CN113813277A - Use of a composition comprising astilbin and/or its isomers in the manufacture of a medicament for the treatment of psoriasis - Google Patents
Use of a composition comprising astilbin and/or its isomers in the manufacture of a medicament for the treatment of psoriasis Download PDFInfo
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Abstract
The invention belongs to the field of natural medicines, and particularly relates to a pharmaceutical composition of astilbin and/or an isomer thereof for treating psoriasis, a preparation and an application thereof, wherein the pharmaceutical composition further comprises polyphenol selected from the following components: one or more of engelhardoside or its isomer, taxifolin, naringenin, quercetin, and resveratrol. The pharmaceutical composition has remarkable treatment effect on the psoriasis-like mouse model and the mouse tail scale model induced by imiquimod, wherein the astilbin and/or isomers thereof and polyphenol in the pharmaceutical composition have remarkable synergistic effect, the effect is better than that of singly using the astilbin, and the pharmaceutical composition is safe and has no adverse reaction, wide application prospect in preparing medicaments for treating psoriasis and important social and economic benefits.
Description
Technical Field
The invention belongs to the field of natural medicines, and particularly relates to a pharmaceutical composition containing astilbin and/or an isomer thereof for treating psoriasis, and a preparation and application thereof.
Background
Psoriasis (Psoriasis), commonly known as Psoriasis, is a chronic, recurrent, inflammatory autoimmune skin disease that is clinically common and mediated by T cells. The clinical manifestations are mainly erythema and hypertrophic white scale which are frequently generated on four limbs, the head and the back of the skin with different shapes and sizes, severe skin damage can be widely generated on the skin of the whole body, hyperpyrexia, pustule, erythroderma-like change and large and small arthrosis of the whole body occur, and psoriasis mainly has lymphocyte infiltration, abnormal hyperplasia of keratinocytes and abnormal secretion of cytokines as the main pathological manifestations. Psoriasis is affected by various factors such as age, sex, race, geographical location, environment, etc., and the prevalence rate of psoriasis varies greatly among people around the world, for example, asian countries such as china and japan have a relatively low prevalence rate as compared with the european and american regions. The disease incidence in China is about 0.47%, and the number of sick people is about 650 thousands. However, according to statistics, the prevalence rate of psoriasis in China tends to rise year by year, and is mostly young and strong. The pathogenesis of psoriasis is not yet determined, and is caused by heredity, immunity, infection and the combined action of various environments. Although the clinical treatment method is wider, the effect is not good enough, the treatment course is long, the repeated treatment is easy, the great stress and pain are caused to the spirit and the body of a patient, the life quality of the patient is seriously influenced, and meanwhile, the heavy burden is caused to the medical care system in China. Therefore, the research on the psoriasis treatment medicine has great scientific significance and social value.
The etiology of psoriasis is currently unknown and it can be activated by a variety of factors, such as trauma, infection, genetics, drugs, environmental factors, etc., which studies suggest is a complex disease caused by the interaction of a variety of genes, immune systems, and environmental factors. The pathophysiological mechanism of psoriasis is very complex, and various treatment methods have more or less certain limitations. For mild psoriasis, local external medicines such as calcipotriol, tretinoin, external glucocorticoid, leflunomide and the like are mainly adopted, while for moderate psoriasis and severe psoriasis, systemic treatment is required, and commonly used systemic treatment medicines include cytotoxic medicines and immunosuppressive medicines such as methotrexate (recommended first-line medicine for moderate and severe plaque psoriasis), glucocorticoid, tacrolimus and the like, and most of the medicines have serious toxic and side effects when the dosage is slightly large and the treatment course is slightly long, so the application is limited. In recent years, monoclonal antibodies and targeted drugs, such as etanercept, adalimumab (anti-TNF- α); secukinumab (anti-IL-17); usunumab (anti-IL-12/IL-23), these drugs are very effective, but are very expensive, not affordable by the salary patients in our country, and present risks of causing infections and malignancies, so that risk gains need to be carefully weighed. Moreover, it has been found that some patients do not respond to the drug during clinical use, or some patients are tolerant to the drug for a period of time.
Therefore, the development of systemic psoriasis treatment drugs with remarkable curative effect, low toxicity and low cost is still urgently needed. In recent years, Chinese medical workers have achieved great achievements in treating psoriasis by using traditional Chinese medicines, and the search of medicines for treating psoriasis from natural sources is considered as an effective way for researching and developing the medicines.
Astilbin and resveratrol have been reported to have the effect of treating psoriasis (see, for example, Zhang Chun hong et al, the influence and mechanism of Astilbin on the proliferation and apoptosis of HaCaT immortalized human keratinocytes, study [ J ] Shandong medicine 2015,55(46): 20-22; Mao Yan Fei et al, experimental study of resveratrol nanoparticles in combination with silk fibroin gel for treating psoriasis [ J ] medicine guide, 2019,12,38(12): 1590-. Through the research of the literature, the related research report that the astilbin and the polyphenol are used for treating the psoriasis in a combined way and generate the synergistic effect is not seen for a while. Chinese patent application 201910056951.3 discloses the application of a composition of astilbin and organic acid in treating psoriasis, but the invention patent technology relates to the combination of astilbin and organic acid, but does not contain active polyphenol ingredients such as engelhardoside and resveratrol.
Disclosure of Invention
The invention aims to solve the defects of the prior art, realize the development and utilization of natural products by adopting a modern pharmaceutical research method, and provide a pharmaceutical composition for treating psoriasis, which contains astilbin and/or isomers thereof and polyphenol with synergistic interaction, and a preparation and application thereof by combining a large amount of pharmacodynamic experiment screening.
Specifically, the invention is realized by the following technical schemes:
in a first aspect, the present invention provides a pharmaceutical composition for the treatment of psoriasis, comprising astilbin and/or its isomers and polyphenols, wherein the weight ratio of astilbin and/or its isomers to polyphenols is 10: 1-1: 10.
alternatively, in the above pharmaceutical composition, the psoriasis is psoriasis vulgaris, erythroderm psoriasis, arthrosis psoriasis, or pustular psoriasis, and the psoriasis is in a progressive, resting, or regressive stage.
Alternatively, in the above pharmaceutical composition, the isomer of astilbin is selected from one or more of neoisoastilbin, isoastilbin or neoastilbin, the polyphenol is selected from one or more of engeletin or its isomer, taxifolin, naringenin, quercetin and resveratrol, and the isomer of engeletin is selected from one or more of isoengeletin, neoengeletin or neoisoengeletin.
The weight ratio of astilbin and/or isomers thereof to polyphenol is 9: 1-1: 9. 8: 1-1: 8. 7: 1-1: 7. 6: 1-1: 6. 5: 1-1: 5. 4: 1-1: 4. 3: 1-1: 3 or 2: 1-1: 2.
alternatively, in the above pharmaceutical composition, the pharmaceutical composition comprises astilbin and isoengeletin; alternatively, astilbin and resveratrol; alternatively, astilbin and naringenin; or; isoastilbin and taxifolin; or astilbin, engeletin and resveratrol; alternatively, astilbin, engeletin and naringenin; or isoastilbin, isoengeletin and taxifolin; or, neoastilbin, resveratrol and taxifolin; alternatively, neoastilbin, quercetin and taxifolin.
Alternatively, in the above pharmaceutical composition, the pharmaceutical composition comprises astilbin in a weight ratio of: isoengeletin ═ 5: 1; alternatively, astilbin: resveratrol ═ 5: 1; alternatively, astilbin: naringenin is 10: 1; alternatively, isoastilbin: taxifolin 10: 1; alternatively, astilbin: engeletin: resveratrol ═ 5:1: 1; alternatively, astilbin: engeletin: naringenin is 5:1: 1; alternatively, isoastilbin: isoengeletin: taxifolin is 5:1: 1; alternatively, new astilbin: resveratrol: taxifolin 10:1: 1; alternatively, neoastilbin: and (3) quercetin: taxifolin 10:1: 1.
in a second aspect, the present invention provides a pharmaceutical formulation for use in the treatment of psoriasis, the pharmaceutical formulation being prepared from a therapeutically effective amount of a pharmaceutical composition according to the first aspect above and a pharmaceutically acceptable carrier.
Alternatively, in the above pharmaceutical preparation, the pharmaceutical preparation is a powder, a tablet, a capsule, a granule, an oral liquid, an injection, a cream, or an ointment.
Preferably, the pharmaceutical formulation is selected from the group consisting of tablets, capsules, granules, creams or ointments.
In a third aspect, the present invention provides the use of a pharmaceutical composition according to the first aspect above or a pharmaceutical formulation according to the second aspect above in the manufacture of a medicament for the treatment of psoriasis.
Alternatively, in the above use, the psoriasis is psoriasis vulgaris, erythroderm psoriasis, joint psoriasis or pustular psoriasis, the psoriasis being in a progressive, quiescent or regressive stage.
Alternatively, in the above use, the medicament inhibits human epidermal keratinocyte hyperproliferation, and the medicament relieves skin inflammatory response, reduces skin damage, and relieves skin erythema, scaling and infiltration.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention is a composition formed by combining natural products, the natural products have synergistic interaction effect in the aspect of treating psoriasis, the drug effect is better than that of the original single component, the combination proportion is further optimized, and better drug effect is realized.
(2) Compared with the prior art, the composition is a composition formed by combining a plurality of natural products, has the characteristic of exerting the drug effect by multiple target points compared with the drugs on the market at present, enhances the pharmacological action and the clinical curative effect, and reduces the toxic and side effect.
(3) Compared with the prior art, the composition is formed by combining a plurality of natural products, has definite chemical components compared with the traditional Chinese medicine extract, can make the formulation of the quality and quantity standard of the medicine and the control of the production quality more targeted, has stable and controllable medicine quality, is convenient for the preparation of various dosage forms, improves the preparation level and the like.
Detailed Description
The inventor of the invention finds that the astilbin and/or the isomer thereof and polyphenol have obvious synergistic effect in the aspect of treating psoriasis for the first time through a large amount of screening in the deep research on the pharmacological mechanism of the astilbin and/or the isomer thereof for treating psoriasis. The present invention has been completed based on this finding.
In order to facilitate the understanding of those skilled in the art, various major active ingredients involved in the present invention will be described below.
Astilbin and engelhardoside belong to flavanonol glycoside compounds, and have the following structures:
astilbin (Astilbin) has the chemical name of (2R,3R)5,7, 3',4' -tetrahydroxydihydroflavonol-3-O-alpha-L-rhamnopyranoside. Astilbin is widely existed in various plants in nature, and 12 families and 15 genera of 26 plants can be separated to obtain astilbin worldwide, which can be used as raw material for extracting astilbin. Astilbin has wide pharmacological activity, and has various pharmacological activities of resisting inflammation, suppressing immunity, suppressing rejection reaction, protecting liver and kidney, resisting oxidation, relieving pain, resisting edema, resisting bacteria, reducing blood sugar, regulating fat metabolism, etc.
The chemical name of Engelitin is (2R,3R)5,7, 4' -trihydroxy dihydroflavonol-3-O-alpha-L-rhamnopyranoside. Engeletin is also widely present in various plants in nature, and has various pharmacological activities of resisting inflammation, resisting cancer, resisting oxidation, treating osteoporosis, protecting liver, treating chronic kidney injury, resisting diabetes, reducing uric acid, etc.
The astilbin isomer refers to the stereoisomerism of astilbin at C-2 and C-3, and has (2R, 3R): astilbin, (2S, 3S): neoastilbin, (2S, 3R): neoisoastilbin, (2R, 3S): isoastilbin, four cis and trans isomers.
The engeletin isomer means that the engeletin has stereoisomerism at C-2 and C-3 positions, (2R, 3R): engeletin, (2S, 3S): neoengelhardoside, (2S, 3R): isoengeletin, (2R, 3S): new isoengeletin.
Taxifolin (Taxifolin), molecular formula C15H12O7(ii) a Molecular weight: 304.25, its chemical name is 3,3',4',5, 7-pentahydroxyflavanone. The taxifolin is a bioflavonoid essence (belonging to vitamin P) extracted from root of Larix gmelinii. The taxifolin is an important natural antioxidant necessary for human body. The taxifolin is found in yew, yellow fir and larch, and the taxifolin is also present in the striated mother tree and the wild cherries in a very small amount. The taxifolin has a special molecular structure of five phenolic hydroxyl groups and can effectively remove free radicals and toxins in a human body, so the taxifolin has broad-spectrum biological activity and pharmacological activity of diminishing inflammation, resisting bacteria, resisting radiation, resisting cancer and viruses, regulating immunity, removing melanin, improving microcirculation and the like, and is a precious raw material for producing foods, medicines and health-care products. The structural formula is as follows:
quercetin (Quercetin), molecular formula C15H10O7(ii) a Molecular weight: 302.236, its chemical name is 3,3',4',5, 7-pentahydroxyflavone. Quercetin belongs to flavonol compounds, has wide plant boundary distribution, has high content in buckwheat stems and leaves, sea buckthorn, hawthorn and onions, and is found in many foods, such as onions, apples, mangoes and the like. In addition, more than 100 kinds of medicinal plants (such as flos Sophorae Immaturus, folium Platycladi, rhizoma Alpiniae Officinarum, flos Farfarae, herba Taxilli, Notoginseng radix, semen Ginkgo, and ramulus Sambuci Williamsii) contain the component. Quercetin is flavonol compound with various biological activities, and can resist free radicals, complex or capture free radicals to prevent lipid peroxidation of organisms; can directly inhibit tumor and effectively play the role of cancer prevention and resistance; has strong biological activity in the aspects of antibiosis, anti-inflammation, anti-allergy and prevention of diabetic complications. In addition, quercetin has effects of lowering blood pressure, enhancing capillary resistance, reducing capillary fragility, reducing blood lipid, dilating coronary artery, and increasing coronary blood flow, and can be used for adjuvant treatment of coronary heart disease and hypertension. Quercetin is non-toxic and, therefore, is effective againstHas important significance for treating and preventing cancer, aging and cardiovascular diseases, and has great development value. The structural formula is as follows:
naringenin (Naringin) with molecular formula C15H12O5(ii) a Molecular weight: 272.25, its chemical name is 4',5, 7-trihydroxyflavanone. Naringenin belongs to flavanone compounds, is present in various herbal medicines and fruits, including grapefruit, bergamot, lime, sour cherry and beans, has the effects of resisting bacteria, resisting inflammation, removing free radicals, resisting oxidation, relieving cough, eliminating phlegm, reducing blood fat, resisting cancer and tumors, relieving spasm, benefiting gallbladder, preventing and treating liver diseases, inhibiting platelet coagulation, resisting atherosclerosis and the like, and can be widely applied to the fields of medicines, foods and the like. The structural formula is as follows:
resveratrol (Resveratrol), formula C14H12O3(ii) a Molecular weight: 228.25, its chemical name is 3,4', 5-trihydroxy-1, 2-diphenylethylene (3,4', 5-stilbenetriol). Resveratrol is a non-flavonoid polyphenolic organic compound and is an antitoxin produced when many plants are stimulated. Resveratrol mainly exists in at least 72 plants of 21 families and 31 genera such as Vitis, Polygonum, Arachis, and Veratrum, and comprises common medicinal plants such as rhizoma Polygoni Cuspidati, semen Cassiae, and mulberry, and crops such as fructus Vitis Viniferae and semen Arachidis Hypogaeae. The main source plants of natural resveratrol are giant knotweed rhizome and grape. Resveratrol has antioxidant, antiinflammatory, antiasthmatic, anticancer, antibacterial, immunoregulatory, and cardiovascular protecting effects. The structural formula is as follows:
as used herein, the various active ingredients in the pharmaceutical compositions of the present invention may be administered in the same pharmaceutical formulation, or may be administered in different pharmaceutical formulations. In the case of administration in different pharmaceutical preparations, the dosage forms of the various active ingredients may be identical or different. Also, the various active ingredients may be administered simultaneously or sequentially.
As used herein, the dosage form of the pharmaceutical preparation of the present invention is powder, tablet, capsule, granule, oral liquid or injection. Preferably, the dosage form of the present invention is a tablet or capsule.
As used herein, the "pharmaceutically acceptable carrier" of the present invention refers to a pharmaceutical carrier conventional in the field of pharmaceutical formulation, and is selected from one or more of fillers, binders, disintegrants, lubricants, suspending agents, wetting agents, pigments, flavoring agents, solvents, and surfactants.
Fillers of the present invention include, but are not limited to, starch, microcrystalline cellulose, sucrose, dextrin, lactose, powdered sugar, glucose, and the like; such lubricants include, but are not limited to, magnesium stearate, stearic acid, sodium chloride, sodium oleate, sodium lauryl sulfate, poloxamers, and the like; such binders include, but are not limited to, water, ethanol, starch slurry, syrup, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, sodium alginate, polyvinylpyrrolidone, and the like; such disintegrants include, but are not limited to, starch effervescent mixtures, i.e., sodium bicarbonate and citric acid, tartaric acid, low substituted hydroxypropylcellulose, and the like; suspending agents include, but are not limited to, polysaccharides such as acacia gum, agar, alginic acid, cellulose ethers, carboxymethyl chitin ester, and the like; including but not limited to water, balanced salt solutions, and the like.
Preferably, the medicament of the present invention can be formulated into various solid oral preparations, liquid oral preparations, and the like. The pharmaceutically acceptable oral solid preparation comprises the following components: powder, common tablet, dispersible tablet, enteric coated tablet, granule, capsule, dripping pill, powder, etc., and oral liquid preparation such as oral liquid, emulsion, etc. Alternatively, the drug of the present invention may be prepared as an injection.
The various dosage forms can be prepared according to the conventional process in the field of pharmaceutical preparation.
As used herein, the various natural product active ingredients of the present invention can be isolated from plants containing the active ingredient by extraction using conventional biological purification methods, or can be purchased from commercially available products.
In the above-mentioned medical applications, the administration time, the administration frequency and the like of each active ingredient are required depending on the specific diagnosis result of the disease state, which is within the technical scope of those skilled in the art. For example, a therapeutic regimen for mice or rats is applied to humans, and the effective dose of all drugs to humans can be converted to the effective dose of the drug to mice or rats, which is also easily accomplished by one of ordinary skill in the art.
The invention is further illustrated with reference to specific examples. It should be understood that the specific embodiments described herein are illustrative only and are not limiting upon the scope of the invention.
The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or instruments used are conventional products which are not known to manufacturers and are available from normal sources.
The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples are all commercially available products unless otherwise specified.
Unless otherwise indicated, all percentages and parts referred to in the present invention are percentages and parts by weight.
Effect embodiment:
1. cell experiments
And (3) culturing the cells: HaCaT cells (HaCaT cells are human immortalized keratinocytes, have proliferation and differentiation characteristics similar to those of keratinocytes, are immortalized, have similarities to the pathological features of hyperproliferation and abnormal differentiation of psoriatic keratinocytes and have been widely used in the research of psoriasis), and are prepared by treating HaCaT cells at 4X 104The solution was inoculated in a prepared DMEM medium at 37 ℃ with 5% CO2And culturing in a cell culture box with saturated humidity. The cells grow adherently, passage begins when the cells grow to cover 80% of the bottom area of the culture flask, and the original culture is poured out during passageAnd (3) culturing the solution, washing the solution for 2 times by using PBS, digesting the solution for 2min by using 0.25% trypsin, removing the trypsin, standing the solution, continuing to digest the solution to cause the cells to shrink and become round, adding a new DMEM culture medium to blow the cells when the cells gradually fall off from the culture bottle, counting the cells, transferring the cells with a certain concentration into a new culture dish, and adding 7mL of the culture medium. Recovering the HaCaT cell strain, preparing a complete growth medium (90% DMEM + 10% FBS), allowing the cell strain to pass by about 80%, taking out the medium, washing twice with calcium-magnesium-free PBS, and adding 1mL of trypsin-EDTA solution. The flask was allowed to stand at 37 ℃ for about 5min until the cells were separated. Adding fresh culture medium with the amount of 3 times of trypsin, blowing and collecting the mixture into a 15mL centrifuge tube, centrifuging the mixture for 5min at 1200r/min, discarding supernatant, re-suspending the cells by using fresh culture medium, washing the cells for 2 times, finally suspending the cells by using 1mL culture medium and counting the cells, and performing amplification culture, wherein the subculture ratio is 1: 3. The culture conditions are as follows: 37 deg.C, 95% air, 5% CO2。
Dissolving tretinoin in DMSO to obtain 125 μmol/L solution, which comprises astilbin, new astilbin, engelhardin, taxifolin, resveratrol, naringenin, quercetin, astilbin + isoengelhardin (5:1), astilbin + resveratrol (5:1), astilbin + naringenin (10:1), isoastilbin + taxifolin (10:1), and flavone composition 1: astilbin + engelhardoside + resveratrol (5:1:1), astilbin + engelhardin + naringenin (5:1:1), flavone composition 2 group: the isoastilbin, the isoengelhardoside, the taxifolin (5:1:1), the neoastilbin, the resveratrol, the taxifolin (10:1:1), the neoisoastilbin, the quercetin and the taxifolin (10:1:1) are dissolved by DMSO to prepare a solution of 100 mu mol/L.
When the cells grow to logarithmic phase, they are digested and counted at 4.0X 104one/mL of the cells were inoculated into a 96-well plate (marginal wells filled with sterile PBS), 100. mu.L per well, incubated at 37 ℃ with 5% CO2Saturated humidity CO2Incubate for 24h (overnight). Adding the corresponding concentration of each drug after the cells adhere to the wall, and continuously adding CO2Culturing in an incubator for the required time, and performing MTT detection. Adding MTT (5g/L) 20. mu.L/well into 96-well plate cell culture, incubating for 4h, carefully sucking off supernatant, adding DMSO 100. mu.L/well, and shaking for 10min to dissolve crystals sufficientlyThe absorbance of each well was measured at a wavelength of 492nm using a microplate reader.
Table 1: comparison of cell proliferation inhibition ratios (x. + -. s) of the respective groups
Note that: in comparison with the blank set, the results,#p is less than 0.01; p <0.05 compared to positive control.
The comparison of the cell proliferation inhibition rates of all groups can be seen in table 1, the single components show cell proliferation inhibition activities of different degrees, and the cell proliferation inhibition activities are remarkably different from those of a blank control group (P <0.01), wherein the astilbin activity is the best, the cell proliferation inhibition activities of the binary combination of the astilbin or isomers thereof and each single component in the polyphenol component are superior to those of the single components and are superior to those of retinoic acid in a positive control, and the combined synergistic effect is embodied.
The ternary composition of astilbin or isomers thereof and polyphenol components has the best cell proliferation inhibition activity, the difference of a positive control group has statistical significance (P <0.05), the ternary compositions show similar combination synergism effect which is better than that of a single component, and the combination synergism effect of the ternary composition is better than that of a related binary composition. It is further shown that the composition formed by the astilbin or the isomer thereof and the polyphenol component produces similar combined synergistic effect.
2. Animal experiments
2.1 imiquimod-induced psoriasis-like model in mice:
before the experiment, 60 male mice of 18-22g Balb/c are anesthetized by pentobarbital sodium intraperitoneal injection (80 mg/kg), the backs of the male mice are unhaired, the skin is exposed to be smooth in the size of about 2cm multiplied by 2cm, and the male mice are raised in a single cage. Randomly dividing into astilbin group, engelhardoside group, resveratrol group and flavone composition 1 group: astilbin: engeletin: resveratrol (5:1:1), flavone composition 2 groups: isoastilbin: isoengeletin: taxifolin (5:1:1), positive drug (tripterygium glycosides tablet) control group and blank control group, 10 of each group. .
The control group of mice is coated with vaseline on the back every day, purified water is used for intragastric administration, and the backs of the other groups of mice are coated with 42mg of imiquimod cream 5% every day. The administration group is administered with purified water for intragastric administration, the flavone composition group 1, the flavone composition group 2, astilbin group, engelhardin group, resveratrol group respectively administered with 25mg/kg corresponding solution for intragastric administration 0.2 mL/time and 2 times/day, and the positive control group administered with 10mg/kg tripterygium wilfordii multioxib tablet solution for intragastric administration 0.2 mL/time and 2 times/day. After 7 days of molding, 80% of mice have red swelling and even skin damage, and the molding is successful. The day of molding is the same as the day of continuous 7 days, and the materials are taken on the 8 th day.
The experimental results are as follows: compared with the normal control group, the ear part of the model control group is red and swollen, the skin damage is serious, a part of scale is covered, and the severity of the skin damage (PASI) is scored. The erythema, scaling and infiltration thickening were each 0-4(0, none; 1, mild; 2, moderate; 3, severe; 4, very severe), and the total score was obtained by summing up the 3 scores, and the results are shown in Table 2.
Table 2: effect of the compositions of the present invention on the degree of skin lesion change in psoriasis-like mice (x. + -.s, n ═ 10)
Note that: in comparison with the blank set, the results,##p is less than 0.01; p <0.01 compared to model group.
And (4) experimental conclusion: as can be seen from Table 2, the model control group has significant difference (P <0.01) from the normal control group, compared with the model control group, the astilbin group, the engelhardin group, the resveratrol group, the flavone composition 1 group and the flavone composition 2 group can effectively relieve psoriasis-like lesion of mice induced by imiquimod, improve pathological forms of red swelling, skin damage and the like of the ears of the mice, and the PASI score of the mice is significantly reduced (P <0.01), wherein the flavone composition 1 group and the flavone composition 2 group have optimal drug effects and are superior to a single group and a positive control group.
2.2 mouse tail scale model:
mouse tail scale model: the rat tail scales lack the granular layer due to normal cornification of the epidermis, and the natural cornification is similar to the human psoriasis epidermis, so the rat tail scales can simulate the characteristics of psoriasis parakeratosis. The model can be used to evaluate the effect of a drug in promoting the formation of the stratum granulosum, and the drug is considered to have an anti-psoriasis effect if the drug can promote the formation of the stratum granulosum of the rat tail.
60 mice with the weight of 18-22g Balb/c are taken, and the weight is half of that of the male and female mice. Randomly divided into astilbin group, engelhardin group, resveratrol group, flavone composition 1 group (astilbin: engelhardin: resveratrol: 5:1:1), flavone composition 2 group (isoastilbin: isoengelhardin: taxifolin: 5:1:1), positive drug control group and blank control group, each group contains 10. The flavone composition group 1, the flavone composition group 2, the astilbin group and the engelhardoside group are respectively administrated with 25mg/kg corresponding solution for intragastric administration for 0.2 mL/time and 2 times/day, and the blank control group is administrated with the same volume of normal saline for 14 days continuously. Mice were sacrificed 24 hours after the last administration, dorsal epidermis about 1.5cm from the tail root was taken, and subjected to conventional tissue sectioning, HE staining, changes in the horny layer, the granular layer, the spinous cell layer, the basal cell layer, the dermal layer, the hair follicle and the like of the skin of the tail were observed under an optical microscope, and the number of scales having granular layers formed among 100 scales was counted (the number of scales having granular layers was counted when the scales epidermis having granular layers arranged in a line between two follicle mouths was counted as having granular layers), to calculate the number of scales having granular layers.
Table 3: comparison of the formation of epidermal particle layer of tail scales in each group of mice (x. + -. s, n ═ 10)
Note that: compared with the blank control group, the composition of the composition,△△P<0.01。
as can be seen from Table 3, the administered group has significant difference (P <0.01) from the blank control group, wherein, the number of scales with granular layer is the most in the flavone composition 1 group and the flavone composition 2 group, which is equivalent to the positive control tripterygium glycosides group. Experimental results show that the astilbin group, the engelhardin group, the resveratrol group, the flavone composition group 1 and the flavone composition group 2 have obvious promotion effects on the formation of the epidermal granular layer of the scales of the rat tail, and the scale number of the granular layer is increased remarkably, so that the astilbin group, the engelhardin group, the resveratrol group, the flavone composition group 1 and the flavone composition group 2 can have treatment effects on psoriasis models, and the treatment effects of the flavone composition group 1 and the flavone composition group 2 are superior to those of the single group.
In addition, in the animal experiments, no obvious adverse reaction exists in the pharmaceutical composition disclosed by the invention, and the experimental animals have good tolerance to the pharmaceutical composition.
Formulation examples:
example 1:
15g of astilbin and 3g of engelhardoside; 75g of microcrystalline cellulose; 50mL of 95% ethanol; 15g of hydroxypropyl cellulose; 120mL of 25% starch slurry; 5g of magnesium stearate, granulating, drying in vacuum at 50 ℃, granulating by using a 30-100-mesh sieve, and pressing into tablets.
Example 2:
15g of astilbin, 3g of engelhardoside and 3g of resveratrol; 75g of microcrystalline cellulose; 50mL of 95% ethanol; 15g of hydroxypropyl cellulose; 120mL of 20% starch slurry; 5g of magnesium stearate, granulating, drying in vacuum at 50 ℃, granulating by using a 60-100-mesh sieve, and filling into capsules.
Example 3:
15g of astilbin, 5g of isoastilbin, 3g of engelhardoside and 3g of resveratrol; 20g of dextrin; 10g of lactose and 120mL of 25% starch slurry; 20g of powdered sugar; granulating with 100 mesh sieve, drying at 50 deg.C, grading with 14 mesh sieve, and packaging.
Example 4:
15g of neoastilbin, 3g of quercetin and 3g of taxifolin; 10g of glyceryl monostearate, 9g of liquid paraffin, 6g of white vaseline, 2g of azone, span-806 g, 2g of sodium dodecyl sulfate, 16g of glycerol and 50g of purified water; dissolving in water bath at 80 deg.C under 500r/min, mixing, stirring for 15min, and cooling to room temperature to obtain ointment.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (10)
1. A pharmaceutical composition for treating psoriasis, comprising: the pharmaceutical composition comprises astilbin and/or isomers thereof and polyphenol, wherein the weight ratio of the astilbin and/or isomers thereof to the polyphenol is 10: 1-1: 10.
2. the pharmaceutical composition of claim 1, wherein: the psoriasis is psoriasis vulgaris, erythrodermic psoriasis, arthrosis or pustular psoriasis, and the psoriasis is in a progressive stage, a resting stage or a regressive stage.
3. The pharmaceutical composition according to claim 1 or claim 2, wherein: the isomer of astilbin is selected from one or more of new isoastilbin, isoastilbin or new astilbin, the polyphenol is selected from one or more of engeletin or isomer thereof, taxifolin, naringenin, quercetin and resveratrol, the isomer of engeletin is selected from one or more of isoengeletin, new engeletin or new isoengeletin, and the weight ratio of astilbin and/or isomer thereof to polyphenol is 9: 1-1: 9. 8: 1-1: 8. 7: 1-1: 7. 6: 1-1: 6. 5: 1-1: 5. 4: 1-1: 4. 3: 1-1: 3 or 2: 1-1: 2.
4. the pharmaceutical composition according to any one of claims 1 to 3, characterized in that: the pharmaceutical composition comprises astilbin and isoengeletin; alternatively, astilbin and resveratrol; alternatively, astilbin and naringenin; or; isoastilbin and taxifolin; or astilbin, engeletin and resveratrol; alternatively, astilbin, engeletin and naringenin; or isoastilbin, isoengeletin and taxifolin; or, neoastilbin, resveratrol and taxifolin; alternatively, neoastilbin, quercetin and taxifolin.
5. The pharmaceutical composition according to any one of claims 1 to 4, characterized in that: the pharmaceutical composition comprises astilbin in a weight ratio: isoengeletin ═ 5: 1; alternatively, astilbin: resveratrol ═ 5: 1; alternatively, astilbin: naringenin is 10: 1; alternatively, isoastilbin: taxifolin 10: 1; alternatively, astilbin: engeletin: resveratrol ═ 5:1: 1; alternatively, astilbin: engeletin: naringenin is 5:1: 1; alternatively, isoastilbin: isoengeletin: taxifolin is 5:1: 1; alternatively, new astilbin: resveratrol: taxifolin 10:1: 1; alternatively, neoastilbin: and (3) quercetin: taxifolin 10:1: 1.
6. a pharmaceutical formulation for treating psoriasis characterized by: the pharmaceutical formulation is made from a therapeutically effective amount of the pharmaceutical composition of any one of claims 1 to 5 and a pharmaceutically acceptable carrier.
7. The pharmaceutical formulation of claim 6, wherein: the pharmaceutical preparation is powder, tablets, capsules, granules, oral liquid, injection, cream or ointment.
8. Use of a pharmaceutical composition according to any one of claims 1 to 5 or a pharmaceutical formulation according to claim 6 or claim 7 in the manufacture of a medicament for the treatment of psoriasis.
9. Use according to claim 8, characterized in that: the psoriasis is psoriasis vulgaris, erythrodermic psoriasis, arthrosis or pustular psoriasis, and the psoriasis is in a progressive stage, a resting stage or a regressive stage.
10. Use according to claim 8 or claim 9, characterized in that: the medicine can inhibit excessive proliferation of human epidermal keratinocyte, relieve skin inflammatory reaction, reduce skin damage degree, and relieve erythema, scale and infiltration of skin.
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| CN202111217645.7A CN113813277A (en) | 2021-10-19 | 2021-10-19 | Use of a composition comprising astilbin and/or its isomers in the manufacture of a medicament for the treatment of psoriasis |
| PCT/CN2021/126302 WO2023065376A1 (en) | 2021-10-19 | 2021-10-26 | Use of composition comprising astilbin and/or isomer thereof in preparation of drug for treating psoriasis |
| AU2021469614A AU2021469614A1 (en) | 2021-10-19 | 2021-10-26 | Use of composition comprising astilbin and/or isomer thereof in preparation of drug for treating psoriasis |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114588147A (en) * | 2022-02-25 | 2022-06-07 | 北京大学深圳医院 | Application of eriodictyol in preventing or treating psoriasis |
| CN114699418A (en) * | 2022-04-02 | 2022-07-05 | 遵义医科大学 | Application of rutin in treating psoriasis |
| CN114869902A (en) * | 2022-05-09 | 2022-08-09 | 黑龙江中医药大学 | Pharmaceutical composition containing tretinoin and geniposide for treating psoriasis |
| IT202200009791A1 (en) * | 2022-05-12 | 2023-11-12 | Innbiotec Pharma S R L | PHARMACEUTICAL COMPOSITION BASED ON GLUTATHIONE AND OLEUROPEIN FOR USE IN THE TREATMENT OF PSORIASIS |
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| CN104208086A (en) * | 2013-06-04 | 2014-12-17 | 广州中医药大学第二附属医院 | Application of astilbin or homolog thereof in preparation of drugs for treating psoriasis |
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| US20030152588A1 (en) * | 2002-01-14 | 2003-08-14 | Hsu-Shan Huang | Chinese traditional medicines for psoriasis |
| CN103463531B (en) * | 2013-09-27 | 2015-03-11 | 张清峰 | Use of rhizoma smilacis glabrae extract in preparation of lipid-lowering and fat-reducing medicines and health-care foods |
| CN105891404A (en) * | 2015-01-18 | 2016-08-24 | 广东省中医院 | Quality control method for traditional Chinese medicine oral liquid for treating psoriasis |
| CN106389453B (en) * | 2015-05-25 | 2019-12-27 | 蔡世珍 | Flavone glycoside composition |
| CN111450107B (en) * | 2019-01-22 | 2021-03-16 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | Application of astilbin organic acid composition in treating psoriasis |
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- 2021-10-26 AU AU2021469614A patent/AU2021469614A1/en active Pending
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| CN104208086A (en) * | 2013-06-04 | 2014-12-17 | 广州中医药大学第二附属医院 | Application of astilbin or homolog thereof in preparation of drugs for treating psoriasis |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114588147A (en) * | 2022-02-25 | 2022-06-07 | 北京大学深圳医院 | Application of eriodictyol in preventing or treating psoriasis |
| CN114699418A (en) * | 2022-04-02 | 2022-07-05 | 遵义医科大学 | Application of rutin in treating psoriasis |
| CN114869902A (en) * | 2022-05-09 | 2022-08-09 | 黑龙江中医药大学 | Pharmaceutical composition containing tretinoin and geniposide for treating psoriasis |
| IT202200009791A1 (en) * | 2022-05-12 | 2023-11-12 | Innbiotec Pharma S R L | PHARMACEUTICAL COMPOSITION BASED ON GLUTATHIONE AND OLEUROPEIN FOR USE IN THE TREATMENT OF PSORIASIS |
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| AU2021469614A1 (en) | 2024-05-02 |
| WO2023065376A1 (en) | 2023-04-27 |
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