AU2002365504B2 - Injection solution comprising an LHRH antagonist - Google Patents
Injection solution comprising an LHRH antagonist Download PDFInfo
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- AU2002365504B2 AU2002365504B2 AU2002365504A AU2002365504A AU2002365504B2 AU 2002365504 B2 AU2002365504 B2 AU 2002365504B2 AU 2002365504 A AU2002365504 A AU 2002365504A AU 2002365504 A AU2002365504 A AU 2002365504A AU 2002365504 B2 AU2002365504 B2 AU 2002365504B2
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- gluconic acid
- antagonist
- injection solution
- aqueous injection
- lactone
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- 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
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- 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
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- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
VERIFICATION OF TRANSLATION RWS Group plc, of Europa House, Marsham Way, Gerrards Cross, Buckinghamshire, England, declare as follows: 1. That the translator responsible for the attached translation is well acquainted with both the English and German languages, and 2. That the attached document is a true and correct translation to the best of RWS Group plc knowledge and belief of:- The specification of International Bureau pamphlet numbered WO 03/045419 International Application No. PCT/EP02/12798.
Date: 14 May 2004 Signature: C. E. SITCH Deputy Managing Director UK Translation Division For and on behalf of RWS Group plc (No witness required) I I (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization international Bureau (43) International publication date June 2003 (05.06.2003) (10) International publication number WO 03/045419 Al PCT (51) International patent classification': 9/08,47/26 (21) International application number: A61K 3&/09. (81) PCT/EP02J 12798 Designated states (national): AE, AG, AL, AM, AT, AU, AZ, BA, BB, BO, BR, BY, BZ, CA, CH, CN, CO. CR, CU, CZ, DE, DK, DM, DM EC, EE, ES, FIL GB. GD, GE, GH, GM, HR. HU, ID, IL, IN, IS. 3P.
KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MY.. MN, MW, MX, M7, NO, NZ, OM, PH, PL, PT, RO, RU, SD. SE, SG, SI. SK, SL, TJ, TM, TN, TR, TIT, TZ, UA, UG, liZ, VN, YU, ZA,
ZMZW.
(22) International filing date: 15 November 2002 (15.11.2002) Language of filing: German German (26) Language of publication: Data relating to the priority: 10157628.5 26 November 2001 (26.11.2001) DE (71) Applicant: ZENTARIS AG [DE/DE]; Weismtlllerstrasse 45, 60314 Frankfurt (DE).
(72) Inventors: SARLIKIOTIS, Werner; Sp. Dima. 31, GR- 190 02 Peania BAUTER, Horst; R~hrenstrasse 12a, 91217 Hersbruck RISCHER, Matthias; Scblesierstrasse 60388 Frankfurt ENGEL, Jorgen; Erlenweg 3, 63755 Alzenau GVTHLEIN, Frank; Westendstrasse 5, 63477 Maintal DI STEFANO, Dominique; Am B6rnchen 14, 65479 Raunheim (DE).
(84) Designated states (regional): ARIPO Patent (GH, GM, KE, IS, MW, MZ. SD, SL, SZ, 17, UG, ZM ZW), Eurasian Patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European Patent (AT, BE, BG, CH. CY, CZ, DE.
DK, EE, ES, F1, FR, GB, OR, IE, IT, LU, MC, NL, FIT, SE, SK, TR), QAPI Patent (BF, BJ, CF. CG, Cl, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Published: With the International Search Report.
For an explanation of the two-letter codes and the other abbreviations, reference is made to the explanations ("Guidance Notes on Codes and Abbreviations") at the beginning of each regular edition of the PCT Gazette.
As printed Title: INJECTION SOLUTION COMPRISING AN LHIIH ANTAGONIST (54) Dczeekbnung: TNIEKTIONSLOSUNG EINES LHRli-ANTAGONISTEN (57) Abstract: The aqueous injection solution comprising an LHII antagonist contains in addition to the LHRH antagonist. such If) as cetrorelix, an organic, physiologically compatible acid and optionally a surfactant and also a framework builder. The LHRH '1antagonist has significantly improved solubility and can be prepared in higher concentrations and with an improved bioavailability.
The aggregation tendency of the LHRH antagonist is significantly reduced.
(57) Zusamnmenfassuag: Die wlissrige Injektionsldsung eines LHRH-Antagonistefl enihklt neberi dern LHRI-Antagonisten, wie 0Cetrorelix eine organische, pbysiolagisch vertzigliche Sbure, und ggf. ein Tensid sowie einen Geallstbildner. Der LHRH-Antagoflist ~.weist cane deutlich verbesserte Lbsichkeit auf, kann in einer ht~heren Konzentration und besseren Bioverftkgbarkeit bereilgesteit ~"werden. Die Aggregationsneigung des LHRI-Antagonisteii wird deutlich hembgesettt.
WO 03/045419 PCT/EP02/12798 Injection solution of an LHRH antagonist Technical field: The invention relates to aqueous injection solutions of an LHRH antagonist using additions of organic, physiologically tolerable acids and/or surfactants and their preparation for prevention of the aggregation of the LHRH antagonist in solution. The injection solutions prepared according to the invention additionally lead to an increase in the bioavailability and make possible the lowering of the injection volume to be administered.
Prior art: In controlled ovarian stimulation followed by egg cell removal and techniques of assisted reproduction, besides LHRH agonists (e.g.
triptorelin, buserelin), LHRH antagonists (cetrorelix, ganirelix) have especially been used for some time, since they avoid the initial increase in endogenous gonadotropin secretion and immediately lead to a competitive inhibition of gonadotropin-releasing hormone [EP 0 788 799 A2; EP 0 299 402 B1]. The LHRH antagonist ganirelix is at present used in a formulation which contains 0.25 mg of ganirelix in 0.5 ml of an aqueous, mannitolcontaining solution in the form of a ready-to-use injection (Orgalutran®).
The LHRH antagonist cetrorelix (Cetrotide®) is at present supplied in two administration forms: a lyophilizate containing 0.25 mg of cetrorelix combined with a ready-to-use syringe which contains 1 ml of water for reconstitution, and a lyophilizate containing 3 mg of cetrorelix combined with a ready-to-use syringe which contains 3 ml of water for reconstitution.
LHRH antagonists, however, are not only used for controlled ovarian stimulation, but can also be used for the therapy of hormone-dependent types of cancer such as, for example, prostate carcinoma. Substances such as abarelix [WO 98/25642] or cetrorelix [WO 00/47234] could be used for this in that the LHRH antagonists could be an alternative to the marketdominating agonists (leuprolide, goserelin) in this therapy. On account of the relatively poor solubility of abarelix in water or physiological media, a depot formulation must be used in order to achieve a long-term action.
There are indications, however, that a long-term action could also be caused by good solubility of the LHRH antagonists Jiang, J. Stakewski, R. Galyean, J. Dykert, C. Schteingart, P. Broqua, A. Aebi, M. L. Aubert, 8. JUN. 2007 18:49 SPRUSON FERGUSON 92615486 NO, 8932 P. D- 2 c1 G. Semple, P. Robson, K. Akinsanya, R. Haigh, P. Riviere, J. Trojnar, J. L. Junien and J.
E. Rivier, 1. Med. Chem., 2001, 44, 453-467].
l'-i Presentation of the Invention 00 SAccording to a first embodiment of the invention, there is provided Aqueous injection solution of an LHRH antagonist comprising a gluconic acid and a mannitol bulking agent, wherein said LHRH antagonist is selected from the group consisting of: cetrorelix, teverelix, D-63153 (Ac-D-Nal-pCI-D-Phe-3-D-Pal-Ser-N-Me-Tyr-D-H-Cite) Nie-Arg-Pro-D-Ala-NH2), ganirelix, abarelix, antide, and azaline B, wherein gluconic N acid is present in a more than equimolar amount based on the amount of LHRH o 10 antagonist, wherein the gluconic acid is added in the form of gluconic acid delta-lactone.
According to a second embodiment of the invention, there is provided a process for the preparation of aqueous injection solution in accordance with the first embodiment of the present invention, wherein an LHRH antagonist, gluconic acid in the form of gluconic acid delta-lactone, the is gluconic acid being present in a more than equimolar amount based on the amount of LHRH antagonist and mannitol as bulking agent are dissolved in water for injection, homogenized and processed for injection purposes; or an LHRH antagonist, mannitol as bulking agent are dissolved using an aqueous saturated solution of gluconic acid delta-lactone, homogenized and processed for injection purposes.
It is the objection of the invention to prepare an injection solution which achieves a low injection volume together with an increased concentration of the LHRH antagonist by means of its improved solubility. At the same time, the aggregation of the LHRH antagonist in the relatively highly concentrated injection solution should be prevented.
It has surprisingly been found that organic, physiologically tolerable acids, particularly carboxylic acids, in particular hydroxycarboxylic acids, but preferably gluconic acid on its own or in combination with surfactants such as, for example, Tween, markedly improve the solubility of LH-RH antagonists and thus markedly reduce the proneness to aggregation of these substances.
The invention therefore makes it possible to prepare LHRH antagonists in relatively high concentration in aqueous solutions for injection. LHRH antagonists which may be COMS ID No: SBMI-07715354 Received by IP Australia: Time 18:51 Date 2007-06-08 8. JUN. 2007 18:49 SPRUSON FERGUSON 92615486 NO. 8932 P. 21 r- 2a 0 mentioned are, for example, cetrorelix, teverelix, D-63 153 (Ac-D-Nal-pCl-D-Phe-3-Dpal-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2) ganirelix, abarelix, antide, azaline Z B. It was seen that an excess of the respective carboxylic acid must be used; equimolar o amounts are not sufficient. Obviously, this effect cannot be explained alone by an in-situ s salt formation with basic amino acid residues present such as, for example, arginine, pyridylalanine, lysine. Likewise, the surfactant concentration must not be chosen to be In too high, since otherwise the solutions foam too much and aggregation is in turn induced by the surfactants.
At the same time, these additions make possible an increase in the bioavailability, since they obviously also slow the spontaneous aggregation in the body after injection or C make possible a more rapid absorption of the substance from the site of action. It was seen that the lowered pH of such injection solutions pH 2.5-3) has no influence on the local tolerability of the injection. By increasing the concentration, it is possible to reduce the volume administered, e.g. in the case of cetrorelix from 3 ml to 1 ml for the 3 mg form. It was likewise shown that by means of these additions a good 3 mg form. It was likewise shown that by means of these additions a good storage stability can be achieved (see Example Although storage for over 6 months at 25°C/60% produced an increase in the impurities, the COMS ID No: SBMI-07715354 Received by IP Australia: Time 18:51 Date 2007-06-08 3 content value in each case was still clearly above 90% (as a rule the lowest value of the use period specification of pharmaceutical products). The turbidity, as a sign of aggregation, increased only slightly. Turbidity values of up to 8 FTU (formazine turbidity unit according to European Pharmacopoeia) are perfectly tolerable.
Preservatives such as, for example, phenol or p-chloro-m-cresol do not interfere and can additionally be used for the preservation of the solutions.
The use of customary bulking agents, such as mannitol, lactose, glucose and fructose, is likewise possible.
Description of a route for carrying out the invention: Example 1 500 mg of cetrorelix 2 g of Tween 2.4 g of gluconic acid delta-lactone g of mannitol were mixed with water for injection to 2 litres to give a homogeneous solution. The solution was then sterile-filtered and dispensed into ampoules. The ampoules were investigated analytically for purity (HPLC), content (HPLC), pH and aggregation (turbidity) initially and after a storage time of 6 months at 2-8 0 C and 25°C/60% rel. humidity.
Analytical results: Example 2 About 500 mg ofD-63153 About 100 mg of Tween About 475 mg of mannitol were adjusted to a pH of about 2.5 using aqueous, saturated gluconic acid 3-lactone solution. A volume of about 50 ml resulted. The mixture was stirred until a clear solution resulted.
Analytical results: The turbidity of the solution was initially 2.4 FTU. After 24 h, 2.1 FTU were measured. The purity profile and the content of the solution (HPLC) remained unchanged.
Structure of the LHRH antagonist D-63153: Ac-D-Nal-pCl-D-Phe-3-D-Pal-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2 Example 3 About 100 mg of teverelix About 100 mg of Tween About 475 mg ofmannitol were adjusted to a pH of about 2.5 using aqueous, saturated gluconic acid a-lactone solution. A volume of about 10 ml resulted. The mixture was stirred until a clear solution resulted.
Analytical results: The turbidity of the solution was initially 6.8 FTU. After 24 h, 8.4 FTU were measured. The purity profile and the content of the solution (HPLC) remained unchanged.
Structure of the LHRH antagonist teverelix: Ac-D-Nal-pCl-D-Phe-3-D-Pal-Ser-Tyr-D-H-Cit-Leu-iPr-Lys-Pro-D-Ala-NH2 [R:\LIBVV]67671 9peciamendments.doc:THR
Claims (2)
- 8. JUN. 2007 18:50 SPRUSON FERGUSON 92615486 NO. 8932 P. 22 1" 0 The claims defining the invention are as follows: 1. Aqueous injection solution of an LHRH antagonist comprising a gluconic 00 acid and a mannitol bulking agent, wherein said LHRIH antagonist is selected from the group consisting of: cetrorelix, teverelix, D-63153 (Ac-D-Nal-pCI-D-Phe-3-D-Pal-Ser-N- Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2), ganirelix, abarelix, antide, and azaline B, o wherein gluconic acid is present in a more than equimolar amount based on the amount of SLHRH antagonist, wherein the gluconic acid is added in the form of gluconic acid delta- tr lactone. 2. 0o surfactant. 3. Tween Aqueous injection solution according to claim 1, further comprising a Aqueous injection solution according to claim 2, wherein the surfactant is 4. Aqueous injection solution according to any one of claims 1 to 3, comprising: 500 mg cetrorelix 2,4 g gluconic acid delta-lactone g Tween 95,0 g mannitol in 2 L water for injection. Aqueous injection solution according to any one of claims 1-3, comprising: 500mgD-63153 100mg Tween 475 mg mannitol adjusted to 50 mL using saturated gluconic acid delta-lactone solution. 6. Aqueous injection solution according to any one of claims 1-3, comprising: 100 mg teverelix 100mg Tween 475 mg mannitol adjusted to 10 mL using saturated gluconic acid delta-lactone solution. 7. Process for the preparation of aqueous injection solution according to any one of claims 1 to 6, wherein an LIRH antagonist, gluconic acid in the form of gluconic acid delta- lactone, the gluconic acid being present in a more than equimolar amount based on the
- 821523- ICC COMS ID No: SBMI-07715354 Received by IP Australia: Time 18:51 Date 2007-06-08 8. JUN. 2007 18:50 SPRUSON FERGUSON 92615486 NO, 8932 P. 23 S6 0 amount of LHRH antagonist and mannitol as bulking agent are dissolved in water for injection, homogenized and processed for injection purposes; or n an LHRI- antagonist, mannitol as bulking agent are dissolved using an o aqueous saturated solution of gluconic acid delta-lactone, homogenized and processed for injection purposes, 8. Aqueous injection solution according to claim 7 wherein said solution further in comprises Tween 80 as a surfactant. Va 9. Aqueous injection solution of an LHIRH antagonist, substantially as ci hereinbefore described with reference to any one of the examples. to 10. Process for the preparation of aqueous injection solution of an LHRH antagonist, substantially as hereinbefore described with reference to any one of the examples. Dated 8 June, 2007 Zentaris GmbH Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON S21i5 3.I.g COMS ID No: SBMI-07715354 Received by IP Australia: Time 18:51 Date 2007-06-08
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10157628.5 | 2001-11-26 | ||
| DE10157628A DE10157628A1 (en) | 2001-11-26 | 2001-11-26 | Solution for injection of an LHRH antagonist |
| PCT/EP2002/012798 WO2003045419A1 (en) | 2001-11-26 | 2002-11-15 | Injection solution comprising an lhrh antagonist |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002365504A1 AU2002365504A1 (en) | 2003-06-10 |
| AU2002365504B2 true AU2002365504B2 (en) | 2007-06-28 |
Family
ID=7706799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002365504A Expired AU2002365504B2 (en) | 2001-11-26 | 2002-11-15 | Injection solution comprising an LHRH antagonist |
Country Status (33)
| Country | Link |
|---|---|
| EP (1) | EP1448221B1 (en) |
| JP (1) | JP4343693B2 (en) |
| KR (1) | KR100936636B1 (en) |
| CN (1) | CN100404068C (en) |
| AR (1) | AR037424A1 (en) |
| AT (1) | ATE350050T1 (en) |
| AU (1) | AU2002365504B2 (en) |
| BR (1) | BRPI0214412B8 (en) |
| CO (1) | CO5580793A2 (en) |
| CY (1) | CY1106401T1 (en) |
| DE (2) | DE10157628A1 (en) |
| DK (1) | DK1448221T3 (en) |
| EA (1) | EA010787B1 (en) |
| ES (1) | ES2276970T3 (en) |
| GE (1) | GEP20063861B (en) |
| HK (1) | HK1073078A1 (en) |
| HR (1) | HRP20040587B1 (en) |
| HU (1) | HU230992B1 (en) |
| IL (2) | IL161894A0 (en) |
| IS (1) | IS2725B (en) |
| ME (1) | ME00499B (en) |
| MX (1) | MXPA04005018A (en) |
| NO (1) | NO333364B1 (en) |
| NZ (1) | NZ533712A (en) |
| PL (1) | PL206199B1 (en) |
| PT (1) | PT1448221E (en) |
| RS (1) | RS51408B (en) |
| RU (1) | RU2322969C2 (en) |
| SI (1) | SI1448221T1 (en) |
| TW (1) | TWI312283B (en) |
| UA (1) | UA81612C2 (en) |
| WO (1) | WO2003045419A1 (en) |
| ZA (1) | ZA200404051B (en) |
Families Citing this family (11)
| 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 |
| ES2426445T3 (en) | 2006-04-07 | 2013-10-23 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| US8999383B2 (en) * | 2008-05-07 | 2015-04-07 | 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 |
| WO2012094598A2 (en) | 2011-01-07 | 2012-07-12 | Merrion Research Iii Limited | Pharmaceutical compositions of iron for oral administration |
| CN103690560B (en) * | 2013-12-17 | 2016-08-17 | 辽宁海思科制药有限公司 | A kind of Invert sugar electrolyte injection pharmaceutical composition and preparation method thereof |
| US10265384B2 (en) | 2015-01-29 | 2019-04-23 | Novo Nordisk A/S | Tablets comprising GLP-1 agonist and enteric coating |
| RU2614234C2 (en) * | 2015-03-31 | 2017-03-23 | Федеральное государственное бюджетное учреждение науки Институт общей генетики им. Н.И. Вавилова Российской академии наук (ИОГЕН РАН) | PHARMACEUTICAL COMPOSITION BASED ON 3-(4-METHYLIMIDAZOLE-1-YL)IMIDAZO[1,2-b][1,2,4,5]TETRAZINE AS ANTI-TUMOR AGENT |
| KR20210157482A (en) * | 2017-01-30 | 2021-12-28 | 안테브 리미티드 | A composition comprising at least one GNRH antagonist |
| DK3811927T3 (en) | 2019-10-24 | 2021-12-13 | Sun Pharmaceutical Ind Ltd | STABLE, PARENTERAL DOSAGE FORM OF CETRORELIXACETATE |
Citations (1)
| 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 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4800191A (en) * | 1987-07-17 | 1989-01-24 | Schally Andrew Victor | LHRH antagonists |
| US5300492A (en) * | 1988-02-10 | 1994-04-05 | Tap Pharmaceuticals | LHRH analogs |
| US5140009A (en) * | 1988-02-10 | 1992-08-18 | Tap Pharmaceuticals, Inc. | Octapeptide LHRH antagonists |
| DE10024451A1 (en) * | 2000-05-18 | 2001-11-29 | Asta Medica Ag | Pharmaceutical dosage form for peptides, process for their preparation and use |
-
2001
- 2001-11-26 DE DE10157628A patent/DE10157628A1/en not_active Withdrawn
-
2002
- 2002-11-15 EP EP02790384A patent/EP1448221B1/en not_active Expired - Lifetime
- 2002-11-15 IL IL16189402A patent/IL161894A0/en unknown
- 2002-11-15 UA UA20040503816A patent/UA81612C2/en unknown
- 2002-11-15 GE GE5568A patent/GEP20063861B/en unknown
- 2002-11-15 WO PCT/EP2002/012798 patent/WO2003045419A1/en active IP Right Grant
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Patent Citations (1)
| 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 |
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Owner name: ZENTARIS IVF GMBH Free format text: FORMER OWNER WAS: ZENTARIS GMBH |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |