A drug for auxiliary treatment of psoriasis, a compound external preparation and a preparation method thereof

Abstract

The present invention discloses a drug for assisting the treatment of psoriasis, a compound external preparation and a preparation method thereof, wherein the active ingredients of the drug include a composite extract prepared from rhubarb extract powder, coptis co-extract powder and scutellaria baicalensis extract powder, and urea, wherein the weight ratio of the total amount of rhubarb extract powder, coptis co-extract powder and scutellaria baicalensis extract powder to the urea is 1:15-36. The technical solution provided by the drug for assisting the treatment of psoriasis, the compound external preparation and the preparation method thereof has the effects of relieving itching, improving skin damage and skin inflammation, and can meet the daily skin care needs of patients with psoriasis vulgaris and the role of assisting treatment during psoriasis attacks.

Description

[0001] The present invention claims the priority of the Chinese patent application filed with the Chinese Patent Office on December 20, 2022, with application number 2022116436496, and application name “A compound external preparation for auxiliary treatment of psoriasis and its preparation method”, the entire contents of which are incorporated by reference into the present invention. Technical Field

[0002] The invention belongs to the technical field of skin care preparations, and specifically relates to a medicine for auxiliary treatment of psoriasis, a compound external preparation and a preparation method thereof. Background Art

[0003] Psoriasis is a common chronic inflammatory skin disease, among which psoriasis vulgaris is the most common. The cause of psoriasis is still unclear. Clinically, it is mostly manifested as red papules, plaques, scales, and itching. The symptoms are mostly on the scalp, limbs, and trunk. The skin of patients with psoriasis vulgaris has barrier dysfunction, which leads to low moisture content in the stratum corneum of the skin, manifested as dry skin and desquamation, usually accompanied by dryness, itching or burning sensation, and prone to redness, skin sensitivity or allergic symptoms. There is no radical cure for psoriasis, and topical drugs for symptomatic treatment are mostly one or more combinations of emollients, vitamin D3 derivatives, retinoic acid, glucocorticoids, etc. Among them, topical drugs such as vitamin D3 derivatives, retinoic acid, and glucocorticoids are limited by adverse reactions of drugs and are not suitable for long-term use by patients with psoriasis. In addition, although emollients are suitable for long-term use and psoriasis patients can benefit from them, the ability of emollients to relieve skin discomfort is limited. Therefore, the current problem that needs to be solved is to develop a non-drug product based on the pathogenesis of psoriasis, which is suitable for long-term use by psoriasis patients and has the effects of moisturizing the skin and relieving psoriasis symptoms.

[0004] Further investigation found that the French patent FR2868952A1, a moisturizing lotion for keratin care and lipid restoration for skin with a tendency to scaly formation, uses a high concentration of urea, a natural moisturizing factor, to achieve strong and long-lasting moisturizing and hydrating effects. This formula patent can relieve skin discomfort caused by low moisture content in the stratum corneum, but lacks the effect of improving the sensitive symptoms, inflammatory symptoms, and skin barrier of psoriasis skin.

[0005] Further investigation found that the traditional Chinese medicine formula "Si Huang", namely the Chinese medicines Scutellaria baicalensis, Phellodendron chinense, Coptis chinensis, and Rhubarb, can be ground into fine powder for external use to treat inflammatory skin diseases, and combined with other Chinese medicine ingredients to make oral liquid, which has a high efficacy for psoriasis (CN1060375C). "Si Huang" mainly treats skin inflammation and has no obvious moisturizing effect. Summary of the invention

[0006] The purpose of the present invention is to provide a compound external preparation for auxiliary treatment of psoriasis, which has the effects of strong moisturizing, anti-inflammatory and antipruritic, relieving skin redness and desquamation, and is suitable for long-term auxiliary treatment of psoriasis.

[0007] The above-mentioned purpose is achieved by the following technical solutions.

[0008] In a first aspect, the present invention provides a drug for assisting the treatment of psoriasis, wherein the active ingredients of the drug include a composite extract prepared from rhubarb extract powder, co-extract powders of phellodendron amurense and coptis chinensis, and scutellaria baicalensis extract powder, and urea, wherein the weight ratio of the total amount of rhubarb extract powder, co-extract powders of phellodendron amurense and coptis chinensis, and scutellaria baicalensis extract powder to the urea is 1:15 to 36.

[0009] In some embodiments, the amounts of the rhubarb extract powder, the co-extract powder of Phellodendron amurense and Coptis chinensis, and the scutellaria baicalensis extract powder are the same.

[0010] In some of the embodiments, the weight ratio of the total amount of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder to the urea is 1:15-34, more preferably 1:15-20.

[0011] In some of the embodiments, the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder are prepared by water extraction or alcohol extraction.

[0012] In some of the embodiments, the alcohol extraction method of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the baicalin extract powder comprises the following steps: respectively soaking rhubarb, equal amounts of Phellodendron chinense and Coptis chinensis, and Scutellaria baicalensis in 7 to 9 times by weight of 45 to 55% ethanol, refluxing extraction to obtain a concentrated extract, letting it stand to obtain a precipitate, and drying the precipitate to obtain the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the baicalin extract powder.

[0013] In some of the embodiments, in the extraction process of the co-extracted powder of Phellodendron chinense and Coptis chinensis and the extracted powder of Scutellaria baicalensis, after reflux extraction to obtain a concentrated extract, an acid is added to the extract, a precipitate is obtained after sedimentation, the precipitate is washed with water until the pH value of the washing liquid is 3.5-4.5, the washed precipitate is taken, and the precipitate is dried to obtain the co-extracted powder of Phellodendron chinense and Coptis chinensis and the extracted powder of Scutellaria baicalensis.

[0014] The second aspect of the present invention provides a compound external preparation for adjuvant treatment of psoriasis, the compound external preparation comprising 100 parts by weight of the following components:

[0015] Compound 8-25 parts

[0016] 75-92 parts of dosage form auxiliary agent;

[0017] Wherein, the composite agent comprises component A, component B and component C:

[0018] The component A comprises: the drug according to any one of claims 1 to 5 and dipotassium glycyrrhizinate, wherein the drug accounts for 3% to 99% of the total amount of the composite, and the weight ratio of the total amount of the rhubarb extract powder, the coptis chinensis and coptis chinensis co-extract powder, and the scutellaria baicalensis extract powder to the dipotassium glycyrrhizinate is 1:10 to 15;

[0019] The B component includes: sweet almond oil and bergamot essential oil;

[0020] The C component includes: sodium hyaluronate, glycerin, and butylene glycol;

[0021] The dosage form adjuvants include emulsifiers, thickeners, antioxidants and water.

[0022] In some of the embodiments, the drug accounts for 3% to 20% of the total amount of the compound, preferably, the drug accounts for 3% to 10% of the total amount of the compound, and further preferably, the drug accounts for 3% to 10% of the total amount of the compound.

[0023] In some embodiments, the B component includes the following components in parts by weight:

[0024] Sweet almond oil 2-20 parts

[0025] 0.1-1 part of bergamot essential oil; and / or,

[0026] The C component includes the following components in parts by weight:

[0027] Sodium hyaluronate 0.01-0.5 parts

[0028] 2-12 parts glycerin

[0029] 1-8 parts of butanediol; and / or,

[0030] The dosage form auxiliary comprises the following components in parts by weight:

[0031] Emulsifier 2-5 parts

[0032] Thickener 0.01-0.8 parts

[0033] Antioxidant 0.1-0.5 parts.

[0034] In some embodiments, the component A further comprises allantoin; preferably, the allantoin is 0.1-1 parts by weight;

[0035] And / or, the B component further comprises shea butter; preferably, the shea butter is 2-5 parts by weight;

[0036] And / or, the C component further comprises polyglycerol; preferably, the polyglycerol is 1-2 parts by weight.

[0037] In some embodiments, the emulsifier is a combination of two or more of methyl glucoside hemistearate, PEG-20 methyl glucoside sesquistearate, and glyceryl stearate / PEG-100 stearate;

[0038] And / or, the thickener is carbomer;

[0039] And / or, the antioxidant is any one of butylated hydroxyanisole and butylated hydroxytoluene;

[0040] And / or, the dosage form adjuvant further comprises a chelating agent, a preservative, a buffer and a pH adjuster;

[0041] And / or, the pH value of the compound external preparation is 5.5-7.

[0042] The third aspect of the present invention provides a method for preparing the compound external preparation for auxiliary treatment of psoriasis based on the above-mentioned method, comprising the following steps:

[0043] Matrix preparation steps: except for rhubarb extract powder, co-extract powder of phellodendron and coptis root, scutellaria extract powder, dipotassium glycyrrhizinate, urea, and bergamot essential oil, other components are divided into two groups according to water solubility and oil solubility, and the components are dissolved / swelled and then heated to 70°C to 80°C to obtain oil-soluble components and water-soluble components respectively, and mixed and stirred to obtain a matrix;

[0044] Discharging step: cooling the substrate to 45-55° C., adding rhubarb extract powder, phellodendron amurense and coptis chinensis co-extract powder, scutellaria baicalensis extract powder, dipotassium glycyrrhizinate, urea, bergamot essential oil, adjusting the pH value of the product to between 5.5 and 7, stirring and homogenizing, and discharging after vacuuming.

[0045] The fourth aspect of the present invention also provides a use of the above-mentioned compound external preparation in the preparation of a preparation for auxiliary treatment of psoriasis.

[0046] In the present invention, research has found that the composite extract prepared from rhubarb extract powder, co-extract powder of Phellodendron amurense and Coptis chinensis, and scutellaria baicalensis extract powder and urea are used in combination, wherein the total amount of rhubarb extract powder, co-extract powder of Phellodendron amurense and Coptis chinensis, and scutellaria baicalensis extract powder and urea in a specific ratio can form a synergistic effect, and can provide excellent anti-inflammatory and skin barrier dysfunction relief effects. The composite external preparation formed by other compositions such as sweet almond oil, bergamot essential oil, sodium hyaluronate, glycerin, butylene glycol, dosage form adjuvants, etc. can provide excellent moisturizing, anti-inflammatory and antipruritic effects, can effectively relieve symptoms such as dryness, desquamation, redness, itching, etc. caused by skin barrier dysfunction, has the effects of relieving itching, improving skin damage and skin inflammation, and can meet the daily skin care needs of patients with psoriasis vulgaris and the role of auxiliary treatment during psoriasis attacks.

[0047] Among them, when the weight ratio of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder to the urea was further optimized to 1:15-20, there was a significant difference in the anti-inflammatory effect between the four-yellow fine powder prepared from rhubarb, Phellodendron chinense, Coptis chinensis, and Scutellaria baicalensis and the urea, and the synergistic effect of the composite extract and urea was significantly better than the effect of the four-yellow fine powder and urea. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 These are pictures of skin lesions of psoriasis model mice in each group of Experimental Example 1 at different days.

[0049] Figure 2 It is the visual field image of the pathological sections of mice in the blank group of Experimental Example 1, the model group, Example 1 and Comparative Example 2.

[0050] Figure 3 This is a graph showing the effect of the four-yellow powder and the composite extract in Experimental Example 2 of the present invention on the number of neutrophil migration in zebrafish embryos, where "***" means p < 0.001;

[0051] Figure 4 This is a graph showing the effects of urea and four yellow powder or composite extract on the number of neutrophil migration in zebrafish embryos in Experimental Example 3 of the present invention, wherein "**" means p < 0.01, and "***" means p < 0.001. DETAILED DESCRIPTION

[0052] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or conditions recommended by the manufacturers. The various commonly used chemical reagents used in the examples are all commercially available products.

[0053] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0054] The specific implementation modes of the present invention are further described below.

[0055] Example 1

[0056] The compound external preparation for auxiliary treatment of psoriasis in this embodiment is made into a cream, and its raw material components are as follows:

[0057] Component 1. 0.01 weight part of scutellaria baicalensis extract powder, 0.01 weight part of co-extract powder of phellodendron amurense and coptis chinensis, 0.01 weight part of rhubarb extract powder; sodium dihydrogen phosphate and sodium dihydrogen phosphate buffer solutions are prepared from sodium dihydrogen phosphate, disodium hydrogen phosphate, and 30 weight parts of purified water.

[0058] The steps of preparing rhubarb extract powder are as follows:

[0059] The medicinal part of rhubarb is soaked in 8 times 50% ethanol, refluxed and extracted twice at 75°C, each time for 120 minutes, and the extracts are combined;

[0060] The extract is concentrated to 1 / 16 of its volume to obtain a concentrated solution, the concentrated solution is allowed to settle in a cool place for 20 hours to obtain a precipitate, and the precipitate is dried to obtain a rhubarb extract powder having a water content of no more than 7 parts by weight.

[0061] The steps for preparing the scutellaria baicalensis extract powder are as follows:

[0062] The medicinal part of Scutellaria baicalensis is soaked in 8 times 50% ethanol, and extracted twice under reflux at 75°C, each time for 120 minutes, and the extracts are combined;

[0063] The extract was concentrated to 1 / 16 of the volume to obtain a concentrated solution, hydrochloric acid solution was added to the concentrated solution, stirred and mixed, the pH of the concentrated solution was adjusted to 1.5, and the concentrated solution was allowed to settle in a cool place for 20 hours;

[0064] After sedimentation, a precipitate is obtained, and purified water is used to wash the precipitate several times until the pH value of the washing liquid is 4.0±0.5. The filter residue after washing is taken and dried into a scutellaria baicalensis extract powder with a water content of no more than 7 parts by weight.

[0065] The preparation steps of co-extracted powder of Phellodendron chinense and Rhizoma Coptidis (1:1) are as follows:

[0066] The medicinal parts of Phellodendron chinense and Coptis chinensis (1:1) were soaked in 8 times 50% ethanol, refluxed and extracted twice at 75°C, each time for 120 minutes, and the extracts were combined;

[0067] The extract was concentrated to 1 / 16 of the volume to obtain a concentrated solution, hydrochloric acid solution was added to the concentrated solution, stirred and mixed, the pH of the concentrated solution was adjusted to 1.5, and the concentrated solution was allowed to settle in a cool place for 20 hours;

[0068] After sedimentation, the precipitate is obtained, and purified water is used to wash the precipitate several times until the pH value of the washing liquid is 4.0±0.5. The filter residue after washing is taken and dried into an extraction powder with a water content of no more than 7 parts by weight.

[0069] Component 2 (water-soluble component). 40 parts by weight of purified water, 0.05 parts by weight of sodium hyaluronate, 0.6 parts by weight of carbomer, 1 part by weight of butylene glycol, 3 parts by weight of glycerol, and 0.05 parts by weight of EDTA-2Na.

[0070] Component 3 (oil-soluble component). 1.5 parts by weight of methyl glucoside hemistearate, 0.6 parts by weight of PEG-20 methyl glucose sesquistearate, 2 parts by weight of glyceryl stearate / PEG-100 stearate, 5 parts by weight of shea butter, 9 parts by weight of sweet almond oil, 0.2 parts by weight of butylated hydroxyanisole, 0.4 parts by weight of phenoxyethanol, and 0.3 parts by weight of p-hydroxyacetophenone.

[0071] Component 4. 1 part by weight of urea and 0.3 part by weight of dipotassium glycyrrhizinate.

[0072] Component 5. Sodium hydroxide.

[0073] Component 6. 0.1 parts by weight of bergamot essential oil.

[0074] The manufacturing process of the compound external preparation into a cream is as follows:

[0075] (i) weighing the raw material of component 1 according to weight, dissolving and dispersing it stably in a buffer solution of disodium hydrogen phosphate and sodium dihydrogen phosphate, heating it to 60° C., soaking it for 0.5 hour, filtering it through a 300-mesh sieve, and taking the filtrate to obtain a composite extract (i.e., a composite extract);

[0076] (ii) Weigh component 2 and component 3 respectively by weight and heat to 80°C;

[0077] (3) Mix the two groups of raw materials in step 2 for 30 seconds, and then start cooling after stirring and dispersing them evenly;

[0078] (iv) When the temperature drops to 50°C, add component 1 and component 4. Keep warm and stir for 30 minutes;

[0079] (V) Adjust the pH value of the material to 6.3 using component 5, add component 6 and purified water, make up the weight to 100 parts by weight, stir and disperse evenly, and prepare a cream for auxiliary treatment of psoriasis.

[0080] Example 2

[0081] The compound external preparation for auxiliary treatment of psoriasis in this embodiment is made into an emulsion, and its raw material components are as follows in parts by weight:

[0082] Component 1. 0.01 weight part of scutellaria baicalensis extract powder, 0.01 weight part of co-extract powder of phellodendron amurense and coptis chinensis, 0.01 weight part of rhubarb extract powder; sodium dihydrogen phosphate and sodium dihydrogen phosphate buffer solutions are prepared from sodium dihydrogen phosphate, disodium hydrogen phosphate, and 30 weight parts of purified water.

[0083] Among them, the preparation method of rhubarb extract powder, scutellaria baicalensis extract powder, and phellodendron amurense and coptis chinensis co-extract powder (1:1) is the same as that in Example 1.

[0084] Component 2 (water-soluble component). 40 parts by weight of purified water, 0.05 parts by weight of sodium hyaluronate, 0.02 parts by weight of carbomer, 2 parts by weight of butylene glycol, 2 parts by weight of glycerol, and 0.1 parts by weight of EDTA-2Na.

[0085] Component 3 (oil-soluble component). 2.5 parts by weight of methyl glucoside hemistearate, 0.95 parts by weight of PEG-20 methyl glucose sesquistearate, 4 parts by weight of sweet almond oil, 0.2 parts by weight of butylated hydroxyanisole, 0.4 parts by weight of phenoxyethanol, and 0.3 parts by weight of p-hydroxyacetophenone.

[0086] Component 4. 0.5 parts by weight of urea and 0.3 parts by weight of dipotassium glycyrrhizinate.

[0087] Component 5. Sodium hydroxide.

[0088] Component 6. 0.1 parts by weight of bergamot essential oil.

[0089] The manufacturing process of the compound external preparation into an emulsion is as follows:

[0090] (i) weighing the raw material of component 1 according to weight, dissolving and dispersing it stably in a buffer solution of disodium hydrogen phosphate and sodium dihydrogen phosphate, heating it to 60° C., soaking it for 0.5 hour, filtering it through a 300-mesh sieve, and taking the filtrate to obtain a composite extract;

[0091] (ii) Weigh component 2 and component 3 respectively by weight and heat to 80°C;

[0092] (3) Mix the two groups of raw materials in step 2 for 30 seconds, and then start cooling after stirring and dispersing them evenly;

[0093] (iv) When the temperature drops to 48°C, add component 1 and component 4. Keep warm and stir for 30 minutes;

[0094] (V) The pH value of the material is adjusted to 6.5 by component 5, component 6 and purified water are added to make up the weight to 100 parts by weight, and the mixture is stirred and dispersed evenly to prepare an emulsion for assisting the treatment of psoriasis.

[0095] Comparative Example 1

[0096] The compound external preparation for auxiliary treatment of psoriasis in this comparative example is made into a cream, and its raw material components are as follows:

[0097] 0.15 parts by weight of sodium hyaluronate, 47 parts by weight of purified water, 3 parts by weight of β-cyclodextrin, 0.6 parts by weight of PEG-240 / HDI copolymer didecyltetradecyl alcohol polyether-20 ether and tridecyl alcohol polyether-6 compound raw materials, 6 parts by weight of butanediol, 2 parts by weight of hexylene glycol, 5 parts by weight of purslane extract, 5 parts by weight of sophora flavescens extract, 5 parts by weight of angelica extract, 0.1 parts by weight of medicinal rhubarb extract, 0.05 parts by weight of EDTA-2Na, 0.25 parts by weight of allantoin, 4.5 parts by weight of sodium chloride, 1.6 parts by weight of sodium lactate, 0.57 parts by weight of lactic acid,

[0098] PEG-20 methyl glucose sesquistearate 0.77 parts by weight, methyl glucoside hemistearate 3.23 parts by weight, jojoba oil 2 parts by weight, shea butter 7 parts by weight, sweet almond oil 2 parts by weight,

[0099] 10 parts by weight of urea,

[0100] 2 parts by weight of propylene glycol, 5 parts by weight of glycerin, 1 part by weight of D-panthenol, 0.6 parts by weight of phenoxyethanol, and 0.5 parts by weight of p-hydroxyacetophenone,

[0101] Sodium hydroxide 0.19 parts by weight,

[0102] The purslane extract, sophora flavescens extract and angelica extract in this compound external preparation are commercially available extracts, wherein the purslane extract contains 10 parts by weight of purslane extract, the sophora flavescens extract contains 10 parts by weight of sophora flavescens extract, and the angelica extract contains 10 parts by weight of angelica extract.

[0103] The preparation process of the compound external preparation into a cream is shown in Example 1.

[0104] Comparative Example 2

[0105] The compound external preparation for auxiliary treatment of psoriasis in this comparative example is made into an emulsion, and its raw material components are as follows:

[0106] 2.5 parts by weight of methyl glucoside hemistearate, 0.95 parts by weight of PEG-20 methyl glucose sesquistearate, 2 parts by weight of jojoba oil, 2 parts by weight of sweet almond oil, 4 parts by weight of butylene glycol, 0.7 parts by weight of p-hydroxyacetophenone,

[0107] 68 parts by weight of purified water, 1 part by weight of β-cyclodextrin, 5 parts by weight of glycerin, 0.01 parts by weight of carbomer U21, 0.8 parts by weight of phenoxyethanol, 3 parts by weight of purslane extract, 3 parts by weight of sophora flavescens extract, 3 parts by weight of angelica extract, 0.1 parts by weight of EDTA-2Na, 0.01 parts by weight of sodium hydroxide, 5 parts by weight of urea, 2.5 parts by weight of sodium chloride, 0.5 parts by weight of D-panthenol, 0.002 parts by weight of sodium hyaluronate,

[0108] 0.28 parts by weight of lactic acid, 0.80 parts by weight of sodium lactate,

[0109] The purslane extract, sophora flavescens extract and angelica extract in this compound external preparation are commercially available extracts, wherein the purslane extract contains 10 parts by weight of purslane extract, the sophora flavescens extract contains 10 parts by weight of sophora flavescens extract, and the angelica extract contains 10 parts by weight of angelica extract.

[0110] The preparation process of the compound external preparation into a cream is shown in Example 2.

[0111] Comparative Example 3

[0112] The present comparative example is a moisturizing lotion suitable for keratin care and lipid restoration of skin with a tendency to scaly formation, and its raw material components are: water, urea (10 parts by weight), sodium chloride, glycerin, C12-13 alkyl lactic acid, sodium lactate, stearic acid-2, liquefied paraffin, shea butter, almond oil, stearic acid-21, jojoba seed oil, beeswax, squalane, soybean sterols, allantoin, panthenol, amyl acetate, lactic acid, hexadecyl alcohol, polydimethylsiloxane, phenoxyethanol, xanthan gum, methylparaben, ammonium acryloyldimethyltaurate / VP copolymer, propylparaben, microcrystalline grains, paraffin, hydroxypropyl starch phosphate, sodium hydroxide, and essence.

[0113] Comparative Example 4

[0114] The present comparative example is a moisturizing lotion suitable for skin with a tendency to scaly formation, and its raw material components are: water, urea (5 parts by weight), glycerol, sorbitol, sodium chloride, sodium citrate, gluconolactone, xanthan gum, calcium gluconate, sodium benzoate, and citric acid.

[0115] Experimental Example 1

[0116] 1. Animal Experiments

[0117] 1. Experimental animals: BALB / c mice

[0118] 2. Experimental Model: Psoriasis Model

[0119] 3. Experimental design: The experimental mice were fed and raised normally for 14 days. There were 8 groups with 10 mice in each group, including 1 blank control group and 7 model groups. The blank control group was smeared with 12.5 mg / cm 2 Vaseline, the model group was smeared with the same dose of imiquimod ointment, and the model was established once a day. The model was completed on the 8th day, and the PASI (lesion area and severity index) score was used as the standard to judge whether the model was successful or not, and the mice with successful modeling were subjected to subsequent experiments. The subsequent experiments were carried out by administering the drug while modeling, with at least 8 hours between modeling and administration for 6 consecutive days. The animals in the model group were randomly divided into a model control group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, and Comparative Example 4 group, and the 12.5 mg / cm 2 The corresponding preparations were given, and the blank control group was given the same dose of vaseline.

[0120] 4. Test content: On the 3rd and 6th days after administration, the number of times the animals twisted their bodies and licked their backs was counted within 30 minutes after administration, and photos were taken to record the condition of the animal's test skin. The PASI (Lesion Area and Severity Index) score was performed on the skin lesions of the test area.

[0121] 2. Experimental Results

[0122] 1. Antipruritic performance test

[0123] Within 30 minutes after administration on the 3rd and 6th days, the number of times the mice licked their backs and twisted their waists was recorded. The data are shown in Table 1:

[0124] Table 1 Statistics of back licking and waist twisting in psoriasis model mice

[0125]

[0126] Compared with the model group and the blank control group, the number of back licking and waist twisting increased significantly (P≤0.05). Compared with the model group: six days after administration, the number of back licking and waist twisting in comparative example group 3, comparative example group 4, and embodiment group 1 were significantly reduced (P≤0.05), the number of back licking in comparative example group 1 and comparative example group 2 was significantly reduced (P≤0.05), the number of waist twisting was not significantly reduced, and the number of back licking and waist twisting in embodiment group 2 was not significantly reduced.

[0127] When the psoriasis model lesions are within a certain range, the degree of reduction of the irritation to the skin lesions by the test substance can be inferred by observing the results of the itch test. From the results, it can be seen that the effect of reducing the irritation to the skin lesions by the Example 1 group, the Comparative Example 3 group, and the Comparative Example 4 group is more obvious, and the Comparative Example 1 and Comparative Example 2 groups have a tendency to reduce skin irritation.

[0128] 2. Skin lesion repair performance test

[0129] The PASI (lesion area and severity index) scoring method was used to compare the skin lesion repair performance of the embodiment and the comparative example. The PASI scoring method scores the severity of erythema, infiltration, and desquamation of the skin in the test area, with 0 to 4 points corresponding to asymptomatic, mild, moderate, severe, and extremely severe skin lesions. The skin lesions of mice in each group are shown in Figure 2. Figure 1 , PASI scores are shown in Table 2.

[0130] Table 2 PASI score statistics of skin lesions in psoriasis model mice

[0131]

[0132]

[0133] The PASI score of the model group was P≤0.05 compared with the blank control group, and the skin of the animals in the model group showed erythema, scaling, and infiltration, which can be judged as the success of the model.

[0134] Compared with the model group, the scores of Example 1 and Example 2 groups were reduced (P≤0.05), the score of Comparative Example 3 group was increased, the score of Comparative Example 4 group was low, the score of Comparative Example 1 group was increased, and the score of Comparative Example 2 group had a decreasing trend.

[0135] From the scoring results, it can be seen that both Example 1 and Example 2 have a more obvious effect of improving skin lesions, and the comparative example 2 group has a trend of improving skin lesions.

[0136] 3. Pathology

[0137] After the 6th day of administration, the mice were killed, and the blank group, the model group, the Example 1 group with a significant improvement effect, and the Comparative Example 2 group with an improvement trend were selected, and the back skin of the mice in the groups was fixed in 10 parts by weight of a neutral formalin buffer solution for pathological section analysis.

[0138] Five visual field images of tissue sections were randomly collected using an optical microscope, and each visual field image was scored using the Baker method. The average score of the five visual fields was taken as the Baker score of the sample. Figure 2 The images are two fields of view of one tissue section in four groups. The statistical results of Baker score of each group are shown in Table 3.

[0139] Table 3 Baker score statistics of pathological sections of psoriasis model mice

[0140]

[0141] Figure 2The visual field images showed that the model group had obvious pathological changes such as epidermal acanthosis thickening, dyskeratosis, Munro microabscesses and inflammatory cell infiltration in the dermis compared with the blank group. Similar pathological changes as those in the model group were observed in Example 1 and Comparative Example 2. In the Baker score, the average scores of Example 1 and Comparative Example 2 were lower than that of the model group, among which Example 1 group had an improvement trend (p>0.05), and Comparative Example 2 group had an improvement effect (p≤0.05).

[0142] From the above, it can be seen that through the above experimental verification, the preparation prepared by the synergistic combination of the composite extract prepared from rhubarb extract powder, Phellodendron chinense and Coptis chinensis co-extract powder, and Scutellaria baicalensis extract powder and urea has the effect of relieving itching, improving skin damage and skin inflammation, and can meet the daily skin care needs of patients with psoriasis vulgaris and serve as an auxiliary treatment during psoriasis attacks.

[0143] Experimental Example 2

[0144] The test components of this experimental example are Sihuang fine powder and composite extract, wherein the preparation method of Sihuang fine powder is as follows: equal amounts of rhubarb, phellodendron and coptis (1:1) and scutellaria baicalensis decoction pieces are crushed and passed through an 80-mesh sieve to obtain Sihuang fine powder.

[0145] The preparation method of the Sihuang composite extract is as follows: equal amounts of the rhubarb extract powder, the co-extract powders of Phellodendron amurense and Coptis chinensis, and the scutellaria baicalensis extract powder prepared according to Example 1 are dissolved in water to obtain the composite extract.

[0146] The test method specifically includes the following steps:

[0147] (1) Setting up a model control group: zebrafish embryos fertilized for 72 hours were taken and placed in a 6-well plate, with 24 embryos in each well. One well was set up for each group. 6 mL of copper sulfate solution (copper sulfate concentration was 1.6 mg / L) was added to each well. After 45 minutes of incubation, the plates were fixed and stained, and photographed to observe and count the number of neutrophil migration in zebrafish embryos.

[0148] (2) Setting up a positive control group: zebrafish embryos fertilized for 72 hours were taken and placed in a 6-well plate, with 24 embryos in each well. One well was set up for each group. 6 mL of a mixed solution of copper sulfate and dexamethasone (copper sulfate concentration was 1.6 mg / L, dexamethasone concentration was 3.96 mg / L) was added to each well. After 45 minutes of incubation, the mixture was fixed and stained, and photographed to observe and count the number of neutrophil migration in zebrafish embryos.

[0149] (3) Setting up the sample groups to be tested: Take zebrafish embryos fertilized for 72 hours and place them in a 6-well plate, with 24 embryos in each well. Set up one well for each group, add 6 mL of copper sulfate and four yellow powder (the concentration of four yellow powder in each group is 0.2%, 1%, and 5%) or compound extract (the concentration of four yellow compound extract in each group is 0.2%, 1%, and 5%) to each well, incubate for 45 minutes, fix and stain, take pictures to observe and count the number of neutrophil migration in zebrafish embryos;

[0150] (4) Statistical analysis: The zebrafish embryos of the blank control group, model control group and test sample group were placed under an upright fluorescence microscope, photographed and saved. The number of neutrophils in the muscle tissue of the zebrafish embryo tail was counted.

[0151] (5) Results: 45 minutes after administration, the number of neutrophil migration in each group of zebrafish was counted. The data are shown in Figure 3 ,in Figure 3 The four yellow extract in the formula refers to the above-mentioned composite extract. Figure 3 It can be seen that compared with the model control group: 45 minutes after administration, the number of neutrophil migration in the positive control group, four yellow fine powder group and compound extract group was significantly reduced (P<0.001), and there was no significant difference in the number of neutrophil migration between four yellow fine powder and compound extract.

[0152] Experimental Example 3

[0153] The test components of this experimental example are urea and four yellow fine powder or composite extract, wherein the preparation method of the four yellow fine powder and the composite extract is the same as that of Experimental Example 2.

[0154] In terms of weight, the compounding ratios of urea and four-yellow fine powder are 5:1, 10:1, 15:1 and 20:1 respectively; the compounding ratios of urea and rhubarb extract powder, phellodendron and coptis co-extract powder, and scutellaria baicalensis extract powder are 5:1, 10:1, 15:1 and 20:1 respectively.

[0155] The specific steps include:

[0156] (1) Setting up a model control group: zebrafish embryos fertilized 72 hours ago were placed in a 6-well plate, with 24 embryos in each well. One well was set up for each group. 6 mL of copper sulfate solution was added to each well. After 45 minutes of incubation, the cells were fixed and stained, and photographed to observe and count the number of neutrophil migration in zebrafish embryos.

[0157] (2) Setting up a positive control group: zebrafish embryos fertilized for 72 hours were taken and placed in a 6-well plate, with 24 embryos in each well. One well was set up for each group. 6 mL of a mixed solution of copper sulfate and dexamethasone (copper sulfate concentration was 1.6 mg / L, dexamethasone concentration was 3.96 mg / L) was added to each well. After 45 minutes of incubation, the mixture was fixed and stained, and photographed to observe and count the number of neutrophil migration in zebrafish embryos.

[0158] (3) Setting up the sample groups to be tested: Take zebrafish embryos fertilized for 72 hours and place them in a 6-well plate, with 24 embryos in each well. Set up one well for each group, and add 6 mL of copper sulfate, urea and four yellow powder (the compound ratios are 5:1, 10:1, 15:1, and 20:1, respectively, and the concentration of four yellow powder in each group is 0.2%) or urea and composite extract (the compound ratios are 5:1, 10:1, 15:1, and 20:1, respectively, and the concentration of composite extract in each group is 0.2%) to each well. After culturing for 45 minutes, fix and stain, take pictures to observe and count the number of neutrophil migration in zebrafish embryos;

[0159] (4) Statistical analysis: The zebrafish embryos of the blank control group, model control group and test sample group were placed under an upright fluorescence microscope, photographed and saved. The number of neutrophils in the muscle tissue of the zebrafish embryo tail was counted.

[0160] (5) Results: 45 minutes after administration, the number of neutrophil migration in each group of zebrafish was counted. The data are shown in Figure 4 ,in Figure 4 The four yellow extract in the formula refers to the above-mentioned composite extract. Figure 4 It can be seen that 45 minutes after administration, the number of neutrophil migration in the positive control group, urea combined with four yellow powder group, and urea combined with compound extract group was significantly reduced (P<0.001). When the urea compounding ratio was 5:1 and 10:1, there was no significant difference in the number of neutrophil migration between the combined four yellow powder and the urea combined with compound extract group. When the urea compounding ratio was 15:1 and 20:1, there was a significant difference in the number of neutrophil migration between the combined four yellow powder and the compound extract.

[0161] In summary, the above experiments verified that when the four-yellow powder and the composite extract were used alone, they both had significant anti-inflammatory effects, and there was no significant difference between them at the same concentration, indicating that the composite extract had similar biological activities to the traditional four-yellow powder when used alone. When urea and four-yellow powder or composite extract were compounded at a ratio of 15:1 and 20:1, the urea-compounded composite extract had better anti-inflammatory effects than the compound four-yellow powder, indicating that the synergistic effect of the composite extract and urea was significantly better than that of the four-yellow powder.

[0162] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0163] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A compound external preparation for auxiliary treatment of psoriasis, characterized in that: The compound external preparation is composed of the following components in 100 parts by weight: Compound 8-25 parts 75-92 parts of dosage form auxiliary agent; Wherein, the composite agent consists of component A, component B and component C: The component A consists of medicine and dipotassium glycyrrhizinate; The active ingredients of the drug are composed of a composite extract prepared from rhubarb extract powder, co-extract powder of phellodendron chinense and coptis chinensis, and scutellaria baicalensis extract powder, and urea, wherein the weight ratio of the total amount of rhubarb extract powder, co-extract powder of phellodendron chinense and coptis chinensis, and scutellaria baicalensis extract powder to the urea is 1:15-36; The amounts of the rhubarb extract powder, the co-extract powder of Phellodendron amurense and Coptis chinensis, and the scutellaria baicalensis extract powder are the same; The rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder are prepared by alcohol extraction; the alcohol extraction method of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder comprises the following steps: soaking rhubarb, equal amounts of Phellodendron chinense and Coptis chinensis, and Scutellaria baicalensis in 7 to 9 times the weight of 45 to 55% ethanol, refluxing to obtain a concentrated extract, standing to obtain a precipitate, and drying the precipitate to obtain the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder; In the extraction process of the co-extracted powder of Phellodendron chinense and Coptis chinensis and the powder of Scutellaria baicalensis, after reflux extraction to obtain a concentrated extract, an acid is added to the extract to obtain a precipitate after sedimentation, the precipitate is washed with water until the pH value of the washing liquid is 3.5-4.5, the washed precipitate is taken, and the co-extracted powder of Phellodendron chinense and Coptis chinensis and the powder of Scutellaria baicalensis are obtained after drying the precipitate; The drug accounts for 3% to 99% of the total amount of the composite, and the weight ratio of the total amount of the rhubarb extract powder, the coptis co-extract powder, and the scutellaria extract powder to the dipotassium glycyrrhizinate is 1:10 to 15; The B component includes: sweet almond oil and bergamot essential oil; The C component includes: sodium hyaluronate, glycerin and butylene glycol; The dosage form adjuvants include emulsifiers, thickeners, antioxidants and water.

2. The compound external preparation according to claim 1, characterized in that: The weight ratio of the total amount of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder to the urea is 1:15-34.

3. The compound external preparation according to claim 2, characterized in that: The weight ratio of the total amount of the rhubarb extract powder, the co-extract powder of Phellodendron chinense and Coptis chinensis, and the scutellaria baicalensis extract powder to the urea is 1:15-20.

4. The compound external preparation according to claim 1, characterized in that: The B component includes the following components in parts by weight: Sweet almond oil 2-20 parts 0.1-1 part of bergamot essential oil; and / or, The C component includes the following components in parts by weight: Sodium hyaluronate 0.01-0.5 parts Glycerin 2-12 parts 1-8 parts of butanediol; and / or, The dosage form auxiliary comprises the following components in parts by weight: Emulsifier 2-5 parts Thickener 0.01-0.8 parts Antioxidant 0.1-0.5 parts.

5. The compound external preparation according to claim 1, characterized in that: The A component further comprises allantoin; and / or, The B component further comprises shea butter; and / or, The C component also includes polyglycerol.

6. The compound external preparation according to claim 5, characterized in that: In parts by weight, the allantoin is 0.1-1 parts; and / or, The shea butter is 2-5 parts by weight; and / or The polyglycerol is 1-2 parts by weight.

7. The compound external preparation according to claim 4, characterized in that: The emulsifier is a combination of two or more of methyl glucoside hemistearate, PEG-20 methyl glucoside sesquistearate, and glyceryl stearate / PEG-100 stearate; And / or, the thickener is carbomer; And / or, the antioxidant is any one of butylated hydroxyanisole and butylated hydroxytoluene; And / or, the dosage form adjuvant further comprises a chelating agent, a preservative, a buffer and a pH adjuster; And / or, the pH value of the compound external preparation is 5.5-7.

8. A method for preparing the compound external preparation for adjuvant treatment of psoriasis according to any one of claims 1 to 7, characterized in that: The steps include: Matrix preparation steps: except for rhubarb extract powder, co-extract powder of phellodendron and coptis root, scutellaria extract powder, dipotassium glycyrrhizinate, urea, and bergamot essential oil, other components are divided into two groups according to water solubility and oil solubility, and the components are dissolved / swelled and then heated to 70°C-80°C to obtain oil-soluble components and water-soluble components respectively, and mixed and stirred to obtain a matrix; Discharging step: cool the substrate to 45-55°C, add rhubarb extract powder, phellodendron amurense and coptis chinensis co-extract powder, scutellaria baicalensis extract powder, dipotassium glycyrrhizinate, urea, bergamot essential oil, adjust the pH value of the product to between 5.5 and 7, stir and homogenize, and then discharge after vacuuming.

Images