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WO2016192098A1 - Composition pharmaceutique contenant de l'acarbose et utilisation de celle-ci dans une immunisation de régulation - Google Patents

Composition pharmaceutique contenant de l'acarbose et utilisation de celle-ci dans une immunisation de régulation Download PDF

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Publication number
WO2016192098A1
WO2016192098A1 PCT/CN2015/080849 CN2015080849W WO2016192098A1 WO 2016192098 A1 WO2016192098 A1 WO 2016192098A1 CN 2015080849 W CN2015080849 W CN 2015080849W WO 2016192098 A1 WO2016192098 A1 WO 2016192098A1
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pharmaceutical composition
acarbose
disease
treating
drug
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English (en)
Chinese (zh)
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陈信华
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Taichung Veterans General Hospital
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Taichung Veterans General Hospital
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Priority to PCT/CN2015/080849 priority Critical patent/WO2016192098A1/fr
Priority to CN201580063655.6A priority patent/CN107106583B/zh
Publication of WO2016192098A1 publication Critical patent/WO2016192098A1/fr
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    • 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
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages

Definitions

  • the present invention relates to a novel use comprising acarbose, in particular for the use of acarbose for the modulation of immunity or for the treatment of immunoinflammatory conditions.
  • Immune inflammation is characterized by the body's immune response being improperly activated.
  • the immune system does not attack infected foreign objects, but attacks and damages the body's own tissues or transplanted tissues. Tissues attacked by the immune system vary from disease to disease. For example, in multiple sclerosis, the immune response is against nerve tissue, while Crohn's disease is against the digestive tract.
  • Immune inflammatory diseases inflict millions of people, including diseases such as asthma, allergic intraocular inflammation, arthritis, atopic dermatitis, atopic eczema, diabetes, hemolytic anemia, inflammatory dermatitis, inflammatory Intestinal or gastrointestinal disorders (eg, Crohn's disease and ulcerative colitis), multiple sclerosis, myasthenia gravis, pruritus/inflammation, psoriasis, rheumatoid arthritis, cirrhosis, and systemic lupus erythematosus.
  • diseases such as asthma, allergic intraocular inflammation, arthritis, atopic dermatitis, atopic eczema, diabetes, hemolytic anemia, inflammatory dermatitis, inflammatory Intestinal or gastrointestinal disorders (eg, Crohn's disease and ulcerative colitis), multiple sclerosis, myasthenia gravis, pruritus/inflammation, psoriasis, rheumatoid arthritis
  • a drug for treating type 2 diabetes acarbose, which is a glucosidase inhibitor drug, and ⁇ -glucosidase on intestinal villi Reversible competitive inhibition to slow down the decomposition of sugars in the small intestine, therefore, delaying the absorption of sugars to avoid the phenomenon of post-prandial hyperglycemia, and achieving a smoother postprandial glycemic control;
  • acarbose which is a glucosidase inhibitor drug
  • ⁇ -glucosidase on intestinal villi Reversible competitive inhibition to slow down the decomposition of sugars in the small intestine
  • the invention provides a pharmaceutical composition for treating an immunoinflammatory condition comprising acarbose.
  • the immune inflammatory condition is: rheumatoid arthritis, cognac, type 1 diabetes, adult sexual history, optic neuromyelitis, Crohn's disease, ulcerative colitis, Asthma, chronic obstructive pulmonary disease, rheumatic polymyalgia, giant cell arteritis, systemic lupus erythematosus, Atopic dermatitis, multiple sclerosis, myasthenia gravis, psoriasis, ankylosing spondylitis, cirrhosis or dryness arthritis.
  • the pharmaceutical composition of the present invention may further comprise a second drug; wherein the second drug is preferably selected from the group consisting of a non-steroidal anti-inflammatory drug (NSAID), a COX-2 inhibitor, Biomolecules, immunomodulators, small molecule immunomodulators, disease modifying antirheumatic drugs (DMARD), jaundice, anticholinergic compounds, beta receptor synergists, bronchodilators, nonsteroidal immunoaffinity protein-dependent immunosuppressants , a group of vitamin D analogs, psoralen, vitamin A acid and 5-aminosalicylic acid.
  • NSAID non-steroidal anti-inflammatory drug
  • the pharmaceutical composition may be in any dosage form, preferably in the form of a lozenge or capsule.
  • the pharmaceutical composition is formulated for topical administration or systemic administration.
  • Another aspect of the invention is the use of acarbose for the preparation of an immunomodulatory drug.
  • Figure 1A A comparison of the incidence of CIA in the experimental and control groups of CIA mice
  • Figure 1B is a graph showing the comparison of the number of diseased feet in the experimental group and the control group of CIA mice;
  • Figure 1C Photograph of the sole of the foot in the experimental group and the control group of the CIA mouse
  • Figure 1D Comparison of arthritis scores between the experimental group and the control group of CIA mice
  • FIG. 1E Histological (H&E) photograph of the ankle joint in the experimental and control groups of CIA mice;
  • Figure 1F shows a histological comparison of infiltration, synovial hyperplasia, and bone erosion of the ankle joint in the experimental and control groups of CIA mice;
  • Figure 2A shows the content of selective cytokines in the paw tissue of the CIA mouse experimental group and the control group by ELISA;
  • Figure 2B shows the content of selective cytokines in serum in the CIA mouse experimental group and the control group by ELISA
  • Figure 3A Comparison of anti-CII IgG in the experimental and control groups of CIA mice
  • Figure 3B Comparison of CII antigen-stimulated proliferation in CIA mice experimental group and control group
  • Figure 3C shows different cells of lymphocyte supernatant in CIA mice experimental group and control group Hormone content comparison chart
  • Figure 4A Comparison of the efficacy of tofarinib 1 mg/kg/day, 5 mg/kg/day, 25 mg/kg/day dose on CIA mice;
  • Figure 4B Comparison of the efficacy of tofacitinib 1 mg/kg/day, acarbose 500 mg/kg/day, acarbose 500 mg/kg/day and tofacitinib 1 mg/kg/day for CIA mice Figure
  • Figure 4C Comparison of the efficacy of tofacitinib 5 mg/kg/day, acarbose 500 mg/kg/day, acarbose 500 mg/kg/day combined with tofacitinib 5 mg/kg/day for CIA mice Figure
  • Fig. 5A is a photograph showing the skin of an experimental group and a control group which were induced by imiquimod 62.5 mg/kg/day and dried with acarbose 500 mg/kg/day;
  • Fig. 5B is a graph showing the comparison of clinical characterization scores between the experimental group and the control group which were induced by imiquimod 62.5 mg/kg/day and dried with acarbose 500 mg/kg/day;
  • FIG. 6A Control group cream induced skin histology (H&E) photos of dried mice;
  • FIG. 6B imiquimod-induced skin histology (H&E) photographs of dried mice
  • Figure 6C H&E photographs of mice treated with imiquimod-induced dryness and acarbose 50 mg/kg/day;
  • Figure 6D H&E photographs of mice treated with imiquimod induced dry acarbose 50 mg/kg/day.
  • the present invention provides a pharmaceutical composition for treating an immunoinflammatory condition comprising acarbose and an acarbose for use in the preparation of an immunomodulatory drug.
  • treating means administering or prescribing a composition to a patient to treat or prevent an immunoinflammatory condition.
  • patient is meant herein any animal (eg, human).
  • Other animals which can be treated by the methods, compositions and kits of the invention include horses, dogs, cats, pigs, goats, rabbits, hamsters, monkeys, guinea pigs, rats, mice, lizards, snakes, sheep, cattle, fish and bird.
  • immune inflammatory condition includes many conditions including, but not limited to, autoimmune diseases, proliferative skin diseases, and inflammatory eczema. Immune inflammatory conditions can cause the body's healthy tissues to be destroyed by the inflammatory process, the immune system to lose control, and the unwanted cells to proliferate.
  • Immunoinflammatory conditions such as acne vulgaris; acute dyspnea syndrome; Addison's disease; allergic rhinitis; allergic intraocular inflammation, ANCA-related small-vascular vasculitis; ankylosing spondylitis; arthritis Asthma; atherosclerosis; atopic dermatitis; autoimmune hemolytic anemia; autoimmune hepatitis; Behcet's disease; Bell's palsy; bullous pemphigoid Cerebral ischemia; chronic obstructive pulmonary disease; cirrhosis; Cogan's syndrome; contact skin disease; COPD; Crohn's disease; Cushing's syndrome; dermatomyositis; Lupus; eosinophilic fasciitis; erythematous nodules; exfoliative dermatitis; fibromyalgia; glomerular sclerosis; giant cell arteritis; gout; gouty arthritis; Eczema; Henoch-Schonlein purpura;
  • the immunoinflammatory condition comprises rheumatoid arthritis, cognac, type 1 diabetes, adult sexual history, optic neuromyelitis, Crohn's disease, ulcerative colitis, asthma , chronic obstructive pulmonary disease, rheumatic polymyalgia, giant cell arteritis, systemic lupus erythematosus, atopic dermatitis, multiple sclerosis, myasthenia gravis, psoriasis, ankylosing spondylitis, cirrhosis or dryness Arthritis or other immunoinflammatory condition associated with dysregulation of the cytokine IL-17.
  • non-skin inflammatory condition includes, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease.
  • skin inflammatory condition or "inflammatory dermatitis” as used herein includes, for example, psoriasis, acute heat neutrophilic skin disease, eczema (eg, arrhythmia eczema, sweat rash, eczema at the small cystic sac), plasma cell limitation.
  • eczema eg, arrhythmia eczema, sweat rash, eczema at the small cystic sac
  • plasma cell limitation e.g, plasma cell limitation.
  • Penile head inflammation penile head dermatitis, Beth's disease (Behcet's condition), eccentric ring erythema, persistent pigmented erythema, polymorphous erythema, ring granuloma, lustrous moss, lichen planus, hardened atrophic moss Chronic simple moss, small spine moss, money-like dermatitis, gangrenous pyoderma, sarcoma, subcorneal impetigo, urticaria and transitional echinodermitis.
  • "Proliferative skin disease” means a benign or malignant disease characterized by accelerated cell division of the epithelium or epidermis.
  • proliferative skin diseases are psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, basal and squamous cell skin cancer, stratified scales, and epidermal keratinization Excessive symptoms, premalignant keratosis, acne and seborrheic dermatitis.
  • proliferative skin diseases are psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, basal and squamous cell skin cancer, stratified scales, and epidermal keratinization Excessive symptoms, premalignant keratosis, acne and seborrheic dermatitis.
  • a particular disease, condition or condition can be characterized as both proliferative skin disease and inflammatory eczema.
  • An example of this disease is psoriasis.
  • the pharmaceutical composition of the present invention may further comprise a second drug.
  • the second drug is preferably selected from the group consisting of a non-steroidal anti-inflammatory drug (NSAID), a COX-2 inhibitor, a biomolecule, an immunomodulator, a small molecule immunomodulator, a disease modifying antirheumatic drug (DMARD), and jaundice.
  • NSAID non-steroidal anti-inflammatory drug
  • COX-2 inhibitor a COX-2 inhibitor
  • biomolecule e.g., a COX-2 inhibitor
  • an immunomodulator e.g., a small molecule immunomodulator
  • DMARD disease modifying antirheumatic drug
  • jaundice e.g., anticholinergic compound, ⁇ -receptor synergist, bronchodilator, non-steroid immunoaffinity protein-dependent immunosuppressant, vitamin D analog, psoralen, vitamin A acid and 5-aminosalicylic acid Group.
  • non-steroidal anti-inflammatory drugs includes, but is not limited to, sodium naproxen, diclofenac sodium, diclofenac potassium, aspirin, sulindac, diflunisal, piroxicam, indomethacin, ibuprofen. , nabumetone, choline magnesium salicylate, sodium salicylate, salicylic acid salicylic acid (sallium), phenoxyprofen, flurbiprofen, ketoprofen, A Sodium chlorfenate, meloxicam, oxaprozin, sulindac and tolmetine.
  • disease-modifying antirheumatic drug includes, but is not limited to, Methotrexate, Azathioprine, Leflunomide, Sulfasalazine, Hydroxychloroquine. ), Tofatinib (Tobactinib).
  • immunomodulator includes, but is not limited to, cyclosporin, imiquimod.
  • antihistamine as used herein means a compound which blocks the action of histamine.
  • Antihistamine types include, but are not limited to, ethanolamine, ethylenediamine, phenothiazine, alkylamine, piperazine, and piperidine.
  • non-steroidal immunoaffinity protein-associated immunosuppressive agent or “NsIDI” as used herein means any non-steroidal agent that reduces the production or secretion of primary inflammatory cytokines, binds to immunoaffinity proteins, or causes a primary inflammatory response. Down regulation. NsIDI includes calcium calcineurin inhibitors such as cyclosporine, heparin (licrolimus), ascomycin, pimecrolimus and other phospholyase activities that inhibit calcineurin Agent (peptide, peptide fragment, chemically modified peptide or peptide mimetic).
  • calcium calcineurin inhibitors such as cyclosporine, heparin (licrolimus), ascomycin, pimecrolimus and other phospholyase activities that inhibit calcineurin Agent (peptide, peptide fragment, chemically modified peptide or peptide mimetic).
  • NsIDI also includes rapamycin (sirolimus) and everolimus, which binds to FK506-binding protein, FKBP-12, and blocks antigen-induced hyperplasia of leukocytes. And cytokine secretion.
  • small molecule immunomodulator as used herein means a non-steroidal, non-NsIDI compound that reduces the production or secretion of primary inflammatory cytokines, leading to downregulation of the primary inflammatory response, or by immunoaffinity protein-non-dependent The way to regulate the immune system.
  • small molecule immunomodulators are p38 MAP kinase inhibitors such as VX 702 (Vertex Pharmaceuticals), SCIO 469 (Scios), doramapimod (Boehringer Ingelheim), RO 30201195 (Roche) and SCIO 323 ( Scios), TACE inhibitors such as DPC 333 (Bristol Myers Squibb), ICE inhibitors such as pranalcasan (Vertex Pharmaceuticals), IMPDH inhibitors such as mycophenolate (Roche) and Meli Merimepodib (Vertex Pharamceuticals).
  • the dosage of the pharmaceutical composition of the present invention can be adjusted to the condition of the patient according to the skilled person, providing a sufficient amount of the active ingredient, or alternatively a low dose, a medium dose or a high dose.
  • the dose effect administered can be judged by a skilled physician using any standard method suitable for the intended indication.
  • the term "low dose” means at least 5% lower than the minimum recommended recommended dose for a particular compound (to treat any human condition in a given path) (eg, at least 10%, 20%, 50%, 80%, 90%) Or even 95%)
  • a low dose of a corticosteroid administered by inhalation is different from a low dose of a corticosteroid administered orally.
  • high dose means a dose that is at least 5% higher than the highest standard recommended for a particular compound (to treat any human condition) (eg, at least 10%, 20%, 50%, 100%, 200%, or even 300). %).
  • Medium dose means that the dose is between a low dose and a high dose.
  • sufficient amount means the amount of the combination of the compounds of the present invention which is required to treat or prevent immune inflammation in a clinically relevant manner.
  • the amount of active compound used to practice the present invention to treat an immune inflammatory disease varies depending on the mode of administration, age, weight, and general health of the patient.
  • Specific routes of administration of the pharmaceutical composition of the present invention include, but are not limited to, topical administration, transdermal and systemic administration (for example, intravenous, intramuscular, inhalation, rectal, collar, vaginal, intraperitoneal, Intra-articular, intraocular or oral administration). Any of the aforementioned routes of administration can be administered in conjunction with conventional drugs for treating immunoinflammatory conditions.
  • the pharmaceutical composition of the present invention may be in any of various forms such as tablets, capsules, pills, powders, granules, suspensions, emulsifiers, solutions, gels (including hydrogels), pastes, ointments, creams, Plaster, infusion, osmotic delivery, suppository, enema, injection, implant, spray or aerosol.
  • Such compositions may be formulated according to conventional pharmaceutical specifications, preferably oral dosage forms such as tablets, capsules, or syrups; or rectal administration, such as suppositories; or other dosage forms, such as sustained release or sustained release dosage forms, and the like. .
  • each compound can be formulated by methods known in the art.
  • the first and second medicaments can be formulated simultaneously or separately.
  • the first and second medicaments are administered simultaneously or nearly simultaneously; if administered simultaneously, they may be formulated together in the same pill, capsule, liquid, and the like.
  • the pharmacokinetic profile of each agent can be appropriately matched.
  • Individual or separately formulated medicaments can be packaged together into a single kit.
  • An unrestricted kit embodiment includes, for example, two pills, one pill and powder, a suppository and a vial solution, and two external creams.
  • the kit can include optional accessories that will help the patient to be administered
  • the unit dose, ingredients include, for example, vials for infusion powders, syringes, custom IV delivery systems, inhalants, and the like.
  • the unit dose kit can include instructions for preparing and administering the composition.
  • the kit can be manufactured as a single dose for one patient, multiple doses for a particular patient (which can be the same dose or the effectiveness of individual compounds as the treatment progresses); or the kit can include multiple patients Multiple doses administered ("big package").
  • the kit can be combined in a carton, blister pack, bottle, tube, and the like.
  • sustained release or “controlled release” means that the therapeutically active ingredient is released from the formulation at a controlled rate such that the ingredient is prolonged ( For example, about 12-24 hours) maintain therapeutically effective blood levels (below the level of toxicity) so that a 12 hour or 24 hour dosage form can be made.
  • the data source was a population-based, matched case-control study using the National Health Insurance Research Database (NHIRD) 1999-2011 from Taiwan.
  • NHIRD National Health Insurance Research Database
  • the NHIRD randomly selected millions of participants in 2000 to form a representative database containing potentially disabling autoimmune diseases, including rheumatoid arthritis (RA).
  • RA rheumatoid arthritis
  • the diagnosis of RA was further verified by the American College of Rheumatology RA Classification Standard (1987).
  • the patient was initially diagnosed with Diabetes Day [International Classification Disease, Ninth Revision, Clinical Revision (ICD9-CM) Code 250.x] after January 1, 2000, and at the same time prescribe any antidiabetic drug for ⁇ 28 days. Listed as DM patients.
  • the DM diagnostic date is used to measure the duration of the DM course as the time to prescribe the initial antidiabetic drug.
  • RA Rheumatoid arthritis
  • Non-rheumatoid arthritis (non-RA) control group
  • acarbose, metformin, thiazolidinedione (TZD), insulin or sulfonylurea/glinide were used for 28 days or more in one year before the date of the indicator.
  • Acarbose users are classified as high-dose users and low-dose users based on the median annual cumulative dose.
  • DM duration Geographical areas, DM duration, and DM terminal organ disease (ICD9-CM code 250.1-9) are listed as potential disruptors. The geographical area was chosen because it was found in the previous study that the RA risk was related. In addition, DM duration and DM terminal organ disease represent the severity of DM. The DM duration is defined as the period from the date of the initial antidiabetic drug to the date of the indicator. Other interfering factors include the Charlson comorbidity index (CCI) rewritten by Deyo et al. (Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.J Clin Epidemiol.
  • CCI Charlson comorbidity index
  • Table 3 Single variable related to the risk of rheumatoid arthritis and newly treated diabetic patients And multivariate adjustment odds ratio 95% confidence interval
  • Example 2 Mouse experiment confirmed acarbose treatment of rheumatoid arthritis
  • mice from each group obtained representative ankle joints on day 38 and fixed, decalcified and embedded in paraffin.
  • Each joint section (5M) was stained with hematoxylin and eosin (H&E) followed by a conventional method (Wooley PH. Collagen-induced arthritis in the mouse. Methods Enzymol. 1988; 162: 361-373.) Observed by a microscope. Synovial hyperplasia, cell infiltration, cartilage destruction, and histopathological changes of bone erosion were blindly graded by pathologists and given 0-3 points according to the following criteria, 0: no change; 1: mild change; 2: moderate Change; 3: Severe change.
  • Each group collected mouse paw tissue on day 38 and frozen in liquid nitrogen, expelling the sample to contain PBS in the protease inhibitor to homogenize the tissue homogenizer. The homogenate was centrifuged for 30 minutes, and the supernatant was collected and diluted to 1 mg/ml tissue protein per ml as a stock solution. The contents of TNF-a, IL-1b, IL-6, IFN-g, IL-17, IL-10 and TGF-b (R&D Systems) were determined in an ELISA kit (Peprotech).
  • mice were bled on day 38 after CII immunization and their serum was analyzed by ELISA titration using anti-CII IgG antibodies. Briefly, each well of an ELISA microplate (Thermo Fisher Scientific, NY, USA) was coated with 10 ⁇ g/200 ml of type II chicken collagen and incubated overnight at 4 °C. To avoid non-specific binding, the antibodies were washed and blocked with 3% bovine serum albumin (BSA) (BD Biosciences) in Tris buffer; the test sera were serially diluted and incubated overnight at 4 °C in a well plate.
  • BSA bovine serum albumin
  • the bound IgG was detected by diluting 1:5000 with HRP-conjugated sheep anti-mouse IgG as a secondary antibody; after washing, the well plate was ABTS (Roche Diagnostic Systems, IN, USA) was used as a matrix reaction, and the reaction was stopped with H 2 SO 4 , and the absorbance was measured at 450 nm with an ELISA reader.
  • CIA has been widely used to cause arthritis that exhibits the pathological features of human RA.
  • acarbose can prevent progression of CIA in the DBA/1 mouse model.
  • water-administered CIA mice control group
  • mice treated with 500 mg/kg/day acarbose had a significant reduction in the incidence of CIA (Fig. 1A) and the number of diseased feet (Fig. 1B), and visual confirmation
  • Fig. 1C erythema and joint stiffness in the hind paw
  • Fig. 1D arthritis score
  • oral treatment with acarbose 100 mg/kg/day had no significant development and severity in CIA. effect.
  • Hormones such as TNF-alpha, IL-6 and IL-17 are significantly reduced.
  • mice were randomly divided into four groups, and a dose of 1 mg/kg/day, a dose of 5 mg/kg/day, a dose of 25 mg/kg/day of tofacitinib, and water were used as a control group, respectively.
  • Two doses were administered daily from 7 to 38 days after the first immunization; the clinical characterization of the severity of mouse paw arthritis was performed using a conventional scoring system.
  • mice were randomized into four groups, each receiving a dose of 1 mg/kg/day of tofacitinib, a dose of 500 mg/kg/day of acarbose, and a dose of 1 mg/kg/day.
  • Tofacitinib combined with a 500 mg/kg/day dose of acarbose and water as a control group, administered twice daily for 7 to 38 days after the first immunization; clinical characterization of the severity of arthritis in the paw of mice With a conventional scoring system.
  • the general acarbose is used to treat the second type diabetes dose, which is better than the dose of 1 mg/kg/day of tofacitinib which is generally used for the treatment of rheumatoid arthritis. Efficacy; and when combined, the effect is better than single administration.
  • acarbose 500 mg/kg/day and tofacitinib 5 mg/kg/day can be used for the treatment of rheumatoid arthritis; and when the two are combined, the effect is more remarkable.
  • Cognac mice were obtained by conventional techniques. Briefly, after removing the hair on the back of the mouse, 62.5 mg of commercially available imiquimod (IMQ) ointment ((Aldara; 3M Pharmaceuticals) was applied daily on the back of the mouse. After a total of 6 days, on the 7th day, the mice were photographed and sacrificed, and the back skin was taken out for section analysis. Acarbose was started one week before the start of the application of imiquimod (IMQ) ointment. Oral feeding until the end of the experiment (Day 6), the dose was 500 mg / kg or 100 mg / kg.
  • IMQ imiquimod
  • the clinical scoring standard is based on the clinical Psoriasis Area and Severity Index (PASI), which is mainly classified into five grades according to its erythema and scaling. 0 means no change, 1 to 4 points, the higher the score, the more serious the erythema and desquamation.
  • PASI clinical Psoriasis Area and Severity Index
  • mice inducing dryness with imiquimod (IMQ) 62.5 mg/kg/day had a remarkable therapeutic effect after administration of acarbose 500 mg/kg/day.
  • acarbose 500mg/kg can significantly slow down the imiquimod (IMQ)-induced mice, resulting in epidermal hypertrophy (acanthosis), thickening of the stratum corneum, and Remaining nuclei and parakeratosis.
  • acarbose can be used for the treatment of rheumatoid arthritis, dryness and other immune inflammatory diseases, and it is confirmed that it can regulate the effect of IL-17, so it can be more widely used with IL- 17 related immune inflammatory conditions.

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Abstract

L'invention concerne une composition pharmaceutique contenant de l'acarbose, et l'utilisation de celle-ci dans la préparation de médicaments pour le traitement de maladies immunitaires et inflammatoires.
PCT/CN2015/080849 2015-06-05 2015-06-05 Composition pharmaceutique contenant de l'acarbose et utilisation de celle-ci dans une immunisation de régulation Ceased WO2016192098A1 (fr)

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CN201580063655.6A CN107106583B (zh) 2015-06-05 2015-06-05 包含阿卡波糖之医药组合物及其用于免疫调节之用途

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1823795A (zh) * 2005-12-30 2006-08-30 刘展欣 一种治疗糖尿病的药物组合物及其制备方法

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EP1218015A2 (fr) * 1999-10-08 2002-07-03 Novartis AG Procede de traitement de troubles du metabolisme
GB2465796A (en) * 2008-12-01 2010-06-02 Bee Kang Tan Metformin for the therapeutic use of conditions with raised serum amyloid A levels

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1823795A (zh) * 2005-12-30 2006-08-30 刘展欣 一种治疗糖尿病的药物组合物及其制备方法

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Title
LUO, YAFANG ET AL.: "The Effect of Novomix 30 Penfill Combined with Acarbose to Treat LADA", CLINICAL DISCUSSION, vol. 48, no. 3, 31 January 2010 (2010-01-31) *

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