[go: up one dir, main page]

CN100404068C - 含有lhrh拮抗剂的注射液 - Google Patents

含有lhrh拮抗剂的注射液 Download PDF

Info

Publication number
CN100404068C
CN100404068C CNB028234901A CN02823490A CN100404068C CN 100404068 C CN100404068 C CN 100404068C CN B028234901 A CNB028234901 A CN B028234901A CN 02823490 A CN02823490 A CN 02823490A CN 100404068 C CN100404068 C CN 100404068C
Authority
CN
China
Prior art keywords
injection
tween
milligrams
aqueous solution
lhrh
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
CNB028234901A
Other languages
English (en)
Other versions
CN1592630A (zh
Inventor
W·萨利克缇斯
H·鲍尔
M·理施尔
J·恩格尔
F·古斯雷恩
D·迪斯提法诺
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zentaris IVF GmbH
Aeterna Zentaris GmbH
Original Assignee
Zentaris AG
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 Zentaris AG filed Critical Zentaris AG
Publication of CN1592630A publication Critical patent/CN1592630A/zh
Application granted granted Critical
Publication of CN100404068C publication Critical patent/CN100404068C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
    • A61P5/12—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/36—Antigestagens

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Diabetes (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Dermatology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

含有LHRH拮抗剂的注射水溶液除了LHRH拮抗剂之外含有例如西曲瑞克，有机生理耐受酸和可有可无的表面活性剂还有填充剂。所述LHRH拮抗剂显著改善了溶解性并且能以更高浓度制备并且具有改进的生物利用率。LHRH拮抗剂聚集倾向显著减小。

Description

含有LHRH拮抗剂的注射液
技术领域：
本发明涉及用于防止LHRH-拮抗剂在溶液中聚集的利用加入有机生理耐受酸和/或表面活性剂的LHRH拮抗剂的注射水溶液，和它们制备。根据本发明制备的注射液额外导致生物利用率的提高并且使减小要施用的注射体积成为可能。
现有技术：
在卵细胞去除和辅助繁殖技术之前的受控卵巢刺激中，除了LHRH激动剂(例如曲普瑞林，布舍瑞林)之外，有时特别使用LHRH拮抗剂(西曲瑞克，加尼瑞克)，因为它们避免最初的促性腺激素内分泌增加并且立即导致促性腺激素-释放激素的竞争抑制[EP 0 788 799A2；EP 0 299 402 B1]。目前在即用注射剂形式()的含有甘露糖醇的0.5毫升水溶液中含有0.25毫克加尼瑞克的制剂中使用LHRH拮抗剂加尼瑞克。目前以两种给药形式提供LHRH拮抗剂西曲瑞克(
Figure C0282349000042
)：与含有1毫升用于重新配制的水的即用注射器组合的含有0.25毫克西曲瑞克的冻干剂，和与含有3毫升用于重新配制的水的即用注射器组合的含有3毫克西曲瑞克的冻干剂.但是LHRH拮抗剂不只是用于受控卵巢刺激，而且还用于激素依赖型癌症例如前列腺癌的治疗。象阿巴瑞克(abarelix)[WO 98/25642]或西曲瑞克[WO00/47234]这样的物质能用于此目的，在于LHRH拮抗剂可能是针对这种治疗的市场上主要的激动剂(leuprolide，戈舍瑞林)的替代品。注意到Abarelix在水中或者生理介质中相对不好的溶解性，为了实现长期作用，必须使用长效制剂(depot formulation).但是有人指出，LHRH拮抗剂好的溶解性也能引起长效作用[G.Jiang，J.Stakewski，R.Galyean，J.Dykert，C.Schteingart，P.Broqua，A.Aebi，M.L.Aubert，G.Semple，P.Robson，K.Akinsanya，R.Haigh，P.Riviere，J.Trojnar，J.L.Junien和J.E.Rivier，J.Med.Chem.2001，44，453-467]。
本发明的描述：
本发明的目的是制备一种注射液，其利用其改进的溶解性实现LHRH拮抗剂的降低的注射体积和提高的注射浓度.同时，得以防止LHRH拮抗剂在相对高浓缩注射液中的聚集。
令人吃惊地发现，有机生理耐受酸、特别是羧酸、特别是羟基羧酸，但是优选葡糖酸，其自身或者与表面活性剂例如Tween组合，可以显著提高LHRH拮抗剂的溶解性，因此显著减小这些物质的聚集倾向。
因此本发明使得有可能制备用于注射的相对高浓度的LHRH拮抗剂水溶液。可以提到的LHRH拮抗剂是，例如，西曲瑞克，替维瑞克(teverelix)，D-63 153(Ac-D-Nal(2)-D-Cpa-D-Pal(3)-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2)，加尼瑞克，阿巴瑞克，抗排卵肽，azaline B。已发现必须使用过量的各种羧酸；等摩尔量不足够.显然，单独通过与存在的碱性氨基酸残基例如精氨酸，吡啶基丙氨酸，赖氨酸原位生成盐不能解释这种效果。同样，不必选择太高的表面活性剂浓度，因为否则溶液泡沫太多，接着表面活性剂诱导聚集。
同时，这些添加剂使生物利用率提高成为可能，因为它们在注射之后也显著减缓体内自发聚集或者使得物质从作用部位更快地被吸收成为可能。已发现这样的注射液降低的pH(例如pH＝2.5-3)对注射的局部耐受性没有影响。通过提高浓度，有可能降低给药体积，例如在西曲瑞克情况下，3毫克剂型从3毫升减小至1毫升。同样已发现，利用这些添加剂，能实现好的贮存稳定性(参见实施例1)。虽然在25℃/60％下贮存6个月导致杂质增加，但是各种情况下内含物价值仍然毫无疑问在90％以上(作为贯例，药学产品使用期最低值).作为聚集的一个信号，浊度只是稍有增加。最大为8FTU(根据欧洲药典的formazin浊度单位)的混浊值是完全耐受的。
防腐剂，象例如苯酚或对-氯-间-甲酚没有干扰，因此能另外用于溶液的防腐。使用常规的填充剂例如甘露糖醇，乳糖，葡萄糖和果糖同样是可能的。
实施本发明途径的描述：
实施例1
500毫克     西曲瑞克
2克         Tween80
2.4克       葡糖酸δ内酯
95克        甘露糖醇
与注射用水混合至2升得到均匀溶液。然后将溶液灭菌过滤并且分配在安瓿中。在一开始和在2-8℃和25℃/60％相对湿度下贮存6个月之后对安瓿分析测定纯度(HPLC)，含量(HPLC)，pH和聚集(浊度)。
分析结果：
  起始研究   2-8℃6个月之后的研究   25℃/60％相对湿度下6个月之后的研究
  纯度[％]   0.37   0.69   2.32
  含量[％]   100.0   98.7   95.4
  pH   3.12   3.16   3.16
  浊度[FTU]   1.88   2.62   3.92
实施例2
大约500毫克  D-63153
大约100毫克  Tween 80
大约475毫克  甘露糖醇，
用饱和葡糖酸δ内酯水溶液将pH调节至大约2.5。得到大约50毫升的体积。搅拌混合物直到得到澄清溶液。
分析结果：
开始时溶液的浊度是2.4FTU。24小时之后，测得的浊度为2.1FTU。溶液的纯度曲线和含量(HPLC)保持不变。
LHRH拮抗剂D-63153的结构
Ac-D-Nal(2)-D-Cpa-D-Pal(3)-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2
实施例3
大约100毫克  替维瑞克
大约100毫克  Tween 80
大约475毫克  甘露糖醇
用饱和葡糖酸δ内酯水溶液将pH调节至大约2.5。得到大约10毫升的体积。搅拌混合物直到得到澄清溶液。
分析结果：
开始时溶液的浊度是6.8FTU。24小时之后，测得的浊度为8.4FTU。溶液的纯度曲线和含量(HPLC)保持不变。
LHRH拮抗剂替维瑞克的结构
Ac-D-Nal-pCl-D-Phe-3-D-Pal-Ser-Tyr-D-H-Cit-Leu-iPr-Lys-Pro-D-Ala-NH2

Claims (6)

1.LHRH拮抗剂的注射水溶液，其含有葡糖酸、填充剂和任选的表面活性剂，其特征在于相对于LHRH拮抗剂的量，葡糖酸以多于等摩尔的量存在，且葡糖酸以葡糖酸δ内酯的形式加入，以甘露糖作为填充剂，并任选地加入Tween 80作为表面活性剂，
所述的LHRH拮抗剂选自西曲瑞克，替维瑞克和D-63153，即Ac-D-Nal(2)-D-Cpa-D-Pal(3)-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2，加尼瑞克，阿巴瑞克，抗排卵肽和Azaline B。
2.根据权利要求1的注射水溶液，其进一步含有Tween 80作为表面活性剂。
3.根据权利要求1的注射水溶液，其中在2升注射用水中含有：
500毫克西曲瑞克
2.4g葡糖酸δ内酯
2.0克Tween 80
95.0克甘露糖醇。
4.根据权利要求1的注射水溶液，其含有
500毫克D-63153
100毫克Tween 80
475毫克甘露糖醇，
其使用饱和葡糖酸δ内酯溶液调节至50毫升。
5.根据权利要求1的注射水溶液，含有
100毫克替维瑞克
100毫克Tween 80
475毫克甘露糖醇，
其使用饱和葡糖酸δ内酯溶液调节至10毫升。
6.权利要求1-5任一项所述的注射水溶液的制备方法，其特征在于，择一地
-将LHRH拮抗剂、葡糖酸δ内酯形式的葡糖酸，其中相对于LHRH拮剂抗的量，葡糖酸以多于等摩尔的量存在、作为填充剂的甘露糖醇、以及任选的作为表面活性剂的Tween 80溶解于注射用水，进行用于注射目的的匀化和处理，或者
-使用葡糖酸δ内酯的饱和水溶液溶解LHRH拮抗剂、作为填充剂的甘露糖醇、以及任选的作为表面活性剂的Tween 80，进行用于注射目的的匀化和处理。
CNB028234901A 2001-11-26 2002-11-15 含有lhrh拮抗剂的注射液 Expired - Lifetime CN100404068C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10157628A DE10157628A1 (de) 2001-11-26 2001-11-26 Injektionslösung eines LHRH-Antagonisten
DE10157628.5 2001-11-26

Publications (2)

Publication Number Publication Date
CN1592630A CN1592630A (zh) 2005-03-09
CN100404068C true CN100404068C (zh) 2008-07-23

Family

ID=7706799

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB028234901A Expired - Lifetime CN100404068C (zh) 2001-11-26 2002-11-15 含有lhrh拮抗剂的注射液

Country Status (32)

Country Link
EP (1) EP1448221B1 (zh)
JP (1) JP4343693B2 (zh)
KR (1) KR100936636B1 (zh)
CN (1) CN100404068C (zh)
AR (1) AR037424A1 (zh)
AT (1) ATE350050T1 (zh)
AU (1) AU2002365504B2 (zh)
BR (1) BRPI0214412B8 (zh)
CO (1) CO5580793A2 (zh)
CY (1) CY1106401T1 (zh)
DE (2) DE10157628A1 (zh)
DK (1) DK1448221T3 (zh)
EA (1) EA010787B1 (zh)
ES (1) ES2276970T3 (zh)
GE (1) GEP20063861B (zh)
HR (1) HRP20040587B1 (zh)
HU (1) HU230992B1 (zh)
IL (2) IL161894A0 (zh)
IS (1) IS2725B (zh)
ME (1) ME00499B (zh)
MX (1) MXPA04005018A (zh)
NO (1) NO333364B1 (zh)
NZ (1) NZ533712A (zh)
PL (1) PL206199B1 (zh)
PT (1) PT1448221E (zh)
RS (1) RS51408B (zh)
RU (1) RU2322969C2 (zh)
SI (1) SI1448221T1 (zh)
TW (1) TWI312283B (zh)
UA (1) UA81612C2 (zh)
WO (1) WO2003045419A1 (zh)
ZA (1) ZA200404051B (zh)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7658938B2 (en) 1999-02-22 2010-02-09 Merrion Reasearch III Limited Solid oral dosage form containing an enhancer
US8119159B2 (en) 1999-02-22 2012-02-21 Merrion Research Iii Limited Solid oral dosage form containing an enhancer
RU2437662C2 (ru) 2006-04-07 2011-12-27 Меррион Рисерч Iii Лимитед Твердая пероральная лекарственная форма, содержащая усилитель
CA2723558A1 (en) 2008-05-07 2009-11-12 Merrion Research Iii Limited Compositions of gnrh related compounds and processes of preparation
US9089484B2 (en) 2010-03-26 2015-07-28 Merrion Research Iii Limited Pharmaceutical compositions of selective factor Xa inhibitors for oral administration
BR112013017169A2 (pt) 2011-01-07 2016-10-04 Merrion Res Iii Ltd composições farmacêuticas de ferro para administração oral
CN103690560B (zh) * 2013-12-17 2016-08-17 辽宁海思科制药有限公司 一种转化糖电解质注射液药物组合物及其制备方法
WO2016120378A1 (en) 2015-01-29 2016-08-04 Novo Nordisk A/S Tablets comprising glp-1 agonist and enteric coating
RU2614234C2 (ru) * 2015-03-31 2017-03-23 Федеральное государственное бюджетное учреждение науки Институт общей генетики им. Н.И. Вавилова Российской академии наук (ИОГЕН РАН) Фармацевтическая композиция на основе 3-(4-Метилимидазол-1-ил)имидазо[1,2-b][1,2,4,5]тетразина в качестве противоопухолевого средства
ES2878094T3 (es) * 2017-01-30 2021-11-18 Antev Ltd Una composición que comprende al menos un antagonista de la GnRH
SI3811927T1 (sl) 2019-10-24 2022-03-31 Sun Pharmaceutical Industries Ltd Stabilna parenteralna dozirna oblika cetroreliks acetata

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021194A2 (en) * 1999-09-23 2001-03-29 Zentaris Ag Method for the therapeutic management of endometriosis and fallopian tube obstruction
WO2001087265A2 (de) * 2000-05-18 2001-11-22 Zentaris Ag Pharmazeutische darreichungsform für peptide, verfahren zu deren herstellung und verwendung

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4800191A (en) * 1987-07-17 1989-01-24 Schally Andrew Victor LHRH antagonists
US5140009A (en) * 1988-02-10 1992-08-18 Tap Pharmaceuticals, Inc. Octapeptide LHRH antagonists
US5300492A (en) * 1988-02-10 1994-04-05 Tap Pharmaceuticals LHRH analogs
DE4305225A1 (de) * 1993-02-19 1994-08-25 Asta Medica Ag Neues Herstellverfahren für Cetrorelix Lyophilisat

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021194A2 (en) * 1999-09-23 2001-03-29 Zentaris Ag Method for the therapeutic management of endometriosis and fallopian tube obstruction
WO2001087265A2 (de) * 2000-05-18 2001-11-22 Zentaris Ag Pharmazeutische darreichungsform für peptide, verfahren zu deren herstellung und verwendung

Also Published As

Publication number Publication date
AR037424A1 (es) 2004-11-10
BRPI0214412B1 (pt) 2016-01-05
HRP20040587B1 (en) 2008-01-31
RU2004119821A (ru) 2005-04-20
RS44904A (sr) 2006-10-27
TW200300352A (en) 2003-06-01
GEP20063861B (en) 2006-06-26
TWI312283B (en) 2009-07-21
RS51408B (sr) 2011-02-28
PL369548A1 (en) 2005-05-02
EA010787B1 (ru) 2008-10-30
CN1592630A (zh) 2005-03-09
IL161894A0 (en) 2005-11-20
EP1448221A1 (de) 2004-08-25
WO2003045419A1 (de) 2003-06-05
CO5580793A2 (es) 2005-11-30
RU2322969C2 (ru) 2008-04-27
KR20040058312A (ko) 2004-07-03
DE10157628A1 (de) 2003-06-12
BR0214412A (pt) 2004-09-14
UA81612C2 (ru) 2008-01-25
HRP20040587A2 (en) 2004-10-31
JP2005510544A (ja) 2005-04-21
ATE350050T1 (de) 2007-01-15
IS2725B (is) 2011-03-15
AU2002365504A1 (en) 2003-06-10
ES2276970T3 (es) 2007-07-01
NO20042449L (no) 2004-06-11
IS7251A (is) 2004-05-06
HUP0401986A3 (en) 2012-09-28
PL206199B1 (pl) 2010-07-30
DK1448221T3 (da) 2007-03-19
ZA200404051B (en) 2005-05-25
SI1448221T1 (sl) 2007-06-30
KR100936636B1 (ko) 2010-01-14
HUP0401986A2 (hu) 2005-01-28
ME00499B (me) 2011-10-10
DE50209193D1 (de) 2007-02-15
PT1448221E (pt) 2007-03-30
HU230992B1 (hu) 2019-08-28
HK1073078A1 (zh) 2005-09-23
AU2002365504B2 (en) 2007-06-28
JP4343693B2 (ja) 2009-10-14
BRPI0214412B8 (pt) 2021-05-25
CY1106401T1 (el) 2011-10-12
NO333364B1 (no) 2013-05-13
NZ533712A (en) 2006-01-27
MXPA04005018A (es) 2004-08-11
EP1448221B1 (de) 2007-01-03
EA200400742A1 (ru) 2004-12-30
IL161894A (en) 2014-05-28

Similar Documents

Publication Publication Date Title
US7790686B2 (en) Injection solution of an LHRH antagonist
CN100404068C (zh) 含有lhrh拮抗剂的注射液
CA2348167C (en) Pharmaceutical administration form for peptides, process for its preparation, and use
KR100633280B1 (ko) 약제학적 활성 펩티드의 서방형 투여 형태 및 이의 제조 방법
JP2023027082A (ja) テベレリクス－ｔｆａ組成物
KR20140091652A (ko) 안정적이며 바로 사용 가능한 세트로레릭스 주사액
HK1073078B (zh) 含有lhrh拮抗剂的注射液
HK1081855B (zh) 持续释放的药物活性肽施用形式及其制备方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1073078

Country of ref document: HK

C14 Grant of patent or utility model
GR01 Patent grant
ASS Succession or assignment of patent right

Owner name: ZANTALLIS IVF CO., LTD.

Free format text: FORMER OWNER: ATENAI ZANTARISCORP CORP.

Effective date: 20090821

C41 Transfer of patent application or patent right or utility model
C56 Change in the name or address of the patentee

Owner name: ATENAI ZANTARISCORP CORP.

Free format text: FORMER NAME: ZANTARISCORP CORP.

CP01 Change in the name or title of a patent holder

Address after: Frankfurt, Germany

Patentee after: AETERNA ZENTARIS GmbH

Address before: Frankfurt, Germany

Patentee before: Zentaris GmbH

TR01 Transfer of patent right

Effective date of registration: 20090821

Address after: Frankfurt, Germany

Patentee after: Zentaris IVF GmbH

Address before: Frankfurt, Germany

Patentee before: AETERNA ZENTARIS GmbH

REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1073078

Country of ref document: HK

CX01 Expiry of patent term

Granted publication date: 20080723

CX01 Expiry of patent term