Application of scutellarin and salidroside combination in treatment of solar dermatitis

Abstract

The invention discloses application of a combination of scutellarin and salidroside in treatment of solar dermatitis, finds that the combination of scutellarin and salidroside has a synergistic effect on treatment of solar dermatitis for the first time, and provides a brand new and effective drug combination strategy for treatment of solar dermatitis. A new thought is provided for research and development of anti-solar dermatitis drugs, and the application value and the industrial conversion prospect are good.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biomedicine, and particularly relates to application of wild scutellarein and salidroside in treatment of solar dermatitis. BACKGROUND

[0002] Solar dermatitis is an acute inflammatory reaction caused by excessive exposure of the skin to ultraviolet light, mainly caused by medium wave ultraviolet light (UVB). The clinical manifestations are erythema, edema, burning pain, and severe cases can have blisters, peeling, and even systemic symptoms (such as fever, headache). Long-term repeated attacks can increase the risk of skin cancer. At present, the treatment drugs for solar dermatitis mainly include topical treatment drugs and systemic treatment drugs. Among them, the topical treatment drugs mainly include glucocorticoid drugs (such as hydrocortisone cream, mometasone furoate) and non-steroidal anti-inflammatory drugs (such as flufenamic acid butyl ointment); the systemic treatment drugs mainly include oral glucocorticoids (such as prednisone, which needs to be guided by a doctor), oral non-steroidal anti-inflammatory drugs (such as ibuprofen, aspirin) and oral antihistamines (such as loratadine).

[0003] At present, the action of the existing solar dermatitis treatment drugs is only limited to symptom control (such as relieving redness and pain), and its curative effect is single, and it cannot simultaneously improve various pathological changes of solar dermatitis (such as inflammatory reaction, skin oxidation, barrier damage). In addition, most of the existing treatment drugs have side effects, such as long-term use of topical glucocorticoid drugs can cause skin atrophy, telangiectasia or pigmentation, oral glucocorticoid drugs can cause immunosuppression and other systemic side effects; topical non-steroidal anti-inflammatory drugs can cause allergy in some patients, and oral non-steroidal anti-inflammatory drugs can cause gastrointestinal mucosal damage; oral antihistamines can cause drowsiness, dry mouth, gastrointestinal discomfort and other side effects.

[0004] Therefore, it is urgent to develop new solar dermatitis treatment drugs. SUMMARY

[0005] In order to solve the above technical problems existing in the prior art, the purpose of the present application is to provide the application of wild scutellarein and salidroside in the treatment of solar dermatitis.

[0006] The present application first found that the combination of wild scutellarein and salidroside has a significant synergistic effect on the treatment of solar dermatitis, and there is no related research or report on the application of wild scutellarein and salidroside in the treatment of solar dermatitis.

[0007] The present application realizes the above-mentioned application purposes by adopting the following technical solutions:

[0008] The first aspect of the present application provides the application of wild scutellarein or a pharmaceutically acceptable salt thereof, and salidroside or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing solar dermatitis.

[0009] Further, the mass ratio of the Scutellarein or its pharmaceutically acceptable salt and the Salidroside or its pharmaceutically acceptable salt is 1: (0.1-10);

[0010] Optionally, the mass ratio of the Scutellarein or its pharmaceutically acceptable salt and the Salidroside or its pharmaceutically acceptable salt is 1:1.

[0011] Further, the pharmaceutically acceptable salt of the Scutellarein is a compound formed by the Scutellarein and a pharmaceutically acceptable salt.

[0012] Optionally, the pharmaceutically acceptable salt of the Salidroside is a compound formed by the Salidroside and a pharmaceutically acceptable salt.

[0013] Optionally, the pharmaceutically acceptable salt is hydrochloride, sulfate, nitrate, phosphate, acetate, carbonate, maleate, citrate, hydrobromide, tartrate, hydroiodide, bicarbonate and / or benzoate.

[0014] Further, the medicine further comprises a pharmaceutically acceptable excipient.

[0015] Optionally, the excipient comprises a filler, a binder, a disintegrant, a lubricant, a solvent, a co-solvent, a stabilizer and / or a preservative.

[0016] Further, the dosage form of the medicine is an external liquid preparation, an external semi-solid preparation, a patch, a film, an external emulsion, a foam and / or a gel ointment.

[0017] In the present application, the Scutellarein (SCU) is a flavonoid isolated from Scutellaria baicalensis Georgi, with a CAS registration number of 27740-01-8, a molecular formula of C 21 H 18 O 12 and a molecular weight of 462.37, which has the effects of reducing cerebral vascular resistance, improving cerebral blood circulation, increasing cerebral blood flow and resisting platelet aggregation, and is clinically used for the treatment of paralysis after cerebrovascular disease. Currently, there is no relevant research or report on the application of Scutellarein in the treatment of solar dermatitis. The specific source of the Scutellarein is not particularly limited in the present application, and those skilled in the art can purchase it through a conventional route according to the above specific information provided in the present application.

[0018] In the present application, the Salidroside (SAL) is a prolyl endopeptidase inhibitor, with a CAS registration number of 10338-51-9, a molecular formula of C 14 H 20O7, with a molecular weight of 300.30, has the effects of anti-fatigue, anti-aging, anti-hypoxia, anti-tumor, detoxification, etc., has an influence on central nervous mediators, and can reduce the level of 5-hydroxytryptamine to correct it or make it reach a normal level. The specific source of the rhodioloside in the present application is not particularly limited, and those skilled in the art can purchase it through a conventional route according to the above specific information provided by the present application.

[0019] In the present application, the pharmaceutically acceptable salt of the scutellarein or the pharmaceutically acceptable salt of the rhodioloside refers to a pharmaceutically acceptable salt of the scutellarein or the rhodioloside, which means those carboxylic acid salts, amino acid addition salts, etc. of the compound (the above scutellarein or rhodioloside) of the present application that are suitable for use in contact with the patient within the scope of sound medical judgment, do not produce undue toxicity, irritation, allergic response, etc., are commensurate with a reasonable benefit / risk ratio, and are effective for their intended use, including (if possible) the zwitterionic form of the compound (the above scutellarein or rhodioloside) of the present application.

[0020] In some embodiments, the pharmaceutically acceptable salt of the scutellarein or the pharmaceutically acceptable salt of the rhodioloside refers to the pharmaceutically acceptable salt of the scutellarein or the pharmaceutically acceptable salt of the rhodioloside prepared by performing a salt modification on the scutellarein or the rhodioloside.

[0021] In some embodiments, the salt used in the salt modification process includes but is not limited to: inorganic acid salt, organic acid salt, organic base salt, metal salt, quaternary ammonium salt, complex salt.

[0022] Among them, the inorganic acid salt includes but is not limited to: hydrochloride, sulfate, phosphate, nitrate, hydrobromide, hydroiodide, carbonate, bicarbonate, borate. The organic acid salt includes but is not limited to: acetate, citrate, tartrate, maleate, fumarate, succinate, lactate, malate, benzoate, p-toluenesulfonate, methanesulfonate, ethanesulfonate. The organic base salt includes but is not limited to: triethylamine salt, diethylamine salt, ethanolamine salt, diethanolamine salt, pyridine salt, piperazine salt, morpholine salt, glycine salt, lysine salt, arginine salt. The metal salt includes but is not limited to: sodium salt, potassium salt, magnesium salt, aluminum salt. The complex salt includes but is not limited to: ferrous ammonium sulfate, potassium sodium tartrate.

[0023] In the present application, the salt modification of the compound is a technical means for optimizing the physicochemical properties and biological characteristics in drug research and development. The core principle is to form stable ionic bonds between molecules through acid-base reaction, convert the free compound into a salt form with a specific crystal form, and improve the solubility, stability, bioavailability and formulation adaptability of the drug. This process needs to achieve controllable preparation of salt type through systematic crystallization process, which covers six key links (determination of the acidity and basicity of the small molecule compound to be modified and the salt modification site, selection of solvent system, salt formation reaction, crystallization and separation, drying and characterization, quality control and optimization).

[0024] In some embodiments, the skilled person in the art can prepare the corresponding pharmaceutically acceptable wild jatamansi glycoside salt or pharmaceutically acceptable salvia miltiorrhiza glycoside salt according to the above-mentioned salt modification of wild jatamansi glycoside or salvia miltiorrhiza glycoside according to the common knowledge in the art. The present application does not have special requirements for the specific preparation method of the wild jatamansi glycoside salt or the salvia miltiorrhiza glycoside salt. Any technical solution for applying the wild jatamansi glycoside, salvia miltiorrhiza glycoside, wild jatamansi glycoside salt and / or salvia miltiorrhiza glycoside salt to the anti-sunlight dermatitis will fall within the protection scope of the present application.

[0025] In some embodiments, the filler, also known as diluent, is an auxiliary material for increasing the volume or weight of the drug preparation. The main role is to make the dosage form (such as tablets, powders, pastes) reach the specification for easy production, molding or use (such as tablets need enough weight to be successfully compressed, pastes need enough volume to be evenly coated); ensure the uniform dispersion of active ingredients (wild jatamansi glycoside, salvia miltiorrhiza glycoside) in the preparation, avoid uneven dosage. For example, zinc oxide powder, talc, calcium carbonate (all are inert powders, no skin irritation, and zinc oxide also has the effects of astringency and skin protection, suitable for slight exudation of skin lesions in acute stage of sunlight dermatitis) can be selected for external use paste / ointment; microcrystalline cellulose, lactose, mannitol (microcrystalline cellulose has certain adhesion, and mannitol has good taste and small irritation to gastrointestinal tract) can be selected for oral auxiliary dosage form (such as tablets for adjusting body immunity).

[0026] In some embodiments, the adhesive is an auxiliary material that can bond drug powders or particles to each other, or adhere the preparation to the skin / mucosa, the core function being to ensure the formation of solid preparations (such as tablets, granules) and prevent disintegration; enable the stable adhesion of topical patches, gel ointments to the skin surface, and ensure the sustained penetration of drugs (especially suitable for the use of drugs on exposed parts of sunlight-induced dermatitis, which need to resist friction and sweat). For example, topical patches / gel ointments (core adapted dosage forms) can use pressure-sensitive adhesives (such as acrylate pressure-sensitive adhesives, rubber pressure-sensitive adhesives) to enable the repeated adhesion of patches to the skin, and no residue or irritation to damaged skin when peeled off; sodium polyacrylate, xanthan gum (gel ointment base): has both adhesive and gel-forming effects, has strong moisturizing properties, and is suitable for sensitive skin lesions; oral tablets can use hydroxypropyl methylcellulose (HPMC), povidone (PVP) (dissolved in water to form a viscous solution, which bonds powders into particles, and the hardness of the tablets is qualified after compression).

[0027] In some embodiments, the disintegrant is an auxiliary material that promotes the rapid disintegration and fragmentation of solid preparations (such as tablets, capsules) in the body (gastrointestinal tract or skin surface) to release active ingredients, the core function being to accelerate the disintegration of tablets in the gastrointestinal tract for oral preparations, and to promote the rapid disintegration of films on the skin surface after encountering sweat / moisture for topical fast-dissolving films, to release drugs (avoiding the impact of residual film layer on skin feel). For example, oral tablets can use cross-linked povidone (PVPP), sodium carboxymethyl starch (CMS-Na), and low-substituted hydroxypropyl cellulose (L-HPC) (which has strong water absorption and swelling capacity, can quickly destroy the tablet structure, and release baicalin and salidroside); topical fast-dissolving films can use cross-linked sodium carboxymethyl cellulose (CCMC-Na) (which swells and disintegrates rapidly upon contact with moisture on the skin surface, without affecting skin ventilation).

[0028] In some embodiments, the lubricant is an auxiliary material that reduces friction between drug powders / particles and production equipment, or improves the skin feel of the preparation, the core function being to prevent powder adhesion to the die during solid preparation production (such as tablet compression, capsule filling), to ensure smooth tablet surface and successful formation; in topical preparations, to reduce friction during application and improve skin tolerance (suitable for damaged skin of sunlight-induced dermatitis). For example, oral tablets / capsules can use magnesium stearate, micro-powder silica, and talc (magnesium stearate is the most commonly used lubricant, has a small amount (0.1%-1%) and is non-irritating; micro-powder silica also has a flow-aiding effect, avoiding powder caking); topical creams / gels can use polyethylene glycol (PEG 400 / 6000), and glycerol (a small amount of addition can reduce the viscosity of the base, making the application smoother, and glycerol also has a moisturizing effect, suitable for dry skin lesions).

[0029] In some embodiments, the solvent is a liquid excipient for dissolving or dispersing the active ingredients (scutellarein, salidroside), is the core component of the liquid preparation (solution, spray, film coating), and functions to form a uniform liquid system of the solid active ingredients, facilitating application or spraying; adjusting the solubility of the drug to control the release rate. For example, the external solution / spray can be selected from 75% ethanol solution, propylene glycol, and polyethylene glycol (PEG 300 / 400) (75% ethanol has a slight bactericidal effect, propylene glycol and PEG can improve the solubility of the drug, and the skin irritation is lower than that of pure ethanol); the water phase of the cream / gel can be selected from purified water and physiological saline (as the water phase of the oil-in-water cream, it dissolves water-soluble excipients and simultaneously supplements skin moisture).

[0030] In some embodiments, the cosolvent is an excipient that can significantly improve the solubility of the active ingredients in the solvent, and the core function is to solve the problem of insufficient solubility of scutellarein and salidroside (medium solubility) in a single solvent, avoid turbidity or precipitation of the solution, ensure that the drug concentration meets the standard, and improve skin permeability. For example, propylene glycol and glycerol (both have the functions of solvent and cosolvent, can synergistically improve the solubility of glycosides with ethanol, and have strong moisturizing properties); polysorbate 80 (Tween 80) and polyoxyethylene castor oil (non-ionic surfactants, which can make glycosides more uniformly dispersed by reducing surface tension, are suitable for cream and microemulsion, and have low skin irritation); hydroxypropyl-β-cyclodextrin (HP-β-CD) (cyclic molecular structure, which can form inclusion compounds with glycosides, significantly improve solubility, and have good biocompatibility, suitable for sensitive skin).

[0031] In some embodiments, the stabilizer is an excipient that prevents degradation, oxidation, and discoloration of the active ingredients (scutellarein, salidroside) during storage or use, and the core function is to ensure the stability of the drug potency (glycoside components are easily affected by light, high temperature, and oxidation), prolong the shelf life of the preparation, and avoid skin irritation by degradation products (drugs for solar dermatitis need to be strictly controlled for impurities). For example, common stabilizers include antioxidants (vitamin E, sodium bisulfite, tertiary butyl hydroxyanisole (BHA), etc.), light stabilizers (titanium dioxide, zinc oxide, etc.), and pH regulators (citric acid-sodium citrate buffer pair, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer pair, etc.).

[0032] In some implementations, the preservative is an excipient that inhibits the growth and reproduction of microorganisms (bacteria, fungi) in the formulation. Its core function is to prevent the formulation (especially water-containing dosage forms, such as solutions, creams, and gels) from being contaminated by microorganisms during storage or use (microbial contamination may increase the risk of photodermatitis infection), ensuring medication safety, especially for multi-dose formulations. For example, phenoxyethanol (the most commonly used topical preservative, which inhibits both bacteria and fungi, has low irritation, and is suitable for sensitive skin, especially for children or facial use); potassium sorbate and sodium benzoate (organic acid preservatives, suitable for liquid formulations and aqueous phases of creams, with high safety and better efficacy in acidic environments); ethylparaben (a broad-spectrum preservative with strong antibacterial effects, suitable for ointments and gels, but the dosage needs to be controlled (≤0.1%) to avoid allergic reactions in a few individuals); and chlorhexidine alcohol (which has both bactericidal and preservative effects, suitable for sprays and films, with low skin irritation and no residue).

[0033] In some embodiments, the drug is in the form of a topical liquid preparation. Liquid preparations have the advantages of rapid onset of action, easy application, and no stickiness, making them suitable for the acute phase of photodermatitis (such as redness, swelling, and slight exudation) or hair-covered areas such as the scalp and beard area. This avoids the possibility of dosage form residue affecting skin breathability. The topical liquid preparation includes, but is not limited to, topical solutions, topical sprays, and ointments.

[0034] In some embodiments, the dosage form of the drug is a topical semi-solid preparation. Semi-solid preparations (ointments, creams, gels, etc.) have the characteristics of good moisturizing properties, long drug residence time, and controllable permeability, making them suitable for the subacute phase (reduced redness and swelling, no exudation) or chronic phase (thickened skin, dryness and itching) of photodermatitis. They can form a protective film on the skin surface, reducing secondary stimulation from ultraviolet rays. The topical semi-solid preparations include, but are not limited to: ointments, creams, gels, and pastes.

[0035] In some implementations, the drug is in the form of a patch. The topical patch consists of a backing layer (such as non-woven fabric or plastic film), a drug reservoir layer (a gel or pressure-sensitive adhesive containing two glycosides), an adhesive layer, and a protective layer. After being applied to the skin lesion, the drug slowly penetrates through the stratum corneum of the skin, with a long duration of action (usually 8-12 hours). It is suitable for chronic skin lesions that require long-term maintenance of efficacy, and its use does not affect daily activities.

[0036] In some embodiments, the drug is in the form of a film (coating), which uses a polymeric film-forming material (such as polyvinyl alcohol or povidone) as a carrier, dissolves or disperses two glycosides to form a liquid, and after being applied to the skin lesion, the solvent evaporates rapidly to form a transparent film covering the skin surface, which can protect the skin lesion from external stimuli (such as dust and ultraviolet rays) and allow the drug to be slowly released under the film and penetrate into the deep layers of the skin.

[0037] In some embodiments, the dosage form of the medicine is an external emulsion, which utilizes the small particle size (10-100 nm), high solubility and strong skin permeability of microemulsion or nanoemulsion to wrap the two glycosides in the emulsion droplets, thereby improving the skin absorption efficiency of the medicine (especially suitable for glycoside components with slightly weaker liposolubility), and meanwhile, the emulsion base has good moisturizing property, which is suitable for the treatment of solar dermatitis of dry and sensitive skin.

[0038] In some embodiments, the dosage form of the medicine is a foam agent, which is prepared by using a surfactant (such as sodium dodecyl sulfate) as a foaming agent and a suitable solvent, and generates fine foam after being pressed, and the foam breaks quickly after being applied to the skin lesions, so that the medicine is uniformly distributed on the skin surface, and the foam agent has the advantages of easy absorption of liquid preparations and moisturizing property of semi-solid preparations, and is suitable for solar dermatitis in the armpit, groin and other wrinkle parts (the foam can penetrate into the wrinkle to avoid uneven application).

[0039] In some embodiments, the dosage form of the medicine is a gel ointment, which is a common dosage form for external use of traditional Chinese medicine, and is prepared by using a water-soluble polymer material (such as sodium polyacrylate) as a base, adding a humectant such as glycerol and propylene glycol, and dispersing the two glycosides therein to form a soft ointment, which is suitable for the treatment of solar dermatitis of children or people with sensitive skin due to its strong moisturizing property, good air permeability and small skin irritation.

[0040] The second aspect of the present application provides a combined pharmaceutical composition for treating and / or preventing solar dermatitis.

[0041] Further, the combined pharmaceutical composition comprises scutellarein or a pharmaceutically acceptable salt thereof, and rhodioside or a pharmaceutically acceptable salt thereof.

[0042] Optionally, the mass ratio of the scutellarein or a pharmaceutically acceptable salt thereof, and the rhodioside or a pharmaceutically acceptable salt thereof is 1:(0.1-10).

[0043] Optionally, the mass ratio of the scutellarein or a pharmaceutically acceptable salt thereof, and the rhodioside or a pharmaceutically acceptable salt thereof is 1:1.

[0044] The third aspect of the present application provides a pharmaceutical preparation for treating and / or preventing solar dermatitis.

[0045] Further, the pharmaceutical preparation comprises the combined pharmaceutical composition according to the second aspect of the present application.

[0046] In some embodiments, the dosage form of the pharmaceutical preparation is an external liquid preparation, an external semi-solid preparation, a patch, a film, an external emulsion, a foam agent and / or a gel ointment.

[0047] The fourth aspect of the present application provides the use of scutellarein or a pharmaceutically acceptable salt thereof in the preparation of a medicine for treating and / or preventing solar dermatitis.

[0048] Further, the pharmaceutically acceptable salt of scutellarein is a compound formed by scutellarein and a pharmaceutically acceptable salt;

[0049] Optionally, the pharmaceutically acceptable salt is hydrochloride, sulfate, nitrate, phosphate, acetate, carbonate, maleate, citrate, hydrobromide, tartrate, hydroiodide, bicarbonate and / or benzoate;

[0050] Optionally, the medicine further comprises a pharmaceutically acceptable excipient;

[0051] Optionally, the excipient comprises a filler, a binder, a disintegrant, a lubricant, a solvent, a co-solvent, a stabilizer and / or a preservative;

[0052] Optionally, the dosage form of the medicine is an external liquid preparation, an external semi-solid preparation, a patch, a film, an external emulsion, a foam and / or a gel ointment.

[0053] The fifth aspect of the present application provides use of scutellarein or a pharmaceutically acceptable salt thereof, and / or rhodioloside or a pharmaceutically acceptable salt thereof in the preparation of a medicine for inhibiting the level of inflammatory factors TNFα, IL-6 and / or IL-1β in skin tissue, increasing the level of GSH in skin tissue and / or inhibiting the level of MDA in skin tissue;

[0054] Optionally, the mass ratio of scutellarein or a pharmaceutically acceptable salt thereof, and rhodioloside or a pharmaceutically acceptable salt thereof is 1:(0.1-10);

[0055] Optionally, the mass ratio of scutellarein or a pharmaceutically acceptable salt thereof, and rhodioloside or a pharmaceutically acceptable salt thereof is 1:1.

[0056] In addition, the present application also provides a method for treating and / or preventing solar dermatitis, which comprises administering to a subject in need a therapeutically and / or prophylactically effective amount of scutellarein or a pharmaceutically acceptable salt thereof and rhodioloside or a pharmaceutically acceptable salt thereof as described in the first aspect of the present application, the pharmaceutical composition as described in the second aspect of the present application, or the pharmaceutical preparation as described in the third aspect of the present application.

[0057] In the present application, the treatment refers to, for a subject who has been diagnosed as having solar dermatitis, a process of relieving symptoms, controlling disease progression, promoting wound healing, and reducing complications by administering the medicine (or composition, preparation) of the present application, the core goal of which is to intervene in the disease that has occurred and improve the pathological state, rather than only prevent the onset. Specifically, it is manifested as relieving clinical symptoms, controlling inflammation progression, repairing skin damage, and reducing recurrence and complications.

[0058] In the present application, the prevention refers to the process of reducing the probability of occurrence of solar dermatitis or alleviating the severity after the occurrence of solar dermatitis by applying the drug (or composition, preparation) of the present application in advance for subjects who have not yet occurred solar dermatitis but have the risk of occurrence, the core goal of which is to block the key link of disease occurrence and avoid or weaken the disease rather than treating the disease after occurrence. The targeted population includes but is not limited to: people without a history of solar dermatitis but with a high risk, people with a history of solar dermatitis.

[0059] In the present application, the effective amount refers to the minimum dose or dose range of wild jatrorrhizine or its pharmaceutically acceptable salt, rhodioside or its pharmaceutically acceptable salt, pharmaceutical composition and / or pharmaceutical preparation given to subjects (such as humans or experimental animals) to achieve the expected goal of treating solar dermatitis or preventing the occurrence / aggravation of solar dermatitis. Among them, the therapeutically effective amount is for solar dermatitis that has occurred (such as symptoms of redness, swelling, burning, itching, and blistering on the skin), which needs to quickly relieve symptoms, reduce inflammatory response (such as reducing skin MDA levels, increasing GSH levels, etc.), and promote skin lesion healing, usually with a relatively high dose (to counteract the existing inflammation). The prophylactically effective amount is for the situation where the disease has not occurred but there is a risk (such as people who are about to be exposed to strong ultraviolet light environment, people with a history of solar dermatitis), which needs to enhance the skin's tolerance to ultraviolet light, inhibit the release of ultraviolet-induced inflammatory factors, and reduce oxidative damage, usually with a dose lower than the therapeutically effective amount (without needing to counteract the existing inflammation, only needing to protect in advance).

[0060] It should be noted that the effective amount is not a fixed value, and the clinician can make routine adjustments according to the specific actual situation of the subject (age, weight, skin sensitivity, severity of the disease, liver and kidney function, etc. of the subject, dosage form, frequency of drug administration, drug purity, etc.).

[0061] In some embodiments, the subjects include various animal populations, including both human individuals and non-human animals. Among them, the specific types of non-human animals can be divided into vertebrates and invertebrates: under the category of vertebrates, it includes mammals and non-mammals, among which mammals include non-human primates (especially higher primates with close genetic relationship with humans), sheep, pigs, cattle as domestic animals, dogs, cats as pets, and rodents (such as mice, rats), guinea pigs, rabbits commonly used in experimental research, and other mammals such as goats; non-mammals include birds such as chickens, and amphibians (such as frogs, toads), reptiles (such as lizards, snakes), etc. In specific embodiments of the present application, from the perspective of the specificity and practicality of drug application, the subject is preferably a human.

[0062] Compared with the prior art, the present application has the following advantages and beneficial effects:

[0063] The present application first discovers that the combination of scutellarein and salidroside has a synergistic effect on reducing the inflammatory factors TNF-α and IL-1β in the skin tissue of the mouse model of solar dermatitis and reducing the oxidative stress product MDA in the skin tissue of the mouse model of solar dermatitis. The combination of the drugs has a treatment effect on solar dermatitis that is significantly better than that of scutellarein alone and salidroside alone. This synergistic treatment effect is unexpected for those skilled in the art based on the prior art. The present application provides a new and effective drug combination strategy for the treatment of solar dermatitis and provides a new idea for the research and development of anti-solar dermatitis drugs, which has good application value and industrial transformation prospects. BRIEF DESCRIPTION OF DRAWINGS

[0064] Figure 1 Figure 1 is a corresponding result graph of the skin barrier damage and inflammation exacerbation of the mouse model of solar dermatitis, wherein A is a graph of the back skin of the mouse on day 0, day 1, day 2 and day 4 after UVB irradiation; B is a graph of the redness, thickening, desquamation and scabbing of the skin of the mouse; C is a graph of the trans-epidermal water loss (TEWL) of the skin of the mouse on different days after irradiation, with 5 mice in each group; D is a graph of the TNFα content of the skin of the mouse on different days after irradiation, with 5 mice in each group; E is a graph of the IL-6 content of the skin of the mouse on different days after irradiation, with 5 mice in each group; F is a graph of the IL-1β content of the skin of the mouse on different days after irradiation, with 5 mice in each group, wherein the data in C-F are represented by mean ± standard deviation, statistical analysis is performed by One-way ANOVA and Dunnett-t test, * represents P < 0.05, ** represents P < 0.01, *** represents P < 0.001, and **** represents P < 0.0001;

[0065] Figure 2 Figure 2 is a corresponding result graph of the increased keratinocyte apoptosis, increased neutrophils in the skin and damaged epidermal barrier of the mouse model of solar dermatitis, wherein A is a graph of the H&E staining and immunohistochemical staining of the back skin of the mouse on day 0, day 1, day 2 and day 4 after UVB irradiation, with a scale of 50 μm; B is a graph of the relative epidermal thickness on different days after irradiation, with 5 mice in each group; C is a graph of the number of CC3 positive cells in the skin section of the mouse on different days after irradiation, with 3 mice in each group; D is a graph of the number of Ly6G positive cells in the skin section of the mouse on different days after irradiation, with 3 mice in each group, wherein the data in B-D are represented by mean ± standard deviation, statistical analysis is performed by One-way ANOVA and Dunnett-t test, * represents P < 0.05, ** represents P < 0.01, *** represents P < 0.001, and **** represents P < 0.0001;

[0066] Figure 3Figure 6: The corresponding result graphs of the skin barrier of the mouse model of solar dermatitis improved by the scutellarein preparation and the inhibition of inflammatory response and oxidative stress thereof, wherein, A: the mouse back skin diagram of the control group and the scutellarein group on day 0, day 1, day 2 and day 3 after UVB irradiation; B: the trans-epidermal water loss (TEWL) of the mouse skin on day 3 after irradiation, 5 mice in each group; C: the TNFα content of the mouse skin on day 3 after irradiation, 4 mice in each group; D: the IL-6 content of the mouse skin on day 3 after irradiation, 4 mice in each group; E: the IL-1β content of the mouse skin on day 3 after irradiation, 4 mice in each group; F: the MDA content of the mouse skin on day 3 after irradiation, 4 mice in each group; G: the GSH content of the mouse skin on day 3 after irradiation, 4 mice in each group, wherein the data in B-G are expressed as mean ± standard deviation, statistical analysis uses One-way ANOVA and Dunnett-t test, * represents P < 0.05, *** represents P < 0.001, **** represents P < 0.0001;

[0067] Figure 4 Figure 7: The corresponding result graphs of the inhibition of neutrophil infiltration in the skin of the mouse model of solar dermatitis by the scutellarein preparation and the improvement of the epidermal barrier structure thereof, wherein, A: the H&E staining and immunohistochemical diagram of the mouse back skin of the control group and the scutellarein group on day 3 after UVB irradiation; the scale is 50 μm; B: the relative epidermal thickness of the mouse of the control group and the scutellarein group on day 3 after irradiation, 4 mice in each group; C: the number of CC-3 positive cells in the skin section of the mouse of the control group and the scutellarein group on day 3 after irradiation, 4 mice in each group; D: the number of Ly6G positive cells in the skin section of the mouse on day 3 after irradiation, 4 mice in each group, wherein the data in B-D are expressed as mean ± standard deviation, statistical analysis uses One-way ANOVA and Dunnett-t test, ** represents P < 0.01, ns represents no significant difference;

[0068] Figure 5 Figure 8: The corresponding result graphs of the synergistic improvement of the inflammatory response and oxidative stress of the mouse model of solar dermatitis by scutellarein and rhodioside, wherein, A: the back skin diagram of each group of mice on day 3 after UVB irradiation; B: the TNFα content of the skin of each group of mice on day 3 after UVB irradiation; C: the IL-1β content of the skin of each group of mice on day 3 after UVB irradiation; D: the IL-6 content of the skin of each group of mice on day 3 after UVB irradiation; E: the GSH content of the skin of each group of mice on day 3 after UVB irradiation; F: the MDA content of the skin of each group of mice on day 3 after UVB irradiation, wherein the data in B-F are expressed as mean ± standard deviation, statistical analysis uses One-way ANOVA and Dunnett-t test, * represents P < 0.05, ** represents P < 0.01, *** represents P < 0.001, **** represents P < 0.0001;

[0069] Figure 6 Corresponding results of the inhibition of neutrophil infiltration and improvement of epidermal barrier by scutellarein and salidroside, H&E staining and immunohistochemical staining of the back skin of mice in each group on day 3 after UVB irradiation; the scale is 50 μm. DETAILED DESCRIPTION

[0070] The application will be further described below in conjunction with specific examples. The following specific examples are only used to explain the application and should not be understood as limiting the application. Those skilled in the art can understand that various changes, modifications, replacements and variations can be made to the examples without departing from the principles and purposes of the application, and the scope of the application is defined by the claims and their equivalents. The experimental consumables, reagents and raw materials used in the application are readily available to those skilled in the art, and can be obtained from commercial channels if not otherwise specified, and the experimental methods of the application not specified in the application are usually implemented according to conventional conditions or according to the conditions recommended by the manufacturer. In particular, the following examples are only used to illustrate the application and should not limit the scope of the application in any way. It should be noted that the experimental conditions and results described in the following examples are only used to illustrate the application and should not and will not limit the application described in detail in the claims.

[0071] Example 1 Construction of a model of solar dermatitis in mice

[0072] 1. Experimental materials

[0073] C57BL6J mice were purchased from Nanjing Jiquan Pharmaceutical Company, male, 6 weeks old, a total of 20; the mouse depilatory cream brand was Veet (VEET), with a product number of 2888174 and produced in the United Kingdom; the medium wave ultraviolet (UVB) lamp tube was produced by Philips Company, with a product number of TL20W / 12RS; the power of the UVB lamp tube was measured by a UV-AB measuring instrument (TM-213, Tenmars) as 431 μW / cm 2 ; the transdermal water loss measuring instrument brand was ASCH, with a product number of AS-VT100 and produced in Japan; the levels of cytokines TNFα, IL-6 and IL-1β in the skin were detected by ELISA (enzyme-linked immunosorbent assay) kits, which were purchased from Enzyme Immune Company in China, with product numbers of MM-0132M1, MM-0163M1 and MM-0040M1, respectively.

[0074] 2. Experimental methods

[0075] (1) The backs of 20 6-week-old male C57BL6J mice were depilated to expose the back skin;

[0076] (2) After 24 hours of depilation, the mice were placed in a tray of 30 cm (length) x 20 cm (width) x 3 cm (height), and the tray was covered with a wire mesh to limit the vertical movement of the mice;

[0077] (3) The mice were irradiated with a UVB lamp tube at a distance of about 40 cm from the tray, and the dose was 300 mJ / cm 2 , and the irradiation time was about 12 minutes according to the power of the lamp tube;

[0078] (4) The irradiated mice were randomly divided into 4 groups of 5 mice each, and the skin appearance of the mice was observed and photographed immediately after irradiation, 1 day after irradiation, 2 days after irradiation, and 4 days after irradiation, respectively; the transdermal water loss was detected by a transdermal water loss measuring instrument;

[0079] (5) The skin tissues of the mice were taken after euthanasia immediately after irradiation, 1 day after irradiation, 2 days after irradiation, and 4 days after irradiation, respectively, 180 μL of PBS was added to each 20 mg of skin tissue, and homogenization was performed using a vibration ball mill, 4°C, 5,000 rpm centrifugation for 15 minutes, and the supernatant was taken to a new EP tube;

[0080] (6) The levels of TNFα, IL-6 and IL-1β were detected according to the ELISA kit instructions: dilute the standard, set up blank wells (blank control wells without sample and enzyme-labeled reagent, the same for the rest of the steps), standard wells, and sample wells. Add 50 μL of standard to the enzyme-labeled coating plate, and then add 40 μL of sample diluent to the sample well, and then add 10 μL of sample to be tested (the final dilution of the sample is 5 times); after sealing the plate with a sealing film, incubate at 37°C for 30 minutes; dilute the concentrated washing solution 30 times with distilled water and reserve; carefully remove the sealing film, discard the liquid, and shake dry, add enough washing solution to each well, stand for 30 seconds, then discard, repeat 5 times, and pat dry; add 50 μL of enzyme-labeled reagent to each well, except for the blank wells; after sealing the plate with a sealing film, incubate at 37°C for 30 minutes; carefully remove the sealing film, discard the liquid, and shake dry, add enough washing solution to each well, stand for 30 seconds, then discard, repeat 5 times, and pat dry; add 50 μL of color developing agent A to each well, then add 50 μL of color developing agent B, mix gently, incubate at 37°C in the dark for 10 minutes; add 50 μL of stop solution to each well to stop the reaction (at this time the blue color turns yellow); set the blank wells to zero, and measure the absorbance (OD value) of each well at 450 nm wavelength. The measurement should be performed within 15 minutes after adding the stop solution; plot the standard curve on the coordinate paper with the concentration of the standard as the abscissa and the OD value as the ordinate, and according to the OD value of the sample, find the corresponding concentration from the standard curve; multiply by the dilution factor to get the actual concentration of the sample.

[0081] 3. Experimental results

[0082] C57BL6J mice were depilated for 24 hours and then irradiated with a UVB light source (300 mJ / cm 2 ). The skin appearance of mice was observed and photographed at the end of irradiation (Day 0), 1 day after irradiation (Day 1), 2 days after irradiation (Day 2), and 4 days after irradiation (Day 4), respectively. It was found that the mouse skin turned red and the skin vessels dilated 1 day after irradiation, the mouse skin slightly thickened and desquamation appeared 2 days after irradiation, and the mouse skin significantly thickened and edema, with scabbing and desquamation, 4 days after irradiation Figure 1 A and 1B), indicating that the mouse model of solar dermatitis was successfully established.

[0083] Transdermal water loss is an important indicator of epidermal barrier function, so we used a transdermal water meter to detect the transdermal water loss of mice. The results showed that the transdermal water loss of mouse skin significantly increased 4 days after irradiation Figure 1 C), indicating that ultraviolet light caused damage to the epidermal barrier function of mice. In addition, we also detected the levels of inflammatory factors TNFα, IL-6 and IL-1β in the skin tissue of mice by ELISA kit, and found that ultraviolet irradiation caused an increase in inflammatory factors in the skin of mice, especially 1 day after irradiation Figure 1 D-F). The above results showed that the mouse model of solar dermatitis was successfully established, and the model showed damage to the epidermal barrier function and exacerbated inflammation.

[0084] Example 2 H&E staining and immunohistochemical staining of solar dermatitis mouse skin

[0085] 1. Experimental materials

[0086] Mouse skin H&E staining and immunohistochemistry were detected by Servicebio, Cleaved Caspase 3 antibody was produced by Servicebio in Wuhan, with the product number GB11532-100, and the concentration of use was 1:500; Ly6G antibody was produced by Servicebio in Wuhan, with the product number GB11229-100, and the concentration of use was 1:200; K10 (Cytokeratin 10) antibody was produced by Abeam, with the product number ab76318, and the concentration of use was 1:500; Loricrin antibody was produced by Abeam, with the product number ab198994, and the concentration of use was 1:100.

[0087] 2. Experimental method

[0088] Mouse skin H&E staining was performed by Savirus, following the procedure: mouse skin tissue was fixed in 4% paraformaldehyde solution for 48 hours, then dehydrated with 70%, 80%, 90%, 95%, 100% ethanol solution, cleared with xylene, and embedded with wax for 1 hour. Subsequently, the embedded tissue was sectioned into thin slices (4 μm) using a microtome (RM2125 RTS, Leica, Wetzlar, Germany), and adhered to glass slides. After rehydrating with gradient ethanol, the glass slides were stained with hematoxylin for 3 minutes, washed with distilled water, and then stained with 1% eosin solution for 1 minute, followed by dehydration with gradient ethanol, clearing with xylene, and mounting and observation.

[0089] Mouse skin immunohistochemical staining was performed by Savirus, following the procedure: after rehydrating the mouse skin sections, they were placed in 0.01 M citrate buffer (pH 6.0) and heated for 5 minutes for antigen retrieval; after washing with PBS, they were incubated with 5% normal goat serum for 1 hour, then the above-mentioned antibodies were added and incubated at 4°C overnight; after washing with PBS, they were stained with hematoxylin for 3 minutes, washed with distilled water, dehydrated with gradient ethanol, cleared with xylene, and mounted and observed.

[0090] 3. Experimental results

[0091] Mouse skin tissue was taken immediately after UVB irradiation (Day 0), 1 day after irradiation (Day 1), 2 days after irradiation (Day 2), and 4 days after irradiation (Day 4), and subjected to H&E staining and immunohistochemistry. H&E staining showed that the epidermis of the mice gradually thickened after UVB irradiation, with the most significant thickening on the fourth day after irradiation (Figures 1A and 2A). Figure 2 The apoptosis marker Cleaved Caspase-3 (CC-3) increased after UVB irradiation, with the most significant increase on the first and second days after irradiation, indicating that UV irradiation caused apoptosis of keratinocytes in the epidermis (Figures 1B and 2B). Figure 2 The neutrophil marker Ly6G increased significantly on the fourth day after irradiation, indicating that UV irradiation induced inflammation in the skin (Figures 1C and 2C). Figure 2 In addition, the epidermal differentiation markers K10 and Loricrin positive cells increased on the fourth day after irradiation, but the staining was lighter, indicating that the epidermal barrier had not yet returned to normal (Figures 1D and 2D). Figure 2 The above pathological staining results showed that the keratinocyte apoptosis increased, the neutrophils in the skin increased, and the epidermal barrier was damaged in the mouse model of solar dermatitis.

[0092] Example 3. Baicalin formulation improves skin barrier, anti-inflammatory, and antioxidant effects in a mouse model of solar dermatitis

[0093] 1. Experimental materials

[0094] Scutellarin was purchased from MCE, Cat. No. HY-N0751. 50 mg of Scutellarin was dissolved in 75% ethanol solution, and the volume was adjusted to 5 mL to prepare a Scutellarin solution with a concentration of 1% (w / v%). The solution was used for skin administration in mice. The levels of MDA and GSH in the skin were detected by ELISA kits, which were purchased from Enzyme Immunoassay Company in China, Cat. Nos. MM-0897M1 and MM-0661M1, respectively. The other reagents were the same as in Example 1.

[0095] 2. Experimental method

[0096] (1) The dorsal skin of 10 six-week-old male C57BL6J mice was exposed by removing the hair on the back;

[0097] (2) After 24 hours of hair removal, the mice were placed in a tray with a size of 30 cm (length) x 20 cm (width) x 3 cm (height), and the tray was covered with a wire mesh to limit the vertical movement of the mice;

[0098] (3) The mice were irradiated with a UVB lamp tube at a distance of about 40 cm from the tray, and the dose was 300 mJ / cm 2 , and the irradiation time was about 12 minutes according to the power of the lamp;

[0099] (4) The Scutellarin group was applied with the Scutellarin preparation at 0 hour, 12 hours, 24 hours, 36 hours, 48 hours, and 60 hours after irradiation, and the control group was applied with 75% ethanol at the same time points. Each mouse was applied with 100 μL;

[0100] (5) The appearance of the skin of the mice was observed and photographed at the end of irradiation (Day 0), 1 day after irradiation (Day 1), 2 days after irradiation (Day 2), and 3 days after irradiation (Day 3), respectively. The transdermal water loss was measured by a transdermal water loss meter;

[0101] (6) The mice were euthanized on the 3rd day after irradiation, and the skin tissue was taken. The levels of TNFα, IL-6, IL-1β, MDA, and GSH were detected by ELISA kits according to the procedures in Example 1.

[0102] 3. Experimental results

[0103] Mice were exposed to UVB and then treated with either 75% ethanol (control group) or scutellarin (scutellarin group). Skin appearance was observed immediately after irradiation (Day 0), 1 day after irradiation (Day 1), 2 days after irradiation (Day 2), and 3 days after irradiation (Day 3). Compared to the control group (Vehicle mice), mice in the scutellarin group had less skin scaling on day 2 after irradiation, lower skin thickness on day 3, and no scab formation. Figure 3 A) indicates that baicalin can alleviate photodermatitis in mice. Simultaneously, on the 3rd day after irradiation, the transdermal water loss in the baicalin group was significantly less than that in the control group, indicating that baicalin improves skin barrier function. Figure 3 B). Subsequently, the levels of inflammatory factors TNFα, IL-6, and IL-1β in mouse skin tissue were detected using an ELISA kit. The results showed that the levels of these inflammatory factors in the *Scutellaria baicalensis* group were significantly lower than those in the control group, indicating that baicalin inhibited the skin inflammatory response. Figure 3 CE). Furthermore, we further examined malondialdehyde (MDA), an indicator of oxidative stress in mouse skin, and reduced glutathione (GSH), an antioxidant indicator, and found that the MDA level in the baicalin group was significantly lower than that in the control group ( Figure 3 F), while GSH levels were significantly higher than in the control group (F). Figure 3 (G) indicates that baicalin significantly reduces oxidative stress in the skin of mice with a photodermatitis model. These results suggest that baicalin preparations have anti-photodermatitis effects, and its efficacy is related to its ability to improve the skin barrier, its anti-inflammatory properties, and its antioxidant effects.

[0104] Example 4: Baicalin preparation inhibits skin inflammation and improves the epidermal barrier in a mouse model of photodermatitis.

[0105] 1. Experimental materials

[0106] Same as Example 2.

[0107] 2. Experimental Methods

[0108] On the third day after UVB irradiation, the skin of mice in the control group and the baicalin group was subjected to H&E staining and immunohistochemistry, with the specific steps being the same as in Example 2.

[0109] 3. Experimental Results

[0110] Skin tissues from mice in the control group and the baicalin group were collected 3 days after UVB irradiation and subjected to H&E staining and immunohistochemistry. Compared with the control group, the baicalin group mice had lower epidermal thickness ( Figure 4 (A and 4B). There was no significant difference in the number of apoptotic keratinocytes between the two groups of mice, indicating that the baicalin preparation does not affect cell apoptosis. Figure 4A and 4C). The number of neutrophils in the SCU group was significantly less than that in the control group, indicating that the SCU preparation inhibited skin inflammation Figure 4 A and 4D). In addition, the positive signals of the epidermal differentiation markers K10 and Loricrin in the SCU group were significantly stronger than those in the control group, indicating that the SCU preparation improved the epidermal barrier Figure 4 A). In summary, the SCU preparation inhibited skin inflammation and improved the epidermal barrier in the mouse model of solar dermatitis.

[0111] Example 5: SCU and SAL combined synergistic treatment of solar dermatitis

[0112] 1. Experimental materials

[0113] SCU was produced by MCE Company, with item number HY-N0751. 50 mg of SCU was dissolved in 75% ethanol solution, and the volume was made up to 5 mL, which was prepared into a 1% SCU solution (w / v%). SAL was produced by MCE Company, with item number HY-N0109. 50 mg of SAL was dissolved in 75% ethanol solution, and the volume was made up to 5 mL, which was prepared into a 1% SAL solution (w / v%). 50 mg of SCU was dissolved in the above-mentioned 5 mL of 1% SAL solution, which was prepared into a combined administration solution (the mass ratio of the two was 1:1). The MDA and GSH levels in the skin were detected by ELISA (enzyme-linked immunosorbent assay) kit, which was purchased from Enzyme Immune Company in China, with item numbers MM-0897M1 and MM-0661M1, respectively. The remaining reagents were the same as in Example 1.

[0114] 2. Experimental methods

[0115] (1) 24 six-week-old male C57BL6J mice were divided into a control group (Vehicle), a SCU group (SCU), a SAL group (SAL), and a combined administration group (SCU+SAL), with 6 mice in each group. The back of each mouse was shaved to expose the skin.

[0116] (2) After 24 hours of shaving, the mice were placed in a tray with a size of 30 cm (length) x 20 cm (width) x 3 cm (height), and the tray was covered with a wire mesh to limit the vertical movement of the mice;

[0117] (3) The mice were irradiated with a UVB lamp tube at a distance of about 40 cm from the tray, with a dose of 300 mJ / cm 2 , and the irradiation time was about 12 minutes according to the power of the lamp;

[0118] (4) The baicalin group (SCU), rhodioloside group (SAL), and combined drug administration group (SCU+SAL) were treated with the above-mentioned baicalin solution, rhodioloside solution, and combined drug administration solution at 0, 12, 24, 36, 48, and 60 hours after irradiation, respectively. The control group (Vehicle) was treated with 75% ethanol at the same time point after irradiation. Each mouse was treated with 100 μL.

[0119] (5) Observe and photograph the appearance of the mouse skin 3 days after irradiation;

[0120] (6) The mice were euthanized on the 3rd day after irradiation, and skin tissue was taken. The levels of TNFα, IL-6, IL-1β, MDA and GSH were detected by ELISA kit according to the steps in Example 1.

[0121] 3. Experimental Results

[0122] Observation of mouse skin on day 3 after UVB irradiation revealed that, compared with the control group (Vehicle mice), mice in the baicalin group (SCU) and rhodioloside group (SAL) showed no obvious skin damage or crusting, but their skin still exhibited wrinkles and thickening; while the skin of mice in the combined drug administration group was almost completely normal. Figure 5 A) indicates that the combined administration is more effective than the single administration. Subsequently, the levels of inflammatory factors TNFα, IL-6, and IL-1β in mouse skin tissue were detected using an ELISA kit. It was found that the levels of these inflammatory factors in the combined administration group were significantly lower than those in the control group, and also lower than those in the baicalin group and the rhodioloside group (A). Figure 5 (BD), indicating that the combined administration had a better anti-inflammatory effect. Furthermore, by further detecting malondialdehyde (MDA), an indicator of oxidative stress in mouse skin, and reduced glutathione (GSH), an antioxidant indicator, it was found that the GSH level in the combined administration group was significantly higher than that in the control group, and also higher than that in the baicalin group and the rhodioloside group; the MDA level in the combined administration group was significantly lower than that in the control group, and also lower than that in the baicalin group and the rhodioloside group. Figure 5 The results (E and 5F) indicate that the antioxidant effect of the combined administration is superior to that of the single administration. These results suggest that the combined administration is significantly more effective than the single administration in treating photodermatitis.

[0123] To verify whether the combined use of baicalin (SCU) and rhodioloside (SAL) has a synergistic therapeutic effect on photodermatitis, this embodiment further validates the effect using the King's formula and relevant data as follows:

[0124] The Jin's formula is a commonly used calculation formula in the field of pharmacology for quantitatively evaluating the interaction relationship of two drugs in combination, and its core function is to scientifically judge the interaction type of two drugs by comparing the actual combined effect with the theoretical additive effect, and to provide an objective basis for rational drug use and drug combination research and development. Specifically, the Jin's formula: Q = E a+b / (E a +E b -E a ×E b ), wherein E a+b is the inhibition rate of combined drugs, E a and E b are the inhibition rates of A drug and B drug alone, Q is the ratio of the two, Q < 0.85 is antagonistic, 0.85 ≤ Q < 1.15 is additive, and Q ≥ 1.15 is synergistic.

[0125] Figure 5 The TNF-α levels in each group in B are as follows: the control group (C) TNF-α level = 1080 ng / L, the scutellarein group (A) TNF-α level = 1010 ng / L, the rhodioside group (B) TNF-α level = 1010 ng / L, and the scutellarein + rhodioside group (A+B) TNF-α level = 865.6 ng / L; the inhibition rate of scutellarein (A) alone is calculated as E a =[(C-A) / C]×100%=[(1080-1010) / 1080]×100%=6.48%; the inhibition rate of rhodioside (B) alone is calculated as E b =[(C-B) / C]×100%=[(1080-1010) / 1080]×100%=6.48%; the inhibition rate of scutellarein + rhodioside (A+B) combination is calculated as E a+b =[(C-A+B) / C]×100%=[(1080-865.6) / 1080]×100%=19.85%; the Q value is calculated by substituting the Jin's formula: Q = E a+b / (E a +E b -E a ×E b )=19.85% / (6.48%+6.48%-6.48%×6.48%) = 1.58 > 1.15, that is, Q > 1.15, therefore, the combination of scutellarein + rhodioside has a significant synergistic effect on the reduction of inflammatory factor TNF-α in mouse skin tissue;

[0126] Figure 5The levels of each group of IL-1β in C are as follows: control group (C) IL-1β level = 114.1 ng / L, wild jatamansi glycoside group (A) IL-1β level = 103.5 ng / L, rhodioloside group (B) IL-1β level = 102.1 ng / L, wild jatamansi glycoside + rhodioloside group (A+B) IL-1β level = 87.76 ng / L; calculate the inhibition rate of wild jatamansi glycoside (A) alone: E a =[(C-A) / C]x100%=[(114.1-103.5) / 114.1]x100%=9.29%; calculate the inhibition rate of rhodioloside (B) alone: E b =[(C-B) / C]x100%=[(114.1-102.1) / 114.1]x100%=10.52%; calculate the inhibition rate of wild jatamansi glycoside + rhodioloside (A+B) combined: E a+b =[(C-A+B) / C]x100%=[(114.1-87.76) / 114.1]x100%=23.09%; substitute the Jin's formula to calculate Q value: Q=E a+b / (E a +E b -E a x E b )=23.09% / (9.29%+10.52%-9.29% x 10.52%) = 1.23 > 1.15, that is, Q > 1.15, therefore, wild jatamansi glycoside + rhodioloside two drugs combined also have a significant synergistic effect on reducing inflammatory factor IL-1β in mouse skin tissue;

[0127] Figure 5 The levels of each group of MDA in F are as follows: control group (C) MDA level = 10.87 nmol / L, wild jatamansi glycoside group (A) MDA level = 9.72 nmol / L, rhodioloside group (B) MDA level = 9.83 nmol / L, wild jatamansi glycoside + rhodioloside group (A+B) MDA level = 8.37 nmol / L; calculate the inhibition rate of wild jatamansi glycoside (A) alone: E a =[(C-A) / C]x100%=[(10.87-9.72) / 10.87]x100%=10.58%; calculate the inhibition rate of rhodioloside (B) alone: E b =[(C-B) / C]x100%=[(10.87-9.83) / 10.87]x100%=9.57%; calculate the inhibition rate of wild jatamansi glycoside + rhodioloside (A+B) combined: E a+b=[ (C-A+B) / C] x 100% = [ (10.87-8.37) / 10.87] x 100% = 23.00%; Substituting into the Chou-Talalay formula to calculate Q value: Q = E a+b / (E a +E b -E a x E b )= 23.00% / (10.58% + 9.57% - 10.58% x 9.57%) = 1.20 > 1.15, that is, Q > 1.15, therefore, the combination of Scutellariae Radix and Rhodiolosides has a significant synergistic effect on the reduction of MDA, an oxidative stress product, in the skin tissue of mice;

[0128] In summary, the combination of Scutellariae Radix and Rhodiolosides has a significant synergistic effect on the reduction of TNF-α and IL-1β, inflammatory factors, in the skin tissue of the mouse model of solar dermatitis (Q > 1.15), and also has a significant synergistic effect on the reduction of MDA, an oxidative stress product, in the skin tissue of mice (Q > 1.15), that is, the combination of Scutellariae Radix and Rhodiolosides has a significant synergistic effect on the treatment of solar dermatitis, and this synergistic treatment effect is unexpected for those skilled in the art based on the prior art.

[0129] Example 6 Synergistic inhibition of inflammation and improvement of barrier by combined administration of Scutellariae Radix and Rhodiolosides

[0130] 1. Experimental materials

[0131] The same as in Example 2.

[0132] 2. Experimental method

[0133] On the third day after UVB irradiation, the skin of mice in the control group, the Scutellariae Radix group, the Rhodiolosides group, and the combined administration group was subjected to H&E staining and immunohistochemistry, and the specific steps were the same as in Example 2.

[0134] 3. Experimental results

[0135] On the third day after UVB irradiation, the skin tissue of mice in the control group, the Scutellariae Radix group, the Rhodiolosides group, and the combined administration group was subjected to H&E staining and immunohistochemistry. The results showed that the epidermal thickness and the number of neutrophils in the combined administration group were significantly lower than those in the control group, and lower than those in the Scutellariae Radix group and the Rhodiolosides group; while the epidermal differentiation marker K10 in the combined administration group was significantly stronger than that in the control group, and stronger than that in the Scutellariae Radix group and the Rhodiolosides group, indicating that the inflammation inhibition and barrier improvement of the combined administration were better than those of single administration Figure 6 .

Claims

1. The use of baicalin or its pharmaceutically acceptable salt, and rhodioloside or its pharmaceutically acceptable salt in combination in the preparation of a medicament for the treatment and / or prevention of photodermatitis.

2. The application according to claim 1, characterized in that, The mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10); Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:

1.

3. The application according to claim 1, characterized in that, The medicinally usable salt of baicalin is a compound formed by baicalin and the medicinally usable salt; Optionally, the pharmaceutically acceptable salt of rhodioloside is a compound formed by rhodioloside and a pharmaceutically acceptable salt; Optionally, the pharmaceutically acceptable salt is a hydrochloride, sulfate, nitrate, phosphate, acetate, carbonate, maleate, citrate, hydrobromide, tartrate, hydroiodide, bicarbonate, and / or benzoate.

4. The application according to claim 1, characterized in that, The drug also contains pharmaceutically acceptable excipients; Optionally, the excipients include fillers, binders, disintegrants, lubricants, solvents, cosolvents, stabilizers, and / or preservatives.

5. The application according to claim 1, characterized in that, The dosage form of the drug is a topical liquid preparation, a topical semi-solid preparation, a patch, a film, a topical emulsion, a foam, and / or a gel.

6. A combination pharmaceutical composition for treating and / or preventing photodermatitis, characterized in that, The combined pharmaceutical composition comprises baicalin or its pharmaceutically acceptable salt, and rhodioloside or its pharmaceutically acceptable salt; Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10); Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:

1.

7. A pharmaceutical preparation for treating and / or preventing photodermatitis, characterized in that, The pharmaceutical preparation comprises the combination pharmaceutical composition of claim 6.

8. Use of baicalin or its pharmaceutically acceptable salts in the preparation of medicaments for the treatment and / or prevention of photodermatitis.

9. The application according to claim 8, characterized in that, The medicinally usable salt of baicalin is a compound formed by baicalin and the medicinally usable salt; Optionally, the pharmaceutically acceptable salt is a hydrochloride, sulfate, nitrate, phosphate, acetate, carbonate, maleate, citrate, hydrobromide, tartrate, hydroiodide, bicarbonate and / or benzoate. Optionally, the drug may further comprise pharmaceutically acceptable excipients; Optionally, the excipients include fillers, binders, disintegrants, lubricants, solvents, cosolvents, stabilizers and / or preservatives; Optionally, the dosage form of the drug is a topical liquid preparation, a topical semi-solid preparation, a patch, a film, a topical emulsion, a foam, and / or a gel.

10. The use of baicalin or its pharmaceutically acceptable salts, and / or rhodioloside or its pharmaceutically acceptable salts, in the preparation of drugs for inhibiting the levels of inflammatory factors TNFα, IL-6 and / or IL-1β in skin tissue, increasing the level of GSH in skin tissue and / or inhibiting the level of MDA in skin tissue; Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10); Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:1.

Images