WO2014187185A1 - Utilisation d'une composition pharmaceutique pour traiter la dermatite et l'eczéma - Google Patents

Utilisation d'une composition pharmaceutique pour traiter la dermatite et l'eczéma Download PDF

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WO2014187185A1
WO2014187185A1 PCT/CN2014/073135 CN2014073135W WO2014187185A1 WO 2014187185 A1 WO2014187185 A1 WO 2014187185A1 CN 2014073135 W CN2014073135 W CN 2014073135W WO 2014187185 A1 WO2014187185 A1 WO 2014187185A1
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oxymatrine
derivative
glycyrrhizic acid
dermatitis
pharmaceutical composition
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PCT/CN2014/073135
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English (en)
Chinese (zh)
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施惠娟
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Shi Huijuan
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • composition as a preparation for the treatment of dermatitis and eczema
  • the invention belongs to the field of medicine and relates to the application of a pharmaceutical composition for preparing and preventing dermatitis and eczema.
  • the pharmaceutical composition comprises a pharmaceutically acceptable form of oxymatrine (oxymatrine, matrine, isomatrine) and glycyrrhizic acid or both, and derivatives thereof, and compositions containing the same
  • the kit further includes a glycyrrhizic acid matrine salt and a glycyrrhizic acid ginseng salt.
  • dermatitis and eczema skin diseases are common diseases in dermatology.
  • the etiology and pathogenesis of dermatitis and eczema are not clear. The cause is quite complicated. Most of them are caused by allergies. It is an allergic reaction caused by the interaction of various internal and external factors. However, some dermatitis and eczema are not related to allergies. Changes in patient reactivity often involve a variety of factors, some of which are unclear and yet to be studied in the future.
  • Genetic factors Some types of eczema are closely related to heredity. Eczema patients often have certain allergies and family history of allergic diseases.
  • Infectious factors some eczema and microbial infections related. These microorganisms include Staphylococcus aureus, Malassezia, airborne fungi such as Alternaria, Fusarium, Penicillium, Aspergillus fumigatus, Fusarium, Penicillium chrysogenum, Aspergillus niger and Rhizopus oryzae.
  • Dietary factors There are many kinds of human foods, which can be generally divided into plants, animals, minerals.
  • eczema chronic gastrointestinal diseases, gastrointestinal dysfunction, malnutrition, chronic alcoholism, intestinal parasites, metabolic disorders, endocrine disorders and other factors are the causes of eczema.
  • the external factors of eczema may be various physical and chemical stimuli, such as eczema induced by sun exposure; cold can make the skin dry and chapped; when hot, the skin is sweaty and easy to be impregnated, and itching and scratching. Excessive use of soap, detergent, etc. in life can damage the barrier function of the skin, lose its protective function, and cause certain irritants or sensitizers to enter the body and cause eczema.
  • Eczema is a delayed type of allergic reaction, and mast cells play a key role in the pathogenesis. Degranulation of mast cells causes classical rapid allergic reactions on the one hand, and eosinophils, chemokines, leukotrienes and arachidonic acid-derived organisms released on the other hand, in 4-8 hours. After infiltrating the polymorphonuclear cells in the original degranulated cells, after 24-48 hours, the polymorphonuclear cells were gradually replaced by mononuclear cell infiltration by the inhibitory factor released by them, and with macrophages. The infiltration of cells and fibroblasts together forms a delayed type of allergic reaction, which causes tissue damage to increase the stress of the mucosa, and is easy to respond to specific and non-specific stimuli, resulting in repeated episodes of eczema.
  • Calcineurin inhibitors These drugs include tacrolimus ointment and pimecrolimus cream, which have good curative effect on dermatitis and eczema, and have strong selective anti-inflammatory effects, which can be relatively long-term. Use it for all affected areas. The adverse reactions were mainly a short-term cauterization and irritation after administration, and no obvious systemic adverse reactions were found, and no adverse reactions of glucocorticoids were observed.
  • Topical antibiotic preparations Since bacteria or fungi can induce or aggravate the condition by producing superantigen or as an allergen, when glucocorticoids are used, especially when exudative skin lesions are treated, early antibiotics are added.
  • Bacterial or antifungal drugs can help control the condition, but should be avoided for long-term use.
  • Antipruritic 5% Doxepin cream or non-steroidal anti-inflammatory drugs can effectively reduce the symptoms of rash in a short period of time, and can be used interchangeably with glucocorticoid preparation or calcineurin inhibitor.
  • Others Depending on the disease and skin lesions, wet compress, zinc oxide oil (paste), tar, black bean distillate, etc. may be selected.
  • drug treatment with systemic treatment (1) antihistamines and cell membrane stabilizers: According to different conditions and medications, first- or second-generation antihistamines can be selected.
  • Anti-infective drugs For patients with severe disease (especially those with exudation) or those who have confirmed secondary bacterial or fungal infections, anti-infective drugs can be given for a short period of time.
  • Glucocorticoids For patients with severe disease, short-term and medium-dose medications can be given. After the condition is improved, the drug should be gradually reduced and stopped in time to avoid adverse reactions caused by long-term use or to stop the drug too quickly and cause the disease to rebound.
  • Allergen-specific desensitization therapy It is a main antigenic substance that cannot be avoided and confirmed or suspected by skin test or other methods, and is made into a certain concentration of leachate, and is injected by gradually increasing the dose and concentration, and repeatedly injecting a specific antigen to the patient to promote the body. Produce the corresponding antibody.
  • Immunosuppressive agents For patients with severe disease and difficult to control conventional therapy, cyclosporine, azathioprine and mycophenolate mofetil may be used as appropriate.
  • anti-leukotriene treatment can be divided into leukotriene antagonist (LTAA) and leukotriene inhibitor.
  • Tranilast Tranilast, glycyrrhizic acid and multivitamins can be used for the treatment of dermatitis and eczema. It is helpful to use interferon for dermatitis and eczema treatment, but it is often necessary to maintain medication for a longer period of time.
  • Chinese medicine treatment According to clinical symptoms and signs, TCM syndrome differentiation and treatment.
  • physical therapy ultraviolet light, phototherapy. There are many treatments mentioned above, but they all have their limitations and adverse reactions.
  • glucocorticoids can cause certain skin adverse reactions (such as skin atrophy, telangiectasia, dilatation, hirsutism, glucocorticoid acne, bacteria). Infection, purpura, etc., long-term extensive external or oral systemic adverse reactions (iatrogenic adrenal insufficiency, Cushing's syndrome, psychotic symptoms, glaucoma, cataracts and menstrual cycle disorders, etc.).
  • Matrine is a potent anti-inflammatory drug with hormone-like effects and no hormonal side effects. Studies have shown that it mainly inhibits leukocyte migration, stabilizes lysosomal membranes, promotes free radical scavenging, and inhibits the synthesis of inflammatory mediators such as histamine and lymphokines. Or release and inhibit inflammatory activity; oxymatrine has strong immunomodulatory effects, can be through the host antibody levels, immune cells The effects of changes, cytokines and other inflammatory regulatory factors exert their anti-inflammatory effects; however, effective extracts of matrine or matrine have side effects such as diuretic sodium in the clinic, which may cause patients with excessive urine output to be unsuitable.
  • Glycyrrhizin has anti-inflammatory, anti-allergic, anti-viral, liver-protecting effects, etc., but the steroid-like effect of glycyrrhizic acid, long-term oral administration of active ingredients extract of licorice or glycyrrhizic acid and its derivatives may cause sodium and water retention in patients. Serious adverse reactions such as high blood pressure and hypokalemia.
  • the present invention provides a novel drug combination which has additive and synergistic effects on dermatitis and eczema and has a lower toxic side effect, and its preparation for the treatment of dermatitis and eczema. Summary of the invention
  • oxymatrine oxymatrine, matrine
  • glycyrrhizic acid or a derivative thereof can provide a particularly beneficial therapeutic effect on dermatitis and eczema without Obvious side effects were observed.
  • This pharmaceutical composition is particularly suitable for the treatment of dermatitis and eczema, including neurodermatitis, eczema (acute, subacute and chronic eczema), atopic dermatitis, seborrheic dermatitis, pruritus, contact dermatitis, urticaria , chronic lichen-like dermatitis, auto-sensitive dermatitis, infectious eczema-like dermatitis, stasis dermatitis, pruritus, nodular pruritus, photoperceptive dermatitis.
  • This pharmaceutical composition can also be combined with existing techniques for treating dermatitis and eczema such as: ultraviolet radiation, red and blue light irradiation, antihistamines and topical ointment applications.
  • the content of oxymatrine or a derivative thereof is 50 to 2000 mg, more preferably 100 to 1500 mg, still more preferably 300 to 1000 mg, and the content of glycyrrhizic acid or a derivative thereof is 30 to 2000 mg, more preferably 30 to 1500 mg, still more preferably 100 ⁇ 1000mg.
  • Simultaneous administration includes administration of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof, or administration of a separate preparation of each active agent substantially simultaneously.
  • Sequential administration refers to administration of oxymatrine or a derivative thereof, glycyrrhizic acid or a derivative thereof according to a clinical treatment schedule in chronological order.
  • the scalar amount of oxymatrine or its derivative and glycyrrhizic acid or its derivative given by the present invention is given with respect to the compound itself, for example, 100 mg of the hydrochloride form of oxymatrine means hydrochloric acid containing 50 mg of oxymatrine. The amount of salt.
  • the active drug is preferably administered in the form of a pharmaceutical composition
  • the composition may include a plurality of drugs or only one drug.
  • the pharmaceutical composition can be prepared according to a conventional pharmaceutical preparation by mixing the above content range of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof in an appropriate amount in a pharmaceutically acceptable form with an acceptable carrier. preparation.
  • Oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof are administered as pharmaceutically active agents, respectively, in pharmaceutically acceptable forms thereof, including pharmaceutically acceptable salts, esters and solvates.
  • the oxymatrine or a derivative thereof of the present invention comprises oxymatrine, oxymatrine, matrine, isoporcine or a pharmaceutically acceptable salt thereof (including hydrochloride, sulfate, acetate, phosphate, Fumarate and various amino acid salts).
  • Glycyrrhizic acid or a derivative thereof includes glycyrrhizic acid, glycyrrhizin, isoglycyrrhizic acid, isoglycyrrhizinate, glycyrrhizinate, etc.
  • glycyrrhizinate includes glycyrrhizin Usable salts, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizin, sodium glycyrrhizinate, potassium glycyrrhizinate and calcium glycyrrhizinate. Also included are the glycyrrhizic acid matrine salt and the glycyrrhizic acid ginseng salt.
  • the pharmaceutical composition may be formulated in a form suitable for oral administration, injection administration, transdermal administration, transmucosal absorption administration or other dosage forms in the form of the above-mentioned mass ratios.
  • the pharmaceutical composition can be prepared into a large or small volume injection, a lyophilized powder, a sterile powder, or the like, or can be a tablet, a capsule, a powder, a dropping pill, a pellet, a granule, a lozenge, In the form of a suppository, oral solution or sterile parenteral solution or suspension, or other dosage forms such as emulsions, ointments and the like.
  • the oral liquid preparation may be in the form of an emulsion, a sugar paddle or the like, or may be present as a dry product, and reconstituted with water or other suitable carrier before use.
  • Excipients include, without limitation, physiologically acceptable pharmaceutically acceptable excipients and pharmaceutically acceptable excipients.
  • the medicinal excipients include one or more of sodium chloride, mannitol, povidone K30, glucose, and lactose, and combinations thereof.
  • compositions of the invention are preferably in a single dosage form.
  • binders such as sugar paddle, gum arabic, gelatin, sorbitol, tragacanth, polyvinylpyrrolidone, hypromellose, dextrin.
  • polyethylene glycol, etc. fillers, such as lactose, sugar, corn starch, calcium phosphate, sorbitol, glycine, etc.; tableting lubricants, such as magnesium stearate, polyethylene glycol, etc.; disintegrating agents, such as starch , polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; pharmaceutically acceptable wetting agent, such as sodium decyl sulfate; suspension agents, such as sorbitol, sugar paddle, methyl cellulose, gelatin , hydroxyethyl cellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated edible ester; etc.; emulsifiers, such as lecithin, sorbitan monooleate, gum arabic, etc.; anhydrous carrier (may include Edible oil), such as almond oil, distilled coconut oil, Or oily esters; preservatives such as methylparaben, propyl ester, sorbic acid, etc.
  • the preparation method employs a preparation method conventional in the art.
  • the two active ingredients can be prepared in unit liquid form, respectively, in a sterile vehicle, and are suspended or dissolved in the carrier depending on the concentration employed.
  • the active ingredient can be dissolved in water for injection and sterilized by filtration, and then poured into a container and sealed for storage.
  • adjuvants commonly used in injections such as preservatives, buffers, pH adjusters, osmo-regulators, solubilizers, stabilizers, antioxidants and the like may be added for intravenous administration.
  • the single-flavor active preparation or the pharmaceutical composition in the pharmaceutical composition can be formulated into a sustained-release preparation such as sustained-release pellets or controlled-release pellets according to a conventional method.
  • the pharmaceutical composition is preferably formulated in unit doses in an amount suitable for the relevant daily dose. It can be administered 1 to 6 times a day, but it is most preferably administered once a day (injection administration) or 3 times (oral administration and external administration).
  • the sum of the contents of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof in the composition may be from 0.1% to 99%, preferably from 1% to 60%, based on the total amount of the administration and the requirements of the preparation.
  • the present invention has proved by a large number of experiments that a pharmaceutical composition of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof has a particularly remarkable effect for treating dermatitis and eczema, and has a lower toxic side effect.
  • a pharmaceutical composition of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof has a particularly remarkable effect for treating dermatitis and eczema, and has a lower toxic side effect.
  • Example 1 Comparison of Acute Toxicity of Oxymatrine, Glycyrrhizic Acid and Their Compositions in Kunming Kunming mice were randomly divided into a normal control group and a test drug group, each group consisting of ten, half male and half female. Except the normal control group, the test group was intraperitoneally injected (ip) with a large dose of oxymatrine, glycyrrhizin, and a combination of the two components once for 7 days, and the death time and number of deaths of the animals were recorded.
  • ip intraperitoneally injected
  • Clinical data The clinical diagnosis is consistent with patients with generalized eczema, and the clinical diagnosis is in accordance with acute wetness.
  • the patients were randomly divided into four groups: oxymatrine treatment group (group A), compound glycyrrhizin treatment group (group B), oxymatrine combined with compound glycyrrhizin treatment group (group C), and control group (D). Group), 10 cases in each group, half male and half female. There were no significant differences in age, gender, and severity of the four groups (P > 0.05).
  • the symptoms and signs of the patients were observed on the day of the first visit and after two weeks of treatment (including itching, erythema, papules, exudation, erosion, infiltration or lichenification, keratinized desquamation, etc.), and each indicator was pressed at each evaluation.
  • Integral value (Total score of the initial diagnosis day - Total of points after 2 weeks of treatment) / Total score of the initial diagnosis day X 100%. Cure: Integral value reduction > 95%; Significant effect: The integral value is reduced by 61% ⁇ 95%; Better: The integral value is reduced by 20 ⁇ 60%; The integral value is reduced by ⁇ 20%.
  • Group A oxymatrine treatment group
  • Group B compound glycyrrhizin treatment group
  • Group C oxymatrine combined with compound glycyrrhizin treatment group
  • Group 0 control group.
  • the oxymatrine and glycyrrhizin are pre-pulverized through an 80 mesh sieve, and the lactose is sieved through an 80 mesh sieve for use.
  • the above-mentioned fine powder which has been sieved is weighed according to the above prescription, and uniformly mixed.
  • the mixed powder is placed in a mixer, and pure water is added while stirring, and stirred for 15 minutes to obtain a soft material, granulation, and wet granules 50 to 60. Dry at °C, whole grain, add sodium hydroxymethyl starch, magnesium stearate, mix and compress, then obtain.
  • a water-soluble solvent is added dropwise under stirring to precipitate a white precipitate; finally, at 50 ° C, respectively.
  • Sodium chloride is stirred and dissolved with water for injection, and then oxymatrine and diamine glycyrrhizinate are separately added, and the stirring is continued to completely dissolve the water for injection to the total amount, filtered to clear, sealed, and sterilized.
  • One of the above ingredients and the above-mentioned auxiliary materials are respectively sieved through an 80 mesh sieve, uniformly mixed, and the povidone is made into a soft material, granulated with a 14-mesh nylon sieve, dried at 50 to 60 ° C, and sieved to a uniform size of 14 mesh, and uniformly mixed. After the tableting is made.
  • Dissolve one of the above ingredients in water add 80g of starch, 20g of sugar powder, add appropriate amount of flavor, mix well, granulate with 14 ⁇ 16 mesh, dry at 60 °C, and package.
  • One of the above components is separately sieved with each of the above-mentioned excipients, and uniformly mixed, and packaged in a hard capsule, that is, obtained.
  • Microcrystalline cellulose, oxymatrine and glycyrrhizin were pre-pulverized through an 80 mesh sieve, and weighed according to the prescription of the pellet 1 and mixed uniformly.
  • the aqueous solution of hydroxypropylmethylcellulose was used as a binder to prepare pellets. Dry at 50 ⁇ 60°C, 20 ⁇ 30 mesh pellets, spare.
  • the prepared and selected pellets are placed in a fluidized bed, and are sprayed by hot air suspension using a bottom spray method.
  • the inlet air temperature is 55 ° C
  • the bed temperature is controlled at 30 ° C, and the peristaltic pump is adjusted.
  • the coating liquid was supplied at a rate of 5 g of the slurry per minute, and the atomization pressure was 2 bar.
  • the flow of the pellet was continuously sprayed. After the nozzle was finished, the air volume was reduced, and the pellet was dried at 40 ° C for a while under a slight boiling state. After taking out, it was dried in an oven at 40 ° C for 24 hours, and the weight gain was about 18%.
  • the aim of this study was to investigate the effects of oxymatrine and glycyrrhizic acid diamine on serum IL-2 and TNF- ct levels in mice with acute dermatitis and eczema, and to explore the mechanism of protecting acute dermatitis and eczema mice.
  • Methods The animal model of acute dermatitis and eczema was replicated by external application of 1% DNFB50ul to stimulate the skin tissue of mice. All mice were evenly coated with l% DNFB10ul on both sides of the right ear and the left ear was coated with an equal amount of 4:1 acetone olive oil. The mixture was administered with different doses of oxymatrine and glycyrrhizic acid diamine.
  • mice After 5 days of experiment, the thickness of the ears of the mice was measured, the redness of the ears was scored, and the thickness of the ears of the mice was measured by electronic digital calipers. Blood was taken from the eyeball, serum was taken after blood coagulation, and serum was taken to determine the contents of IL-2 and TNF-a. Results Oxymatrine, glycyrrhizin diamine, oxymatrine and glycyrrhizic acid diamine could protect acute dermatitis and eczema in mice, and reduce serum IL-2 and TNF- ct levels in mice.
  • mice with acute dermatitis and eczema were treated with 18 ⁇ -glycyrrhizic acid matrine.
  • the animal model of acute dermatitis and eczema was replicated by external application of 1% DNFB50ul to stimulate the skin tissue of mice. All mice were evenly coated with l% DNFB10ul on both sides of the right ear and the left ear was coated with an equal amount of 4:1 acetone olive oil. The mixture was administered with different doses of 18 ⁇ -glycyrrhizic acid matrine.
  • mice After 5 days of experiment, the thickness of the ears of the mice was measured, the redness of the ears was scored, and the thickness of the ears of the mice was measured by electronic digital calipers. Blood, serum was taken after blood coagulation, and serum was taken to determine the contents of IL-2 and TNF-a.
  • 18 ⁇ -glycyrrhizic acid matrine has protective effects on acute dermatitis and eczema in mice, which may improve the inflammatory reaction of skin and decrease the levels of serum IL-2 and TNF-a.
  • Test group 90 19.63 ⁇ 3.71** ⁇ 1.78 ⁇ 0.28 ⁇
  • Example 24 Antagonistic effect of glycyrrhizic acid and oxymatrine complex salt on oxidative stress in a mouse model of chronic dermatitis and eczemaObjective
  • antagonism of glycyrrhizic acid and oxymatrine complex salt on oxidative stress in a mouse model of chronic dermatitis and eczema The mechanism of prevention and treatment of chronic dermatitis and eczema. Methods The mouse model of chronic dermatitis and eczema was replicated by external application of 1% DNFB50ul to stimulate the skin tissue of the abdomen. The mice were treated with different doses of glycyrrhizic acid and oxymatrine compound.
  • mice After 15 days, the serum of the mice was determined by SOD. , MDA, GSH, T-AOC and NO content, and observed the effect of glycyrrhizic acid and oxymatrine complex salt on chronic dermatitis and eczema in mice. Results Glycyrrhizin and oxymatrine complex salts 80, 40 and 20 mg.kg- 1 can all protect acute dermatitis and eczema in mice. Glycyrrhizin and oxymatrine complex salt 80mg/kg can increase chronic dermatitis and eczema.
  • Serum serum SOD and T-AOC content (P ⁇ 0.05, P ⁇ 0.01), decreased MDA, GSH and NO content (PO.Ol); glycyrrhizic acid oxymatrine combined salt 40mg/kg can reduce serum MDA and NO content in mice with chronic dermatitis and eczema (P ⁇ 0.05) , P ⁇ 0.01).
  • the combination of glycyrrhizin and oxymatrine complex salt has protective effect on experimental chronic dermatitis and eczema. This effect may be related to lowering serum MDA, GSH and NO content and increasing SOD and T-AOC content.
  • Clinical data The clinical diagnosis is consistent with patients with generalized neurodermatitis.
  • the clinical diagnosis is consistent with 40 patients with generalized neurodermatitis.
  • There are no serious visceral diseases such as liver and kidney dysfunction, no active tuberculosis, hypertension, diabetes, cataract history, and women who are pregnant or lactating.
  • the patients were randomly divided into four groups: oxymatrine treatment group ( ⁇ group), magnesium isoglycyrrhizinate treatment group ( ⁇ group), oxymatrine combined with magnesium isoglycyrrhizinate treatment group (group C), and control group (group D), each group of ten cases. Both men and women. There were no statistical differences in age, sex, and severity of the four groups ( ⁇ > 0.05).
  • the symptoms and signs of the patients were observed on the day of the first diagnosis and two weeks after the treatment, and each indicator was pressed at each evaluation.
  • Integral value (Total score of the initial diagnosis day - Total points after 2 weeks of treatment) / Total score of the first day of diagnosis is 100%. Cure: Integral value reduction >95%; Significant effect: The integral value is reduced by 61% ⁇ 95%; Improved: The integral value is reduced by 20 ⁇ 60%; The integral value is reduced by ⁇ 20%.
  • Example 26 Oral administration of oxymatrine and glycyrrhizic acid diamine for the treatment of seborrheic dermatitis 1 data and method 1.1
  • Clinical data The clinical diagnosis of 8 patients with seborrheic dermatitis, 4 males and 4 females, aged 25 to 46 years, had no treatment within one month, no serious visceral diseases such as liver and kidney dysfunction, no activity Tuberculosis, hypertension, diabetes, history of cataract, eradication of pregnancy, lactation women. Patients were randomly divided into treatment group and control group: 4 cases in each group, half male and half female. There were no significant differences in age, gender, and severity of disease between the two groups (P > 0.05).
  • Integral value (Total score of the initial diagnosis day - Total of points after 2 weeks of treatment) / Total score of the initial diagnosis day X 100%. Cure: Integral value reduction > 95%; Significant effect: The integral value is reduced by 61% ⁇ 95%; Better: The integral value is reduced by 20 ⁇ 60%; The integral value is reduced by ⁇ 20%.
  • Treatment group 4 1 (50.0) 3(50.0) 100.0 0(00.0) 0(0.0)
  • control group 4 0 (0.0) 1 (25.0) 25.0 1 (25.0) 2 (50.0)
  • Example 27 Oral solution made of oxymatrine and glycyrrhizin for the treatment of stasis dermatitis
  • Clinical data The clinical diagnosis of 20 patients with stasis dermatitis, male and female, aged 20 to 55 years, no systemic treatment within one month, no serious visceral diseases such as liver and kidney dysfunction, no active tuberculosis, hypertension Disease, diabetes, cataract history, eradication of pregnancy, lactating women. Patients were randomly divided into treatment group and control group: 4 cases in each group, male and female. There were no significant differences in age, gender, and severity of disease between the two groups (P > 0.05).
  • Example 28 Capsules made of oxymatrine and glycyrrhizin for treatment of nodular pruritus
  • the treatment group consists of oxymatrine and glycyrrhizin capsules (oxymatrine 0.6g and glycyrrhizin 0.45g) ; levocetirizine capsule 5mg, once a day, treatment for 4 weeks is a
  • the course of treatment is performed after the end of the course of treatment.
  • the symptoms and signs of the patients were observed on the day of the first visit and after 4 weeks of treatment (including itching, erythema, papules, exudation, erosion, infiltration or lichenification, keratinized desquamation, etc.), and each indicator was pressed at each evaluation.
  • Integral value (Total score of the initial diagnosis day - Total of points after 2 weeks of treatment) / Total score of the initial diagnosis day X 100%. Cure: Integral value reduction > 95%; Significant effect: The integral value is reduced by 61% ⁇ 95%; Better: The integral value is reduced by 20 ⁇ 60%; The integral value is reduced by ⁇ 20%.
  • Capsules made of oxymatrine and glycyrrhizin have significant effects in treating nodular pruritus, with an effective rate of 100% and no adverse reactions.
  • Example 29 Combination of oxymatrine and glycyrrhizin for the treatment of progressive pigmentary purpura-like dermatitis
  • Clinical data The clinical diagnosis of 10 patients with progressive pigmentary purpura-like dermatitis, male and female, ages 38 to 60 years old, no systemic treatment within one month, no serious visceral diseases such as liver and kidney dysfunction, no Active tuberculosis, hypertension, diabetes, cataract history.
  • Integral value (Total score of the initial diagnosis day - Total of points after 2 weeks of treatment) / Total score of the initial diagnosis day X 100%. Cure: Integral value reduction > 95%; Significant effect: The integral value is reduced by 61% ⁇ 95%; Better: The integral value is reduced by 20 ⁇ 60%; The integral value is reduced by ⁇ 20%.

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Abstract

L'invention concerne une composition pharmaceutique comprenant de la kushenine et de l'acide glycyrrhizique ou des dérivés de ceux-ci ainsi que l'utilisation de la composition pour préparer un médicament permettant de prévenir et de traiter la dermatite et l'eczéma, le rapport pondéral de la kushenine ou d'un dérivé de celle-ci sur l'acide glycyrrhizique ou un dérivé de celui-ci étant de: 10:1-1:10.
PCT/CN2014/073135 2013-05-20 2014-03-10 Utilisation d'une composition pharmaceutique pour traiter la dermatite et l'eczéma WO2014187185A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112843113A (zh) * 2021-03-23 2021-05-28 南京医科大学 一种用于治疗接触性皮炎的制剂

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105311044B (zh) * 2014-07-18 2019-03-19 施惠娟 一种药物组合物作为制备治疗皮肤血管炎药物中的应用
CN105311043B (zh) * 2014-07-18 2019-03-19 施惠娟 组合物在制备治疗代谢障碍性皮肤病的制备药物中的应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1695624A (zh) * 2004-05-12 2005-11-16 江苏恒瑞医药股份有限公司 含有苦参素和甘草酸的药物组合物及其应用
CN101361790A (zh) * 2008-09-12 2009-02-11 中国人民武装警察部队医学院 治疗皮炎湿疹、蚊虫叮咬所致瘙痒药物及用途
CN101422474A (zh) * 2005-09-28 2009-05-06 江苏正大天晴药业股份有限公司 供静脉用异甘草酸镁制剂在治疗皮肤病中的应用
CN101460158A (zh) * 2006-03-24 2009-06-17 意大利法尔马科特拉皮克研究所公开有限公司 用于治疗和/或预防唇部单纯疱疹感染的局部用喷雾组合物
CN101633683A (zh) * 2008-07-26 2010-01-27 刘力 抗肝炎药物及其制备和用途
CN102614213A (zh) * 2012-02-23 2012-08-01 武汉华纳联合药业有限公司 甘草酸、甘草次酸或其盐的用途及其凝胶组合物和制备方法
CN102772405A (zh) * 2012-08-23 2012-11-14 施惠娟 苦参碱治疗银屑病的新的用途方法
CN102973560A (zh) * 2012-12-03 2013-03-20 施惠娟 苦参碱治疗皮炎湿疹新的用途方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102370697A (zh) * 2011-10-27 2012-03-14 吴克 一种用于急慢性湿疹、皮炎的护理霜

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1695624A (zh) * 2004-05-12 2005-11-16 江苏恒瑞医药股份有限公司 含有苦参素和甘草酸的药物组合物及其应用
CN101422474A (zh) * 2005-09-28 2009-05-06 江苏正大天晴药业股份有限公司 供静脉用异甘草酸镁制剂在治疗皮肤病中的应用
CN101460158A (zh) * 2006-03-24 2009-06-17 意大利法尔马科特拉皮克研究所公开有限公司 用于治疗和/或预防唇部单纯疱疹感染的局部用喷雾组合物
CN101633683A (zh) * 2008-07-26 2010-01-27 刘力 抗肝炎药物及其制备和用途
CN101361790A (zh) * 2008-09-12 2009-02-11 中国人民武装警察部队医学院 治疗皮炎湿疹、蚊虫叮咬所致瘙痒药物及用途
CN102614213A (zh) * 2012-02-23 2012-08-01 武汉华纳联合药业有限公司 甘草酸、甘草次酸或其盐的用途及其凝胶组合物和制备方法
CN102772405A (zh) * 2012-08-23 2012-11-14 施惠娟 苦参碱治疗银屑病的新的用途方法
CN102973560A (zh) * 2012-12-03 2013-03-20 施惠娟 苦参碱治疗皮炎湿疹新的用途方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112843113A (zh) * 2021-03-23 2021-05-28 南京医科大学 一种用于治疗接触性皮炎的制剂

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