WO2014187186A1 - Utilisation d'une composition pharmaceutique comprenant de la kushenine et de l'acide glycyrrhizique pour traiter le psoriasis - Google Patents

Utilisation d'une composition pharmaceutique comprenant de la kushenine et de l'acide glycyrrhizique pour traiter le psoriasis Download PDF

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WO2014187186A1
WO2014187186A1 PCT/CN2014/073137 CN2014073137W WO2014187186A1 WO 2014187186 A1 WO2014187186 A1 WO 2014187186A1 CN 2014073137 W CN2014073137 W CN 2014073137W WO 2014187186 A1 WO2014187186 A1 WO 2014187186A1
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oxymatrine
glycyrrhizic acid
derivative
psoriasis
treatment
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PCT/CN2014/073137
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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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61P17/06—Antipsoriatics

Definitions

  • the invention belongs to the field of medicine and relates to the use of a pharmaceutical composition for the preparation of a prophylactic and therapeutic psoriasis.
  • 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 Kit, in addition to glycyrrhizic acid salt and glycyrrhizin
  • Psoriasis is a common disease in dermatology, and it is a frequently-occurring disease. There is currently no ideal drug for treating this disease. The etiology and pathogenesis of psoriasis are unclear. It is generally believed that psoriasis is a multi-gene genetic disease in which multiple factors interact, and finally the keratinocytes proliferate through the immune-mediated common pathway. Psoriasis is generally thought to be associated with genetics, immunity, infection, regulation of proliferation and differentiation of keratinocytes, endocrine, neuropsychiatric factors, metabolic disorders, microcirculation, and hemorheology. The onset of psoriasis is associated with bacterial, fungal and viral infections.
  • keratinocyte proliferation in the basal layer of the epidermis.
  • the mitotic cycle is shortened to 37.5 hours.
  • the epidermal turnover time is shortened from normal skin to 28 days to 3-4 days.
  • Histopathological keratinization, keratin formation The cells are in a proliferating state. Lymphocyte and monocyte infiltration in psoriatic lesions is an important pathological feature of psoriasis, indicating that the immune system is involved in the development of the disease.
  • the onset of psoriasis is associated with bacterial, fungal and viral infections.
  • the drugs and methods for treating psoriasis mainly include: 1. Anti-tumor drugs
  • Methotrexate is a folate reductase inhibitor that prevents DNA synthesis during epidermal cell proliferation, inhibits mitosis of the nucleus, inhibits the proliferation of activated lymphocytes in the body, and attenuates the function and inhibition of CD8 cells.
  • the chemotaxis of neutrophils is the standard medication for systemic treatment of psoriasis, but its therapeutic amount and poisoning amount are very close. Long-term medication can cause extensive fibrosis and cirrhosis of the liver, so it should be safe when applied.
  • glucocorticoids Currently generally do not advocate the use of glucocorticoids, because the effective dose is often large, can cause serious side effects, and after the reduction or withdrawal, can occur "rebound” phenomenon Or induce severe pustular and erythrodermic psoriasis, generally only used for erythrodermic, articular or generalized pustular silver shavings and other Ineffective; 3, vitamin A acid drugs: such mechanism of drug treatment of psoriasis are mainly of epidermal proliferation and differentiation, and regulate immune function.
  • Liazol is an imidazole derivative, a retinoic acid mimic and a retinoic acid metabolism blocker , but not belonging to vitamin A acid, by increasing the amount of endogenous vitamin A in tissues and blood to exert its effects, common side effects are itching, dryness, cheilitis, etc.; 7, antibiotics and vitamins: clinically many silver The occurrence and recurrence of psoriasis and bacteria, true It is related to microbial infections such as bacteria and viruses. Anti-infective treatment can be used for these cases.
  • Oxymatrine has direct anti-inflammatory effects, immunomodulatory effects, inhibition of tumor proliferation, differentiation and apoptosis, antiviral bactericidal action, anti-hypoxia, vasodilation, hypolipidemic, antiarrhythmia, sedation, antipyretic, cooling, Improve the role of various indicators of blood rheology.
  • oxymatrine In the central nervous system, oxymatrine has the effects of sedative, analgesic, antipyretic, and cooling; digestive system, which has anti-liver damage and effectively protects liver cells; oxymatrine has anti-tumor effect and can effectively inhibit human liver cancer
  • the cell line HepG2 proliferates and has direct killing effect; in the cardiovascular system, oxymatrine has anti-hypoxia, vasodilator, hypolipidemic, antiarrhythmia and the like.
  • Direct anti-inflammatory effects of oxymatrine Matrine is a potent anti-inflammatory drug with hormone-like effects and no hormonal side effects;
  • Immunomodulatory effects of oxymatrine Oxymatrine has a strong immunomodulatory effect, It exerts its anti-inflammatory effect by affecting the host's antibody level, immune cell changes, cytokines and other inflammatory regulatory factors; anti-tumor mechanism: oxymatrine can inhibit tumor proliferation, induce differentiation and apoptosis;
  • Antiviral bactericidal action of ginseng Oxymatrine has direct antiviral bactericidal activity and a broad spectrum of bactericidal activity.
  • the direct anti-inflammatory action of oxymatrine can inhibit the inflammatory reaction of psoriasis, and the antiviral bactericidal action can treat psoriasis caused by infection.
  • oxymatrine can regulate psoriasis.
  • Immune response inhibition of keratinocyte proliferation, anti-oxidation, psoriasis patients with significant microcirculation and hemorheological changes, the degree of abnormality and psoriasis The condition is related, and oxymatrine has the effect of improving blood rheology.
  • Oxymatrine has sedative, analgesic, antipyretic, and cooling effects in the central nervous system, and can regulate psoriasis caused by neuropsychiatric factors. Psoriasis is easily associated with liver, cardiovascular, and metabolic diseases, and effective western medicine for treating psoriasis often has side effects such as liver and kidney damage and increased blood lipids. Oxymatrine has anti-liver damage and effectively protects liver cells. At the same time, it has anti-hypoxia, vasodilator, anti-arrhythmia, hypolipidemic and other effects, effectively preventing the occurrence of psoriasis complications.
  • 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 an additive and synergistic effect on psoriasis and a lower toxic side effect, and its preparation for the treatment of psoriasis.
  • a pharmaceutical composition of oxymatrine (oxymatrine, matrine) or a derivative thereof and glycyrrhizic acid or a derivative thereof can provide a particularly beneficial therapeutic effect on psoriasis, and No obvious side effects were observed.
  • This pharmaceutical composition is particularly suitable for the treatment of psoriasis, including the treatment of various types of psoriasis.
  • the pharmaceutical composition can also be combined with existing techniques for treating psoriasis such as: ultraviolet radiation, retinoic acid formulations, and biologic formulation applications.
  • It is an object of the present invention to provide a pharmaceutical composition for treating psoriasis comprising the sequential or simultaneous administration of a pharmaceutically acceptable amount, or a pharmaceutically effective dose.
  • glycyrrhizic acid matrine salt and the glycyrrhizic acid ginseng salt are also included.
  • the weight ratio of oxymatrine or its derivative to glycyrrhizic acid or its derivative in the composition is
  • 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 respectively in a pharmaceutically acceptable form thereof (including pharmaceutically acceptable salts, esters and solvates, and also includes glycyrrhizic acid matrine salt and glycyrrhizic acid) Sensate salt.) administered as a pharmaceutically active agent.
  • the oxymatrine or a derivative thereof of the present invention includes oxymatrine, oxymatrine, matrine, isoporcine or its drug Salts (including hydrochlorides, sulfates, acetates, phosphates, fumarates, and various amino acid salts).
  • Glycyrrhizic acid or its derivatives include glycyrrhizic acid, glycyrrhizin, isoglycyrrhizic acid, isoglycyrrhizinate, glycyrrhizinate, glycyrrhizinate including glycyrrhizin available medicinal salt, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid Glycosides, sodium glycyrrhizinate, potassium glycyrrhizinate and calcium glycyrrhizinate.
  • 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 a gel or hydrogenated edible ester or the like; an emulsifier such as lecithin, sorbitan monooleate, gum arabic, etc.; an anhydrous carrier (which may include an edible oil), such as almond oil, distilled coconut oil, or an oily ester; Preservatives, such as methylparaben, propyl ester, sorbito
  • the two active ingredients can be prepared in unit liquid form separately from the sterile carrier, and suspended or dissolved in the carrier depending on the concentration used.
  • 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 for 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 remarkable effect of treating psoriasis with lower toxic side effects.
  • a pharmaceutical composition of oxymatrine or a derivative thereof and glycyrrhizic acid or a derivative thereof has a remarkable effect of treating psoriasis with lower toxic side effects.
  • mice Comparison of acute toxicity of oxymatrine, glycyrrhizic acid and their compositions in mice
  • Kunming mice were randomly divided into normal control group and test drug group, with 10 rats in each group, half male and half female. Except for 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 time of death and the number of deaths were recorded.
  • Example 2 Therapeutic effect of compound glycyrrhizin combined with oxymatrine on psoriasis
  • PASI score Efficacy criteria According to the PASI score, patients are required to take no bath within 24 hours before the efficacy is judged. The clinical cure was reduced by more than 90% after treatment; the PASI score was reduced by 60% to 89%; the PASI score was reduced by 20% to 59%; and the PASI score was reduced by 20% or less. Effectiveness is calculated by clinical recovery and significant effect.
  • 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.
  • 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.
  • Lactose 8g Dissolve one of the above ingredients in water, add 80g of starch, 20g of sugar powder, add appropriate amount of essence, 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 dispensed in a hard capsule.
  • 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 eczema vaginal epithelial tissue was stimulated by injection of estrogen to replicate the animal model of psoriasis. At the same time, different doses of 18 ⁇ -glycyrrhizic acid matrine were given. After 10 days, the serum of the mice was determined by IL-2. , IL-10 and TNF- ⁇ content, and observed the effect of 18 ⁇ -glycyrrhizic acid matrine on mitosis of mouse vaginal epithelial cells.
  • 18 ⁇ -glycyrrhizic acid matrine has a protective effect on experimental psoriasis, which may be related to inhibiting epidermal cell proliferation and lowering serum IL-2 and TNF-a levels, and increasing IL-10 levels.
  • Example 23 Antagonistic effect of glycyrrhizic acid and oxymatrine complex salt on oxidative stress in a psoriasis mouse model
  • Glycyrrhizin and oxymatrine complex salts 80, 40 and 20 mg.kg- 1 could inhibit mitosis of mouse vaginal epithelium (PO.01); glycyrrhizic acid oxymatrine complex salt 80 mg/kg could increase estrogen cycle Serum SOD and T-AOC content (PO.05, PO.01), decreased MDA, GSH and NO content (PO.01); oxymatrine 40mg/kg It can reduce serum MDA and NO levels in estrogen-positive mice (P ⁇ 0.05 PO.01).
  • the compound salt of glycyrrhizic acid has protective effect on experimental psoriasis, which may inhibit the proliferation of epidermal cells and decrease the content of serum MDA GSH and NO.
  • SOD is related to the content of T-AOC.
  • Table 5 Glycyrrhizin and oxymatrine complex salt on estrogen cycle vaginal epithelial mitosis model mouse serum SOD MDA
  • EXAMPLE 24 Effect of oxymatrine and glycyrrhizin composition (5:1) on cell proliferation, antigen expression and apoptosis of estrogen-induced mouse vaginal epithelial cells
  • the eczema vaginal epithelial tissue was stimulated by injection of estrogen to replicate the animal model of psoriasis. Different doses of oxymatrine and glycyrrhizin were used to intervene. After 10 days, immunohistochemistry and end were applied. Labeling technique (TU EL) was used to detect the cell proliferation and antigen (PCNA) expression and apoptosis of vaginal epithelial cells in each group.
  • TU EL labeling technique
  • PCNA cell proliferation and antigen
  • PASI score Efficacy criteria According to the PASI score, patients are required to take no bath within 24 hours before the efficacy is judged. The clinical cure was reduced by more than 90% after treatment; the PASI score was reduced by 60% to 89%; the PASI score was reduced by 20% to 59%; and the PASI score was reduced by 20% or less. Effectiveness is calculated by clinical recovery and significant effect.
  • Treatment group 4 2(50.0) 2(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)
  • Oxymatrine combined with magnesium isoglycyrrhizinate has a significant effect on the treatment of psoriasis, with an effective rate of 100% and no adverse reactions.
  • Example 26 Oral treatment of psoriasis with oxymatrine and glycyrrhizic acid diamine
  • PASI score Efficacy criteria According to the PASI score, patients are required to take no bath within 24 hours before the efficacy is judged. The clinical cure was reduced by more than 90% after treatment; the PASI score was reduced by 60% to 89%; the PASI score was reduced by 20% to 59%; and the PASI score was reduced by 20% or less. Effectiveness is calculated by clinical recovery and significant effect.
  • 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)
  • the efficacy criteria are based on the PASI score and require the patient not to take a bath within 24 hours prior to the outcome.
  • Clinical recovery is reduced by more than 90% after treatment; PSA score is reduced by 60% to 89%; progress is reduced by 20% to 59% of PASI score; Reduce the PASI score by less than 20%. Effectiveness is calculated by clinical recovery and significant effect.
  • the treatment group A intravenous infusion of oxymatrine injection 0. 6gl00ml / d and compound glycyrrhizin injection 120mg / d; group B intravenous infusion of oxymatrine injection 0. 6gl00ml / d and compound Glycyrrhizin injection 120mg / d, combined with narrow-spectrum UVB treatment of patients with skin lesions (using Waldmann UVB therapeutic apparatus), the initial dose is 0. 25J / cm2, and then gradually increased according to skin reactions, generally increased every 2 times 0 02-0.
  • Group C is given a narrow-spectrum UVB treatment for skin lesions of patients
  • Group D is compound glycyrrhizin injection 120 mg/d. All the four groups were combined with 5% salicylic acid ointment, and all were treated for 4 weeks. After the treatment, the curative effect was judged.
  • Group A, group B, group C and group D were compared, a P ⁇ 0.05 was statistically significant; group A, group B was compared with group C, b P ⁇ 0. 05 is statistically different; group B, group C and group A, e P ⁇ 0.05 was statistically significant; adverse reactions group A and group B did not have adverse reactions; group C 1 case of self-reported urine The amount increased; 2 patients in group D developed fatigue, mild abdominal distension, 1 patient developed hypokalemia, and 2 patients developed mild edema symptoms. None of the four groups affected treatment.
  • Example 29 Clinical efficacy of oxymatrine combined with glycyrrhizin in the treatment of psoriasis vulgaris
  • Composition group ⁇ . 8.16 ⁇ 7.03 11.36 ⁇ 3.32
  • composition group had a P ⁇ 0.05, aa P ⁇ 0.01 compared with the Avi A group; b P ⁇ 0.05 compared with before treatment in the same group, bb P ⁇ 0.01 Table 15
  • the blood lipids and liver function before treatment in the two groups were normal.
  • composition group had a P ⁇ 0.05, aa P ⁇ 0.01 compared with the Avi A group ; b P ⁇ 0.05, b b P ⁇ 0.01 after treatment in the same group compared with the treatment group; Weekly C P ⁇ 0.05, CC P ⁇ 0.01 Table 16 Number of people who returned to PASI50 after stopping treatment after reaching PASI50 after treatment
  • composition group had a P ⁇ 0.05 aa P ⁇ 0.01 compared with the Avi A group; b P ⁇ 0.05 b b P ⁇ 0.01 compared with the pre-treatment group after treatment ; the same group was compared with the treatment for 8 weeks.
  • OMT group 1 1. 37 ⁇ 10. 97 + 6. 94 ⁇ 5. 02 + 3. 73 ⁇ 2. 21 +
  • the accompanying metabolic syndrome is significantly improved, and the skin lesions continue to improve after stopping the drug; the recurrence rate is low after stopping the drug.
  • the composition can not only inhibit epidermal proliferation, but also has significant therapeutic effect on skin lesions of psoriasis, has mild clinical side effects, can also adjust the internal environment of the body, and fundamentally treats psoriasis, which is used for psoriasis.
  • the treatment of the disease has broad prospects and is expected to become a new good medicine for the treatment of psoriasis.
  • Example 30 Combination of oxymatrine and glycyrrhizin for the treatment of erythrodermic psoriasis 1 Materials and methods
  • Therapeutic method is given intravenous infusion of oxymatrine injection 0. 6gl00ml / d and compound glycyrrhizin injection 120mg / d ; skin dry topical Vaseline ointment, are treated for 6 weeks, after the end of the treatment The efficacy is judged.
  • PASI change value (PASI total score before treatment - PASI total score after treatment) / PASI total score X 100% before treatment.
  • the cure is the complete regression of the skin lesions or the PASI change value >90%; the marked effect is the PASI change value of 61% ⁇ 90%; the effective PASI change value is 31% ⁇ 60%; the invalidity is the PASI change value of 30% or the lesion is aggravated.
  • the total effective rate is cured and markedly effective.
  • PASI change value (PASI total score before treatment - PASI total score after treatment) / PASI total score X 100% before treatment.
  • the cure is the complete regression of the skin lesions or the PASI change value >90%; the marked effect is the PASI change value of 61% ⁇ 90%; the effective PASI change value is 31% ⁇ 60%; the invalidity is the PASI change value of 30% or the lesion is aggravated.
  • the total effective rate is cured and markedly effective.
  • the combination of oxymatrine and glycyrrhizin has a significant effect on the treatment of erythrodermic psoriasis with an effective rate of 100% and no adverse reactions.
  • Example 31 Combination of oxymatrine and glycyrrhizin in the treatment of pustular psoriasis psoriasis
  • Therapeutic method is given intravenous infusion of oxymatrine injection 0. 6gl00ml / d and compound glycyrrhizin injection 120mg / d ; skin dry topical Vaseline ointment, are treated for 6 weeks, after the end of the treatment The efficacy is judged.
  • PASI change value (PASI total score before treatment - total PASI score after treatment) / Total PASI score before treatment X 100%.
  • the cure is the complete regression of the skin lesions or the PASI change value >90%; the effective value is the PASI change value 61% ⁇ 90%; the effective PASI change value is 31% ⁇ 60%; the invalid is the PASI change value 30% or the skin lesion is aggravated.
  • the total effective rate is cured and markedly effective.
  • PASI change value (PASI total score before treatment - PASI total score after treatment) / Total PASI score before treatment X 100%.
  • the skin lesions After treatment, the skin lesions all resolved or the PASI change value was >90%; the marked effect was PASI change value 61% ⁇ 90%; the effective PASI change value was 31% ⁇ 60%; the invalid value was PASI change value 30% or the skin lesion was aggravated.
  • the total effective rate is cured and markedly effective.

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  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une composition pharmaceutique comprenant de le kushenine et de l'acide glycyrrhizique ou des dérivés de ceux-ci ainsi que l'utilisation de la composition pour préparer un médicament utilisé pour prévenir et traiter le psoriasis, le rapport de poids de la kushenine ou un dérivé de celle-ci sur l'acide glycyrrhizique ou un dérivé de celui-ci étant de 10:1-1:10.
PCT/CN2014/073137 2013-05-20 2014-03-10 Utilisation d'une composition pharmaceutique comprenant de la kushenine et de l'acide glycyrrhizique pour traiter le psoriasis WO2014187186A1 (fr)

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CN201310186912.8 2013-05-20
CN201310186912.8A CN104161764B (zh) 2013-05-20 2013-05-20 含有苦参素和甘草酸的药物组合物制备治疗银屑病的应用

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WO2014187186A1 true WO2014187186A1 (fr) 2014-11-27

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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

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CN101618106B (zh) * 2009-07-17 2012-02-29 吉林草还丹药业有限公司 一种用于治疗银屑病的药物组合物

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* 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

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CN104161764B (zh) 2018-06-08

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