WO2021101295A1 - 카바메이트 화합물을 포함하는 경구용 약제학적 조성물 및 그 제조방법 - Google Patents
카바메이트 화합물을 포함하는 경구용 약제학적 조성물 및 그 제조방법 Download PDFInfo
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- WO2021101295A1 WO2021101295A1 PCT/KR2020/016427 KR2020016427W WO2021101295A1 WO 2021101295 A1 WO2021101295 A1 WO 2021101295A1 KR 2020016427 W KR2020016427 W KR 2020016427W WO 2021101295 A1 WO2021101295 A1 WO 2021101295A1
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- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- pharmaceutically acceptable
- active ingredient
- oral pharmaceutical
- starch
- Prior art date
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Definitions
- the present invention relates to an oral pharmaceutical composition
- R 1 , R 2 , A 1 and A 2 are as defined herein.
- the carbamate compound represented by the following Formula 1 (carbamate aryl-2-tetrazoryl ethyl ester) and its preparation method are described in detail in International Patent Publications WO 2006/112685 A1, WO 2010/150946 A1 and WO 2011/046380 A2 And these documents are incorporated herein by reference.
- R 1 and R 2 are each independently hydrogen, halogen, perfluoroalkyl having 1 to 8 carbon atoms, alkyl having 1 to 8 carbon atoms, thioalkoxy having 1 to 8 carbon atoms, and alkoxy having 1 to 8 carbon atoms. Is selected from the group consisting of; One of A 1 and A 2 is CH, and the other is N.
- carbamate compound of Formula 1 is a carbamate compound of Formula 2 (carbamic acid (R)-1-(2-chlorophenyl)-2-tetrazol-2-yl)ethyl ester) have:
- the carbamate compound of Formula 2 is known as an effective anticonvulsant agent used in diseases of the central nervous system, but no studies have been disclosed on a specific formulation for oral administration to apply it to the human body. In order for drugs to be applied to the human body, formulation design is essential. In order to exhibit an effect as a drug, specific formulations such as tablets, capsules, injections, and ointments are required.
- the solubility (1.8 to 2.0 mg/mL) of the carbamate compound of Formula 1 in the in vivo pH range (pH 1.2 to 6.8) does not limit the absorption of tablets having the main component of 12.5 to 400 mg (BCS; Amidon, GL et al., Pharmaceutical research, 12: 413-420 (1995)).
- the particle size of the compound is predicted not to significantly affect the formulation uniformity. Rather, micronization directly affects the flowability and stability of the main ingredient drug, thereby affecting the content uniformity and content. Not recommended for sexual purposes.
- the present inventors have found that the dissolution rate is variable even though the carbamate compound of Formula 1 has a high solubility.
- the dissolution rate of a formulation is a prerequisite for rapid and consistent therapeutic effect and quality control, and if the dissolution rate is variable, it may cause problems in the quality control of the formulation, so studies have been repeated to solve this.
- the present inventors have derived that by controlling the average particle size of the particles of the carbamate compound of Formula 1 included in the formulation by micronization, the formulation can consistently achieve an excellent dissolution rate. That is, the present invention is surprising in that it cannot be easily derived by a person skilled in the art to make it possible to control the dissolution rate by micronizing the carbamate compound of Formula 1 above.
- an object of the present invention is to provide an oral pharmaceutical composition and a method for preparing the same, comprising the carbamate compound of Formula 1, its isomer, or a pharmaceutically acceptable salt, solvate, or hydrate thereof as an active ingredient.
- R 1 and R 2 are each independently hydrogen, halogen, perfluoroalkyl having 1 to 8 carbon atoms, alkyl having 1 to 8 carbon atoms, thioalkoxy having 1 to 8 carbon atoms, and alkoxy having 1 to 8 carbon atoms. Is selected from the group consisting of; One of A 1 and A 2 is CH, and the other is N.
- an oral solid preparation exhibiting a rapid and consistent therapeutic effect by achieving excellent disintegration power and a rapid dissolution rate.
- the term "particle” refers to individual drug substance particles, whether the particles are present alone or agglomerated. That is, the pharmaceutical composition of the present invention containing the carbamate compound of Formula 1 may contain an aggregate having a particle diameter of 300 ⁇ m or more (d(0.9)). However, when the particle diameter (d(0.9)) of the main drug particles constituting the aggregate is less than 300 ⁇ m, 250 ⁇ m or less, 200 ⁇ m or less, 150 ⁇ m or less, 130 ⁇ m or less, or 100 ⁇ m or less, the aggregate itself is It satisfies the particle size conditions defined in the invention and the composition is considered to be within the scope of the invention.
- references to the particle size such as particle diameter (d(0.9)), particle diameter (d(0.5)), etc. are all carbamate compound particles of Formula 1 in the sample. Means that the average of is less than or equal to the calculated volume for a spherical particle having a diameter equal to a given diameter, based on the assumption that the shape of the particle is spherical.
- the particle size distribution is known to those of skill in the art and can be measured by laser light scattering techniques such as those disclosed and discussed further below.
- the particle size of the carbamate compound of Formula 1 was measured using a Malvern particle size analyzer.
- d(0.9) means that 90% of the particle volume has a diameter in a specific diameter d range. Specifically, it means that the particle diameter (d(0.9)) of the point where the cumulative frequency of the volume distribution reaches 90% by accumulating from the smaller particle diameter is within the range of the specific diameter d.
- d(0.5) means that 50% of the volume of the particle has a diameter in a range of a specific diameter d. Specifically, it means that the particle diameter (d(0.5)) at the point where the cumulative frequency of the volume distribution reaches 50% by accumulating from the smaller particle diameter is within the range of the specific diameter d.
- the present invention provides an oral pharmaceutical composition containing a carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof, and a method for preparing the same.
- R 1 and R 2 are each independently hydrogen, halogen, perfluoroalkyl having 1 to 8 carbon atoms, alkyl having 1 to 8 carbon atoms, thioalkoxy having 1 to 8 carbon atoms, and alkoxy having 1 to 8 carbon atoms. Is selected from the group consisting of; One of A 1 and A 2 is CH, and the other is N.
- the carbamate compound of Formula 1, its isomer, or a pharmaceutically acceptable salt, solvate, or hydrate thereof accumulates from the smaller particle diameter, so that the cumulative frequency of the volume distribution is 90%.
- the particle diameter (d(0.9)) of the reaching point has a particle diameter distribution of less than 300 ⁇ m, and more specifically, the particle diameter (d(0.9)) is 250 ⁇ m or less, 200 ⁇ m or less, 150 ⁇ m or less, 130 ⁇ m or less, or It may have a particle diameter distribution of 100 ⁇ m or less.
- the lower limit of the particle diameter (d(0.9)) may be, for example, more than 0 ⁇ m, more than 30 ⁇ m, or more than 50 ⁇ m, but is not limited thereto.
- the carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate, or hydrate thereof accumulates from the smaller particle diameter, so that the cumulative frequency of the volume distribution is
- the particle diameter (d(0.5)) of the point reaching 50% may be in the range of 5 to 80 ⁇ m, and more specifically, the particle diameter (d(0.5)) is 7 to 70 ⁇ m, 10 to 60 ⁇ m, or 15 to It may be in the range of 50 ⁇ m.
- the pharmaceutical composition of the present invention may be any solid preparation known in the art.
- the solid preparation may be in the form of a tablet or capsule, and more specifically, may be in the form of a compressed tablet, a dragee, a film-coated tablet, a hard capsule or a soft capsule.
- it may be a tablet, in particular, a compressed tablet or a film-coated tablet form of an oral solid preparation, but is not limited thereto.
- the oral solid preparation according to the present invention preferably exhibits the following dissolution criteria when dissolving in vitro is tested. That is, the oral solid preparation exhibits dissolution properties such that the amount of the drug exceeding 81% by weight is dissolved within 30 minutes, preferably 85% by weight or more, more preferably 90% by weight or more, and even more Preferably, it exhibits dissolution properties such that an amount of 91% by weight or more of the drug is dissolved within 30 minutes.
- test results are established as an average for a given number, usually six dosage forms (eg, tablets, capsules, suspensions or other dosage forms).
- the dissolution test is typically performed in an aqueous medium buffered to the pH range observed in the gastrointestinal tract (1 to 7.4) and adjusted to 37° C. ( ⁇ 1° C.) to maintain physiological suitability together.
- a paddle typically rotating at 50-75 rpm, is used to test the dissolution rate of the tablet.
- the amount of the dissolved carbamate compound of Formula 1 can be determined conventionally by HPLC.
- the dissolution test functions as a quality control tool.
- the oral pharmaceutical composition of the present invention contains 5 mg to 400 mg of the active ingredient (i.e., the carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof). It may be contained in a dosage of, and more specifically, the active ingredient may be contained in a dosage of 12.5mg, 25mg, 50mg, 100mg, 150mg or 200mg.
- the active ingredient i.e., the carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
- the oral solid pharmaceutical composition of the present invention when the oral solid pharmaceutical composition of the present invention is a tablet, the tablet is pharmaceutically acceptable with a carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
- the possible additives may be mixed directly or prepared by dry/wet granulation.
- the pharmaceutically acceptable carrier may be selected from the group consisting of a diluent, a disintegrant, a lubricant, and any combination thereof, but is not limited thereto.
- the pharmaceutically acceptable carrier may further include a surfactant.
- the diluent is corn starch, pre-gelatinized starch, potato starch, flour starch, glutinous rice starch, sweet potato starch, tapioca starch, rice starch, beeswax corn starch, sucrose, lactose anhydride, lactose hydrate , Mannitol, sorbitol, xylitol, lactitol, maltitol and erythritol, synthetic aluminum silicate, hydroxypropyl starch, microcrystalline cellulose, and crystalline cellulose. Specifically, it may be one or more selected from the group consisting of lactose hydrate, synthetic aluminum silicate, hydroxypropyl starch, microcrystalline cellulose, and crystalline cellulose.
- microcrystalline cellulose may be used as the first diluent, and lactose may be used as the second diluent.
- the disintegrant is low-substituted hydroxypropyl cellulose, microcrystalline cellulose, starch, lactose anhydride, lactose hydrate, sodium starch glycolate, crospovidone, carboxymethylcellulose and pharmaceutically acceptable salts thereof, hydroxy It may be one or more selected from the group consisting of propyl cellulose, corn starch, and croscarmellose and pharmaceutically acceptable salts thereof. Specifically, selected from the group consisting of sodium starch glycolate, crospovidone, carboxymethyl cellulose and pharmaceutically acceptable salts thereof, hydroxypropyl cellulose, corn starch, and croscarmellose and pharmaceutically acceptable salts thereof. There may be more than one type. More specifically, it may be sodium starch glycolate, but is not limited thereto.
- the lubricant is silicon dioxide, colloidal anhydrous silica, magnesium trisilicate, tribasic calcium phosphate, calcium silicate, magnesium silicate, colloidal silicon dioxide, powdered cellulose, starch, talc, magnesium stearate, talc , Light anhydrous silicic acid, sodium stearyl fumarate, polyethylene glycol, mineral oil, hydrogenated vegetable oil, zinc stearate and stearic acid may be one or more selected from the group consisting of, more specifically colloidal silicon dioxide, magnesium stearate Or it may be a combination of these, but is not limited thereto.
- the surfactant is polysorbate 80, oleoyl macrogolglyceride, linoleoyl, macrogolglyceride caprylocaproyl, polyoxyglyceride, hydroxypropylmethylcellulose (HPMC), hydroxy It may be one or more selected from the group consisting of propylcellulose (HPC), sodium carboxymethylcellulose, polyvinipyrrolidone, lauryl sulfate sodium, sodium oleate, and sodium dioctylsulfosuccinate. Specifically, it may be one or more selected from the group consisting of sodium lauryl sulfate, sodium oleate, and sodium dioctylsulfosuccinate. More specifically, it may be sodium lauryl sulfate, but is not limited thereto.
- the oral pharmaceutical composition of the present invention when prepared through direct mixing and tableting may contain the following components:
- oral pharmaceutical composition of the present invention when prepared through direct mixing and tableting may contain the following components:
- the pharmaceutical composition of the present invention may contain other components such as a binder, a film coating agent, a colorant, a fragrance, a sweetener, a flavoring agent, and a color preservative within the range not impairing the object of the present invention.
- the pharmaceutical composition when the pharmaceutical composition according to the present invention is in the form of a film-coated tablet, the pharmaceutical composition may include a film coating agent.
- the film coating agent may be included in a weight of 2% to 4% by weight based on the total weight of the pharmaceutical composition, which includes a film-forming agent, a plasticizer, a lubricant and optionally one or more pigments.
- the film-coated tablet may be prepared by additionally performing a coating step after direct mixing and tableting.
- the film coating agent may be a conventional film coating agent, such as Opadry.
- a preferred active ingredient is a carbamate compound of formula (2), an isomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof:
- the present invention also includes the step of mixing the particles of the carbamate compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt, solvate, or hydrate thereof as an active ingredient with a pharmaceutically acceptable carrier, followed by tableting, ,
- the average particle size (d(0.9)) of the lower 90% of the active ingredient particles is less than 300 ⁇ m, providing a method of preparing a pharmaceutical composition for oral use.
- the tableting may be performed according to any method known in the art, and preferably, may be a direct mixed tableting.
- the oral pharmaceutical composition prepared by the above method may be, for example, a circular, oval, rectangular, rectangular, cylindrical, or other suitable shape, and may be changed in size according to the concentration of the therapeutic agent. .
- the pharmaceutical composition according to the present invention when it is in the form of a coated tablet, it may further include a step of coating after tableting.
- the film tablet may be a film-coated tablet, and typically, the film coating agent may be included in a weight of 2% to 4% by weight based on the total weight of the pharmaceutical composition.
- Film coatings may include film-forming agents, plasticizers, lubricants and optionally one or more pigments.
- the film coating agent may be a conventional film coating agent, such as Opadry.
- the pharmaceutical composition provided according to the present invention can be used for the prevention or treatment of diseases of the central nervous system.
- the central nervous system disease is anxiety, depression, convulsion, epilepsy, migraine, bipolar disorder, drug abuse, smoking, ADHD, obesity, sleep disorder, stroke, neuroapthic pain, It may be selected from cognitive impairment, neurodegeneration, and muscle spasms, but is not limited thereto.
- treat As used herein, the terms “treat”, “treating” and “treatment” are to eliminate all or part of the disease and/or its accompanying symptoms.
- the components were mixed and tableted (direct mixing tableting). Thereafter, the tablet was film-coated using a coating base according to a conventional coating method for tablets.
- Samples were removed after 10, 20, 30, 45 and 60 minutes from the start of the test and analyzed for test compounds at 215 nm by HPLC.
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Abstract
Description
Claims (20)
- 활성 성분으로서 하기 화학식 1의 카바메이트 화합물, 이의 이성질체, 또는 이의 약제학적으로 허용 가능한 염, 용매화물 또는 수화물의 입자; 및 약제학적으로 허용 가능한 담체;를 포함하고, 여기서 상기 활성 성분 입자의 입자 직경(d(0.9))이 300㎛ 미만인, 경구용 약제학적 조성물:[화학식 1]상기 식에서, R1 및 R2는, 각각 독립적으로, 수소, 할로겐, 탄소수 1 내지 8의 퍼플루오로알킬, 탄소수 1 내지 8의 알킬, 탄소수 1 내지 8의 티오알콕시 및 탄소수 1 내지 8의 알콕시로 이루어진 군으로부터 선택되며; A1 및 A2 중 어느 하나는 CH이고, 다른 하나는 N이다.
- 제1항에 있어서, 상기 활성 성분 입자의 입자 직경(d(0.9))이 250㎛ 이하인, 경구용 약제학적 조성물.
- 제1항에 있어서, 상기 활성 성분 입자의 입자 직경(d(0.9))이 150㎛ 이하인, 경구용 약제학적 조성물.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 활성 성분이 5mg 내지 400mg 포함되는 것인, 경구용 약제학적 조성물.
- 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 약제학적으로 허용되는 담체는 희석제, 붕해제 및 윤활제로 이루어진 군으로부터 선택되는 1종 이상인, 경구용 약제학적 조성물.
- 제5항에 있어서, 상기 약제학적으로 허용되는 담체는 계면활성제를 추가로 포함하는, 경구용 약제학적 조성물.
- 제5항 또는 제6항에 있어서, 상기 희석제는 옥수수 전분, 사전 겔화된(pre-gelatinized) 전분, 감자 전분, 밀가루 전분, 찹쌀 전분, 고구마 전분, 타피오카 전분, 쌀 전분, 밀랍 옥수수 전분, 수크로오스, 유당 무수물, 유당 수화물, 만니톨, 솔비톨, 자일리톨, 락티톨, 말티톨 및 에리스리톨, 합성규산알루미늄, 히드록시프로필 전분, 미결정셀룰로오스 및 결정셀룰로오스로 이루어진 군으로부터 선택되는 1종 이상인, 경구용 약제학적 조성물.
- 제5항 내지 제7항 중 어느 한 항에 있어서, 상기 붕해제는 저치환도 히드록시프로필셀룰로오스, 미결정 셀룰로오스, 전분, 유당 무수물, 유당 수화물, 전분글리콜산나트륨, 크로스포비돈, 카르복시메틸셀룰로오스 및 그의 약제학적으로 허용 가능한 염, 히드록시프로필셀룰로오스, 옥수수전분, 및 크로스카멜로오스 및 그의 약제학적으로 허용 가능한 염으로 이루어진 군으로부터 선택되는 1종 이상인, 경구용 약제학적 조성물.
- 제5항 내지 제8항 중 어느 한 항에 있어서, 상기 윤활제는 이산화규소, 콜로이드성 무수 실리카, 삼규산마그네슘, 삼염기성 인산칼슘, 규산칼슘, 규산마그네슘, 콜로이드성 이산화규소, 분말화된 셀룰로스, 전분, 활석, 스테아르산마그네슘, 탈크, 경질무수규산, 스테아릴푸마르산나트륨, 폴리에틸렌글리콜, 광유, 수소화된 식물성 오일, 스테아르산아연 및 스테아르산으로 이루어진 군으로부터 선택되는 1종 이상인, 경구용 약제학적 조성물.
- 제5항 내지 제9항 중 어느 한 항에 있어서, 약제학적 조성물 총 중량을 기준으로, 상기 활성 성분 5중량% 내지 35중량%, 상기 희석제 55중량% 내지 90중량%, 상기 붕해제 2중량% 내지 6중량% 및 상기 윤활제 0.1중량% 내지 4중량%를 포함하는, 경구용 약제학적 조성물.
- 제1항 내지 제11항 중 어느 한 항에 있어서, 압축정제, 다중압축정제, 당의정, 필름코팅정, 경질캡슐 또는 연질캡슐 형태인, 경구용 약제학적 조성물.
- 활성 성분으로서 상기 화학식 1의 카바메이트 화합물, 이의 이성질체, 또는 이의 약제학적으로 허용 가능한 염, 용매화물 또는 수화물의 입자를 약제학적으로 허용 가능한 담체와 혼합 후 타정하는 단계를 포함하며, 여기서 상기 활성 성분 입자의 입자 직경(d(0.9))이 300㎛ 미만인, 경구용 약제학적 조성물의 제조방법:[화학식 1]상기 식에서, R1 및 R2는, 각각 독립적으로, 수소, 할로겐, 탄소수 1 내지 8의 퍼플루오로알킬, 탄소수 1 내지 8의 알킬, 탄소수 1 내지 8의 티오알콕시 및 탄소수 1 내지 8의 알콕시로 이루어진 군으로부터 선택되며; A1 및 A2 중 어느 하나는 CH이고, 다른 하나는 N이다.
- 제13항에 있어서, 상기 활성 성분과 약제학적으로 허용 가능한 담체와의 혼합이 직접혼합타정에 의하여 수행되는, 경구용 약제학적 조성물의 제조방법.
- 제13항 또는 제14항에 있어서, 상기 활성 성분 입자의 입자 직경(d(0.9))이 250㎛ 이하인, 경구용 약제학적 조성물의 제조방법.
- 제13항 내지 제15항 중 어느 한 항에 있어서, 상기 경구용 약제학적 조성물 내에 상기 활성 성분이 5mg 내지 400mg 포함되는 것인, 경구용 약제학적 조성물의 제조방법.
- 제13항 내지 제16항 중 어느 한 항에 있어서, 상기 약제학적으로 허용되는 담체는 희석제, 붕해제 및 윤활제로 이루어진 군으로부터 선택되는 1종 이상인, 경구용 약제학적 조성물의 제조방법.
- 제17항에 있어서, 상기 약제학적으로 허용되는 담체는 계면활성제를 추가로 포함하는, 경구용 약제학적 조성물의 제조방법.
- 제13항 내지 제19항 중 어느 한 항에 있어서, 상기 경구용 약제학적 조성물이, 압축정제, 다중압축정제, 당의정, 필름코팅정, 경질캡슐 또는 연질캡슐 형태인, 경구용 약제학적 조성물의 제조방법.
Priority Applications (12)
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CA3157788A CA3157788A1 (en) | 2019-11-22 | 2020-11-20 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
CN202080080400.1A CN114867469A (zh) | 2019-11-22 | 2020-11-20 | 包含氨基甲酸酯化合物的口服药物组合物及其制备方法 |
MX2022006104A MX2022006104A (es) | 2019-11-22 | 2020-11-20 | Composicion farmaceutica oral que comprende compuesto de carbamato y metodo de preparacion para la misma. |
IL293096A IL293096A (en) | 2019-11-22 | 2020-11-20 | A pharmaceutical preparation for oral administration containing a carbamate compound and a method for its preparation |
KR1020227019724A KR20220104746A (ko) | 2019-11-22 | 2020-11-20 | 카바메이트 화합물을 포함하는 경구용 약제학적 조성물 및 그 제조방법 |
BR112022009533A BR112022009533A2 (pt) | 2019-11-22 | 2020-11-20 | Composição farmacêutica para administração oral, e, método para preparar uma composição farmacêutica |
US17/778,450 US20230000763A1 (en) | 2019-11-22 | 2020-11-20 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
EP20888989.9A EP4062906A4 (en) | 2019-11-22 | 2020-11-20 | ORAL PHARMACEUTICAL COMPOSITION COMPRISING A CARBAMATE COMPOUND AND METHOD FOR PREPARING THIS COMPOSITION |
JP2022529517A JP2023503088A (ja) | 2019-11-22 | 2020-11-20 | カルバメート化合物を含む経口用医薬組成物及びその製造方法 |
AU2020389425A AU2020389425A1 (en) | 2019-11-22 | 2020-11-20 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
CONC2022/0008616A CO2022008616A2 (es) | 2019-11-22 | 2022-06-21 | Composición farmacéutica oral que comprende compuesto de carbamato y método de preparación para la misma |
US18/157,953 US20230157947A1 (en) | 2019-11-22 | 2023-01-23 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
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US17/778,450 A-371-Of-International US20230000763A1 (en) | 2019-11-22 | 2020-11-20 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
US18/157,953 Continuation US20230157947A1 (en) | 2019-11-22 | 2023-01-23 | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor |
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US (2) | US20230000763A1 (ko) |
EP (1) | EP4062906A4 (ko) |
JP (1) | JP2023503088A (ko) |
KR (1) | KR20220104746A (ko) |
CN (1) | CN114867469A (ko) |
AU (1) | AU2020389425A1 (ko) |
BR (1) | BR112022009533A2 (ko) |
CA (1) | CA3157788A1 (ko) |
CL (1) | CL2022001317A1 (ko) |
CO (1) | CO2022008616A2 (ko) |
IL (1) | IL293096A (ko) |
MX (1) | MX2022006104A (ko) |
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WO2022250499A1 (en) * | 2021-05-28 | 2022-12-01 | Sk Biopharmaceuticals Co., Ltd. | Oral aqueous suspension formulations comprising carbamate compound |
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KR20200074157A (ko) * | 2017-11-14 | 2020-06-24 | 에스케이바이오팜 주식회사 | 카바메이트 화합물을 포함하는 조현병의 예방, 경감 또는 치료용 배합물 |
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US20230157947A1 (en) | 2023-05-25 |
AU2020389425A1 (en) | 2022-06-02 |
EP4062906A1 (en) | 2022-09-28 |
BR112022009533A2 (pt) | 2022-08-02 |
CO2022008616A2 (es) | 2022-08-09 |
CA3157788A1 (en) | 2021-05-27 |
IL293096A (en) | 2022-07-01 |
MX2022006104A (es) | 2022-06-14 |
CN114867469A (zh) | 2022-08-05 |
US20230000763A1 (en) | 2023-01-05 |
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