WO2022255760A1 - Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie diabétique accompagnée d'hypertension - Google Patents

Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie diabétique accompagnée d'hypertension Download PDF

Info

Publication number
WO2022255760A1
WO2022255760A1 PCT/KR2022/007699 KR2022007699W WO2022255760A1 WO 2022255760 A1 WO2022255760 A1 WO 2022255760A1 KR 2022007699 W KR2022007699 W KR 2022007699W WO 2022255760 A1 WO2022255760 A1 WO 2022255760A1
Authority
WO
WIPO (PCT)
Prior art keywords
weeks
group
fimasartan
blood pressure
mmhg
Prior art date
Application number
PCT/KR2022/007699
Other languages
English (en)
Korean (ko)
Inventor
김봉석
김수희
정승희
강혜정
한수은
김종연
Original Assignee
주식회사 보령
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 주식회사 보령 filed Critical 주식회사 보령
Publication of WO2022255760A1 publication Critical patent/WO2022255760A1/fr

Links

Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating diabetic kidney disease, comprising fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof. More specifically, the present invention relates to a pharmaceutical composition capable of preventing or inhibiting the progression of diabetic kidney disease and effectively improving various symptoms associated with diabetic kidney disease accompanied by hypertension.
  • Diabetes mellitus is a type of metabolic disease, such as lack of insulin secretion or normal function, and is characterized by hyperglycemia in which the concentration of glucose in the blood increases. Hyperglycemia causes various symptoms and signs and excretes glucose through urine. .
  • Peripheral neuropathy, autonomic neuropathy, macrovascular complications, microvascular complications, and other chronic complications can result if diabetic patients are exposed to hyperglycemia for a long time.
  • Diabetic kidney disease is one of the complications caused by diabetes, and is the most important cause of chronic renal failure, and occupies a large proportion of the causative diseases of all dialysis patients.
  • Diabetic kidney disease is mostly asymptomatic in the early stages, and as it progresses, there are no obvious symptoms other than proteinuria appearing in urine tests. Thus, the onset of diabetic kidney disease is diagnosed by the finding of microalbuminuria (excretion of albumin in urine 30 mg - 300 mg/24h).
  • Another clinical significance of diabetic kidney disease is the significant increase in mortality.
  • the mortality rate of type 1 diabetic patients with overt proteinuria compared to normal people is significantly higher than that of type 1 diabetic patients with normoalbuminuria and normal people. That is, among diabetic patients, in the case of patients having kidney disease due to diabetes, the mortality rate is significantly increased.
  • Such diabetic kidney disease tends to increase its share in kidney disease with the increase in diabetic patients, and in particular, kidney disease patients caused by type 2 diabetes continues to increase.
  • Patent Document 1 Korean Patent Registration No. 0354654
  • An object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetic kidney disease accompanied by hypertension, comprising fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof. .
  • An object of the present invention is to provide a use of fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof for preventing or treating diabetic kidney disease accompanied by hypertension.
  • An object of the present invention is to provide a method for preventing or treating diabetic kidney disease accompanied by hypertension, comprising administering fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof. will be.
  • the present invention provides a pharmaceutical composition for preventing or treating diabetic kidney disease accompanied by hypertension, comprising fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof.
  • the pharmaceutical composition according to the present invention may prevent diabetic kidney disease accompanied by hypertension, including fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof.
  • a pharmaceutical composition for treatment wherein the pharmaceutical composition has a systolic blood pressure of 140 mmHg or more and less than 180 mmHg and a diastolic blood pressure of less than 110 mmHg; Estimated Glomerular Filtration Rate (eGFR) greater than or equal to 30 ml/min/1.73 m 2 ; and to subjects with albuminuria of 30 mg/g or greater.
  • eGFR Estimated Glomerular Filtration Rate
  • the diabetes may be type 2 diabetes.
  • the pharmaceutically acceptable salt may be a fimasartan potassium salt.
  • the hydrate may be fimasartan potassium salt trihydrate.
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to any one of (1) to (4) above may be for oral administration.
  • the fimasartan, pharmaceutically acceptable salt thereof, stereoisomer thereof, or hydrate or solvate thereof according to any one of (1) to (5) above may be administered once a day.
  • the fimasartan, pharmaceutically acceptable salt thereof, stereoisomer thereof, or hydrate or solvate thereof according to any one of (1) to (6) above is administered once a day for about 24 weeks. It can be.
  • the daily dose of the fimasartan, pharmaceutically acceptable salt thereof, stereoisomer thereof, or hydrate or solvate thereof according to any one of (1) to (7) above is about 60 mg to It may be about 120 mg.
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to any one of (1) to (8) above can reduce albuminuria in the subject. .
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to any one of (1) to (10) above has an estimated glomerular filtration rate within about 24 weeks of administration ( eGFR) can be reduced.
  • fimasartan according to any one of (1) to (11) above, wherein the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof lowers the systolic and diastolic blood pressure of the subject.
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to any one of (1) to (12) above lowers the systolic blood pressure of the subject to less than 140 mmHg. can be lowered to
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to any one of (1) to (13) above lowers the systolic blood pressure of the subject to less than 130 mmHg. can be lowered to
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof is a cardiovascular complex evaluation variable within about 24 weeks of administration.
  • the cardiovascular composite endpoint was selected from the group consisting of myocardial infarction (MI), stroke, hospitalization due to heart failure and unstable angina, coronary artery revascularization, peripheral vascular revascularization, and death.
  • MI myocardial infarction
  • the renal composite evaluation variable may be at least one selected from the group consisting of a decrease of about 50% or more in estimated glomerular filtration rate (eGFR) compared to baseline, progression to end-stage renal failure, and death.
  • eGFR estimated glomerular filtration rate
  • the systolic blood pressure (SBP) may be sitting systolic blood pressure (SiSBP), and the diastolic blood pressure (DBP) may be sitting diastolic blood pressure (SiDBP) ) can be.
  • the diabetic nephropathy accompanied by hypertension refers to renal failure in patients with diabetes accompanied by hypertension, and is a representative complication caused by diabetes.
  • the glomeruli inside the kidney is damaged due to hyperglycemia caused by diabetes, and kidney function is deteriorated, resulting in kidney disease.
  • Diabetic kidney disease accompanied by hypertension does not show any special symptoms other than the detection of fine albumin in the urine, so treatment is generally delayed, and as a result, it leads to chronic renal failure, requiring kidney transplantation or death. do.
  • diabetic kidney disease it is important to prevent diabetic kidney disease from occurring in a subject with diabetes accompanied by hypertension, or to delay the occurrence of diabetic kidney disease as much as possible.
  • diabetic kidney disease accompanied by hypertension develops, it is important to improve the symptoms or prevent the symptoms from worsening, thereby suppressing the progression of diabetic kidney disease accompanied by hypertension or delaying the progression of the disease. .
  • Fimasartan a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof can effectively prevent or treat kidney disease caused by diabetes accompanied by hypertension.
  • the composition according to the present invention can prevent diabetic kidney disease accompanied by hypertension from reaching chronic renal failure, thereby significantly reducing the patient's mortality.
  • diabetic kidney disease accompanied by hypertension leads to chronic renal failure, it eventually leads to dialysis. It is possible to delay or delay the start of dialysis.
  • the prevention refers to any action that prevents or suppresses the occurrence of diabetic kidney disease accompanied by hypertension or symptoms thereof by administering the pharmaceutical composition according to the present invention, or delays the onset of the disease.
  • the composition of the present invention is administered to a subject who develops diabetes accompanied by hypertension but does not have diabetic kidney disease accompanied by hypertension, the occurrence of diabetic kidney disease accompanied by hypertension or symptoms thereof is prevented. can be prevented or delayed.
  • the treatment improves and ameliorates diabetic kidney disease accompanied by hypertension or its symptoms by administering the pharmaceutical composition according to the present invention, or inhibits the progression of diabetic kidney disease accompanied by hypertension. It also refers to all actions that delay or delay the deterioration of diabetic kidney disease accompanied by hypertension.
  • the composition of the present invention when the composition of the present invention is administered to a subject suffering from diabetic kidney disease accompanied by high blood pressure, diabetic kidney disease accompanied by high blood pressure or symptoms thereof can be alleviated or improved.
  • the composition of the present invention is administered to a subject suffering from diabetic kidney disease accompanied by hypertension, the progression of diabetic kidney disease accompanied by hypertension or its symptoms is inhibited or delayed, thereby diabetic kidney disease accompanied by hypertension.
  • the death rate due to diabetic kidney disease accompanied by hypertension can be significantly reduced by preventing chronic renal failure, and the start of dialysis can be delayed.
  • the treatment includes reducing mortality due to diabetic kidney disease accompanied by hypertension or delaying the start of dialysis.
  • composition of the present invention prevents the occurrence of albuminuria and / or proteinuria, reduces the amount of albuminuria and / or proteinuria, when administered to a subject with diabetes with hypertension or a subject with diabetic kidney disease with hypertension , may delay the increase in albuminuria and/or proteinuria.
  • the composition of the present invention can delay the decrease in estimated glomerular filtration rate when administered to a subject with diabetes accompanied by hypertension or a subject with diabetic kidney disease accompanied by hypertension.
  • albuminuria is a type of proteinuria in which albumin is not filtered by the kidneys and is excreted out of the body through urine.
  • Gastric albuminuria is measured as the albumin-creatinine ratio in urine by collecting the first morning urine.
  • composition of the present invention When the composition of the present invention is administered to a subject with diabetes accompanied by hypertension or a subject with diabetic kidney disease accompanied by hypertension, it can prevent albuminuria from increasing or reduce the level, or the level is increased can delay
  • albuminuria in the subject is reduced.
  • the reduction rate of albuminuria may be about 30% or more.
  • albuminuria excretion can be reduced to about 300 mg/g or less in a subject whose albuminuria excretion is greater than about 300 mg/g.
  • albuminuria excretion can be reduced to less than about 30 mg/g in a subject with albuminuria excretion of about 300 mg/g or less.
  • the reduction of albuminuria may be about 300 mg/g or more, about 400 mg/g or more, or about 500 mg/g or more. At about 24 weeks of administration, the reduction in albuminuria may be about 500 mg/g or more.
  • the estimated glomerular filtration rate may decrease within about 24 weeks of administration.
  • composition of the present invention When administering the composition of the present invention, systolic and diastolic blood pressure are reduced.
  • the subject's systolic blood pressure may drop to less than 140 mmHg, or less than 130 mmHg.
  • composition of the present invention When the composition of the present invention is administered to a subject with diabetes accompanied by hypertension or a subject with diabetic kidney disease accompanied by hypertension, it can prevent glomerular sclerosis and fibrosis, thickening of the basement membrane in the glomerulus, and improve the above symptoms. or to prevent worsening of the symptoms by suppressing the symptoms or delaying their progression.
  • composition of the present invention When the composition of the present invention is administered to a subject with diabetic kidney disease accompanied by hypertension, it can prevent or delay chronic renal failure by preventing or slowing the progression of diabetic kidney disease accompanied by hypertension, and as a result, the subject It can significantly reduce mortality or delay the start of dialysis.
  • composition of the present invention can sufficiently and effectively prevent or treat diabetic kidney disease accompanied by hypertension even when only fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof is used as an active ingredient. .
  • compositions of the present invention exhibit sufficient safety in the subject. For example, even if the composition of the present invention is administered to a subject with diabetes accompanied by hypertension or a subject with diabetic kidney disease accompanied by hypertension, hyperkalemia and resulting irregular heartbeat or cardiac arrest occur within about 24 weeks of administration. does not cause myocardial infarction or cerebral infarction, does not result in hospitalization for heart failure and unstable angina, does not result in the possibility of coronary revascularization and peripheral revascularization, and does not result in functional or tracheal renal artery stenosis It does not cause renal impairment such as acute renal failure. There is little or no toxicity, including other side effects.
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof according to the present invention can be safely administered to subjects with diabetes accompanied by hypertension or diabetic kidney disease accompanied by hypertension. .
  • composition according to the present invention hardly generates a cardiovascular composite endpoint and/or a renal composite endpoint within an administration period of about 24 weeks.
  • the cardiovascular composite evaluation variable is at least one selected from the group consisting of myocardial infarction (MI), stroke, hospitalization due to heart failure and unstable angina, coronary artery revascularization, peripheral vascular revascularization, and death, and renal composite
  • the evaluation variable is one or more selected from the group consisting of a decrease of about 50% or more in estimated glomerular filtration rate (eGFR) compared to baseline, progression to end-stage renal failure, and death.
  • MI myocardial infarction
  • eGFR estimated glomerular filtration rate
  • the subject refers to animals including humans, and includes, for example, mice, rats, other rodents, rabbits, dogs, pigs, cats, cows, sheep, horses, primates and humans. It may be a mammal, preferably a primate or a human, more preferably a human.
  • the diabetes may be insulin-dependent type 1 diabetes or non-insulin-dependent type 2 diabetes.
  • it may be non-insulin dependent type 2 diabetes.
  • the fimasartan may be a compound represented by Formula 1 below.
  • the pharmaceutically acceptable salt refers to inorganic acid salts, organic acid salts, and metal salts commonly used by pharmaceutical manufacturers to prepare pharmaceuticals, and examples of inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, or phosphoric acid.
  • organic acids include citric acid, acetic acid, lactic acid, tartaric acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, maleic acid, benzoic acid, gluconic acid, glycolic acid, succinic acid, 4-morpholineethanesulfonic acid , Camphorsulfonic acid, 4-nitrobenzenesulfonic acid, hydroxy-O-sulfonic acid, 4-toluenesulfonic acid, calacturonic acid, emboic acid, glutamic acid, aspartic acid, adipic acid, or camsylic acid may be used, and the metal is sodium, Potassium, calcium or magnesium may be used.
  • the fimasartan salt may preferably be a fimasartan potassium salt, hydrochloride, calcium salt, sulfate, adipate salt, camsylate salt or besylate salt, more preferably a potassium salt.
  • a fimasartan potassium salt hydrochloride, calcium salt, sulfate, adipate salt, camsylate salt or besylate salt, more preferably a potassium salt.
  • These can be purchased commercially, and can be prepared by a known method (eg, Republic of Korea Patent Registration No. 0354654).
  • the hydrate may include a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.
  • the solvate may include a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces.
  • the solvent refers to a common organic solvent used in the production of organic compounds, for example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 1-acetate, acetone, acetic acid, no Sol, tetrahydrofuran, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, isobutyl acetate, n-butyl acetate, dimethyl sulfoxide, pentane, heptane, etc., but examples thereof are limited to the solvates of the present invention. It is not.
  • the hydrate and solvate may contain water or solvent in a ratio of about 0.25 to about 10 moles, for example, about 0.5 mole, about 1 mole, about 1 mole of fimasartan potassium. 1.5 mol, about 2 mol, about 2.5 mol, about 3 mol, about 5 mol, etc., more preferably about 1 mol or about 3 mol of water per 1 mol of fimasartan potassium.
  • the pharmaceutical composition may include fimasartan potassium salt monohydrate or fimasartan potassium salt trihydrate.
  • the pharmaceutical composition may contain fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof in an amount of about 5% to about 60% by weight based on the total weight of the composition. It may be included, preferably about 10% by weight to about 50% by weight.
  • the pharmaceutical composition may further include a pharmaceutically acceptable additive.
  • pharmaceutically acceptable means physiologically acceptable and, when administered to humans, usually does not cause allergic reactions such as gastrointestinal disorders, dizziness, or similar reactions. As for commonly used, reference may be made to Remington's Pharmaceutical Science (latest edition), Mack Publishing Company, Easton PA.
  • the additives may be carriers, excipients, extenders, antioxidants, buffers, fillers, anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifiers, suspending agents, surfactants and preservatives.
  • the additives include lactose, dextrose, calcium silicate, corn starch, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Methyl Cellulose, Polyvinylpyrrolidone, Water, Methylhydroxybenzoate, Propylhydroxybenzoate, Talc, Stearic Acid, Magnesium Stearate, Calcium Stearate, Mineral Oil, Saline, Glucose Solution, Pseudosugar Solution, Alcohol, Glycol , ether (eg polyethylene glycol 400), oil, fatty acid, fatty acid ester, glyceride, or a mixture thereof.
  • the additives that may be included in the composition according to the present invention are not limited to the materials listed above, and these are only examples.
  • the pharmaceutical composition of the present invention may be formulated according to a conventional method, and may be prepared as a preparation for oral administration or a preparation for parenteral administration.
  • the pharmaceutical composition of the present invention may be formulated for oral administration.
  • the preparation for oral administration may be a solid preparation such as tablets, pills, powders, granules, capsules, etc., or liquid preparations such as suspensions, solutions for internal use, emulsions, syrups, etc., preferably solid preparations. It can be one, more preferably it can be a tablet.
  • additives used include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate , gelatin, talc, and the like.
  • compositions When the pharmaceutical composition is formulated as a liquid formulation for oral administration, various additives such as simple diluents such as water, liquid, and paraffin, wetting agents, sweeteners, fragrances, preservatives, preservatives, and coloring agents may be added to the pharmaceutical composition to be formulated.
  • the additives include water, saline, aqueous glucose solution, similar aqueous sugar solution, alcohol, glycol, ether (eg polyethylene glycol 400), oil, fatty acid, fatty acid ester, glycerine Ride etc. are mentioned.
  • the content of the additives included in the pharmaceutical composition is not particularly limited and may be appropriately adjusted within the range of content used in conventional formulations.
  • the pharmaceutical composition contains fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof in an amount of about 1 mg to about 240 mg, or about 1 mg to about 240 mg of fimasartan. about 120 mg, about 30 mg to about 180 mg, about 60 mg to about 120 mg, about 60 mg or about 120 mg.
  • the pharmaceutical composition may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically applied), and the dosage is the patient's weight, age, sex, health
  • the range may vary depending on the condition, diet, administration time, administration method, administration period or interval, excretion rate, constitutional specificity, nature of the preparation, severity of the disease, and the like.
  • fimasartan can be administered orally so that the dosage is about 1 mg to about 240 mg per day, preferably about 30 mg to about 180 mg per day. may be applied once a day or divided into several times.
  • the daily dosage of the fimasartan, its pharmaceutically acceptable salt, its stereoisomer or its hydrate or solvate in the pharmaceutical composition is about 1 mg to about 240 mg, about 1 mg to about 120 mg, about 30 mg to about 180 mg, about 60 mg to about 120 mg, about 60 mg or about 120 mg.
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof or a hydrate or solvate thereof is about 1 mg to about 240 mg, or about 1 mg to about It may be administered once a day at a dose of 120 mg, about 30 mg to about 180 mg, about 60 mg to about 120 mg, about 60 mg or about 120 mg.
  • the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof or a hydrate or solvate thereof is about 1 mg to about 240 mg, or about 1 mg to about 120 mg, about 30 to about 180 mg, about 60 mg to about 120 mg, about 60 mg or about 120 mg may be administered once a day for about 24 weeks.
  • the pharmaceutical composition may further contain active ingredients having other pharmacological activities in addition to the fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof.
  • the composition of the present invention may further include an antihypertensive agent, a diuretic agent, a therapeutic agent for hyperlipidemia, an antiobesity agent, or a therapeutic agent for diabetes.
  • the composition of the present invention contains amlodipine, nifedipine, verapamil, diltiazem, nicardipine, Lercardipine, atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, simvastatin, rosuvastatin, nicotinic acid, theophylline, caffeine, theobromine, aminophylline, hydrochlorothiazide, bendroflumethiazide, alogl liptin, saxagliptin, sitagliptin, metformin, exenatide, rosiglitazone, pioglitazone, tolbutamide, troglitazone, leptin, ephedrine, fenfluramine, fluoxetine, and the like.
  • the pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy, and biological response modifiers for the improvement, alleviation, treatment, or prevention of diabetic kidney disease.
  • the present invention prevents or prevents diabetic kidney disease accompanied by hypertension by administering a pharmaceutical composition containing fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof to a subject.
  • a pharmaceutical composition containing fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof provides a way to treat
  • the subject has a systolic blood pressure of 140 mmHg or more and less than 180 mmHg and a diastolic blood pressure of less than 110 mmHg; an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min/1.73 m 2 ; and albuminuria greater than or equal to 30 mg/g.
  • eGFR estimated glomerular filtration rate
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof for preventing or treating diabetic kidney disease accompanied by hypertension.
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof or a hydrate or solvate thereof has a systolic blood pressure of 140 mmHg or more and less than 180 mmHg and a diastolic blood pressure of less than 110 mmHg; an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min/1.73 m 2 ; and albuminuria of 30 mg/g or greater;
  • eGFR estimated glomerular filtration rate
  • the present invention relates to the use of fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof for the preparation of a medicament for preventing or treating diabetic kidney disease accompanied by hypertension. to provide.
  • fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof or a hydrate or solvate thereof has a systolic blood pressure of 140 mmHg or more and less than 180 mmHg and a diastolic blood pressure of less than 110 mmHg; an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min/1.73 m 2 ; and albuminuria of 30 mg/g or greater;
  • eGFR estimated glomerular filtration rate
  • the pharmaceutical composition according to the present invention comprising fimasartan, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a hydrate or solvate thereof, can effectively prevent or treat diabetic kidney disease accompanied by hypertension.
  • the pharmaceutical composition according to the present invention can prevent or inhibit the onset of diabetic kidney disease accompanied by hypertension, and also improve diabetic kidney disease accompanied by hypertension or diabetic kidney disease accompanied by hypertension. The progression or worsening of the disease can be inhibited.
  • Test group A is a standard blood pressure control group with a target systolic blood pressure of less than 140 mmHg
  • test group B is a strict blood pressure control group with a target systolic blood pressure of less than 130 mmHg.
  • ACEI/ARB Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker
  • - Urine protein satisfies one or more of the following conditions
  • CKD chronic kidney disease
  • ACR albuminuria
  • PCR proteinuria
  • At least 2 results of albuminuria (ACR) excretion of 30 mg/g to 300 mg/g (or mg/day) or proteinuria (PCR) excretion of 150 mg/g to 500 mg/g (or mg/day) within 12 months
  • ACR albuminuria
  • PCR proteinuria
  • CKD chronic kidney disease
  • Insulin-dependent diabetes or uncontrolled diabetes those who have changed the type of oral or injection hypoglycemic agent within 12 weeks prior to screening (Visit 1), or those whose HbA1c exceeds 10% at screening (Visit 1) ]
  • autoimmune diseases or connective tissue diseases such as all chronic inflammatory conditions or wasting diseases requiring chronic anti-inflammatory treatment, rheumatoid arthritis, systemic lupus erythematosus, etc.
  • Surgical or medical diseases that may affect drug absorption, distribution, metabolism, and excretion, and any of the following (but not limited to): gastrectomy, gastro-enterostomy ) or history of major gastrointestinal surgery, such as small bowel resection, gastrointestinal bypass, or gastrointestinal stapling, current active gastritis, gastrointestinal/rectal bleeding, active inflammatory bowel syndrome within the past 12 months, etc.
  • Placebo Placebo of Kanarb® tablets 60 mg
  • This phase 3 clinical trial was planned to compare and evaluate the efficacy of fimasartan (test group) on the change in albuminuria (ACR) in patients with diabetic kidney disease accompanied by hypertension, and to confirm the safety.
  • the subject visits the clinical trial institution and receives an ACEI / Antihypertensive drugs other than ARB were added or existing drugs were increased.
  • Group A was a standard blood pressure control group (SBP ⁇ 140 mmHg), and group B was a strict blood pressure control group (SBP ⁇ 130 mmHg).
  • Randomly assigned subjects took the clinical trial drug (fimasartan) corresponding to each administration group for 24 weeks, and then for an additional 120 weeks, while all subjects took fimasartan, disclosed into two groups according to blood pressure control criteria, group 2 , parallel trials are underway.
  • group 2 the dose increase of the investigational drug and concomitant administration of other blood pressure lowering drugs were performed according to the prescribed dose titration criteria.
  • the blood pressure control group was conducted with a single blinding so that group A and group B could be identified, and from Visit 4 (Week 4), the target blood pressure for each group was To control, under the judgment of the previous investigator, the clinical trial drug was doubled or an additional antihypertensive agent other than ACEI/ARB was administered.
  • subjects had a total of 7 visits [screening visit, pre-baseline visit, baseline visit, Visit 4 (4W), Visit 5 (8W), Visit 6 (12W), Visit 7 (24W)], and prescribed tests and evaluations were conducted at each visit.
  • Cardiovascular composite endpoint occurrence of myocardial infarction (MI) and stroke, hospitalization due to heart failure and unstable angina, coronary revascularization and peripheral vascular revascularization revascularization), death (all caused death)
  • MI myocardial infarction
  • stroke hospitalization due to heart failure and unstable angina
  • death all caused death
  • Renal complex evaluation variables when eGFR decreases by 50% or more from baseline, when progression to ESRD is confirmed (initiation of long-term dialysis or kidney transplantation), and death (all caused death)
  • Demographic data and baseline characteristics of all subjects included in this clinical trial were summarized for each administration group using the Full Analysis Set (FAS).
  • FAS Full Analysis Set
  • descriptive statistics number of subjects, mean, standard deviation, median, minimum value, maximum value
  • categorical data were summarized by frequency (N) and ratio (%).
  • N frequency
  • ratio %
  • the main analysis target group was PPS (Per Protocol Set), but the FAS (Full Analysis Set) was also analyzed and evaluated together.
  • Descriptive statistics (number of subjects, mean, standard deviation, median value, minimum value, maximum value) were presented for each administration group for albuminuria levels and change rates at baseline (Visit 2) and week 24 (Visit 7).
  • a one-sample t-test was conducted for the change rate within the administration group, and a two-sample t-test was performed for the difference between the two groups. If the data did not satisfy normality according to the normality test (Shapiro-Wilk statistic), the Wilcoxon signed rank test was used to test the change rate within the treatment group, and the Wilcoxon rank sum test was used to measure the difference between the two groups.
  • cardiovascular, renal, combined cardiovascular and renal composite endpoints was estimated using Kaplan-Meier curves, and median values and 95% confidence intervals were presented. In addition, differences between groups were tested using the Log-rank test. In addition, descriptive statistics (number of subjects, average, standard deviation, median, minimum, maximum) of SBP values at baseline and 24 weeks from baseline for each group were presented.
  • a one-sample t-test or Wilcoxon signed rank test was performed according to the results of the normality test (Shapiro-Wilk statistic) to conduct a within-group test, and the difference between groups was analyzed using covariance analysis with the baseline value as a covariate and the administration group as a factor. was tested, and the least squared mean (Least Squared Mean) and standard error (standard error) of each group and between groups were presented.
  • Adverse reactions were standardized and presented as SOC (System Organ Class) and PT (Preferred Term) using MedDRA (Medical Dictionary for Regulatory Activities) version 22.1, and the proportion of subjects with adverse reactions in each administration group and 95% of them Confidence intervals are presented. All adverse events were organized according to severity, causality, action, treatment, and outcome, and adverse events and serious adverse events that were related to investigational drugs were also organized separately. Chi-square test or Fisher's exact test was performed to test whether there was a difference in the incidence of adverse events between groups.
  • Normal or Abnormal NCS normal or clinically meaningless abnormal
  • Abnormal CS clinically meaningful abnormal
  • the LS (Least Square) Mean ( ⁇ SE) of the change in albuminuria (mg/g) at 4, 8, 12, and 24 weeks from baseline in the fimasartan-administered group in PPS was at 4 weeks -313.62 ( ⁇ 47.73)mg/g, Fimasartan group at 8 weeks -422.77 ( ⁇ 48.03)mg/g, -523.33 ( ⁇ 55.46)mg/g at 12 weeks, -575.51 ( ⁇ 60.76 at 24 weeks) ) mg/g. All showed statistically significant decreases at 4, 8, 12, and 24 weeks from baseline.
  • the LS mean ( ⁇ SE) of the fimasartan group for the change in eGFR at 4, 8, 12, and 24 weeks from baseline in PPS was -0.88 ( ⁇ 0.72) mL/min at 4 weeks. /1.73m2, -2.19 ( ⁇ 0.69)mL/min/1.73m2 at 8 weeks, -2.91 ( ⁇ 0.74)mL/min/1.73m2 at 12 weeks, -4.66 ( ⁇ 0.72)mL/ at 24 weeks At min/1.73m2, there was a statistically significant decrease in eGFR change in all of the administration groups at 8, 12, and 24 weeks from the baseline, except for the 4th week.
  • the average ( ⁇ SD) eGFR change rate (%) at 4, 8, 12, and 24 weeks from baseline in the fimasartan-administered group was -1.15 ( ⁇ 14.16)% at 4 weeks, 8 -4.05 ( ⁇ 11.99)% at week, -5.56 ( ⁇ 14.19)% at 12 weeks, and -8.49 ( ⁇ 13.55)% at 24 weeks.
  • Statistically significant eGFR reduction rates (%) were shown at 8, 12, and 24 weeks from the baseline, excluding the 4th week.
  • the albuminuria excretion was 300 mg/g at 4, 8, 12, and 24 weeks compared to baseline in the fimasartan group.
  • the percentage of subjects who changed below was 11.29% (14/124) at 4 weeks, 20.16% (25/124) at 8 weeks, 17.74% (22/124) at 12 weeks, and 17.74% (22/124) at 24 weeks The time point appeared in 26.61% (33/124 people).
  • the albuminuria excretion was less than 30 mg/g at 4, 8, 12, and 24 weeks compared to baseline in the fimasartan group.
  • the percentage of subjects who changed was 3.85% (1/26 patients) at 4 weeks, 11.54% (3/26 patients) at 8 weeks, 11.54% (3/26 patients) at 12 weeks, and 11.54% (3/26 patients) at 24 weeks. 30.77% (8/26).
  • the proportion of subjects whose albuminuria decreased by 30% or more at 4, 8, 12, and 24 weeks compared to the baseline of the fimasartan group in PPS was 50.67% (76/150 patients) at 4 weeks, 57.33% (86/150 patients) at 8 weeks, 65.33% (98/150 patients) at 12 weeks, and 70.67% (106/150 patients) at 24 weeks.
  • group A standard blood pressure control group; SBP ⁇ 140 mmHg
  • group B strict blood pressure control group; SBP ⁇ 130 mmHg
  • group A at 4 weeks -209.49 ( ⁇ 47.04) mg/g , Group B -296.72 ( ⁇ 48.35)mg/g, at 8 weeks, Group A -301.44 ( ⁇ 48.26)mg/g, Group B -378.06 ( ⁇ 48.61)mg/g, at 12 weeks, Group A -382.48 ( ⁇ 56.74) mg/g, group B -409.07 ( ⁇ 57.98) mg/g, at 24 weeks, group A -394.94 ( ⁇ 60.60) mg/g, group B -530.56 ( ⁇ 61.62) mg/g. All treatment groups showed a statistically significant decrease in albuminuria at all time points (all p ⁇ 0.0001).
  • the LS Mean Difference ( ⁇ SE) for the change in albuminuria between the administration groups (group A - group B) was 87.24 ( ⁇ 67.46) mg/g at 4 weeks, 76.62 ( ⁇ 68.51) mg/g at 8 weeks, 12 weeks 26.59 ( ⁇ 81.16)mg/g at the time point and 135.62 ( ⁇ 86.47)mg/g at the 24th week. There was no statistically significant difference between the administration groups at 4, 8, 12, and 24 weeks.
  • the average ( ⁇ SD) change in albuminuria at 4, 8, 12, and 24 weeks from baseline was -16.35 ( ⁇ 45.46)% in group A at 4 weeks, -18.99 ( ⁇ 39.03)% in group B, and -18.99 ( ⁇ 39.03)% in group A at 8 weeks from baseline.
  • the mean difference ( ⁇ SE) for the change in albuminuria between the administration groups was 2.64 ( ⁇ 4.99)% at 4 weeks, 7.36 ( ⁇ 5.61)% at 8 weeks, 1.55 ( ⁇ 5.34)% at 12 weeks, and 24 weeks was 7.09 ( ⁇ 6.88)%.
  • group B Strict BP Control
  • group A Standard BP Control
  • the eGFR change (LS Mean ( ⁇ SE)) at 4, 8, 12, and 24 weeks from the baseline according to the blood pressure control criteria was -0.55 ( ⁇ 0.71)mL/min/1.73m2 in group A at 4 weeks.
  • both groups A and B showed a statistically significant decrease in eGFR compared to the baseline.
  • the LS Mean Difference ( ⁇ SE) for the difference in eGFR change between blood pressure control standards was 0.01 ( ⁇ 1.02) mL/min/1.73m2 at 4 weeks and 0.46 ( ⁇ 0.99) mL/min/1.73m2 at 8 weeks.
  • the mean ( ⁇ SD) eGFR change rate at 4, 8, 12, and 24 weeks from baseline was -1.25 ( ⁇ 13.04)% in group A at 4 weeks, -0.34 ( ⁇ 12.78)% in group B, and -0.34 ( ⁇ 12.78)% in group B at 8 weeks.
  • the mean difference ( ⁇ SE) for the eGFR change rate between the administration groups was -0.91( ⁇ 1.52)% at 4 weeks, -0.31( ⁇ 1.57)% at 8 weeks, and -1.23( ⁇ 1.66)% at 12 weeks, 24
  • the main time point was -0.42 ( ⁇ 1.64)%, and the difference in change rate between the administration groups was not statistically significant at all time points.
  • albuminuria excretion was 300 mg/g at 4, 8, 12, and 24 weeks compared to the baseline according to blood pressure control criteria.
  • the percentage of subjects who changed below was 12.10% (15/124) in group A at 4 weeks, 7.32% (9/123) in group B, 16.13% (20/124) in group A at 8 weeks, 12.20% (15/123) in group B, 16.94% (21/124) in group A at 12 weeks, 11.38% (14/123) in group B and 21.77% (27/124) in group A at 24 weeks ), 23.58% (29/123) in group B, and there was no statistically significant difference between the administration groups at any time point.
  • the ratio of subjects whose albuminuria excretion changed to less than 30 mg/g at 4, 8, 12, and 24 weeks from baseline was 6.90% (2/29) in group A at 4 weeks, Group B 4.00% (1/25 patients), at 8 weeks, group A 6.90% (2/29 patients), group B 12.00% (3/25 patients), at 12 weeks, group A 6.90% (2/29 patients) ), group B 16.00% (4/25 patients), at 24 weeks, group A 20.69% (6/29 patients), group B 20.00% (5/25 patients).
  • the proportion of subjects whose albuminuria excretion changed to less than 30 mg/g was high, there was no statistically significant difference between the two administration groups at all time points.
  • the ratio of subjects whose albuminuria decreased by 30% or more at 4, 8, 12, and 24 weeks compared to the baseline according to the blood pressure control criteria in PPS was 40.52% (62/153) in group A at 4 weeks persons), Group B 42.57% (63/148 persons), Group A 47.06% (72/153 persons) at 8 weeks, Group B 47.30% (70/148 persons), Group A 53.59% (82 persons) at 12 weeks /153 patients), 55.41% (82/148 patients) in group B, and 53.59% (82/153 patients) in group A and 68.92% (102/148 patients) in group B at 24 weeks.
  • the proportion of subjects whose eGFR decreased by 50% or more at weeks 4, 8, 12, and 24 compared to the baseline according to the blood pressure control criteria in PPS was 50% or more at 4 and 12 weeks. There were no subjects who decreased, and 0.65% (each 1/153) occurred in group A at 8 weeks and 24 weeks, but there was no statistically significant difference between the administration groups.
  • the 4-week time point was -13.51 ( ⁇ 1.20) mmHg, -16.96 ( ⁇ 1.23) mmHg at 8 weeks, -19.12 ( ⁇ 1.18) mmHg in the fimasartan group at 12 weeks, and -16.53 ( ⁇ 1.23) mmHg at 24 weeks.
  • the fimasartan group showed a statistically significant decrease from baseline at 4, 8, 12, and 24 weeks (all p ⁇ 0.0001).
  • SADRs serious adverse drug reactions
  • the purpose of this clinical trial was to evaluate the efficacy and safety of fimasartan and blood pressure control criteria when administered orally for 24 weeks in patients with diabetic kidney disease accompanied by hypertension.
  • the eGFR change amount and change rate at 4, 8, 12, and 24 weeks compared to the baseline showed a significant decrease in eGFR at 8, 12, and 24 weeks, except for the 4-week time point.
  • the pharmaceutical composition according to the present invention can have a systolic blood pressure of 140 mmHg or more and less than 180 mmHg and a diastolic blood pressure of less than 110 mmHg; an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min/1.73 m 2 ; And it can be administered to a subject having albuminuria of 30 mg/g or more to prevent or treat diabetic kidney disease accompanied by hypertension.
  • eGFR estimated glomerular filtration rate

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)

Abstract

La composition pharmaceutique de la présente invention peut prévenir ou traiter efficacement une néphropathie diabétique accompagnée d'hypertension par blocage, suppression ou retardement de l'apparition d'une néphropathie diabétique accompagnée d'hypertension à l'avance ou en atténuant la néphropathie diabétique accompagnée d'hypertension ou en supprimant la progression d'une néphropathie diabétique accompagnée d'hypertension.
PCT/KR2022/007699 2021-06-01 2022-05-30 Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie diabétique accompagnée d'hypertension WO2022255760A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020210070939A KR20220162456A (ko) 2021-06-01 2021-06-01 고혈압을 동반한 당뇨병성 신장질환의 예방 또는 치료용 약학적 조성물
KR10-2021-0070939 2021-06-01

Publications (1)

Publication Number Publication Date
WO2022255760A1 true WO2022255760A1 (fr) 2022-12-08

Family

ID=84324416

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/007699 WO2022255760A1 (fr) 2021-06-01 2022-05-30 Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie diabétique accompagnée d'hypertension

Country Status (2)

Country Link
KR (1) KR20220162456A (fr)
WO (1) WO2022255760A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101345876B1 (ko) * 2012-01-31 2013-12-30 인제대학교 산학협력단 피마사르탄을 함유하는 세포, 조직 또는 장기 보존용 조성물
KR20140008049A (ko) * 2012-07-10 2014-01-21 보령제약 주식회사 심부전증 예방, 완화 및 치료용 약학 조성물 및 이를 포함하는 복합제제
KR101414873B1 (ko) * 2012-06-28 2014-07-03 보령제약 주식회사 피마살탄 및 히드로클로로티아지드가 함유된 약제학적 조성물
KR20170006938A (ko) * 2015-07-10 2017-01-18 보령제약 주식회사 만성 신부전의 예방 또는 치료용 조성물
KR102022694B1 (ko) * 2019-02-20 2019-09-18 주식회사 네비팜 약학 조성물
KR102233673B1 (ko) * 2016-01-27 2021-03-30 보령제약 주식회사 당뇨병성 신장질환의 예방 또는 치료용 약학적 조성물

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR19990081093A (ko) 1998-04-25 1999-11-15 조생현 피리미디논 화합물, 이를 함유하는 약제학적 조성물 및 이의제조방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101345876B1 (ko) * 2012-01-31 2013-12-30 인제대학교 산학협력단 피마사르탄을 함유하는 세포, 조직 또는 장기 보존용 조성물
KR101414873B1 (ko) * 2012-06-28 2014-07-03 보령제약 주식회사 피마살탄 및 히드로클로로티아지드가 함유된 약제학적 조성물
KR20140008049A (ko) * 2012-07-10 2014-01-21 보령제약 주식회사 심부전증 예방, 완화 및 치료용 약학 조성물 및 이를 포함하는 복합제제
KR20170006938A (ko) * 2015-07-10 2017-01-18 보령제약 주식회사 만성 신부전의 예방 또는 치료용 조성물
KR102233673B1 (ko) * 2016-01-27 2021-03-30 보령제약 주식회사 당뇨병성 신장질환의 예방 또는 치료용 약학적 조성물
KR102022694B1 (ko) * 2019-02-20 2019-09-18 주식회사 네비팜 약학 조성물

Also Published As

Publication number Publication date
KR20220162456A (ko) 2022-12-08

Similar Documents

Publication Publication Date Title
WO2018030879A1 (fr) Composition pharmaceutique comprenant comme principes actifs de l'amodiaquine et un médicament anti-diabète, destinée à la prévention ou le traitement du diabète
WO2011052950A2 (fr) Composition pharmaceutique contenant un composé indole
WO2021246797A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'un cancer et contenant un agent antiviral et un antidépresseur en tant que principes actifs
WO2021256861A1 (fr) Nouvel inhibiteur de sécrétion d'acide et son utilisation
WO2020106119A1 (fr) Composition pharmaceutique comprenant des inhibiteurs de l'histone-désacétylase 6
WO2022255760A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie diabétique accompagnée d'hypertension
WO2019182276A1 (fr) Préparation d'une association de produits pharmaceutiques comprenant de l'ézétimibe et de la rosuvastatine
WO2016052866A1 (fr) Composition pharmaceutique solide comportant de l'amlodipine et du losartan
WO2010044637A2 (fr) Composition pharmaceutique et medicament pour la prevention et le traitement de diabetes ou de l'obesite comprenant comme principe actif, un compose qui inhibe l'activation de dipeptidyl peptidase-iv
WO2018199636A1 (fr) Formulation combinée comprenant un inhibiteur de la hmg-coa réductase et un bloqueur des canaux calciques
WO2022240218A1 (fr) Composition pharmaceutique de régulation de la tension artérielle chez un sujet souffrant d'accident ischémique cérébral ou d'attaque ischémique transitoire
WO2020204609A1 (fr) Composition pharmaceutique comprenant de l'esoméprazole ou un sel pharmaceutiquement acceptable de ce dernier, et présentant un profil à double libération
WO2018151580A1 (fr) Préparation pharmaceutique à libération immédiate et à libération prolongée contenant du chlorhydrate d'itopride
WO2022075780A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'une vessie hyperactive
WO2021100897A1 (fr) Composition pharmaceutique pour la prévention ou le traitement du cancer, comprenant un composé à base de biguanide et du ferrocène ou un dérivé de ferrocène en tant que principes actifs
WO2024076177A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'une néphropathie et/ou du diabète sucré, comprenant de l'énavogliflozine
WO2018101762A1 (fr) Composition pharmaceutique de prévention ou de traitement d'une lésion rénale aiguë ischémique, comprenant un dérivé tricyclique ou un sel pharmaceutiquement acceptable de ce dernier
WO2022203432A1 (fr) Composition pharmaceutique contenant du fumarate de diméthyle en tant que principe actif, présentant un paramètre pharmacocinétique spécifique
WO2016209061A1 (fr) Préparation composite de mosapride et de rabéprazole
WO2021251644A1 (fr) Préparation pharmaceutique complexe, pour la prévention ou le traitement d'une maladie cardiovasculaire, comprenant de l'amlodipine, du losartan et de la chlortalidone dans un comprimé monocouche
WO2024063568A1 (fr) Composition et polythérapie pour le traitement du diabète sucré de type 2
WO2019139365A1 (fr) Nouveau dérivé d'oxazole phénylsulfonyle et son utilisation
WO2020130696A1 (fr) Composition comprenant un composé inhibant le cyp4a utilisé comme principe actif pour la prévention ou le traitement de maladies métaboliques
WO2019078592A1 (fr) Composition pharmaceutique pour la prévention ou le traitement de maladies cardiovasculaires accompagnées de diabète, comprenant de l'amlodipine, du losartan et de la rosuvastatine, et préparation composite comprenant celle-ci
WO2009125944A2 (fr) Préparation pharmaceutique contenant un inhibiteur des canaux calciques non dihydropyridine et un inhibiteur du récepteur de l'angiotensine 2

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22816419

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE