WO2022265442A1 - 1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산을 포함하는 경구용 제제 - Google Patents
1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산을 포함하는 경구용 제제 Download PDFInfo
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- WO2022265442A1 WO2022265442A1 PCT/KR2022/008582 KR2022008582W WO2022265442A1 WO 2022265442 A1 WO2022265442 A1 WO 2022265442A1 KR 2022008582 W KR2022008582 W KR 2022008582W WO 2022265442 A1 WO2022265442 A1 WO 2022265442A1
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Classifications
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- 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
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
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Definitions
- the present invention is an oral formulation containing a high content of 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid) and having an excellent average dissolution rate without including a pH adjusting agent. It's about formulations.
- Xanthine oxidase is an enzyme that converts hypoxanthine into xanthine and converts the formed xanthine into uric acid. Diseases associated with uric acid accumulation, such as related diseases, can be effectively treated.
- Korean Patent Publication No. 1751325 (Patent Document 1) relates to substances that inhibit the activity of xanthine oxidase, 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carb A boxylic acid (formula 1 below) and a method for preparing the compound are provided, and Korean Patent Publication No. 1424013 (Patent Document 2) provides various types of crystal forms obtained using various solvents and a method for preparing the same.
- a pH modifier is added to increase solubility at a specific pH.
- Methods that induce drug release are generally used.
- an enteric coating that prevents dissolution or release by gastric acid before reaching the small intestine is used to induce absorption in the small intestine, which is the main absorption organ of the drug, or enteric encapsulation Drug release is controlled in a variety of ways, such as by preventing absorption or release at a specific pH.
- 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid of Formula 1 or a pharmaceutically acceptable salt thereof is used as an active pharmaceutical ingredient (API).
- API active pharmaceutical ingredient
- Patent Document 1 Republic of Korea Patent Publication No. 1751325 (2017.06.21.), A novel compound effective as a xanthine oxidase inhibitor, a method for preparing the same, and a pharmaceutical composition containing the same
- Patent Document 2 Korean Patent Publication No. 1424013 (2014.07.22.), 1-(3-cyano-1-isopropyl-indol-5-yl) pyrazole-4-carboxylic acid crystalline form and its manufacturing method
- a high content of 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API, while at a target pH of pH 6.8 It is an object to be solved by the present invention to derive an oral formulation having a specifically high dissolution rate.
- the present invention includes an API of 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof and an excipient, particularly the pH
- an oral formulation having a specifically high dissolution rate at a target pH even without a regulator or an enteric coating layer, and a method for preparing the oral formulation.
- the oral formulation of the present invention has a dissolution rate of 65% or more in 15 minutes, 80% or more in 30 minutes, and 60 minutes when using 900 ml of pH 6.8 buffer as a dissolution medium and using a paddle with a rotation speed of 50 rpm.
- the dissolution rate in is more than 90%.
- the content of the API contained in the oral preparation of the present invention is 50mg, 100mg or 200mg per preparation.
- the oral formulation of the present invention is used for the treatment or prevention of xanthine oxidase-related diseases selected from the group consisting of hyperuricemia, gout, heart failure, cardiovascular diseases, hypertension, diabetes, kidney diseases, inflammatory and joint diseases, and inflammatory bowel diseases. .
- Oral preparations containing 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof according to the present invention as an API are pH adjusting agents Alternatively, even if it does not contain an enteric coating layer, it shows a dissolution characteristic that shows a specifically high dissolution rate at the target pH of pH 6.8, so high productivity and patient intake convenience with a small weight or size can be expected through the use of minimal additives and process simplification. can
- Figure 2 is the result of analyzing the average dissolution rate (%) of the capsule according to the pH of the dissolution medium (buffer).
- dissolution and release represent the dissolution of an oral preparation in a buffer in the dissolution test method using the paddle method of the dissolution test method of the Korean Pharmacopoeia, and the dissolution rate or average dissolution rate by analyzing the concentration of API dissolved in the buffer.
- dissolution and release have the same meaning and may be used interchangeably without being distinguished from each other.
- oral formulation may be any formulation known in the art, for example, tablets, capsules, granules, powders, oral solutions, syrups, or pills, but is not limited thereto.
- the oral formulation used in the examples of the present invention contains API 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid and pharmaceutically acceptable additives. It is a tablet or capsule.
- pharmaceutically acceptable salt means a salt form of a compound that does not cause serious irritation to the organism to which the compound is administered and does not impair the biological activity and physical properties of the compound.
- 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid which is an API included in the oral formulation of the present invention, can be converted into a salt thereof by a conventional method. .
- human xanthine oxidase-related diseases refers to diseases that can be treated or prevented by inhibiting human xanthine oxidase, such as hyperuricemia, gout, heart failure, cardiovascular diseases, hypertension, diabetes, diabetes-related complications, Kidney disease, joint disease, inflammatory bowel disease, etc. may be mentioned, but is not limited to only the above-mentioned diseases.
- the diabetes-related complications include hyperlipidemia, arteriosclerosis, obesity, hypertension, retinopathy, renal failure, and the like.
- treatment means stopping or delaying the progression of a disease when used on an object showing symptoms of disease
- prevention means stopping or delaying the symptoms of disease when used on an object that does not show symptoms of disease but is at high risk. means to do
- an API selected from 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof is included in a high content, but at a dissolution rate Various studies were conducted on oral preparations with excellent or good bioavailability.
- the inventors of the present invention provide an oral formulation comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API,
- an oral formulation comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API
- the present invention includes 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof, and as an excipient a pH adjusting agent or enteric-soluble
- a pH adjusting agent or enteric-soluble Provided is an oral preparation having a high dissolution rate that does not include a coating layer.
- the oral preparation may be a tablet or capsule.
- oral preparations In preparing oral formulations, various types of pharmaceutically acceptable excipients are added to optimize basic physical properties such as compression, hardness, friability, and flowability.
- oral preparations must first pass through the digestive tract, including the stomach, for their action, and since the stomach is a strong acidic environment of pH 1-2, which can cause API degradation, the oral preparations are In order to prevent dissolution (or release), various release control methods are being studied.
- a typical method for controlling the release of the oral preparation is to include an enteric coating layer on the outside of the oral preparation to prevent dissolution in an acidic environment, use a pH adjusting agent to dissolve in a desired pH environment, or use various types of polymers.
- Westernization techniques are being used.
- all of these methods have disadvantages in that the size of the preparation is increased by the use of additional excipients or the addition of a coating layer, thereby reducing the convenience of taking, and inevitably lowering productivity due to an additional process in the production process.
- the oral preparation of the present invention is an oral preparation having an excellent dissolution rate even if it does not contain a pH adjusting agent or an enteric coating layer.
- the present invention includes i) 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API, ii) a pH adjusting agent Or it provides an oral preparation that does not contain an enteric coating layer and a method for preparing the oral preparation.
- the oral preparation of the present invention Since the oral preparation of the present invention was hardly eluted when pH 1.2 buffer or pH 4.5 buffer was used as the dissolution medium in the uncoated state, the oral preparation of the present invention does not require an enteric coating layer.
- the oral formulation of the present invention shows a very low dissolution rate of less than 10% at 60 minutes when purified water is used as a dissolution medium.
- the oral formulation of the present invention has a dissolution rate of 65% or more in 15 minutes and 80% or more in 30 minutes in the uncoated state when using 900 ml of pH 6.8 buffer as a dissolution medium and using a paddle with a rotation speed of 50 rpm. , the dissolution rate at 60 minutes is more than 90%. Therefore, even if the oral preparation of the present invention does not contain a pH adjusting agent, it can be expected to have a very excellent dissolution rate specifically at pH 6.8, which is the desired pH, and to have excellent bioavailability reflecting this.
- the oral formulation of the present invention is hardly eluted in the stomach, but is specifically eluted in the intestine and absorbed in the body.
- the oral preparation further includes one or more excipients selected from pharmaceutically acceptable diluents, disintegrants, glidants, lubricants, and the like.
- the excipients such as the diluent, the disintegrant, the glidant, and the lubricant, any ones known to be commonly used in the art may be used.
- the diluent may be used in an amount of 30 to 50% by weight, 40 to 50% by weight, or 45 to 50% by weight based on the total weight of the oral formulation.
- the disintegrant may be used in an amount ranging from 1 to 10% by weight or 1 to 5% by weight based on the total weight of the oral formulation.
- the glidant may be used in an amount ranging from 0.1 to 5% by weight, 0.2 to 3% by weight, or 0.3 to 2% by weight based on the total weight of the oral tablet.
- the lubricant may be used in an amount ranging from 0.1 to 10% by weight, 0.3 to 5% by weight, or 0.5 to 4% by weight based on the total weight of the oral formulation.
- the diluent may be selected from the group consisting of microcrystalline cellulose (MCC), lactose monohydrate, lactose anhydride, lactose, starch, mannitol, carboxymethylcellulose, sorbitol, and combinations thereof, but is limited thereto. it is not going to be
- the disintegrant may be selected from the group consisting of low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, sodium starch glycolate, F-melt, and combinations thereof, but is not limited thereto.
- the glidant may be selected from the group consisting of talc, silicon dioxide, and mixtures thereof, but is not limited thereto.
- the lubricant may be selected from the group consisting of magnesium stearate, silicon dioxide, talc, light anhydrous silicic acid, sodium stearyl fumarate, and combinations thereof, but is not limited thereto.
- the oral formulation may be administered once a day, and may be taken daily.
- the content of the API included in the oral preparation is 30 to 50% by weight, 35 to 50% by weight, 40 to 50% by weight, 45 to 50% by weight, 30 to 45% by weight based on the total weight of the oral preparation, 35 to 45 wt%, 40 to 45 wt%, 30 to 40 wt%, or 35 to 40 wt%.
- the API is 50 to 500 mg, 50 to 400 mg, 50 to 300 mg, 50 to 200 mg, 50 to 100 mg, 100 to 500 mg, 100 to 400 mg, 100 to 300 mg, 100 to 200 mg per unit dosage form , 200-500 mg, 200-400 mg, 200-300 mg, 300-500 mg, or 300-400 mg.
- the API may include, for example, 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, 400 mg or 455 mg per unit dosage form.
- the API content contained in the oral formulation of the present invention is 95% to 105%, 96% to 105%, 97% to 105%, 98% to 105%, 99% to 105%, 100% to 105%, 95% to 100%, 96% to 100%, 97% to 100%, 98% to 100%, or 99% to 100%.
- the API content may be 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more, and 105% or less, 104% or less, 103% or less, 102% or less, 101% or less , or less than 100%.
- the present invention includes the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API, and as an excipient a pH adjusting agent or Provided is an oral preparation for treating or preventing human xanthine oxidase-related diseases that does not include an enteric coating layer.
- the present invention contains the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API and uses a pH adjusting agent or an enteric agent as an excipient.
- a method for treating or preventing human xanthine oxidase-related diseases using an oral formulation that does not include a coating layer is provided.
- the present invention includes the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid or a pharmaceutically acceptable salt thereof as an API, and as an excipient a pH adjusting agent or Provided is a use for preparing an oral preparation for treating or preventing human xanthine oxidase-related diseases that does not include an enteric coating layer.
- Tablets for oral use were prepared by the following manufacturing method.
- 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid (API) and a glidant are mixed and then milled to prepare a first mixture . Thereafter, a diluent, a disintegrant, and a lubricant, which are components not included in the first mixture, were mixed and then sized to prepare a second mixture.
- tableting was performed using a rotary tablet press (Modul P, GEA, Belgium) under conditions of a preload of 5.0 kN and a main pressure of 14 to 15 kN to prepare uncoated tablets.
- a rotary tablet press Modul P, GEA, Belgium
- PRUV® used as a lubricant is a trade name and is a component of sodium stearyl fumarate.
- Oral capsules were prepared by the following manufacturing method.
- 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid (API) and a diluent are mixed and milled to prepare a first mixture. Thereafter, a lubricant, which is a component not included in the first mixture, was mixed and then sized to prepare a second mixture.
- the second mixture was prepared by putting 430.0 mg into capsules using a capsule filling machine (manual or automatic).
- Classification ingredient content (mg/T) content ratio (%) API 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid 100.0 45.5 diluent MCC 102 (microcrystalline cellulose) 104.8 47.9 disintegrant crospovidone 9.7 4.4 glidant Colloidal silicon dioxide (SiO 2 ) 1.1 0.2 glidant PRUV® 4.4 2.0 Tablet total weight (mg) 220.0 100.0
- Classification ingredient content (mg/T) content ratio (%) API 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid 100.0 23.3 diluent Starcap 1500® 326.0 75.8 glidant magnesium stearate 4.0 0.9 Total mixture weight (mg) 430.0 81.59 capsule Hard Gelatin Capsule 97.0 18.41 Total capsule weight (mg) 527.0 100.0
- the weight of the capsule is selected based on the average of the maximum weight range of 106.7 mg and the minimum weight of 87.3 mg, 97.0 mg)
- the dissolution test was performed on the previously prepared uncoated tablets using the dissolution test solutions (dissolution medium) of the following Examples and Comparative Examples.
- the dissolution method used the paddle method of the dissolution test method of the Korean Pharmacopoeia, and the stirring speed was 50 rpm and the dissolution temperature was 37 ⁇ 0.5 ° C.
- Example 1 the dissolution rate of the previously prepared uncoated tablet was measured in 900 ml of a pH 6.8 phosphate buffer-water mixture (1:1), which is the second liquid of the dissolution test method of the Korean Pharmacopoeia.
- Comparative Example 1 was prepared by dissolving 7.0 ml of hydrochloric acid and water in 2.0 g of sodium chloride, which is the first liquid of the dissolution test method of the Korean Pharmacopoeia, to prepare a first liquid of 1000 ml, and then using 900 ml of the first liquid to prepare uncoated tablets. The dissolution rate of was measured.
- the first liquid has a pH of 1.2, a hydrochloric acid concentration of 0.1 mol/L, and is colorless and transparent.
- a buffer solution of 1000 ml was prepared by dissolving 2.99 g of sodium acetate hydrate (trihydrate) and 1.66 g of acetic anhydride in water at pH 4.5.
- the dissolution rate of the previously prepared uncoated tablet was measured using 900 ml of the pH 4.5 buffer as an elution medium.
- the solution obtained in the above dissolution test was filtered through a 0.45 ⁇ m membrane filter, and the API, 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4 was obtained by using the UPLC method. - The concentration of carboxylic acid was analyzed.
- the specific analysis conditions are as follows.
- Example 2 the dissolution rate of the previously prepared capsule was measured in the same dissolution medium and conditions as in Example 1.
- Example 1 (pH 6.8) Comparative Example 1 (pH 1.2) Comparative Example 2 (pH 4.5) Average dissolution rate (10 minutes) (%) 58.4 ⁇ 1.6 N/D N/D Average dissolution rate (15 minutes) (%) 71.8 ⁇ 1.8 N/D N/D Average dissolution rate (30 minutes) (%) 88.6 ⁇ 1.9 N/D N/D Average dissolution rate (45 minutes) (%) 93.8 ⁇ 2.0 N/D N/D Average dissolution rate (60 minutes) (%) 95.8 ⁇ 2.0 N/D N/D
- Tablets (uncoated tablets) prepared using the components listed in Table 1 in the corresponding contents were hardly eluted in buffer solutions of pH 1.2 (Comparative Example 1) and pH 4.5 (Comparative Example 2).
- pH 6.8 buffer the 10-minute average dissolution rate was 58.4 ⁇ 1.6%
- the 15-minute average dissolution rate was 71.8 ⁇ 1.8%
- the 30-minute average dissolution rate was 88.6 ⁇ 1.9%
- the 45-minute average dissolution rate was 93.8 ⁇ 2.0%
- the 60-minute average dissolution rate was The dissolution rate was 95.8 ⁇ 2.0%.
- the dissolution pattern of the oral capsule containing the same API as the uncoated tablet was tested at pH 6.8 (Example 2), pH 1.2 (Comparative Example 3) and pH 4.5 (Comparative Example 4) using the dissolution test method of the Korean Pharmacopoeia. It was analyzed through the analysis method mentioned above. The analysis results are shown in Table 4.
- Example 2 (pH 6.8) Comparative Example 3 (pH 1.2) Comparative Example 4 (pH 4.5) Average dissolution rate (10 minutes) (%) 58.4 ⁇ 7.9 1.2 ⁇ 0.0 1.9 ⁇ 0.2 Average dissolution rate (15 minutes) (%) 75.2 ⁇ 7.8 1.3 ⁇ 0.0 2.3 ⁇ 0.2 Average dissolution rate (30 minutes) (%) 89.1 ⁇ 6.9 1.5 ⁇ 0.0 3.2 ⁇ 0.2 Average dissolution rate (45 minutes) (%) 93.1 ⁇ 6.6 1.6 ⁇ 0.0 3.7 ⁇ 0.1 Average dissolution rate (60 minutes) (%) 95.5 ⁇ 6.9 1.7 ⁇ 0.1 3.9 ⁇ 0.1
- Oral capsules prepared using the components listed in Table 2 in the corresponding contents were hardly eluted in buffer solutions of pH 1.2 (Comparative Example 2) and pH 4.5 (Comparative Example 3), similar to tablets (uncoated tablets), and were not eluted in a buffer solution of pH 6.8.
- the 10-minute average dissolution rate was 58.4 ⁇ 7.9%
- the 15-minute average dissolution rate was 75.2 ⁇ 7.8%
- the 30-minute average dissolution rate was 89.1 ⁇ 6.9%
- the 45-minute average dissolution rate was 93.1 ⁇ 6.6%
- the 60-minute average dissolution rate was 95.5 ⁇ 6.9%.
- it was confirmed that the tablets and capsules containing the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid as an API showed similar dissolution patterns.
- the oral preparation of the present invention hardly dissolves at pH 1.2 even in an uncoated tablet state, when the oral preparation is in the form of a tablet, there is no need to apply an enteric coating to prevent dissolution in the stomach.
- the oral formulation of the present invention shows a very high dissolution rate, with a 60-minute average dissolution rate of 90% or more, specifically at pH 6.8 even without a pH adjusting agent, so the bioavailability also reflects this. Therefore, it can be expected to be excellent.
Abstract
Description
분류 | 성분 | 함량 (㎎/T) |
함량비 (%) |
API | 1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산 | 100.0 | 45.5 |
희석제 | MCC 102(미결정셀룰로오스) | 104.8 | 47.9 |
붕해제 | 크로스포비돈 | 9.7 | 4.4 |
유동화제 | 콜로이달이산화규소(SiO2) | 1.1 | 0.2 |
활택제 | PRUV® | 4.4 | 2.0 |
정제 총 중량(㎎) | 220.0 | 100.0 |
분류 | 성분 | 함량 (㎎/T) |
함량비 (%) |
API | 1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산 | 100.0 | 23.3 |
희석제 | Starcap 1500® | 326.0 | 75.8 |
활택제 | 마그네슘 스테아레이트 | 4.0 | 0.9 |
혼합물 총 중량(㎎) | 430.0 | 81.59 | |
캡슐 | Hard Gelatin Capsule | 97.0 | 18.41 |
캡슐 총 중량(㎎) | 527.0 | 100.0 |
실시예 1 (pH 6.8) |
비교예 1 (pH 1.2) |
비교예 2 (pH 4.5) |
|
평균용출률(10분)(%) | 58.4±1.6 | N/D | N/D |
평균용출률(15분)(%) | 71.8±1.8 | N/D | N/D |
평균용출률(30분)(%) | 88.6±1.9 | N/D | N/D |
평균용출률(45분)(%) | 93.8±2.0 | N/D | N/D |
평균용출률(60분)(%) | 95.8±2.0 | N/D | N/D |
실시예 2 (pH 6.8) |
비교예 3 (pH 1.2) |
비교예 4 (pH 4.5) |
|
평균용출률(10분)(%) | 58.4±7.9 | 1.2±0.0 | 1.9±0.2 |
평균용출률(15분)(%) | 75.2±7.8 | 1.3±0.0 | 2.3±0.2 |
평균용출률(30분)(%) | 89.1±6.9 | 1.5±0.0 | 3.2±0.2 |
평균용출률(45분)(%) | 93.1±6.6 | 1.6±0.0 | 3.7±0.1 |
평균용출률(60분)(%) | 95.5±6.9 | 1.7±0.1 | 3.9±0.1 |
Claims (9)
Priority Applications (6)
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EP22825365.4A EP4342458A1 (en) | 2021-06-17 | 2022-06-17 | Oral formulation containing 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid |
CA3221172A CA3221172A1 (en) | 2021-06-17 | 2022-06-17 | Oral formulation containing 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid |
CN202280039088.0A CN117642154A (zh) | 2021-06-17 | 2022-06-17 | 含有1-(3-氰基-1-异丙基-吲哚-5-基)吡唑-4-甲酸的口服制剂 |
BR112023026540A BR112023026540A2 (pt) | 2021-06-17 | 2022-06-17 | Formulação oral contendo ácido 1-(3-ciano-1-isopropil-indol-5-il)pirazol-4-carboxílico |
AU2022292414A AU2022292414A1 (en) | 2021-06-17 | 2022-06-17 | Oral formulation containing 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid |
CONC2023/0017610A CO2023017610A2 (es) | 2021-06-17 | 2023-12-15 | Formulación compuesta para dosificación oral que comprende ácido 1-(3-ciano-1-isopropil-indol-5-il)pirazol-4-carboxílico |
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KR10-2021-0078801 | 2021-06-17 |
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EP (1) | EP4342458A1 (ko) |
KR (1) | KR20220168999A (ko) |
CN (1) | CN117642154A (ko) |
AR (1) | AR126164A1 (ko) |
AU (1) | AU2022292414A1 (ko) |
BR (1) | BR112023026540A2 (ko) |
CA (1) | CA3221172A1 (ko) |
CO (1) | CO2023017610A2 (ko) |
TW (1) | TW202302091A (ko) |
WO (1) | WO2022265442A1 (ko) |
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CN106008488A (zh) * | 2016-05-20 | 2016-10-12 | 广东东阳光药业有限公司 | 氰基吲哚类衍生物及其制备方法和用途 |
-
2022
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- 2022-06-17 WO PCT/KR2022/008582 patent/WO2022265442A1/ko active Application Filing
- 2022-06-17 BR BR112023026540A patent/BR112023026540A2/pt unknown
- 2022-06-17 AU AU2022292414A patent/AU2022292414A1/en active Pending
- 2022-06-17 KR KR1020220073848A patent/KR20220168999A/ko not_active Application Discontinuation
- 2022-06-17 EP EP22825365.4A patent/EP4342458A1/en active Pending
- 2022-06-17 TW TW111122650A patent/TW202302091A/zh unknown
- 2022-06-17 CA CA3221172A patent/CA3221172A1/en active Pending
- 2022-06-17 CN CN202280039088.0A patent/CN117642154A/zh active Pending
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KR20090128488A (ko) * | 2007-04-11 | 2009-12-15 | 깃세이 야쿠힌 고교 가부시키가이샤 | (아자)인돌 유도체 및 그 의약 용도 |
KR20110132599A (ko) * | 2009-03-31 | 2011-12-08 | 깃세이 야쿠힌 고교 가부시키가이샤 | 인돌리진 유도체 및 그 의약용도 |
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KR101751325B1 (ko) | 2009-10-07 | 2017-06-27 | 주식회사 엘지화학 | 잔틴 옥시다아제 저해제로서 효과적인 신규 화합물, 그 제조방법 및 그를 함유하는 약제학적 조성물 |
KR20120114174A (ko) * | 2011-04-06 | 2012-10-16 | 주식회사 엘지생명과학 | 1-(3-시아노-1-아이소프로필-인돌-5-일)피라졸-4-카르복실산의 결정형과 그의 제조방법 |
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TW202302091A (zh) | 2023-01-16 |
EP4342458A1 (en) | 2024-03-27 |
BR112023026540A2 (pt) | 2024-03-05 |
CA3221172A1 (en) | 2022-12-22 |
CO2023017610A2 (es) | 2024-03-07 |
CN117642154A (zh) | 2024-03-01 |
KR20220168999A (ko) | 2022-12-26 |
AU2022292414A1 (en) | 2024-01-04 |
AR126164A1 (es) | 2023-09-27 |
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