Application of baicalin combined with rhodioloside in the treatment of photodermatitis

Abstract

This invention discloses the application of baicalin and rhodioloside in the treatment of photodermatitis. This invention is the first to discover that the combination of baicalin and rhodioloside has a synergistic effect on the treatment of photodermatitis. This invention provides a new and effective drug combination strategy for the treatment of photodermatitis, and provides new ideas for the research and development of anti-photodermatitis drugs, with good application value and industrial transformation prospects.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of baicalin and rhodioloside in the treatment of photodermatitis. Background Technology

[0002] Photodermatitis is an acute inflammatory reaction of the skin caused by excessive exposure to ultraviolet (UV) radiation, primarily caused by UVB. Clinical manifestations include erythema, edema, and burning pain; severe cases may present with blisters, peeling, and even systemic symptoms (such as fever and headache). Long-term, recurrent episodes may increase the risk of skin cancer. Currently, treatments for photodermatitis mainly include topical and systemic medications. Topical medications primarily include corticosteroids (such as hydrocortisone cream and mometasone furoate) and nonsteroidal anti-inflammatory drugs (NSAIDs) (such as flufenamic acid butyl ester ointment); systemic medications primarily include oral corticosteroids (such as prednisone, requiring a doctor's guidance), oral NSAIDs (such as ibuprofen and aspirin), and oral antihistamines (such as loratadine).

[0003] Currently, existing medications for photodermatitis are limited to symptom control (such as relieving redness, swelling, and pain), and their efficacy is singular, failing to simultaneously improve the multiple pathological changes of photodermatitis (such as inflammatory response, skin oxidation, and barrier damage). Furthermore, most existing medications have side effects. For example, long-term use of topical corticosteroids can lead to skin atrophy, telangiectasia, or pigmentation; oral corticosteroids may cause systemic side effects such as immunosuppression. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may cause allergies in some patients, while oral NSAIDs may cause gastrointestinal mucosal damage. Oral antihistamines may cause side effects such as drowsiness, dry mouth, and gastrointestinal discomfort.

[0004] Therefore, there is an urgent need to develop new drugs for the treatment of photodermatitis. Summary of the Invention

[0005] In order to solve the above-mentioned technical problems existing in the field, the purpose of this invention is to provide the application of baicalin and rhodioloside in the treatment of photodermatitis.

[0006] This invention is the first to discover that the combination of baicalin and rhodioloside has a significant synergistic effect in the treatment of photodermatitis. Currently, there are no related studies or reports on the application of the combination of baicalin and rhodioloside in the treatment of photodermatitis.

[0007] The present invention achieves the above-mentioned objectives by adopting the following technical solution:

[0008] The first aspect of the invention provides the use of baicalin or a pharmaceutically acceptable salt thereof, and rhodioloside or a pharmaceutically acceptable salt thereof, in combination in the preparation of a medicament for the treatment and / or prevention of photodermatitis.

[0009] Furthermore, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10);

[0010] Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:1.

[0011] Furthermore, the medicinally usable salt of baicalin is a compound formed by baicalin and the medicinally usable salt;

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

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

[0014] Furthermore, the drug also contains pharmaceutically acceptable excipients;

[0015] Optionally, the excipients include fillers, binders, disintegrants, lubricants, solvents, cosolvents, stabilizers, and / or preservatives.

[0016] Furthermore, 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.

[0017] In this invention, scutellarin (SCU) is a flavonoid substance isolated from Scutellaria baicalensis, with CAS Registry Number 27740-01-8 and molecular formula C. 21 H 18 O 12 With a molecular weight of 462.37, it has the effects of reducing cerebrovascular resistance, improving cerebral blood circulation, increasing cerebral blood flow, and inhibiting platelet aggregation. Clinically, it is used to treat paralysis after cerebrovascular disease. Currently, there are no relevant studies or reports on the application of baicalin in the treatment of photodermatitis. This invention does not impose any particular restrictions on the specific source of the baicalin, and those skilled in the art can obtain it through conventional channels based on the specific information provided above.

[0018] In this invention, salidroside (SAL) is a prolylendopeptidase inhibitor, with CAS Registry Number 10338-51-9 and molecular formula C. 14 H 20O7, with a molecular weight of 300.30, possesses anti-fatigue, anti-aging, anti-hypoxia, anti-tumor, and detoxification effects. It also influences central nervous system neurotransmitters, reducing serotonin levels and bringing them back to normal. This invention does not impose any particular restriction on the specific source of the rhodioloside; those skilled in the art can obtain it through conventional means based on the specific information provided above.

[0019] In this invention, the pharmaceutically acceptable salts of baicalin or rhodioloside refer to pharmaceutically acceptable salts of baicalin or rhodioloside, representing carboxylates, amino acid addition salts, etc., of the compounds of this invention (baicalin or rhodioloside), which are suitable for patient contact within a reliable medical judgment range without producing inappropriate toxicity, irritation, allergic reactions, etc., and are effective for their intended use, in proportion to a reasonable benefit / risk ratio, including (if possible) zwitterionic forms of the compounds of this invention (baicalin or rhodioloside).

[0020] In some embodiments, the medicinal salt of baicalin or the medicinal salt of rhodioloside refers to the medicinal salt of baicalin or rhodioloside prepared by salting modification of baicalin or rhodioloside.

[0021] In some embodiments, the salts used in the salt-forming modification process include, but are not limited to: inorganic acid salts, organic acid salts, organic base salts, metal salts, quaternary ammonium salts, and complex salts.

[0022] The inorganic acid salts include, but are not limited to: hydrochlorides, sulfates, phosphates, nitrates, hydrobroms, hydroiodates, carbonates, bicarbonates, and borates. The organic acid salts include, but are not limited to: acetates, citrates, tartrates, maleates, fumarates, succinates, lactates, malates, benzoates, p-toluenesulfonates, methanesulfonates, and ethanesulfonates. The organic base salts include, but are not limited to: triethylamine salts, diethylamine salts, ethanolamine salts, diethanolamine salts, pyridine salts, piperazine salts, morpholine salts, glycine salts, lysine salts, and arginine salts. The metal salts include, but are not limited to: sodium salts, potassium salts, magnesium salts, and aluminum salts. The complex salts include, but are not limited to: ferrous ammonium sulfate and potassium sodium tartrate.

[0023] In this invention, the salt-forming modification of the compound is a technical means to optimize the physicochemical properties and biological characteristics in drug development. Its core principle is to form stable ionic bonds between molecules through acid-base reactions, transforming the free compound into a salt form with a specific crystal structure, thereby improving the drug's solubility, stability, bioavailability, and formulation suitability. This process requires a systematic crystallization process to achieve controllable preparation of the salt form. The complete process covers six key steps (determining the acidity / basicity and salt-forming sites of the small molecule compound to be salted, selecting the solvent system, salt-forming reaction, crystallization and separation, drying and characterization, and quality control and optimization).

[0024] In some embodiments, those skilled in the art can prepare the corresponding medicinal salts of baicalin or rhodioloside by salting them according to common knowledge in the art. This invention does not specify a particular method for preparing the medicinal salts of baicalin or rhodioloside, and any technical solution that applies baicalin, rhodioloside, medicinal salts of baicalin, and / or medicinal salts of rhodioloside to anti-photodermatitis will fall within the protection scope of this invention.

[0025] In some implementations, the filler, also known as a diluent, is an excipient used to increase the volume or weight of a pharmaceutical preparation. Its main function is to bring the dosage form (such as tablets, powders, or pastes) to a specification that facilitates production, molding, or use (e.g., tablets need sufficient weight for successful compression, and pastes need sufficient volume for uniform application); and to ensure that the active ingredient (baicalin, rhodioloside) is uniformly dispersed in the preparation, avoiding uneven dosage. For example, for topical pastes / ointments, zinc oxide powder, talc, and calcium carbonate can be used (all are inert powders, non-irritating to the skin, and zinc oxide also has astringent and skin-protecting effects, suitable for mild exudative lesions in the acute phase of photodermatitis); for oral adjuvant dosage forms (such as tablets used to regulate the body's immunity), microcrystalline cellulose, lactose, and mannitol can be used (microcrystalline cellulose also has some binding properties, and mannitol has a good taste and is less irritating to the gastrointestinal tract).

[0026] In some implementations, the adhesive is an excipient that enables drug powders or granules to adhere to each other or the formulation to the skin / mucous membrane. Its core function is to ensure the formation of solid dosage forms (such as tablets and granules) and prevent disintegration; and to enable topical patches and gels to adhere stably to the skin surface, ensuring continuous drug penetration (especially suitable for use on exposed areas of photodermatitis, where resistance to friction and sweat is required). For example, pressure-sensitive adhesives (such as acrylate pressure-sensitive adhesives and rubber pressure-sensitive adhesives) can be used for topical patches / gels (core suitable dosage forms), allowing the patch to adhere repeatedly to the skin without leaving residue or irritating damaged skin upon removal; sodium polyacrylate and xanthan gum (gel matrix): have both adhesive and gel-forming functions, strong moisturizing properties, and are suitable for sensitive skin lesions; hydroxypropyl methylcellulose (HPMC) and povidone (PVP) can be used for oral tablets (which form a viscous solution after dissolving in water, enabling powder to bind into granules, and achieving acceptable hardness after compression).

[0027] In some implementations, the disintegrant is an excipient that promotes the rapid disintegration and breakdown of solid dosage forms (such as tablets and capsules) in the body (gastrointestinal tract or skin surface) to release the active ingredient. Its core function is, in oral dosage forms, to accelerate the disintegration of tablets in the gastrointestinal tract, facilitating drug dissolution and absorption; and in topical fast-dissolving films, to promote rapid disintegration of the film upon contact with sweat / moisture on the skin surface, releasing the drug (avoiding film residue that affects skin feel). For example, oral tablets may use crospovidone (PVPP), sodium carboxymethyl starch (CMS-Na), or low-substituted hydroxypropyl cellulose (L-HPC) (which has strong water absorption and swelling capacity, rapidly disrupting the tablet structure and releasing baicalin and rhodioloside); topical fast-dissolving films may use crospovidone carboxymethyl cellulose sodium (CCMC-Na) (which rapidly swells and disintegrates upon contact with moisture on the skin surface without affecting skin permeability).

[0028] In some implementations, the lubricant is an excipient that reduces friction between the drug powder / particles and the production equipment or improves the skin feel of the formulation. Its core function is in solid dosage form production (such as tableting and capsule filling) to prevent powder from adhering to the die, ensuring a smooth tablet surface and smooth forming. In topical formulations, it reduces friction during application and improves skin tolerance (suitable for skin damaged by photodermatitis). For example, magnesium stearate, micronized silica gel, and talc can be used in the production of oral tablets / capsules (magnesium stearate is the most commonly used lubricant, used in small amounts (0.1%-1%) and is non-irritating; micronized silica gel also has a flow-aiding effect, preventing powder from clumping); polyethylene glycol (PEG 400 / 6000) and glycerin (a small amount added can reduce the viscosity of the matrix, making application smoother, while glycerin also has a moisturizing effect, suitable for dry skin lesions) can be used in topical creams / gels.

[0029] In some implementations, the solvent is a liquid excipient used to dissolve or disperse the active ingredients (baicalin, rhodioloside), and is a core component of liquid formulations (solutions, sprays, films). Its function is to form a homogeneous liquid system of the solid active ingredients, facilitating application or spraying; to regulate drug solubility; and to control the drug release rate. For example, topical solutions / sprays may use 75% ethanol, propylene glycol, or polyethylene glycol (PEG 300 / 400) (75% ethanol also has a mild bactericidal effect, while propylene glycol and PEG can improve drug solubility and are less irritating to the skin than pure ethanol); the aqueous phase of creams / gels may use purified water or physiological saline (as the aqueous phase of oil-in-water creams, it dissolves water-soluble excipients and replenishes skin moisture).

[0030] In some implementations, the cosolvent is an excipient that significantly improves the solubility of the active ingredient in a solvent. Its core function is to address the insufficient solubility of baicalin and rhodioloside (with moderate solubility) in a single solvent, preventing solution turbidity or precipitation, ensuring the drug concentration meets standards, and simultaneously improving skin permeability. Examples include propylene glycol and glycerin (which act as both solvents and cosolvents, synergistically improving glycoside solubility with ethanol and possessing strong moisturizing properties); polysorbate 80 (Tween 80); polyoxyethylene castor oil (a nonionic surfactant that reduces surface tension to achieve more uniform glycoside dispersion, suitable for creams and microemulsions, and with low skin irritation); and hydroxypropyl-β-cyclodextrin (HP-β-CD) (a cyclic molecular structure that forms inclusion complexes with glycosides, significantly improving solubility, and possessing good biocompatibility, suitable for sensitive skin).

[0031] In some implementations, the stabilizer is an excipient that prevents the active ingredients (baicalin, rhodioloside) from degrading, oxidizing, or discoloring during storage or use. Its core function is to ensure stable drug potency (glycosides are easily affected by light, high temperature, and oxidation), extend the shelf life of the formulation, and prevent degradation products from irritating the skin (medications for photodermatitis require strict control of impurities). Commonly used stabilizers include antioxidants (vitamin E, sodium bisulfite, tert-butyl-p-hydroxyanisole (BHA), etc.), light stabilizers (titanium dioxide, zinc oxide, etc.), and pH adjusters (citric acid-sodium citrate buffer pairs, sodium dihydrogen phosphate-disodium hydrogen phosphate buffer pairs, 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 drug is formulated as a topical emulsion. The topical emulsion (microemulsion / nanoemulsion) utilizes the small particle size (10-100 nm), high solubility, and strong skin permeability of microemulsions or nanoemulsions to encapsulate two glycosides in emulsion droplets, thereby improving the skin absorption efficiency of the drug (especially suitable for glycosides with slightly weak lipid solubility). At the same time, the emulsion matrix has good moisturizing properties, making it suitable for the treatment of photodermatitis in people with dry and sensitive skin.

[0038] In some embodiments, the drug is in the form of a foaming agent, which is made with a surfactant (such as sodium lauryl sulfate) as a foaming agent and a suitable solvent. When pressed, it produces fine foam. After being applied to the skin lesion, the foam breaks up quickly, and the drug is evenly distributed on the skin surface. It combines the easy absorption of liquid preparations with the moisturizing properties of semi-solid preparations, and is suitable for photodermatitis in folded areas such as the armpits and groin (the foam can penetrate deep into the folds and avoid uneven application).

[0039] In some implementations, the drug is in the form of a gel ointment, which is a common dosage form for external use of traditional Chinese medicine. It uses water-soluble polymer materials (such as sodium polyacrylate) as a base, adds moisturizers such as glycerin and propylene glycol, disperses two glycosides in it, and makes a soft ointment. It is applied to the skin lesion, has strong moisturizing properties, good breathability, and low skin irritation, and is suitable for the treatment of photodermatitis in children or people with sensitive skin.

[0040] A second aspect of the invention provides a combined pharmaceutical composition for treating and / or preventing photodermatitis.

[0041] Furthermore, the combined pharmaceutical composition comprises baicalin or its pharmaceutically acceptable salt, and rhodioloside or its pharmaceutically acceptable salt;

[0042] Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10);

[0043] Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:1.

[0044] A third aspect of the present invention provides a pharmaceutical preparation for treating and / or preventing photodermatitis.

[0045] Furthermore, the pharmaceutical preparation comprises the combination pharmaceutical composition described in the second aspect of the present invention.

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

[0047] A fourth aspect of the invention provides the use of baicalin or its pharmaceutically acceptable salt in the preparation of medicaments for the treatment and / or prevention of photodermatitis.

[0048] Furthermore, the medicinally usable salt of baicalin is a compound formed by baicalin and the medicinally usable salt;

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

[0050] Optionally, the drug may further comprise pharmaceutically acceptable excipients;

[0051] Optionally, the excipients include fillers, binders, disintegrants, lubricants, solvents, cosolvents, stabilizers and / or preservatives;

[0052] 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.

[0053] The fifth aspect of the invention provides the use of baicalin or a pharmaceutically acceptable salt thereof, and / or rhodioloside or a pharmaceutically acceptable salt thereof, in the preparation of medicaments 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;

[0054] Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:(0.1-10);

[0055] Optionally, the mass ratio of baicalin or its medicinal salt to rhodioloside or its medicinal salt is 1:1.

[0056] Furthermore, the present invention also provides a method for treating and / or preventing photodermatitis, the method comprising administering to a subject in need a therapeutic and / or preventative effective amount of baicalin or a pharmaceutically acceptable salt thereof and rhodioloside or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention, a pharmaceutical composition as described in the second aspect of the present invention, or a pharmaceutical preparation as described in the third aspect of the present invention.

[0057] In this invention, the treatment refers to the process of applying the drug (or composition, formulation) of this invention to a subject diagnosed with photodermatitis to relieve symptoms, control disease progression, promote skin lesion healing, and reduce complications. The core objective is to intervene in the existing disease and improve the pathological state, rather than merely preventing its onset. Specifically, this manifests as relieving clinical symptoms, controlling inflammation progression, repairing skin damage, and reducing recurrence and complications.

[0058] In this invention, prevention refers to the process of reducing the probability of developing photodermatitis or alleviating its severity in subjects who have not yet developed it but are at risk of developing it, by pre-administering the drug (or composition, formulation) of this invention. The core objective is to block key steps in the development of the disease, avoiding or weakening the disease, rather than treating existing cases. The target population includes, but is not limited to: individuals with no history of photodermatitis but at high risk, and individuals with a history of photodermatitis.

[0059] In this invention, the effective dose refers to the lowest dose or dose range of baicalin or its pharmaceutically acceptable salts, rhodioloside or its pharmaceutically acceptable salts, pharmaceutical compositions and / or pharmaceutical preparations administered to a subject (e.g., human or laboratory animal) to achieve the expected goal of treating or preventing the occurrence / exacerbation of photodermatitis. The therapeutic effective dose is for existing photodermatitis (such as symptoms like redness, burning, itching, and blisters), requiring rapid symptom relief, reduction of inflammatory response (e.g., lowering skin MDA levels, increasing GSH levels), and promotion of lesion healing; the dose is usually relatively high (to counteract existing inflammation). The preventive effective dose is for pre-existing but risky situations (e.g., impending exposure to strong ultraviolet radiation, or a history of photodermatitis); it requires enhancing skin tolerance to ultraviolet radiation, inhibiting the release of ultraviolet-induced inflammatory factors, and reducing oxidative damage; the dose is usually lower than the therapeutic effective dose (no need to counteract existing inflammation, only preventative protection).

[0060] It should be noted that the effective dose is not a fixed value. Clinicians can make routine adjustments based on the specific circumstances of the subject (the subject's age, weight, skin sensitivity, severity of illness, liver and kidney function, drug dosage form, dosing frequency, drug purity, etc.).

[0061] In some implementations, the subjects include various animal groups, including both human individuals and non-human animals. The specific types of non-human animals can be divided into vertebrates and non-vertebrates: Vertebrates include mammals and non-mammals. Mammals include non-human primates (especially higher primates closely related to humans), livestock such as sheep, pigs, and cattle, pets such as dogs and cats, and rodents commonly used in experimental research (such as mice and rats), guinea pigs, rabbits, and other mammals such as goats; non-mammals include birds such as chickens, amphibians (such as frogs and toads), reptiles (such as lizards and snakes), etc. In specific implementations of this invention, from the perspective of the targeted and practical application of the drug, the subjects are preferably humans.

[0062] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0063] This invention is the first to discover that the combination of baicalin and rhodioloside has a synergistic effect on reducing inflammatory factors TNF-α and IL-1β and oxidative stress product MDA in the skin tissue of mice with photodermatitis. The therapeutic effect of this combined drug composition on photodermatitis is significantly better than that of baicalin or rhodioloside alone. This synergistic therapeutic effect is a technical effect that could not have been expected by those skilled in the art based on existing technology. This invention provides a new and effective drug combination strategy for the treatment of photodermatitis, and provides new ideas for the research and development of anti-photodermatitis drugs, with good application value and industrial transformation prospects. Attached Figure Description

[0064] Figure 1 Figure 1 shows the results of epidermal barrier damage and aggravated inflammatory response in a mouse model of photodermatitis. Figure A shows the skin on the back of mice on days 0, 1, 2, and 4 after UVB irradiation; Figure B shows the redness, thickening, desquamation, and crusting of the mouse skin; Figure C shows the transepidermal water loss (TEWL) of mice at different days after irradiation (n=5 mice per group); Figure D shows the TNFα content in the skin of mice at different days after irradiation (n=5 mice per group); Figure E shows the IL-6 content in the skin of mice at different days after irradiation (n=5 mice per group); Figure F shows the IL-1β content in the skin of mice at different days after irradiation (n=5 mice per group). Data in Figures C and D are expressed as mean ± standard deviation. Statistical analysis was performed using 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 1 shows the results of increased keratinocyte apoptosis, increased neutrophils, and impaired epidermal barrier in a mouse model of photodermatitis. Figure A shows H&E staining and immunohistochemical staining of the dorsal skin of mice on days 0, 1, 2, and 4 after UVB irradiation; scale bar is 50 μm. Figure B shows the relative epidermal thickness at different days after irradiation (n=5 per group). Figure C shows the number of CC3-positive cells in skin sections of mice at different days after irradiation (n=3 per group). Figure D shows the number of Ly6G-positive cells in skin sections of mice at different days after irradiation (n=3 per group). Data in Figures B and D are expressed as mean ± standard deviation. Statistical analysis was performed using 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 1 shows the results of how baicalin preparations improved the skin barrier and inhibited inflammatory response and oxidative stress in a mouse model of photodermatitis. Figure A shows the back skin of mice in the control group and the baicalin group on days 0, 1, 2, and 3 after UVB irradiation; Figure B shows the transepidermal water loss (TEWL) of mice 3 days after irradiation (n=5 per group); Figure C shows the TNFα content in the skin of mice 3 days after irradiation (n=4 per group); Figure D shows the IL-6 content in the skin of mice 3 days after irradiation (n=4 per group); Figure E shows the IL-1β content in the skin of mice 3 days after irradiation (n=4 per group); Figure F shows the MDA content in the skin of mice 3 days after irradiation (n=4 per group); Figure G shows the GSH content in the skin of mice 3 days after irradiation (n=4 per group). Data in Figures B and G are expressed as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA and Dunnett-t test. * indicates P < 0.05, *** indicates P < 0.05. 0.001, **** represents P < 0.0001;

[0067] Figure 4 Figure 1 shows the results of the inhibition of neutrophil infiltration and improvement of epidermal barrier structure in a mouse model of photodermatitis by baicalin preparation. Figure A shows the H&E staining and immunohistochemical staining of the back skin of mice in the control group and the baicalin group on day 3 after UVB irradiation; scale bar is 50 μm. Figure B shows the relative epidermal thickness of mice in the control group and the baicalin group on day 3 after irradiation, with 4 mice in each group. Figure C shows the number of CC-3 positive cells in the skin sections of mice in the control group and the baicalin group on day 3 after irradiation, with 4 mice in each group. Figure D shows the number of Ly6G positive cells in the skin sections of mice on day 3 after irradiation, with 4 mice in each group. Data in B and D are expressed as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA and Dunnett-t test. ** represents P < 0.01, and ns represents no significant difference.

[0068] Figure 5 Figure 1 shows the results of the synergistic improvement of inflammatory response and oxidative stress in a mouse model of photodermatitis by baicalin and rhodioloside. Figure A shows the dorsal skin of mice in each group on day 3 after UVB irradiation; Figure B shows the TNFα content in the skin of mice in each group on day 3 after UVB irradiation; Figure C shows the IL-1β content in the skin of mice on day 3 after UVB irradiation; Figure D shows the IL-6 content in the skin of mice on day 3 after UVB irradiation; Figure E shows the GSH content in the skin of mice on day 3 after UVB irradiation; and Figure F shows the MDA content in the skin of mice on day 3 after UVB irradiation. Data in Figures B and F are expressed as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA and Dunnett-t test. * represents P < 0.05, ** represents P < 0.01, *** represents P < 0.001, and **** represents P < 0.0001.

[0069] Figure 6 The results of the synergistic inhibition of neutrophil infiltration and improvement of the epidermal barrier by baicalin and rhodioloside are shown in the figure. H&E staining and immunohistochemical images of the back skin of mice in each group on day 3 after UVB irradiation; scale bar is 50 μm. Detailed Implementation

[0070] The present invention will be further illustrated below with reference to specific embodiments. These embodiments are for illustrative purposes only and should not be construed as limiting the invention. Those skilled in the art will understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the invention. The scope of the invention is defined by the claims and their equivalents. The experimental consumables, reagents, and raw materials used in this invention are readily available to those skilled in the art and, unless otherwise specified, can be obtained commercially. Experimental methods not specifying specific conditions are generally performed under conventional conditions or according to the manufacturer's recommendations. In particular, the following embodiments are for illustrative purposes only and should not limit the scope of the invention in any way. It should be noted that the experimental conditions and results described in the following embodiments are for illustrative purposes only and should not, and will not, limit the invention as described in detail in the claims.

[0071] Example 1: Construction of a mouse model of photodermatitis

[0072] 1. Experimental Materials

[0073] Twenty male C57BL6J mice, 6 weeks old, were purchased from Nanjing Jicui Pharmaceutical Co., Ltd. The mouse hair removal cream was Veet (product number 2888174), manufactured in the UK. The UVB lamp was from Philips (product number TL20W / 12RS). The UVB lamp power was measured at 431 μW / cm² using a UV-AB measuring instrument (TM-213, Tenmars). 2 The transdermal water loss measuring instrument was branded by ASCH, catalog number AS-VT100, and manufactured in Japan. The levels of cytokines TNFα, IL-6, and IL-1β in the skin were detected by ELISA (enzyme-linked immunosorbent assay) kits, all purchased from an enzyme immunoassay company in China, with catalog numbers MM-0132M1, MM-0163M1, and MM-0040M1, respectively.

[0074] 2. Experimental Methods

[0075] (1) Hair was removed from the backs of 20 six-week-old male C57BL6J mice to expose the skin on their backs;

[0076] (2) 24 hours after hair removal, the mice were placed in a tray measuring 30 cm (length) × 20 cm (width) × 3 cm (height), and the tray was covered with wire mesh to restrict the vertical movement of the mice.

[0077] (3) Irradiate the mice with a UVB lamp at a distance of about 40 cm from the tray, with a dose of 300 mJ / cm. 2 Based on the lamp power mentioned above, the irradiation time is approximately 12 minutes.

[0078] (4) The mice after the above irradiation were randomly divided into 4 groups of 5 mice each. The appearance of the mice skin was observed and photographed immediately after the irradiation, 1 day after the irradiation, 2 days after the irradiation and 4 days after the irradiation. Transdermal water loss was detected using a transdermal water loss meter.

[0079] (5) Skin tissue was collected from mice immediately after irradiation, 1 day after irradiation, 2 days after irradiation and 4 days after irradiation. 180 μL of PBS was added to every 20 mg of skin tissue, and the mixture was homogenized using a vibrating ball mill. The mixture was centrifuged at 5,000 rpm for 15 minutes at 4°C, and the supernatant was transferred to a new EP tube.

[0080] (6) Detect TNFα, IL-6 and IL-1β levels according to the ELISA kit instructions: dilute the standard and set up blank wells (blank control wells without sample and enzyme labeling reagent, and the other steps are the same), standard wells and sample wells. Accurately add 50 μL of standard to the enzyme-labeled plate. Add 40 μL of sample diluent to the sample wells, then add 10 μL of the sample to be tested (final sample dilution is 5-fold). Seal the plate with the sealing film and incubate at 37°C for 30 minutes. Dilute the concentrated wash buffer 30 times with distilled water and set aside. Carefully remove the sealing film, discard the liquid, and shake dry. Fill each well with wash buffer, let stand for 30 seconds, then discard. Repeat this process 5 times, then pat dry. Add 50 μL of enzyme-labeled reagent to each well, except for the blank wells. Seal the plate with the sealing film and incubate at 37°C for 30 minutes. Carefully remove the sealing film, discard the liquid, and shake dry. Fill each well with wash buffer, let stand for 30 seconds, then discard. Repeat this process 5 times, then pat dry. Add 50 μL of chromogenic reagent A to each well, then add 50 μL of chromogenic reagent B, gently vortex to mix, and incubate at 37°C in the dark for 10 minutes. Add 50 μL of stop solution to each well. Add μL of the stop solution to terminate the reaction (the blue color will immediately turn yellow); zero the instrument using the blank well and measure the absorbance (OD value) of each well sequentially at a wavelength of 450 nm. Measurements should be performed within 15 minutes of adding the stop solution; plot a standard curve on graph paper with the concentration of the standard on the x-axis and the OD value on the y-axis. Determine the corresponding concentration of the sample from the standard curve based on its OD value; then multiply by the dilution factor to obtain the actual concentration of the sample.

[0081] 3. Experimental Results

[0082] C57BL6J mice were irradiated with a UVB light source (300 mJ / cm²) 24 hours after hair removal. 2 The appearance of mouse skin was observed and photographed immediately after irradiation (Day 0), 1 day after irradiation (Day 1), 2 days after irradiation (Day 2), and 4 days after irradiation (Day 4). It was found that on day 1 after irradiation, the mouse skin became red and vasodilated; on day 2 after irradiation, the mouse skin was slightly thickened and desquamated; and on day 4 after irradiation, the mouse skin was significantly thickened and edematous, accompanied by crusting and desquamation. Figure 1 (A and 1B) indicates that the mouse model of photodermatitis was successfully established.

[0083] Transdermal water loss is an important indicator of epidermal barrier function; therefore, we used a transdermal water meter to detect transdermal water loss in mice. The results showed that transdermal water loss in mice significantly increased on day 4 after irradiation. Figure 1 (C) This indicates that ultraviolet radiation impairs the epidermal barrier function in mice. Furthermore, we used an ELISA kit to detect the levels of inflammatory factors TNFα, IL-6, and IL-1β in mouse skin tissue, finding that ultraviolet radiation increased these inflammatory factors, especially on day 1 post-irradiation. Figure 1 (DF). The above results indicate that the mouse model of photodermatitis was successfully established, and the model is characterized by impaired epidermal barrier function and exacerbated inflammatory response.

[0084] Example 2: H&E staining and immunohistochemical staining of skin in mice with photodermatitis

[0085] 1. Experimental Materials

[0086] H&E staining and immunohistochemistry of mouse skin were performed by Servicebio. Cleaved Caspase 3 antibody was produced by Servicebio (Wuhan Servicebio Biotechnology Co., Ltd.), catalog number GB11532-100, and the concentration used was 1:500; Ly6G antibody was produced by Servicebio (Wuhan Servicebio Biotechnology Co., Ltd.), catalog number GB11229-100, and the concentration used was 1:200; K10 (Cytokeratin 10) antibody was produced by Abcam (Ab76318), and the concentration used was 1:500; Loricrin antibody was produced by Abcam (Ab198994), and the concentration used was 1:100.

[0087] 2. Experimental Methods

[0088] H&E staining of mouse skin was performed by Sewell, following these steps: Mouse skin tissue was fixed in 4% paraformaldehyde solution for 48 hours, then dehydrated with 70%, 80%, 90%, 95%, and 100% ethanol solutions, cleared with xylene, and then immersed in paraffin for 1 hour. The tissue was then embedded, and the embedded tissue was cut into thin sections (4 μm) using a microtome (RM2125 RTS, Leica, Wetzlar, Germany) and adhered to glass slides. After rehydration with graded ethanol, the slides were stained with hematoxylin for 3 minutes, rinsed with distilled water, stained with 1% eosin solution for 1 minute, then dehydrated with graded ethanol, cleared with xylene, mounted, and observed.

[0089] Immunohistochemical staining of mouse skin was performed by Cellex, and the procedure was as follows: After rehydration, mouse skin sections were placed in 0.01 M citrate buffer (pH 6.0) and heated for 5 minutes for antigen retrieval; after rinsing with PBS, they were incubated with 5% normal goat serum for 1 hour, followed by the addition of the above-mentioned antibody and incubation at 4°C overnight; after washing with PBS, they were stained with hematoxylin for 3 minutes, rinsed with distilled water, dehydrated with graded ethanol, cleared with xylene, mounted and observed.

[0090] 3. Experimental Results

[0091] Skin tissues from mice were collected 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) for H&E staining and immunohistochemistry. H&E staining showed that the epidermis of mice gradually thickened after UVB irradiation, with the most significant thickening occurring on day 4. Figure 2 A and 2B). UVB irradiation increased the apoptosis marker Cleaved Caspase-3 (CC-3), with a significant increase on days 1 and 2 post-irradiation, indicating that UV irradiation induces apoptosis of epidermal keratinocytes. Figure 2 A and 2C). The neutrophil marker Ly6G increased significantly on day 4 after irradiation, indicating that ultraviolet radiation induced skin inflammation. Figure 2 A and 2D). Furthermore, the number of K10 and Loricrin-positive cells increased on day 4 post-irradiation, but the staining was lighter, indicating that the epidermal barrier had not yet returned to normal. Figure 2 A). The above pathological staining results indicate increased keratinocyte apoptosis, increased skin neutrophils, and impaired epidermal barrier in the mouse model of photodermatitis.

[0092] Example 3: Baicalin preparation improves skin barrier function, anti-inflammatory effect, and antioxidant effect in a mouse model of photodermatitis.

[0093] 1. Experimental Materials

[0094] Scutellarin, manufactured by MCE (catalog number HY-N0751), was prepared by dissolving 50 mg of scutellarin in 75% ethanol solution and bringing the volume to 5 mL. This yielded a 1% (w / v) scutellarin solution for skin administration to mice. MDA and GSH levels in the skin were detected using an ELISA (enzyme-linked immunosorbent assay) kit purchased from a Chinese enzyme immunoassay company (catalog numbers MM-0897M1 and MM-0661M1, respectively). All other reagents were the same as in Example 1.

[0095] 2. Experimental Methods

[0096] (1) Hair was removed from the backs of 10 six-week-old male C57BL6J mice to expose the skin on their backs;

[0097] (2) 24 hours after hair removal, the mice were placed in a tray measuring 30 cm (length) × 20 cm (width) × 3 cm (height), and the tray was covered with wire mesh to restrict the vertical movement of the mice.

[0098] (3) Irradiate the mice with a UVB lamp at a distance of about 40 cm from the tray, with a dose of 300 mJ / cm. 2 Based on the lamp power mentioned above, the irradiation time is approximately 12 minutes.

[0099] (4) The scutellarin group was treated with the above-mentioned scutellarin preparation at 0, 12, 24, 36, 48 and 60 hours after irradiation, while the control group was treated with 75% ethanol at the same time points after irradiation. Each mouse was treated with 100 μL.

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

[0101] (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.

[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 ( 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 baicalin group was significantly lower than that in the control group, indicating that the baicalin preparation inhibits skin inflammation (A and 4C). Figure 4 A and 4D). Furthermore, the positive signals of epidermal differentiation markers K10 and Loricrin in the baicalin group were significantly stronger than those in the control group, indicating that the baicalin preparation improves the epidermal barrier (A and 4D). Figure 4 A). In summary, baicalin preparations inhibit skin inflammation and improve the epidermal barrier in a mouse model of photodermatitis.

[0111] Example 5: Synergistic treatment of photodermatitis with a combination of baicalin and rhodioloside.

[0112] 1. Experimental Materials

[0113] Scutellarin (SCU), manufactured by MCE (product number HY-N0751), was prepared by dissolving 50 mg of scutellarin in 75% ethanol solution and bringing the volume to 5 mL to obtain a 1% (w / v) scutellarin solution. Salidroside (SAL), manufactured by MCE (product number HY-N0109), was prepared by dissolving 50 mg of salidroside in 75% ethanol solution and bringing the volume to 5 mL to obtain a 1% (w / v) salidroside solution. 50 mg of scutellarin was then dissolved in the aforementioned 5 mL of the 1% salidroside solution to prepare a combined drug delivery solution (the mass ratio of the two solutions was 1:1). The levels of MDA and GSH in the skin were detected using an ELISA (enzyme-linked immunosorbent assay) kit. The kits were purchased from an enzyme immunoassay company in China, with catalog numbers MM-0897M1 and MM-0661M1, respectively. All other reagents were the same as in Example 1.

[0114] 2. Experimental Methods

[0115] (1) Twenty-four 6-week-old male C57BL6J mice were divided into a control group (Vehicle), a baicalin group (SCU), a rhodioloside group (SAL), and a combined drug administration group (SCU+SAL), with 6 mice in each group. The back hair was removed to expose the back skin.

[0116] (2) 24 hours after hair removal, the mice were placed in a tray measuring 30 cm (length) × 20 cm (width) × 3 cm (height), and the tray was covered with wire mesh to restrict the vertical movement of the mice.

[0117] (3) Irradiate the mice with a UVB lamp at a distance of about 40 cm from the tray, with a dose of 300 mJ / cm. 2 Based on the lamp power mentioned above, the irradiation time is approximately 12 minutes.

[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 King's Law is a commonly used formula in pharmacology for quantitatively evaluating the pharmacodynamic interactions of two drugs used in combination. Its core function is to scientifically determine the type of interaction between the two drugs by comparing the actual combined effect with the theoretical sum of effects, thus providing an objective basis for rational drug use and drug combination development. Specifically, the King's Law formula is: Q=E a+b / (E a +E b -E a ×E b ), where E a+b E represents the inhibition rate of combined medication. a and E b The values ​​represent the inhibition rates of drug A and drug B used alone, respectively. Q is the ratio between the two drugs. Q < 0.85 indicates antagonism, 0.85 ≤ Q < 1.15 indicates additive antagonism, and Q ≥ 1.15 indicates synergistic antagonism.

[0125] Figure 5 The TNF-α levels in each group of B are as follows: Control group (C) TNF-α level = 1080 ng / L, Baicalin group (A) TNF-α level = 1010 ng / L, Rhodioloside group (B) TNF-α level = 1010 ng / L, Baicalin + Rhodioloside group (A+B) TNF-α level = 865.6 ng / L; Calculate the inhibition rate of baicalin (A) alone: ​​E a =[(CA) / C]×100%=[(1080-1010) / 1080]×100%=6.48%; Calculate the inhibition rate of rhodioloside (B) alone: ​​E b =[(CB) / C]×100%=[(1080-1010) / 1080]×100%=6.48%; Calculate the inhibition rate of the combined effect of baicalin and rhodioloside (A+B): E a+b =[(C-A+B) / C]×100%=[(1080-865.6) / 1080]×100%= 19.85%; Substitute into King's formula to calculate Q: 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 baicalin and rhodioloside has a significant synergistic effect on reducing the inflammatory factor TNF-α in mouse skin tissue.

[0126] Figure 5The IL-1β levels in each group of C are as follows: Control group (C) IL-1β level = 114.1 ng / L, Baicalin group (A) IL-1β level = 103.5 ng / L, Rhodioloside group (B) IL-1β level = 102.1 ng / L, Baicalin + Rhodioloside group (A+B) IL-1β level = 87.76 ng / L; Calculate the inhibition rate of baicalin (A) alone: ​​E a =[(CA) / C]×100%=[(114.1-103.5) / 114.1]×100%=9.29%; Calculate the inhibition rate of rhodioloside (B) alone: ​​E b =[(CB) / C]×100%=[(114.1-102.1) / 114.1]×100%=10.52%; Calculate the inhibition rate of the combined effect of baicalin and rhodioloside (A+B): E a+b =[(C-A+B) / C]×100%=[(114.1-87.76) / 114.1]×100%= 23.09%; Substitute into King's formula to calculate Q: Q=E a+b / (E a +E b -E a ×E b = 23.09% / (9.29%+10.52%-9.29%×10.52%) = 1.23>1.15, that is, Q>1.15. Therefore, the combination of baicalin and rhodioloside also has a significant synergistic effect on reducing the inflammatory factor IL-1β in mouse skin tissue.

[0127] Figure 5 The MDA levels in each group in F are as follows: Control group (C) MDA level = 10.87 nmol / L, Baicalin group (A) MDA level = 9.72 nmol / L, Rhodioloside group (B) MDA level = 9.83 nmol / L, Baicalin + Rhodioloside group (A+B) MDA level = 8.37 nmol / L; Calculate the inhibition rate of baicalin (A) alone: ​​E a =[(CA) / C]×100%=[(10.87-9.72) / 10.87]×100%=10.58%; Calculate the inhibition rate of rhodioloside (B) alone: ​​E b =[(CB) / C]×100%=[(10.87-9.83) / 10.87]×100%=9.57%; Calculate the inhibition rate of the combined effect of baicalin and rhodioloside (A+B): E a+b=[(C-A+B) / C]×100%=[(10.87-8.37) / 10.87]×100%= 23.00%; Substitute into King's formula to calculate Q: Q=E a+b / (E a +E b -E a ×E b = 23.00% / (10.58%+9.57%-10.58%×9.57%) = 1.20>1.15, that is, Q>1.15. Therefore, the combination of baicalin and rhodioloside also has a significant synergistic effect on reducing the oxidative stress product MDA in mouse skin tissue.

[0128] In summary, the combination of baicalin and rhodioloside has a significant synergistic effect on reducing inflammatory factors TNF-α and IL-1β in the skin tissue of a mouse model of photodermatitis (Q > 1.15), and also has a significant synergistic effect on reducing the oxidative stress product MDA in the mouse skin tissue (Q > 1.15). That is, the combination of baicalin and rhodioloside has a significant synergistic effect on the treatment of photodermatitis, and this synergistic therapeutic effect is a technical effect that could not have been expected by those skilled in the art based on the existing technology.

[0129] Example 6: Combined administration of baicalin and rhodioloside synergistically inhibits inflammation and improves the skin barrier.

[0130] 1. Experimental Materials

[0131] Same as Example 2.

[0132] 2. Experimental Methods

[0133] On the third day after UVB irradiation, the skin of mice in the control group, baicalin group, rhodioloside group, and combined drug administration group was subjected to H&E staining and immunohistochemistry, with the specific steps being the same as in Example 2.

[0134] 3. Experimental Results

[0135] Skin tissues from mice in the control group, baicalin group, rhodioloside group, and combined treatment group were collected 3 days after UVB irradiation and subjected to H&E staining and immunohistochemistry. Results showed that the epidermal thickness and neutrophil count in the combined treatment group were significantly lower than those in the control group, and also lower than those in the baicalin and rhodioloside groups. However, the epidermal differentiation marker K10 in the combined treatment group was significantly higher than that in the control group, and also higher than those in the baicalin and rhodioloside groups, indicating that the combined treatment had superior anti-inflammatory and barrier-improving effects compared to the single treatment. Figure 6 ).

Claims

1. Use of scutellarein or a pharmaceutically acceptable salt thereof, and rhodioloside or a pharmaceutically acceptable salt thereof in combination for the manufacture of a medicament for treating and / or preventing solar dermatitis. The mass ratio of the scutellarein or a pharmaceutically acceptable salt thereof, and the rhodioloside or a pharmaceutically acceptable salt thereof is 1:

1.

2. Use according to claim 1, characterized in that, The pharmaceutically acceptable salt of the scutellarein is a compound formed by the scutellarein and a pharmaceutically acceptable salt.

3. Use according to claim 2, characterized in that, The pharmaceutically acceptable salt is a hydrochloride, a sulfate, a nitrate, a phosphate, an acetate, a carbonate, a maleate, a citrate, a hydrobromide, a tartrate, a hydroiodide, a bicarbonate, and / or a benzoate.

4. Use according to claim 1, characterized in that, The pharmaceutically acceptable salt of the rhodioloside is a compound formed by the rhodioloside and a pharmaceutically acceptable salt.

5. Use according to claim 4, characterized in that, The pharmaceutically acceptable salt is a hydrochloride, a sulfate, a nitrate, a phosphate, an acetate, a carbonate, a maleate, a citrate, a hydrobromide, a tartrate, a hydroiodide, a bicarbonate, and / or a benzoate.

6. Use according to claim 1, characterized in that, The medicament further comprises a pharmaceutically acceptable excipient.

7. Use according to claim 6, characterized in that, The excipient includes a filler, a binder, a disintegrant, a lubricant, a solvent, a co-solvent, a stabilizer, and / or a preservative.

8. The use according to claim 1, characterized in that, The dosage form of the medicament is an external liquid preparation, an external semisolid preparation, a patch, a film, or a foam.

9. Use according to claim 8, characterized in that, The external semisolid preparation is an external emulsion or a gel ointment.

10. A combined pharmaceutical composition for treating and / or preventing solar dermatitis, characterized by, The combination medicament composition comprises scutellarein or a pharmaceutically acceptable salt thereof, and rhodioloside or a pharmaceutically acceptable salt thereof. The mass ratio of the scutellarein or a pharmaceutically acceptable salt thereof, and the rhodioloside or a pharmaceutically acceptable salt thereof is 1:

1.

11. A pharmaceutical preparation for the treatment and / or prevention of solar dermatitis, characterized in that, The pharmaceutical preparation comprises the combination medicament composition according to claim 10.

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