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31. 发明公开

KR1020040078941A 4-아미노-1-히드록시부틸리덴-1,1-비스포스폰산의 제조방법 失效
标题翻译：通过使用非溶性聚磷酸酯作溶剂制备4-氨基-1-羟基丁基锂-1,1-二磷酸或其盐的方法
公开(公告)号：KR1020040078941A
公开(公告)日：2004-09-14
申请号：KR1020030013776
申请日：2003-03-05
申请人： 하나제약 주식회사
发明人： 서경재 , 이상원 , 장사정
IPC分类号： C07F9/38
CPC分类号： C07F9/38
摘要： PURPOSE: A process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof is provided, thereby stably and reproducibly preparing the compound under the mild condition by using nontoxic polyphosphate as a solvent. CONSTITUTION: The process for preparing 4-amino-1-hydroxybutylidene- 1,1-bisphosphonic acid or salts thereof comprises the steps of: bisphosphonication of 4-aminobutylic acid by using a polyphosphate solvent, phosphite and phosphorous trichloride at 70 to 120 deg. C in the air; adding water into the bisphosphonicated compound to hydrolysis; and adding alcohol into the hydrolyzed compound to solidify it.
摘要翻译：目的：提供4-氨基-1-羟基亚丁基-1,1-二膦酸或其盐的制备方法，通过使用无毒多磷酸盐作为溶剂，在温和条件下稳定且可再现地制备化合物。构成：制备4-氨基-1-羟基亚丁基-1,1-二膦酸或其盐的方法包括以下步骤：使用多磷酸盐溶剂，亚磷酸盐和三氯化磷在70至120℃下双膦酸化4-氨基丁酸。 C在空中; 将水加入双膦酸化合物进行水解; 并向水解的化合物中加入醇以使其固化。

32. 发明授权

KR102015516B1 안정성이 개선된 습식과립 정제 및 이의 제조방법 有权
公开(公告)号：KR102015516B1
公开(公告)日：2019-08-28
申请号：KR1020170119363
申请日：2017-09-18
申请人： 하나제약 주식회사
发明人： 곽승환 , 곽미리
IPC分类号： A61K9/20 , A61K47/10 , A61K31/555

33. 发明公开

KR1020110088189A 수지재 앰플의 제조장치 有权
标题翻译：制造塑料电极的装置
公开(公告)号：KR1020110088189A
公开(公告)日：2011-08-03
申请号：KR1020100007978
申请日：2010-01-28
申请人： 화인에프.에이 주식회사 , 하나제약 주식회사
发明人： 박종현
IPC分类号： A61J1/00 , A61J1/06
CPC分类号： B65B3/003 , B65B3/12 , B65B7/161 , B65B35/18 , B65B51/32 , B65B55/24 , B65B61/28
摘要： PURPOSE: A device for manufacturing a plastic ampoule is provided to prevent poor quality and to maintain good productivity. CONSTITUTION: A device for manufacturing a plastic ampoule comprises: a loading unit(20) which is settled on a conveyor in a standing state; a cutting unit(30) which supports an ampoule in a standing state and cuts the entrance of the ampoule; a particle removal unit(40) which supports an ampoule in a standing state and eliminates foreign materials of entrance; a filler(50) which supports in an erect state and injects drug solution; a sealing unit(60) sealing the cut entrance; and an unloading unit(70) discharging the ampoule to the outside of the chamber.
摘要翻译：目的：提供一种用于制造塑料安瓿的装置，以防止质量差并保持良好的生产率。构成：用于制造塑料安瓿的装置包括：装载单元（20），其以静止状态沉积在输送机上; 切割单元（30），其以立式状态支撑安瓿并切割安瓿的入口; 颗粒去除单元（40），其以立式状态支撑安瓿并消除异物入口; 填充物（50），其以直立状态支撑并注射药物溶液; 密封单元（60），密封所述切割入口; 以及将安瓿排放到室外的卸载单元（70）。

34. 发明公开

KR1020110012608A 그라니세트론의 구강속붕해정 및 그의 제조방법 无效
标题翻译： GRANISETRON ORALLY DISINCATRATTING TABLETS及其制造工艺
公开(公告)号：KR1020110012608A
公开(公告)日：2011-02-09
申请号：KR1020090070392
申请日：2009-07-31
申请人： 하나제약 주식회사
发明人： 장사정 , 최옥 , 허홍구 , 윤지영
IPC分类号： A61K9/22 , A61K31/439 , A61K47/26 , A61K9/20
CPC分类号： A61K9/0056 , A61K9/2095 , A61K31/439 , A61K47/26
摘要： PURPOSE: An orally disintegrating tablet(ODT) containing granisetron or pharmaceutically acceptable salt thereof is provided to shield the bitter taste of granisetron and to improve administration compliance. CONSTITUTION: An orally disintegrating tablet contains granisetron or pharmaceutically acceptable salt thereof, sweetener and flavoring, spray-dried lactose hydrate, D-mannitol or mixture thereof as an excipient, crospovidone as a disintegrant, a colloidal silicon dioxide as a first lubricant, and sodium stearylfumarate as a second lubricant. A method for manufacturing the orally disintegrating tablet comprises: a step of pulverizing granisetron or pharmaceutically acceptable salt thereof in a 50um of particle size; a step of adding sweetener and flavoring and mixing; a step of adding excipient and first lubricant for first lubrication; a step of adding crospovidone and second lubricant; and a step of tabletizing.
摘要翻译：目的：提供含有格拉司琼或其药学上可接受的盐的口腔崩解片（ODT），以保护格拉司琼的苦味并提高给药依从性。构成：口腔崩解片含有格拉司琼或其药学上可接受的盐，甜味剂和调味剂，喷雾干燥的乳糖水合物，D-甘露糖醇或其作为赋形剂的混合物，交聚维酮作为崩解剂，胶体二氧化硅作为第一种润滑剂，钠作为第二润滑剂的富马酸硬脂基酯。一种口腔崩解片的制造方法，其特征在于，包括：将粒度为50μm的格拉司琼或其药学上允许的盐粉碎的步骤; 添加甜味剂和调味料和混合物的步骤; 添加赋形剂和第一润滑剂进行第一次润滑的步骤; 加入交聚维酮和第二润滑剂的步骤; 和一个平板化的步骤。

35. 发明授权

KR101002583B1 서방성 고형 제제의 제조방법 有权
标题翻译：缓释固体制剂的制造方法
公开(公告)号：KR101002583B1
公开(公告)日：2010-12-20
申请号：KR1020100098387
申请日：2010-10-08
申请人： 하나제약 주식회사
发明人： 장사정 , 최옥
IPC分类号： A61K9/22 , A61K9/20 , A61K47/44 , A61K31/485
摘要： 본 발명은 왁스(wax) 타입의 부형제와 코포비돈(copovidone)을 포함하여 압축성 및 유동성이 증가하고 부착성이 감소된 수불용성 매트릭스 내에 약물, 예를 들면 옥시코돈 또는 그의 약제학적으로 허용되는 염을 포함하는, 서방성 고형 제제(sustained release solid formulation) 및 그의 제조방법에 관한 것으로서, 본 발명에 따른 제제는 약물을 12 내지 24 시간에 걸쳐 일정하게 방출하는 특성을 가지며 제제화에 사용되는 부형제의 종류와 양이 적고 고가의 장비를 필요로 하지 않아 경제적이며 간편한 방법으로 제조할 수 있다.
摘要翻译：本发明包括盐的压缩性和流动性的增加，以及密合性的药物，例如，允许在降低的水不溶性基质的羟考酮或其药学，包括蜡（蜡）赋形剂和共聚维酮（共聚维酮）的种类以，缓释固体剂型（持续释放固体制剂）和制造方法上，根据本发明的种类和量的赋形剂的制剂具有这样的特性的恒定释放过在12至24小时的药物被用于配制由于它不需要昂贵和昂贵的设备，因此可以以经济和简单的方式制造它。

36. 发明授权

KR101000362B1 이토프라이드의 새로운 제조방법 失效
标题翻译： Itopride和衍生物的新型合成方法
公开(公告)号：KR101000362B1
公开(公告)日：2010-12-13
申请号：KR1020080070915
申请日：2008-07-22
申请人： 하나제약 주식회사
发明人： 장사정 , 이재목 , 강성구 , 공준수
IPC分类号： C07C209/04 , C07C219/28 , C07C217/58
摘要： 본 발명은 화학식 I의 이토프라이드(Itopride)의 새로운 제조방법에 관한 것으로, 구체적으로 a) 화학식 III의 벤즈알데히드 화합물과 벤질아민을 반응시켜 화학식 IV의 이민 화합물을 제조하는 단계; b) 상기 제조된 화학식 IV의 이민 화합물이 귀금속계 촉매 및 암모늄포메이트(HCOONH
4 ), 암모늄아세테이트(CH
3 COONH
4 ), 아세트산, 포름산 및 이들의 혼합물로 이루어진 군에서 선택된 환원제 존재 하에서 환원 및 탈벤질화반응에 의하여 화학식 II의 4-알콕시 벤질아민 화합물을 제조하는 단계; 및 상기 제조된 화학식 II의 4-알콕시 벤질아민 화합물을 화학식 VII의 활성형 에스테르와 축합하여 화학식 I의 이토프라이드를 제조하는 방법으로써 유해한 가스의 발생을 크게 낮추고 안전하면서도 친환경적인 방법으로 이토프라이드를 고수율, 고순도로 제조하는 신규한 방법에 관한 것이다.

상기 식에서, R은 또는 이다.
활성형 에스테르, 축합반응, 벤질아민, 이토프라이드, 소화기계, 소화증상

37. 发明公开

KR1020100114872A 서방성 고형 제제의 제조방법 有权
标题翻译：制造持续释放固体制剂的方法
公开(公告)号：KR1020100114872A
公开(公告)日：2010-10-26
申请号：KR1020100098387
申请日：2010-10-08
申请人： 하나제약 주식회사
发明人： 장사정 , 최옥
IPC分类号： A61K9/22 , A61K9/20 , A61K47/44 , A61K31/485
摘要： PURPOSE: A sustained release solid formulation and method for manufacturing the same are provided to uniformly release drug for 12-24 hours and to economically manufacture without expensive equipment. CONSTITUTION: A method for manufacturing sustained release tablet comprises: a step of mixing oxycodone or pharmaceutically acceptable salt thereof with glyceryl fatty acid ester or copovidone to obtain granules; a step of heating the granules; and a step of tableting. The tablet has oxycodone or pharmaceutically acceptable salt inside a water insoluble matrix. The water insoluble matrix contains excipient and copovidone and is filled with the excipient.
摘要翻译：目的：提供持续释放的固体制剂及其制备方法，以均匀释放药物12-24小时，经济地制造而不需要昂贵的设备。构成：缓释片剂的制造方法包括：将羟考酮或其药学上可接受的盐与甘油脂肪酸酯或共聚维酮混合以获得颗粒的步骤; 加热颗粒的步骤; 和压片的一步。片剂在水不溶性基质内含有羟考酮或药学上可接受的盐。水不溶性基质含有赋形剂和共聚维酮，并填充有赋形剂。

38. 发明公开

KR1020080104910A 서방성 고형 제제 및 그의 제조방법 有权
标题翻译：可持续发布固体制剂及其制造方法
公开(公告)号：KR1020080104910A
公开(公告)日：2008-12-03
申请号：KR1020070052366
申请日：2007-05-29
申请人： 하나제약 주식회사
发明人： 장사정 , 최옥 , 허홍구
IPC分类号： A61K9/22
CPC分类号： A61K9/2013 , A61K9/2009 , A61K9/2054 , A61K31/135
摘要： The sustained release solid preparation is provided to simply and economically manufacture it with the relatively small amount of the additive based on the weight of the unit formulation, and gradually release a drug for a long time. The manufacturing method of the sustained release solid preparation comprises the steps of: coating the drug with the hydrophobic carrier and adsorbing it with an adsorbing agent; mixing the drug with the wax-like lipid excipient to prepare the solid preparation; heating the solid preparation to the temperature higher than the melting point of the wax-like lipid excipient to melt the wax-like lipid excipient and fill the air gap formed inside matrix, thereby reducing the gap fraction; and cooling the solid preparation.
摘要翻译：提供持续释放的固体制剂以基于单位制剂重量的相对少量的添加剂简单且经济地制造，并且长时间地逐渐释放药物。持续释放固体制剂的制备方法包括以下步骤：用疏水载体涂覆药物并用吸附剂吸附; 将药物与蜡状脂质赋形剂混合以制备固体制剂; 将固体制剂加热到高于蜡状脂质赋形剂的熔点的温度以熔化蜡状脂质赋形剂并填充基质内形成的气隙，从而降低间隙分数; 并冷却固体制剂。

39. 发明授权

KR100844336B1 레보부피바카인 및 이의 염산염의 신규한 제조방법 失效
标题翻译：左炔诺酮及其盐酸盐的新合成方法
公开(公告)号：KR100844336B1
公开(公告)日：2008-07-07
申请号：KR1020070004980
申请日：2007-01-16
申请人： 하나제약 주식회사
发明人： 장사정 , 이재목 , 공준수
IPC分类号： C07D211/60
摘要： A method for preparing levobupivacaine and a method for preparing a hydrochloride thereof are provided to require a simple manufacturing process, be easy to handle reagents used for the process, obtain at least 98% of an enantiomeric excess(ee) of the levobupivacaine and synthesize a highly pure levobupivacaine hydrochloride having an optical purity of at least 99%ee by converting the levobupivacaine into a hydrochloride. A method for preparing levobupivacaine comprises the steps of: (a) optically dividing a racemic 2',6'-pipecoloxylidide with (-)-dibenzoyl-L-tartaric acid to prepare (S)-2',6'-pipecoloxylidide having an optical purity of at least 85%ee and represented by a formula(1); (b) reacting the compound of the formula(1) with 1-bromobutane in an organic solvent in the presence of a base to prepare the levobupivacaine represented by a formula(2); and (c) recrystallizing the compound of the formula(2) with cyclohexane to prepare the (S)-bupivacaine of the formula(2) having an optical purity of at least 98%ee. The (S)-bupivacaine of the formula(2) is reacted with HCl in an organic solvent to prepare levobupivacaine hydrochloride having an optical purity of at least 99%ee and represented by a formula(3). Further, the organic solvent is selected from dimethyl formamide, isopropanol or acetonitril.
摘要翻译：提供了制备左布比卡因的方法及其盐酸盐的制备方法，需要简单的制备方法，易于处理用于该方法的试剂，获得至少98％的左旋布比卡因的对映异构体过量（ee）并合成通过将左布比卡因转化为盐酸盐，具有至少99％ee的光学纯度的高纯度左布比卡因盐酸盐。制备左布比卡因的方法包括以下步骤：（a）用（ - ） - 二苯甲酰基-L-酒石酸光学分解外消旋的2'，6'-哌甲氧基，制备（S）-2'，6'-哌甲氧基，其具有至少85％ee的光学纯度并由式（1）表示; （b）在碱的存在下，使有机溶剂中的式（1）化合物与1-溴丁烷反应，制备由式（2）表示的左布比卡因; 和（c）用环己烷重结晶式（2）的化合物以制备具有至少98％ee的光学纯度的式（2）的（S） - 布比卡因。式（2）的（S） - 布比卡因与HCl在有机溶剂中反应，制备光学纯度至少为99％ee并由式（3）表示的盐酸左布比卡因。此外，有机溶剂选自二甲基甲酰胺，异丙醇或乙腈。

40. 发明授权

KR100647068B1 라세믹Ｎ,Ｎ-디이소프로필-3-(2-히드록시-5-메틸페닐)-3-페닐프로판아민의 제조방법 失效
标题翻译： 라세믹N，N-디이소프로필-3-（2-록드록시-5-메틸페닐）-3-페닐프로판아민의제조방
公开(公告)号：KR100647068B1
公开(公告)日：2006-11-23
申请号：KR1020050086024
申请日：2005-09-15
申请人： 하나제약 주식회사
发明人： 장사정 , 이점중
IPC分类号： C07C213/04
摘要： Provided is a method for preparing racemic N,N-diisopropyl-3-(2-hydroxy-5- methylphenyl)-3-phenylpropanamine, which shows good safety, requires a decreased processing time, and produces the target product with high yield. The method for preparing racemic N,N-diisopropyl-3-(2-hydroxy-5- methylphenyl)-3-phenylpropanamine comprises the steps of: (a) reducing a compound represented by the formula II in the presence of a reducing agent and iodine to obtain an alcohol compound represented by the formula III; (b) converting the alcohol compound into a methanesulfonyl compound represented by the formula IV; (c) converting the methanesulfonyl compound into an iodo compound represented by the formula V; (d) reacting the iodo compound with diisopropyl amine to form an amine compound represented by the formula VI; (e) treating the amine compound represented by the formula VI with a phase transition catalyst in an aqueous HBr solution to form racemic N,N-diisopropyl -3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine hydrobromide; and (f) neutralizing the hydrobromide obtained from step (e) with a base to obtain N,N-diisopropyl -3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine represented by the formula I.
摘要翻译：本发明提供一种制备外消旋N，N-二异丙基-3-（2-羟基-5-甲基苯基）-3-苯基丙胺的方法，其显示出良好的安全性，需要减少处理时间并以高产率生产目标产物。制备外消旋N，N-二异丙基-3-（2-羟基-5-甲基苯基）-3-苯基丙胺的方法包括以下步骤：（a）在还原剂存在下还原式II代表的化合物和碘，得到式III所示的醇化合物; （b）将醇化合物转化为式IV表示的甲磺酰基化合物; （c）将甲磺酰基化合物转化为由式V表示的碘代化合物; （d）使碘代化合物与二异丙基胺反应以形成式VI代表的胺化合物; （e）用HBr水溶液中的相转移催化剂处理式VI代表的胺化合物，形成外消旋N，N-二异丙基-3-（2-羟基-5-甲基苯基）-3-苯基丙胺氢溴酸盐; 和（f）用碱中和步骤（e）得到的氢溴酸，得到式I代表的N，N-二异丙基-3-（2-羟基-5-甲基苯基）-3-苯基丙胺。

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