WO2023025220A1 - Composition pharmaceutique d'ibuprofène et d'antagoniste d'ions calcium, et application - Google Patents
Composition pharmaceutique d'ibuprofène et d'antagoniste d'ions calcium, et application Download PDFInfo
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- WO2023025220A1 WO2023025220A1 PCT/CN2022/114659 CN2022114659W WO2023025220A1 WO 2023025220 A1 WO2023025220 A1 WO 2023025220A1 CN 2022114659 W CN2022114659 W CN 2022114659W WO 2023025220 A1 WO2023025220 A1 WO 2023025220A1
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- WIPO (PCT)
- Prior art keywords
- arni
- amlodipine
- pharmaceutical composition
- calculated
- composition according
- Prior art date
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- 241000320892 Clerodendrum phlomidis Species 0.000 title claims abstract description 66
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 33
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 239000005557 antagonist Substances 0.000 title claims abstract description 14
- 229910001424 calcium ion Inorganic materials 0.000 title claims abstract description 14
- 206010020772 Hypertension Diseases 0.000 claims abstract description 14
- 206010019280 Heart failures Diseases 0.000 claims abstract description 13
- 229960000528 amlodipine Drugs 0.000 claims description 67
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 64
- 239000003814 drug Substances 0.000 claims description 27
- 229940079593 drug Drugs 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 13
- HTIQEAQVCYTUBX-KRWDZBQOSA-N (S)-amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-KRWDZBQOSA-N 0.000 claims description 8
- 229950008554 levamlodipine Drugs 0.000 claims description 8
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 claims description 7
- 229960004005 amlodipine besylate Drugs 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- PYNXFZCZUAOOQC-UTKZUKDTSA-N sacubitril Chemical compound C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC(O)=O)=CC=C1C1=CC=CC=C1 PYNXFZCZUAOOQC-UTKZUKDTSA-N 0.000 claims description 6
- 229960003953 sacubitril Drugs 0.000 claims description 6
- TZNOWAJJWCGILX-BTJKTKAUSA-N (z)-but-2-enedioic acid;3-o-ethyl 5-o-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound OC(=O)\C=C/C(O)=O.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl TZNOWAJJWCGILX-BTJKTKAUSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- RWNNRGBCWXOVAC-UHFFFAOYSA-N 1,4-bis[bis(aziridin-1-yl)phosphoryl]piperazine Chemical compound C1CN1P(N1CCN(CC1)P(=O)(N1CC1)N1CC1)(=O)N1CC1 RWNNRGBCWXOVAC-UHFFFAOYSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000036772 blood pressure Effects 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 8
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 6
- 229960004699 valsartan Drugs 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 101100288143 Rattus norvegicus Klkb1 gene Proteins 0.000 description 2
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009530 blood pressure measurement Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000011706 wistar kyoto rat Methods 0.000 description 2
- TZNOWAJJWCGILX-HNUXRKMMSA-N (z)-but-2-enedioic acid;3-o-ethyl 5-o-methyl (4s)-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound OC(=O)\C=C/C(O)=O.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC=C1Cl TZNOWAJJWCGILX-HNUXRKMMSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 229940126905 angiotensin receptor-neprilysin inhibitor Drugs 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 208000038003 heart failure with preserved ejection fraction Diseases 0.000 description 1
- 208000038002 heart failure with reduced ejection fraction Diseases 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Definitions
- the invention belongs to the technical field of pharmaceutical compositions, and relates to a pharmaceutical composition and application of ARNi and a calcium ion antagonist.
- WO2007056546A1 discloses a sodium salt complex (LCZ696) of Valsartan (Sacubitril, AHU377) and its preparation method, which was approved for marketing in China in 2017. The trade name is: (Commodities listed abroad are named 2015) for heart failure. Its molecular structure unit is as follows:
- WO2017125031A1 discloses a series of complexes composed of metabolites of angiotensin receptor antagonist (EXP3174) and NEP inhibitor (Sacubitril), the molecular structural units of which are as follows:
- Amlodipine is a calcium ion antagonist that acts directly on peripheral arterial smooth muscle to reduce peripheral vascular resistance, thereby lowering blood pressure. Its existing forms include racemic amlodipine, levamlodipine, dexamlodipine, or a mixture of levamlodipine and dexamlodipine in any ratio; and, amlodipine can exist in the form of a salt, Including amlodipine besylate, amlodipine maleate, etc.
- the object of the present invention is to provide a pharmaceutical composition, characterized in that the pharmaceutical composition is composed of ARNi and a calcium ion antagonist, wherein the structural unit of ARNi is as follows:
- ARNi The structural formula of ARNi is as follows:
- n is selected from 1, 1.5, 2, 2.5 and 3.
- ARNi can be obtained through the preparation methods of WO2017125031A1 and WO2021143898A1, and the related preparation methods and obtained substances are introduced into this patent.
- ARNi is preferably selected from:
- the calcium ion antagonist is selected from amlodipine.
- the mass ratio of the ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) to amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) is 240: 1.25 ⁇ 20.
- the mass ratio of the ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) to amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) is 240: 1.25, 240:2.5, 240:5, 240:7.5 and 240:10, preferably 240:5.
- ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) in the pharmaceutical composition is selected from 60-480 mg.
- the ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) is selected from 60, 120, 240, 300, 360, 420 and 480 mg.
- the amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) in the pharmaceutical composition is selected from 2.5-10 mg.
- the amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) is selected from 2.5, 5, 7.5 and 10 mg.
- the pharmaceutical composition is composed of ARNi and a calcium ion antagonist, including:
- ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) 120 mg, amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) 2.5 mg;
- ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) 240 mg, amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) 5 mg;
- ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) 360 mg, amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) 7.5 mg;
- ARNi (calculated as anhydrous free acid C 46 H 50 ClN 7 O 7 ) 480 mg, amlodipine (calculated as C 20 H 25 N 2 O 5 Cl) 10 mg.
- amlodipine Selected from racemic amlodipine, levamlodipine Dexamlodipine, or a mixture of levamlodipine and dexamlodipine in any proportion; amlodipine is in the form of a salt, selected from amlodipine besylate Amlodipine maleate, and levamlodipine besylate, levamlodipine maleate wait.
- the pharmaceutical composition also contains more than one pharmaceutically acceptable carrier, and the pharmaceutical composition is prepared into a suitable pharmaceutical dosage form by preparation means, and the dosage form includes solid oral dosage forms and the like.
- the present invention further provides the use of a pharmaceutical composition, wherein the pharmaceutical composition is used in the preparation of medicines for the treatment of heart failure and/or hypertension, and the hypertension includes essential hypertension, so
- the above-mentioned heart failure includes heart failure with reduced ejection fraction and heart failure with preserved ejection fraction.
- the use includes the application of ARNi as a drug for hypertension/heart failure patients poorly controlled by single drug, or the application of calcium ion antagonist as a drug for patients with hypertension/heart failure poorly controlled by single drug.
- the present invention has the following advantages and beneficial effects:
- the present invention provides a combination of ARNi and calcium ion antagonist, the combination achieves synergistic effect through the specific mass ratio of ARNi and calcium ion antagonist, which is beneficial to improve the effect of treating heart failure and/or hypertension.
- the combination of amlodipine and the drug of the present invention increases the exposure of the angiotensin receptor antagonist ARB (the EXP3174 of the ARNi complex of the present invention compared to the valsartan of LCZ696) obvious.
- the use of the drug combination further includes the application of ARNi single-drug poorly controlled hypertension/heart failure patients, or the drug of calcium ion antagonist single-drug poorly controlled hypertension/heart failure patients applications have better results.
- the raw materials used in the present invention can be obtained by known preparation methods in the prior art, including the methods described in WO2017125031A1 and WO2021143898A1.
- ARNi in the embodiment of the present invention is a compound of the following formula, and its usage amount is based on anhydrous free acid C 46 H 50 ClN 7 O 7 :
- amlodipine used is amlodipine besylate, and the usage amount is based on free concentration C 20 H 25 N 2 O 5 Cl:
- ARNi Accurately weigh ARNi, LCZ696 and amlodipine besylate, add 0.5% CMC-Na and vortex dispersion respectively, so that the concentration of ARNi or LCZ696 is 48 mg/mL, and the concentration of amlodipine (free concentration) is 0.125, 0.25, 0.5, 1.0, 2.0 and 4.0 mg/mL.
- EXP3174 after oral administration of ARNi and amlodipine in different ratios to rats showed different changes compared with the single drug administration of the same dose of ARNi. Compared with 240mg/kg ARNi single drug, the exposure decreased (about 11.5%), but with the increase of ARNi and amlodipine ratio, the exposure of EXP3174 increased compared with the ARNi single drug group, Among them, ARNi and amlodipine administered at a ratio of 240:5 increased the exposure of EXP3174 with the highest ratio (increased ratio was 35.8%).
- the rat PK experiment shows that the combination of ARNi and amlodipine of the present invention is better than ARNi alone, and also better than the combination of LCZ696 and amlodipine.
- EXP3174 and AHU377 achieve a synergistic effect of EXP3174 exposure through the combination of the complex ARNi composed of 1.5Ca and amlodipine (according to the free concentration mass ratio of 240:1.25-20, especially the mass ratio of 240:5). Use can enhance the effect for hypertension and/or heart failure.
- WKY rats and SHR rats were purchased from Beijing Weitong Lihua Biotechnology Co., Ltd., and they entered the animal room at the age of 13 weeks, and the experiments were carried out after about 2 weeks of pot life.
- Test substances ARNi, amlodipine and LCZ696 were provided by Shenzhen Xinlitai Pharmaceutical Co., Ltd.
- Drug preparation 0.5% CMC-Na is used for preparation, and the concentration of the prepared drugs is calculated in anhydrous free form.
- mice On the day before the administration, the animals were randomly divided into 4 groups according to their basal blood pressure and body weight. See Table 3 for the specific grouping and administration scheme.
- group 3 and group 4 selected rats with poor blood pressure control (SBP ⁇ 140mmHg) according to the 24h blood pressure control situation to continue the experiment, and group 4 was randomly divided into three groups (group 4, group 5, group 6), see Table 4 for the specific grouping and dosing regimen.
- the amount of ARNi complex used in this example is based on anhydrous free acid C 46 H 50 ClN 7 O 7 .
- the amlodipine used is amlodipine besylate, and its usage amount is calculated by free concentration C 20 H 25 N 2 O 5 Cl.
- WKY rats and SHR rats were purchased from Beijing Weitong Lihua Biotechnology Co., Ltd., and they entered the animal room at the age of 13 weeks, and the experiments were carried out after about 2 weeks of pot life.
- Test substances ARNi and amlodipine were provided by Shenzhen Xinlitai Pharmaceutical Co., Ltd.
- Drug preparation 0.5% CMC-Na is used for preparation, and the concentration of the prepared drugs is calculated in anhydrous free form.
- mice On the day before the administration, the animals were randomly divided into 4 groups according to their basal blood pressure and body weight. See Table 6 for the specific grouping and administration scheme.
- group 3 and group 4 selected rats with poor blood pressure control (SBP ⁇ 140mmHg) according to the 24h blood pressure control situation to continue the experiment, group 3 was randomly divided into two groups (group 3, group 5), See the table for specific groups and dosing regimens. .
- the amount of ARNi complex used in this example is based on anhydrous free acid C 46 H 50 ClN 7 O 7 .
- the amlodipine used is amlodipine besylate, and its usage amount is calculated by free concentration C 20 H 25 N 2 O 5 Cl.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202280006430.7A CN116157119A (zh) | 2021-08-26 | 2022-08-25 | 一种ARNi与钙离子拮抗剂的药物组合物与应用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110985830.4 | 2021-08-26 | ||
CN202110985830 | 2021-08-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2023025220A1 true WO2023025220A1 (fr) | 2023-03-02 |
Family
ID=85322511
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2022/114659 WO2023025220A1 (fr) | 2021-08-26 | 2022-08-25 | Composition pharmaceutique d'ibuprofène et d'antagoniste d'ions calcium, et application |
Country Status (4)
Country | Link |
---|---|
CN (1) | CN116157119A (fr) |
AR (1) | AR126886A1 (fr) |
TW (1) | TW202327582A (fr) |
WO (1) | WO2023025220A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024027779A1 (fr) * | 2022-08-04 | 2024-02-08 | 深圳信立泰药业股份有限公司 | Nouvelle forme cristalline de composé arni, son procédé de préparation et son utilisation |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102702119A (zh) * | 2005-11-09 | 2012-10-03 | 诺瓦提斯公司 | 血管紧张素受体拮抗剂和nep抑制剂的药物组合产品 |
WO2017125031A1 (fr) * | 2016-01-20 | 2017-07-27 | 深圳信立泰药业股份有限公司 | Métabolite antagoniste du récepteur de l'angiotensine ii et composite inhibiteur de la nep, et procédé de préparation associé |
CN109865139A (zh) * | 2017-12-04 | 2019-06-11 | 深圳信立泰药业股份有限公司 | 一种阿利沙坦酯或其盐与钙离子通道拮抗剂的复方药物组合物 |
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2022
- 2022-08-25 TW TW111131990A patent/TW202327582A/zh unknown
- 2022-08-25 WO PCT/CN2022/114659 patent/WO2023025220A1/fr active Application Filing
- 2022-08-25 CN CN202280006430.7A patent/CN116157119A/zh active Pending
- 2022-08-26 AR ARP220102306A patent/AR126886A1/es unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102702119A (zh) * | 2005-11-09 | 2012-10-03 | 诺瓦提斯公司 | 血管紧张素受体拮抗剂和nep抑制剂的药物组合产品 |
WO2017125031A1 (fr) * | 2016-01-20 | 2017-07-27 | 深圳信立泰药业股份有限公司 | Métabolite antagoniste du récepteur de l'angiotensine ii et composite inhibiteur de la nep, et procédé de préparation associé |
CN109865139A (zh) * | 2017-12-04 | 2019-06-11 | 深圳信立泰药业股份有限公司 | 一种阿利沙坦酯或其盐与钙离子通道拮抗剂的复方药物组合物 |
Non-Patent Citations (6)
Title |
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WO2024027779A1 (fr) * | 2022-08-04 | 2024-02-08 | 深圳信立泰药业股份有限公司 | Nouvelle forme cristalline de composé arni, son procédé de préparation et son utilisation |
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