EP0000764A1 - Agent anticonceptionnel contenant une peptide - Google Patents

Agent anticonceptionnel contenant une peptide Download PDF

Info

Publication number: EP0000764A1
Authority: EP; European Patent Office
Prior art keywords: compound; peptide; anticonceptive; agent containing; solution
Prior art date: 1977-08-06
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.): Granted

Application number

EP7878100564A

Other languages

German (de)

English (en)

Other versions

EP0000764B1 (fr

Inventor

Marianne Dr. Von Der Ohe

Jürgen Kurt Dr. Sandow

Wolfrad Dr. Von Rechenberg

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.)

Hoechst AG

Original Assignee

Hoechst 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.)

1977-08-06

Filing date

1978-08-01

Publication date

1979-02-21

1978-08-01 Application filed by Hoechst AG filed Critical Hoechst AG

1978-08-01 Priority to DE8181103936T priority Critical patent/DE2862466D1/de

1979-02-21 Publication of EP0000764A1 publication Critical patent/EP0000764A1/fr

1982-05-05 Application granted granted Critical

1982-05-05 Publication of EP0000764B1 publication Critical patent/EP0000764B1/fr

Status Expired legal-status Critical Current

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 6
239000003433 contraceptive agent Substances 0.000 title description 2
DDCPKNYKNWXULB-RXMQYKEDSA-N (2r)-2-azaniumyl-3-[(2-methylpropan-2-yl)oxy]propanoate Chemical compound CC(C)(C)OC[C@@H]([NH3+])C([O-])=O DDCPKNYKNWXULB-RXMQYKEDSA-N 0.000 claims description 3
102000004196 processed proteins & peptides Human genes 0.000 claims description 3
150000001875 compounds Chemical class 0.000 abstract description 10
230000001817 pituitary effect Effects 0.000 abstract description 3
102000006771 Gonadotropins Human genes 0.000 abstract description 2
108010086677 Gonadotropins Proteins 0.000 abstract description 2
239000002622 gonadotropin Substances 0.000 abstract description 2
229940094892 gonadotropins Drugs 0.000 abstract description 2
IGYOZGDZQWTWSE-SECBINFHSA-N (4R)-4-amino-5-(cyclohexylamino)-5-oxopentanoic acid Chemical compound C1CCC(CC1)NC(=O)[C@@H](CCC(=O)O)N IGYOZGDZQWTWSE-SECBINFHSA-N 0.000 abstract 1
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 abstract 1
229930195711 D-Serine Natural products 0.000 abstract 1
101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 abstract 1
102100024028 Progonadoliberin-1 Human genes 0.000 abstract 1
101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 abstract 1
239000003795 chemical substances by application Substances 0.000 abstract 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 abstract 1
XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 abstract 1
230000002441 reversible effect Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 10
239000000243 solution Substances 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
238000011282 treatment Methods 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
229940125890 compound Ia Drugs 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
239000000203 mixture Substances 0.000 description 5
229960003604 testosterone Drugs 0.000 description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
230000016087 ovulation Effects 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000000829 suppository Substances 0.000 description 3
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
230000001380 anti-conceptive effect Effects 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
238000011866 long-term treatment Methods 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000002504 physiological saline solution Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 1
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
206010062767 Hypophysitis Diseases 0.000 description 1
102000009151 Luteinizing Hormone Human genes 0.000 description 1
108010073521 Luteinizing Hormone Proteins 0.000 description 1
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
206010043298 Testicular atrophy Diseases 0.000 description 1
LDKDGDIWEUUXSH-UHFFFAOYSA-N Thymophthalein Chemical compound C1=C(O)C(C(C)C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C(=CC(O)=C(C(C)C)C=2)C)=C1C LDKDGDIWEUUXSH-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
201000010788 atrophy of testis Diseases 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
229940124558 contraceptive agent Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
229940028334 follicle stimulating hormone Drugs 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229940040129 luteinizing hormone Drugs 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
238000000034 method Methods 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
210000003635 pituitary gland Anatomy 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000005070 sampling Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
230000021595 spermatogenesis Effects 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000002381 testicular Effects 0.000 description 1
231100001044 testicular atrophy Toxicity 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/13—Luteinizing hormone-releasing hormone; related peptides

Definitions

the invention relates to the use of peptides of the general formula I in which X stands for D-serine-tert-butyl ether (la) or D-glutamic acid- ⁇ -cyelohexylamide (Ib), as anticonceptives.
X stands for D-serine-tert-butyl ether (la) or D-glutamic acid- ⁇ -cyelohexylamide (Ib), as anticonceptives.
the compounds of formula I are prepared according to DOS 2 438 350 or the earlier application P 26 17 646.5. After a single dose in doses of 1.4-20 meg (this corresponds to 20-300 ng / kg) intravenously (iv) subcutaneously (sc) or intramuscularly (im) or 50-1000 mcg (which corresponds to 100-5000 ng / kg) ) intranasal (in) in test subjects the release of gonadotropins from the anterior pituitary lobe.
the dosage is e.g. for the connection Ia 3 x 5 meg s.e., i.v. or i.m., but can be safely increased to a multiple, since the peptides according to the invention are non-toxic. In practice one moves between 5-500 mcg daily. In intranasal use, this dose has to be increased by about 100 times because of the absorption of only approx. 1%.
the compounds according to the invention can be used in men to temporarily suppress testosterone production and thus spermatogenesis, and in women to suppress ovulation.
the application for women begins e.g. on the first day of the cycle and is continued for about 14 days. In this way, ovulation is definitely prevented during the treatment period.
the LH level drops to basal values and stimulation of the pituitary gland is no longer possible.
ovulation can be postponed; with longer treatment, it is suppressed. The latter may also apply to the nidation, since both processes depend on the level of the FSH and LH levels.
the preparations used according to the invention contain poptides which are easily broken down into amino acids in the body excreted or metabolized via these amino acids in a physiological manner.
Compounds of formula I can be used e.g. can be administered intravenously intramuscularly or subcutaneously in physiological saline.
a particularly valuable form of medicinal use is particularly suitable for long-term treatment with aqueous or oily preparations for intranasal application.
rectal or vaginal use is also possible.
Testosterone levels were measured by radioimmunoassay. There was a reduction in the plasma testosterone level to approximately 1/3 of the initial value. Testosterone levels were measured again 6 weeks after stopping treatment. They were back to normal.
testicular atrophy occurred during treatment, but testicular size increased significantly 8 weeks after treatment was discontinued and the animals showed normal sex drive.
600 mg of compound Ib are dissolved in 100 l of isotonic aqueous mannitol solution and further treated as in Example 1.
the ampouled solution is freeze-dried for use again in 1 ml of dist. Water dissolved.
1 ml solution is e.g. filled into a container that is equipped with a dispensing metering valve that releases 0.05 ml of the solution per application.
10 g of benzyl alcohol are made up to 0.990 l with 2-octyldodecanol.
10 g of microfine ground compound Ia are added and the mixture is homogenized.
1 - 2 ml of this suspension are filled into small containers.
the containers are equipped with a sampling valve that releases 0.05 ml of the suspension per application.
the filter cake is triturated with saturated NaHCO 3 solution and suction filtered.
Educ. 3.2 g of amorphous mass which is catalytically hydrogenated in methanol with a Pd catalyst analogous to Example 1d. After the hydrogenation has ended, the catalyst is filtered off with suction, the filtrate is concentrated and the residue is triturated with ether.
Educ. 2.2 g of an amorphous mass which without further purification with 1.5 g of Z-Ser-Tyr (Bzl) -OH and 405 mg of 1-hydroxybenzotriazole in a little dimethylformamide is solved. 0.78 ml of N-ethylmorpholine and 660 mg of DDC at 0 ° C. are added to this solution.

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Immunology (AREA)
Medicinal Chemistry (AREA)
Reproductive Health (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmacology & Pharmacy (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

EP78100564A 1977-08-06 1978-08-01 Agent anticonceptionnel contenant une peptide Expired EP0000764B1 (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
DE8181103936T DE2862466D1 (en)	1977-08-06	1978-08-01	Use of a luteinising peptide as anti-contraceptive

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE2735515		1977-08-06
DE19772735515 DE2735515A1 (de)	1977-08-06	1977-08-06	Verwendung von lh-rh-peptiden als antikonzeptive

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
EP81103936.1 Division-Into		1981-05-22

Publications (2)

Publication Number	Publication Date
EP0000764A1 true EP0000764A1 (fr)	1979-02-21
EP0000764B1 EP0000764B1 (fr)	1982-05-05

Family

ID=6015797

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
EP81103936A Expired EP0037127B1 (fr)	1977-08-06	1978-08-01	Utilisation d'un peptide lutéinisant en tant qu'agent anticonceptionnel
EP78100564A Expired EP0000764B1 (fr)	1977-08-06	1978-08-01	Agent anticonceptionnel contenant une peptide

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
EP81103936A Expired EP0037127B1 (fr)	1977-08-06	1978-08-01	Utilisation d'un peptide lutéinisant en tant qu'agent anticonceptionnel

Country Status (5)

Country	Link
US (1)	US4263282A (fr)
EP (2)	EP0037127B1 (fr)
JP (1)	JPS5428831A (fr)
DE (3)	DE2735515A1 (fr)
IT (1)	IT1097629B (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4705695A (en) *	1984-06-13	1987-11-10	Rohm Gmbh Chemische Fabrik	Method for coating pharmaceutical formulations
EP0309863A3 (en) *	1987-09-30	1990-01-10	Mobay Corporation	Composition and method to release an immune reaction to gnrh and method for the immunosterilization of mammals
GB2237571A (en) *	1989-11-01	1991-05-08	Robert Peter Millar	Gonadotropin releasing hormone analogues

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4652443A (en) *	1983-06-07	1987-03-24	Japan Atomic Energy Research Institute	Slow-release composite and process for producing the same
DE3414595A1 (de) *	1984-04-18	1985-10-31	Hoechst Ag, 6230 Frankfurt	Verwendung von gonadoliberin und gonadoliberinagonisten zur behandlung klimakterischer beschwerden
US4762717A (en) *	1986-03-21	1988-08-09	The General Hospital Corporation	Continuous delivery of luteinizing hormone releasing hormone compositions in combination with sex steroid delivery for use as a contraceptive
JPS6311675A (ja) *	1986-07-03	1988-01-19	Nippon Mining Co Ltd	アルミナ基板への無電解めつき方法
US5433219A (en) *	1992-09-23	1995-07-18	Spery; Nanette S.	Receptive condom assembly

Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3914412A (en) *	1973-10-11	1975-10-21	Abbott Lab	{8 Des{13 Gly{9 {0 10 -Gn{13 RH nonapeptide amide analogs in position 6 having ovulation-inducing activity
FR2281132A1 (fr) *	1974-08-09	1976-03-05	Hoechst Ag	Peptides ayant une forte activite d'hormone liberant l'hormone luteinisante ou d'hormone liberant l'hormone folliculostimulante (hl-hl/hl-hfs) et leur procede de preparation et leur application
FR2348913A1 (fr) *	1976-04-22	1977-11-18	Hoechst Ag	Peptides presentant la meme action que la gonadoliberine,leur procede de preparation et leurs applications

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CS180644B2 (en) *	1973-09-29	1978-01-31	Takeda Chemical Industries Ltd	Process for preparing nonapeptides
US3928307A (en) *	1974-11-04	1975-12-23	American Home Prod	P-Glu-D-Phe-Trp-Ser-Tyr-D-Phee-Leu-Arg-Pro-Gly-NH2 and intermediates
US4010261A (en) *	1974-11-25	1977-03-01	Abbott Laboratories	Method to prevent reproduction with [Des-Gly]10 -GN-RH nonadeptide amide analogs in position
US4010256A (en) *	1975-07-30	1977-03-01	Professional Staff Association Of The Los Angeles County Harbor General Hospital	Male contraceptive and method of achieving male contraception
US4034082A (en) *	1976-03-01	1977-07-05	Abbott Laboratories	Method to prevent reproduction in warm-blooded female animals with nonapeptides

1977
- 1977-08-06 DE DE19772735515 patent/DE2735515A1/de not_active Withdrawn
1978
- 1978-08-01 DE DE7878100564T patent/DE2861783D1/de not_active Expired
- 1978-08-01 DE DE8181103936T patent/DE2862466D1/de not_active Expired
- 1978-08-01 EP EP81103936A patent/EP0037127B1/fr not_active Expired
- 1978-08-01 EP EP78100564A patent/EP0000764B1/fr not_active Expired
- 1978-08-04 IT IT26535/78A patent/IT1097629B/it active
- 1978-08-05 JP JP9504178A patent/JPS5428831A/ja active Granted
1979
- 1979-11-20 US US06/096,029 patent/US4263282A/en not_active Expired - Lifetime

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3914412A (en) *	1973-10-11	1975-10-21	Abbott Lab	{8 Des{13 Gly{9 {0 10 -Gn{13 RH nonapeptide amide analogs in position 6 having ovulation-inducing activity
FR2281132A1 (fr) *	1974-08-09	1976-03-05	Hoechst Ag	Peptides ayant une forte activite d'hormone liberant l'hormone luteinisante ou d'hormone liberant l'hormone folliculostimulante (hl-hl/hl-hfs) et leur procede de preparation et leur application
FR2348913A1 (fr) *	1976-04-22	1977-11-18	Hoechst Ag	Peptides presentant la meme action que la gonadoliberine,leur procede de preparation et leurs applications

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, B.85-réference, No. 186906h (1976) & Pept.:Chem., Struc. Biol., Proc. Am., Pept.,Symp., 4-1975, 883-8 *
JOURNAL OF MEDICINAL CHEMISTRY, (Ausg. American Chemical Society) B.19, 1976, Seiten 243-45 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4705695A (en) *	1984-06-13	1987-11-10	Rohm Gmbh Chemische Fabrik	Method for coating pharmaceutical formulations
EP0309863A3 (en) *	1987-09-30	1990-01-10	Mobay Corporation	Composition and method to release an immune reaction to gnrh and method for the immunosterilization of mammals
GB2237571A (en) *	1989-11-01	1991-05-08	Robert Peter Millar	Gonadotropin releasing hormone analogues
GB2237571B (en) *	1989-11-01	1993-10-20	Robert Peter Millar	Analogues of gonadotropin releasing hormone

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EP0037127B1 (fr)	1985-05-22
US4263282A (en)	1981-04-21
DE2735515A1 (de)	1979-02-22
IT7826535A0 (it)	1978-08-04
JPS5428831A (en)	1979-03-03
IT1097629B (it)	1985-08-31
EP0037127A1 (fr)	1981-10-07
JPH0130808B2 (fr)	1989-06-22
EP0000764B1 (fr)	1982-05-05
DE2861783D1 (en)	1982-06-24
DE2862466D1 (en)	1985-06-27

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Publication	Publication Date	Title
DE3750764T2 (de)	1995-06-29	Kontinuierliche verabreichung des luteinisierendes hormon abgebenden hormons in kombination mit sexsteroidverabreichung als empfängnisverhütungsmittel.
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DE69016691T2 (de)	1995-10-05	Lineare Somatostatin-Analoga.
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DD216923A5 (de)	1985-01-02	Verfahren zur herstellung eines peptids
DE3021736A1 (de)	1980-12-18	Neue peptide, verfahren zu deren herstellung und diese enthaltenden arzneimittel
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DE2547721A1 (de)	1976-04-29	Biologisch aktive amide
DE2708125C2 (fr)	1988-11-17
DD202694A5 (de)	1983-09-28	Verfahren zur herstellung von peptiden
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DE69006032T2 (de)	1994-05-05	Verfahren zur behandlung von unfruchtbarkeit oder verminderter fruchtbarkeit bei erwachsenen männern und die verwendung von präparaten in diesem verfahren.