage of the ceramide EOP in the cream is 0.05%.

[0018] Preferably, the weight percentage of the sodium hyaluronate in the cream is 0.005-0.05%. More preferably, the weight percentage of the sodium hyaluronate in the cream is 0.01-0.02%. Even more preferably, the weight percentage of the sodium hyaluronate in the cream is 0.01%.

[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 weight percentage of stearic acid in the cream is 1-10%. More preferably, the weight percentage of stearic acid in the cream is 2-6%. Further preferably, the weight percentage of stearic acid in the cream is 4%.

[0021] Preferably, the weight percentage of the cetyl alcohol in the cream is 0.5-5%. More preferably, the weight percentage of the cetyl alcohol in the cream is 1-2%. Further preferably, the weight percentage of the cetyl alcohol in the cream is 1.5%.

[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%. Further preferably, the weight percentage of sorbitan oleate in the cream is 0.5%.

[0023] Preferably, the cream further comprises one or more of an antioxidant, a preservative, an emollient and a flavoring agent. Further preferably, the cream further comprises an antioxidant, a preservative, an emollient and a flavoring agent.

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

[0025] Preferably, the weight percentage of the antioxidant in the cream is 1-8%. More preferably, the weight percentage of the antioxidant in the cream is 1-5%. Further preferably, the weight percentage of the antioxidant in the cream is 3%.

[0026] Preferably, the weight percentage of the tocopherol in the cream is 1-5%. More preferably, the weight percentage of the tocopherol in the cream is 1-3%. Further preferably, the weight percentage of the tocopherol in the cream is 2%.

[0027] Preferably, the weight percentage of the ascorbyl glucoside in the cream is 0.001-0.05%. More preferably, the weight percentage of the ascorbyl glucoside in the cream is 0.005-0.02%. Further preferably, the weight percentage of the ascorbyl glucoside in the cream is 0.01%.

[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. Further preferably, the preservative is a combination of phenoxyethanol and methylparaben.

[0029] Preferably, the weight percentage of the preservative in the cream is 0.2-2%. More preferably, the weight percentage of the preservative in the cream is 0.5-1.5%. Further preferably, the weight percentage of the preservative in the cream is 0.8-1%.

[0030] Preferably, the weight percentage of phenoxyethanol in the cream is 0.1-2%. More preferably, the weight percentage of phenoxyethanol in the cream is 0.5-1%. Further preferably, the weight percentage of phenoxyethanol in the cream is 0.8%.

[0031] Preferably, the weight percentage of the methylparaben in the emulsifiable paste is 0.1-1%. More preferably, the weight percentage of the methylparaben in the emulsifiable paste is 0.2-0.5%. Further preferably, the weight percentage of the methylparaben in the emulsifiable paste is 0.1%.

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

[0033] Preferably, the weight percentage of the emollient in the cream is 0.1-1%. More preferably, the weight percentage of the emollient in the cream is 0.1-0.5%. Further preferably, the weight percentage of the emollient in the cream is 0.2%.

[0034] Preferably, the weight percentage of the allantoin in the cream is 0.1-1%. More preferably, the weight percentage of the allantoin in the cream is 0.1-0.5%. Further preferably, the weight percentage of the allantoin in the cream is 0.2%.

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

[0036] Preferably, the weight percentage of the flavoring agent in the cream is 0.01-0.1%. More preferably, the weight percentage of the flavoring agent in the cream is 0.02-0.08%. Further preferably, the weight percentage of the flavoring agent in the cream is 0.05%.

[0037] Preferably, the weight percentage of the ginger flower essence in the cream is 0.01-0.1%. More preferably, the weight percentage of the ginger flower essence in the cream is 0.02-0.08%. Further preferably, the weight percentage of the ginger flower essence in the cream is 0.05%.

[0038] Preferably, the solvent is purified water.

[0039] Preferably, the weight percentage of the solvent in the cream is 50-70%. More preferably, the weight percentage of the solvent in the cream is 50-65%. Further preferably, the weight percentage of the solvent in the cream is 55-62%.

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

[0041] Preferably, the cream contains the following components in 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 essence and 50-65% purified water, and the total weight percentage of the above components is 100%.

[0042] More preferably, the cream comprises the following components in 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 essence and 55-62% purified water, and the weight percentages of the above components total 100%.

[0043] Further preferably, the cream contains the following components in weight percentage: 0.1% sea cucumber peptide, 0.5% matrine, 0.1% inositol, 25% glycerin, 4% polydimethylsiloxane, 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 essence and 61.03% purified water.

[0044] A second aspect of the present invention provides a method for preparing the above-mentioned cream, comprising the following steps: (1) Weigh the prescribed amount of antioxidant, emulsifier and oil phase moisturizer, and heat and stir the above oil phase excipients until they are dissolved; (2) Weigh the prescribed amount of solvent, add the prescribed amount of sea cucumber peptide, matrine, inositol, aqueous phase moisturizer, preservative and emollient, stir until all are dissolved, and mix well; (3) Slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) under stirring conditions to emulsify and homogenize, add the prescribed amount of flavoring agent, and stir evenly to obtain the product.

[0045] Preferably, the method comprises the following steps: (1) Weigh the prescribed amount 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 amount of methylparaben, glycerin, ascorbyl glucoside, phenoxyethanol, allantoin, inositol, sodium hyaluronate, sea cucumber peptide and matrine, stir until all are dissolved, and mix thoroughly; (3) Slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) under stirring conditions to emulsify and homogenize, add the prescribed amount of ginger flower essence, and stir evenly to obtain 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. Further 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°C-80°C.

[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. The homogenization is stopped after 2 minutes and the stirring speed is reduced to 500 rpm.

[0049] Preferably, the following steps are further included before adding the ginger flower essence in step (3): opening the condensed water, closing the water after filling the outer layer of the emulsification tank, starting the timer to 15 minutes, then opening the circulating water, and continuing to stir until the temperature reaches 65°C.

[0050] Preferably, after adding the ginger flower essence in step (3), the following steps are further included: turning on the vacuum pump and stirring continuously, when the temperature drops to about 40°C, turning off the condensation water and stopping stirring, opening the pressure reducing valve, and packaging.

[0051] A third aspect of the present invention provides use of the above-mentioned cream in the preparation of a medicine or functional cosmetic for treating skin itching.

[0052] The fourth aspect of the present invention provides use of a moisturizer for improving the chemical stability of matrine in the above cream, wherein the moisturizer comprises lecithin and ceramide EOP.

[0053] Preferably, the weight percentage of the lecithin in the cream is 0.01-0.1%. More preferably, the weight percentage of the lecithin in the cream is 0.02-0.08%. Further preferably, the weight percentage of the lecithin in the cream is 0.05%.

[0054] Preferably, the weight percentage of the ceramide EOP in the cream is 0.01-0.1%. More preferably, the weight percentage of the ceramide EOP in the cream is 0.02-0.08%. Further preferably, the weight percentage of the ceramide EOP in the cream is 0.05%.

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

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

[0057] Preferably, the cream contains the following components in weight percentage: 0.1% sea cucumber peptide, 0.5% matrine, 0.1% inositol, 25% glycerin, 4% polydimethylsiloxane, 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 essence and 61.03% purified water.

[0058] The technical effects produced by the present invention are: 1. The present invention unexpectedly discovered that the combination of sea cucumber peptide, matrine, and inositol as the active ingredients of a cream can synergistically exert its efficacy in treating skin itching. In vitro animal experiments confirmed that the cream of the present invention has a more significant inhibitory effect on the 4-aminopyridine-induced pruritus reaction in mice compared to creams containing only matrine and sea cucumber peptide or only matrine and inositol.

[0059] 2. By optimizing the cream formulation (e.g., sodium hyaluronate concentration, matrine content), and its preparation process parameters (e.g., oil-water mixture temperature, cream outlet temperature, cooling rate), this invention produces a high-quality cream suitable for large-scale industrial production. The cream prepared in this invention exhibits uniform color, no delamination, a fine texture, and no gritty feel, with a pH range of 7-7.5.

[0060] 3. The present invention selects glycerol, polydimethylsiloxane, lecithin, ceramide EOP, and sodium hyaluronate as composite moisturizers, which significantly improve the moisturizing effect of the cream. Surprisingly, in addition to having a moisturizing effect, the moisturizer of the present invention can also significantly improve the chemical stability of matrine, the active ingredient in the cream. In particular, the moisturizing agent combination of lecithin and ceramide EOP inhibits the formation of matrine impurities, significantly improving the stability of the cream of the present invention during production and storage. DETAILED DESCRIPTION

[0061] The present invention will be further described below with reference to the examples and test examples, but the embodiments of the present invention are not limited thereto. The sea cucumber peptides in the examples and test 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 / s), sodium hyaluronate was purchased from Bloomage Biotechnology Co., Ltd. (J100240048, molecular weight 1450 KDa). The experimental methods used in the following examples are all conventional methods unless otherwise specified.

[0062] Example 1, moisturizing and antipruritic medicinal cream 1 of the present invention 1. Prescription (1500g per batch, packaging specification 50g / bottle) 2. Preparation method Step (1): Weigh the prescribed amount of tocopherol, polydimethylsiloxane, sorbitan oleate, stearic acid, cetyl alcohol, lecithin and ceramide EOP respectively, place the above oil phase excipients in a stainless steel barrel, heat and stir until dissolved, and control the oil phase temperature at 75°C; Step (2): Add the prescribed amount of purified water into another stainless steel barrel, add the prescribed amount of methylparaben, heat and stir until the methylparaben is completely dissolved, then add the prescribed amount of glycerin, ascorbyl glucoside, phenoxyethanol, allantoin, inositol, sodium hyaluronate, matrine and sea cucumber peptide, stir until all are dissolved, and mix well; Step (3): slowly add the water phase prepared in step (2) to the oil phase prepared in step (1) under stirring conditions to emulsify, transfer to a small emulsifying tank, and prepare the cream on a machine. Before being put on the machine, the temperature of the oil-water two-phase mixture is controlled at 75°C-80°C; Step (4): Turn on the homogenizer at a homogenizing speed of 8000 rpm and simultaneously turn on the stirring at a speed of 800 rpm. Stop homogenizing after 2 minutes; reduce the stirring speed to 500 rpm, turn on the condensed water, and turn off the water after filling the outer layer of the emulsifying tank, and start timing. After 15 minutes, turn on the circulating water and continue stirring until the temperature reaches 65°C. Add the prescribed amount of ginger flower essence, turn on the vacuum pump, and continue stirring. When the temperature drops to 40°C, turn off the condensed water and stop stirring. Open the pressure reducing valve to complete the cream preparation process. Subpackage to obtain the medicinal cream 1 with moisturizing, antipruritic, soothing and repairing effects of the present invention.

[0063] The cream of Example 1 prepared by the above method has a uniform color, no stratification, is fine, and has no sandy feeling, and has a pH value of 7.2.

[0064] Example 2 The cream of Example 2 was prepared by replacing 0.1% sea cucumber peptide and 0.1% inositol in the prescription of Example 1 with 0.15% sea cucumber peptide and 0.05% inositol, and the remaining components, contents and preparation method were the same as those in Example 1.

[0065] Example 3 The cream of Example 3 was prepared by replacing 0.1% sea cucumber peptide and 0.1% inositol in the prescription of Example 1 with 0.05% sea cucumber peptide and 0.15% inositol, and the remaining components, contents and preparation method were the same as those of Example 1.

[0066] Example 4 The cream of Example 4 was prepared by replacing 0.05% lecithin and 0.05% ceramide EOP in the formula of Example 1 with 0.1% lecithin (i.e., ceramide EOP was omitted), and the remaining components, contents, and preparation method were the same as those of Example 1.

[0067] Example 5 The cream of Example 5 was prepared by replacing 0.05% lecithin and 0.05% ceramide EOP in the formula of Example 1 with 0.1% ceramide EOP (i.e., lecithin was omitted), and the remaining components, contents, and preparation method were the same as those of Example 1.

[0068] Comparative Examples 1-3 (creams with different sodium hyaluronate contents) The sodium hyaluronate content in the formulation of Example 1 was replaced from 0.01% to 0.5%, 0.1% and 0.0% (i.e., not added), respectively. The remaining components, contents and preparation methods except purified water were the same as in Example 1 (purified water was added to a total weight of 1500 g), and comparative examples 1-3 creams were prepared respectively.

[0069] Comparative Examples 4-6 (creams with different process parameters) The temperature of the oil-water phase mixture in step (3) of the preparation method of Example 1 before loading onto the machine was changed to 91° C. The remaining components and preparation method were the same as those of Example 1 to prepare the cream of Comparative Example 4.

[0070] The cream of Comparative Example 5 was prepared by replacing the cream-discharging temperature in step (4) of the preparation method of Example 1 from 40°C to 25°C, and using the remaining components and preparation method as in Example 1.

[0071] The cooling method in step (4) of the preparation method of Example 1, "turn on the condensed water, fill the outer layer of the emulsification tank, turn off the water, start timing to 15 minutes and then turn on the circulating water" was replaced with "turn on the condensed water and circulate it directly", and the remaining components and preparation method were the same as Example 1, to prepare the cream of Comparative Example 6.

[0072] Comparative Examples 7-8 (creams with different matrine contents) The matrine content in the prescription of Example 1 was replaced from 0.5% to 0.8% and 1.0%, respectively. The remaining components, contents, and preparation methods except purified water were the same as those in Example 1 (purified water was added to a total weight of 1500 g) to prepare comparative examples 7-8 creams.

[0073] Comparative Examples 9-10 (creams with different active ingredients) The 0.1% sea cucumber peptide and 0.1% inositol in the prescription of Example 1 were replaced with 0.2% sea cucumber peptide (i.e., inositol was omitted), and the remaining components and contents except purified water and the preparation method were the same as in Example 1 (purified water was added to the total weight of the prescription to 1500 g), to prepare a cream of Comparative Example 9.

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

[0075] Test Example 1: Prescription and process screening test of the medicinal cream of the present invention 1. Sodium hyaluronate dosage screening test Typically, an appropriate concentration of sodium hyaluronate forms a moisturizing film on the skin surface, locking in moisture and reducing water evaporation, keeping the skin hydrated for several hours. The results of a hyaluronic acid dosage screening test showed that in Comparative Examples 1 and 2, after adding 0.5% and 0.1% sodium hyaluronate, the creams had a thin appearance and a film-like feel, which was inconsistent with creams. Further reducing the addition amount to 0.01% (Example 1) resulted in a light, thin cream with the best appearance and feel. Further reducing the sodium hyaluronate concentration to no addition (Comparative Example 3) resulted in the cream again appearing highly fluid. Therefore, the sodium hyaluronate content was ultimately determined to be 0.01%. The creams made with this sodium hyaluronate concentration had an appropriate viscosity, a uniform and lustrous appearance, and met the requirements for a cream.

[0076] 2. Preparation process parameter screening test The quality of the cream is closely related to its preparation method and process parameters. The results of the process parameter screening test show that the preparation method of the prescription of Comparative Example 4 prolongs the time from the oil-water phase mixture being put on the machine to the cream, resulting in the cream having too high viscosity. The preparation method of the prescription of Comparative Example 5 prolongs the creaming time. Although the cream is fine and uniform and has increased viscosity, the time is too long, the production efficiency is low, and it is not suitable for large-scale production operations. The preparation method of the prescription of Comparative Example 6 results in a cream with greater fluidity. In summary, the process parameters of the prescription of Example 1 can be used to obtain an cream that meets large-scale production requirements and has good performance.

[0077] 3. Matrine dosage screening test The pH value of facial cosmetics (such as emulsions and serums) is generally between 6 and 7.5. Test results show that the pH values ​​of the creams in Comparative Examples 7 and 8, respectively, are 7.9 and 8.0, exceeding the appropriate range for facial cosmetics and making them unsuitable for facial use. Therefore, the matrine content should be controlled below 0.5% of the total cream volume.

[0078] Test Example 2: Effect of the cream of the present invention on 4-aminopyridine-induced pruritus model mice 1. Test method Sixty SPF-grade KM mice, half male and half female, were randomly divided into six groups, namely a blank matrix group, groups 1-3 of the present invention's medicinal creams, and groups 1-2 of the comparative example medicinal creams, with 10 mice in each group. Before the experiment, the mice's necks and backs were depilated by approximately 2 cm × 2 cm, and mice with undamaged skin were selected for the experiment. The mice in the blank matrix group were given 0.1 g of a blank matrix containing no drugs (the matrix formula was the same as in Example 1, but without the active ingredients sea cucumber peptide, matrine, and inositol) on the depilatory area. The mice in the medicinal cream groups 1-3 of the present invention and the comparative example medicinal cream groups 1-2 were given 0.1 g of the medicinal creams prepared in Examples 1-3 and Comparative Examples 9-10 on the depilatory area of ​​the mice, respectively. The mice in each experimental group were given the drug for 10 consecutive days, twice a day, once in the morning and once in the evening. One hour after the last dose, mice were subcutaneously injected with 4-aminopyridine at a dose of 1 mg / kg body weight at the back of the neck. The mice were immediately observed for 15 minutes for licking. One lick was counted as one lick when the mice repeatedly turned their heads and licked both sides of their backs until a brief pause occurred. The latency time to licking 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 medicinal cream of the present invention on the pruritus reaction of mice. The test results are shown in Table 1.

[0080] Table 1 Effect of the present invention's medicinal cream 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 (which do not contain inositol or sea cucumber peptide), the pharmaceutical creams of the present invention, groups 1-3, significantly prolonged the pruritus latency time in mice and significantly reduced the number of pruritus episodes in mice (both with statistically significant differences), indicating that the pharmaceutical cream of the present invention has a significant inhibitory effect on the 4-aminopyridine-induced pruritus reaction in mice, indicating that the pharmaceutical cream has a significant effect in improving skin pruritus in patients. It is worth noting that, given the same total amount of active ingredients, sea cucumber peptide and inositol, the pharmaceutical cream prepared in Example 1 was significantly superior to Examples 2-3 in improving the pruritus reaction in mice, producing an unexpectedly excellent effect.

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

[0082] 2. Test results The average values ​​of matrine content in each test group are shown in Table 2 below.

[0083] Table 2 Results of the stability test of the medicinal cream of the present invention at high temperature As shown in Table 2 above, the matrine content of the pharmaceutical creams of Examples 1 and 4-5 did not decrease significantly after storage under high temperature conditions, and the active ingredient content was maintained at above 90%. The matrine content of the pharmaceutical cream of Example 1 remained as high as 97.79% after 10 days of storage. This indicates that the cream of the present invention (Example 1) using 0.05% lecithin and 0.05% ceramide EOP as a combined moisturizer is most effective in improving the chemical stability of matrine, compared to formulations using either 0.1% lecithin (Example 4) or 0.1% ceramide EOP (Example 5) alone as moisturizers. These test results demonstrate that the moisturizer selected in the cream of the present invention can effectively inhibit the formation of impurities from matrine, and the cream of the present invention is expected to have good stability during production and storage.

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

Claims

1. A moisturizing, antipruritic, soothing and repairing cream, characterized in that: The cream contains sea cucumber peptide, matrine, inositol, moisturizing agent, emulsifier and solvent.

2. The cream according to claim 1, characterized in that The weight ratio of sea cucumber peptide to inositol in the cream is (1:3) to (3:1).

3. The cream according to claim 1, characterized in that The moisturizing agent is selected from one or more of glycerin, polydimethylsiloxane, lecithin, ceramide EOP and sodium hyaluronate.

4. The cream according to claim 1, characterized in that The emulsifier is selected from one or more of stearic acid, cetyl alcohol and sorbitan oleate.

5. The cream according to claim 1, characterized in that The cream further comprises one or more of an antioxidant, a preservative, an emollient and a flavoring agent.

6. The cream according to claim 1, characterized in that The cream contains sea cucumber peptide, matrine, inositol, glycerin, polydimethylsiloxane, lecithin, ceramide EOP, sodium hyaluronate, stearic acid, cetyl alcohol, sorbitan oleate, tocopherol, ascorbyl glucoside, phenoxyethanol, methylparaben, allantoin, ginger flower essence and purified water.

7. The cream according to claim 6, characterized in that The cream contains the following components in percentage by weight: 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 essence and 50-65% purified water, and the total percentage by weight of the above components is 100%.

8. The method for preparing the cream according to any one of claims 1 to 7, characterized in that: The method comprises the following steps: (1) Weigh the prescribed amount of antioxidant, emulsifier and oil phase moisturizer, and heat and stir the above oil phase excipients until they are dissolved; (2) Weigh the prescribed amount of solvent, add the prescribed amount of sea cucumber peptide, matrine, inositol, aqueous phase moisturizer, preservative and emollient, stir until all are dissolved, and mix well; (3) Slowly add the aqueous phase prepared in step (2) to the oil phase prepared in step (1) under stirring conditions to emulsify and homogenize, add the prescribed amount of flavoring agent, and stir evenly to obtain the product.

9. Use of the cream according to any one of claims 1 to 7 in the preparation of a medicament for treating skin itching.

10. Use of a moisturizing agent in improving the chemical stability of matrine in the cream according to any one of claims 1 to 7, characterized in that: The moisturizing agent comprises lecithin and ceramide EOP.

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