Abstract: A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

Abstract: A pharmaceutical composition is prepared in the form of microparticles or of an implant comprising a biodegradable polymer selected from poly-1,4-butylene succinate, poly-2,3-butylene succinate, poly-1,4-butylene fumarate and poly-2,3-butylene succinate, incorporating as the active substance the pamoate, tannate, stearate or palmitate of a natural or of a synthetic peptide comprising 3 to 45 amino acids, such as LH-RH, somatostatin, GH-RH or calcitonin, or one of their synthetic analogues or homologues. The preparation comprises dry blending the ingredients in the form of powders, pre-compressing and preheating the mixture and then extruding the pre-compressed and pre-heated mixture. The product resulting from the extrusion step can then be comminuted and finally sieved.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formulaP Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) Z is Gly--NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly--NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, D Met .epsilon.-lauryl D Lys, .epsilon.

Abstract: A method of treatment of androgen-related diseases such as prostate cancer in susceptible male animals, including humans, comprises administering novel antiandrogens and/or novel sex steroid biosynthesis inhibitors as part of a combination therapy. Sex steroid biosynthesis inhibitors, especially those capable of inhibiting conversion of dehydroepiandrosterone (DHEA) or 4-androstenedione (.DELTA..sup.4 -dione) to natural sex steroida (and testosterone into dihydrotestosterone) in peripheral tissues, are used in combination with antiandrogens usually after blockade of testicular hormonal secretions. Antiestrogens can also be part of the combination therapy. Pharmaceutical compositions and two, three, four and five component kits are useful for such combination treatment.

Abstract: Compositions and methods which are effective to inhibit conception and to treat benign gynecological disorders for extended periods of time are described, wherein an effective amount of a gonadotropin hormone releasing hormone composition and an effective amount of an estrogenic composition are provided over a first period of time, in addition to a progestogen and optionally an androgenic composition. According to one protocol, the progestogen is provided for a second, shorter period of time; the progestogen is provided at a higher level for at least 5 to about 20 days, and then at a lower level for the remainder, if any, of the second period of time. In an alternative protocol, the progestogen is provided at a lower level substantially throughout the period of administration of gonadotropin hormone releasing hormone composition and estrogenic composition. An effective amount of the androgenic hormone is optionally provided over the first period of time.

Abstract: Peptides which include unnatural amino acids and which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U.sup.* : ##STR1## where W is (CH.sub.2).sub.n or ##STR2## n is an integer from 1 to 6; and j=1, 2 or 3. Preferably, either Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pridyl or ##STR3## where R.sub.11 is H or acyl.

Abstract: Sustained release microcapsules including a water soluble drug and an organic basic substance as a drug retaining substance of this invention not only have a high rate of incorporation (trapping rate), but also show little initial release so that they can be administered safely and bring about persistent, stable sustained release.

Abstract: A method for preparing a pharmaceutical composition in the form of microparticles, the composition thus obtained and its use for preparing injectable suspensions.

Abstract: Contraceptive devices which are effective for extended periods of time are described, in the form of means for releasing an effective amount of a gonadotropin hormone releasing hormone composition and means for releasing an effective amount of an estrogenic hormone over a first period of time, and means for releasing an effective amount of a progestogen for a second period of time, the second period of time being substantially shorter than and running simultaneously with a portion of the first period of time. The gonadotropin hormone releasing hormone composition is selected from gonadotropin hormone releasing hormone, gonadotropin hormone releasing hormone analogues, gonadotropin hormone releasing hormone agonists, gonadotropin hormone releasing hormone antagonists and mixtures thereof. Contraceptive methods employing the devices are also described.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsiutism, hormono-dependant mammary tumors, treatment and prevention of precociuos puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formulap Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, s-lauryl-D Lys, a-dextran-D Lys, (c) Z is NH-cyclopropyl-or NH-Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Otbu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH.sub.

Abstract: Peptides which include unnatural amino acides and which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-position, the 5-position, the 6-position and/or the 8-position. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U*: ##STR1## where n is an integer from 1 to 6; Y is N--CN, N--CONHR.sub.9, S, O or CH--NO.sub.2 ; R.sub.9 is H, Ac, lower alkyl, aromatic or heterocyclic; X is NH, O, S, M.sub.1 (CH.sub.q).sub.p M.sub.2 or M.sub.1 --(CH.sub.2).sub.p' --M.sub.2 (CH.sub.2).sub.p" --M.sub.3, where M.sub.

Abstract: A hormone composition for producing superovulation in mammals. The composition has a particular ratio of follicle stimulating hormone (FSH) and luteinizing hormone (LH) which produces an optimum ovulation response in mammals and promotes out of season breeding and twinning. The composition can be produced from mammal pituitary glands or by recombinant DNA procedures and can be preserved in a phosphate buffered saline solution of thymol.

Abstract: Delayed-release tablets are formed by incorporating hemicellulose and a matrix-forming adjuvant which does not disintegrate in a pharmaceutical dosage form containing the active substance or substances, preferably as a coated tablet or dragee.

Abstract: A liquid composition for nasal administration of polypeptide/s containing ammonium tartrate and a buffer together with optional adiuvants.

Abstract: The present invention relates to a novel nasal composition comprising a nona- or decapeptide having LHRH agonist or antagonist activity and a surfactant which is a bile acid or a pharmaceutically acceptable salt thereof in a buffered aqueous solution.

Abstract: The invention relates to peptides of the formula ##STR1## in which X is absent or is hydrogen or acyl; A is Pgl, de-hydro-Pro, Pro, D-Thi or D-Pgl or represents optionally substituted D-Nal(2), D-Phe or D-Trp; B is His or optionally substituted D-Phe; C is Trp, D-Thi, D-Pal(3) or optionally substituted D-Trp; D is Tyr, Arg of His; E is D-Ser(R.sup.1), .beta.-Asn, .beta.-Asp-OMe, D-Thi or --NH--CH(CH.sub.2 R.sup.2)--CO--; F is Ser(R.sup.1), Leu, Trp or Phe; G is Gly-NH.sub.2, Aza-Gly-NH.sub.2, D-Ala-NH.sub.2 or NH-alkyl; R.sup.1 is glycosyl and R.sup.2 is hydrogen, acyl, aryl or heteroaryl.The invention also relates to methods for the preparation of these peptides, agents containing them and their use.

Abstract: A decapeptide of the formula: N-AC-A.sup.1 -A.sup.2 -A.sup.3 -Ser-A-.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -A.sup.9, wherein each A.sup.1, A.sup.2, and A.sup.3, independently, is D-.beta.-Nal, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl), D-benzothienyl (2)-Ala, or D-benzothienyl (1)-Ala; A.sup.4 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl), Tyr, Lys, Arg, Leu, Trp, or Nal; A.sup.5 is D-Lys, D-Tyr, D-Arg, D-Phe, D-.beta.-Nal, D-Trp, D-homo-Arg, D-diethyl-homo-Arg, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl), or D-Lys-.epsilon.-NH-R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group); A.sub.6 is Leu, .beta.-Nal, p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, C.sub.2 F.sub.5, C.sub.1-3 alkyl), or Trp; A.sup.7 is Arg, Lys, or Lys .epsilon.-NH-R (where R is H, a branched or straight chain C.sub.1 -C.sub.6 alkyl group, or an aryl group); A.sub.8 is Pro; and A.sup.

Abstract: A combination therapy for treatment of selected sex steroid dependent cancers in susceptible warm-blooded animals comprising administering to such animals whose hormone output of their testes or ovaries, respectively, is blocked a therapeutically effective amount of an antiandrogen and/or an antiestrogen and/or at least one inhibitor of sex steroid biosynthesis or pharmaceutical compositions thereof wherein the selected sex steroid dependent cancer are, for example, testicular cancer, ovarian cancer, renal cancer or uterine cancer is disclosed.

Abstract: A bioerodible pellet capable of administering an even and continuous dose of a peptide over a period of up to a year, when subcutaneously implanted, is provided. The bioerodible implant is a partially-fused pellet, which pellet has a peptide drug homogeneously-bound in a matrix of a melted and recrystallized, nonpolymer carrier. Preferably, the nonpolymer carrier is a steroid and in particular is cholesterol or a cholesterol derivative. In one embodiment, the peptide drug is growth hormone-releasing hormone. A method for making the bioerodible pellet also is provided.

Abstract: A method for preventing conception in mammals which includes administering to the mammals a composition containing (1) free LHRH or its analog and (2) an immunogenic conjugate between LHRH or its analog and a carrier protein. Free LHRH or its analog acts to prevent conception in the mammal during the period from administration to about 6 weeks; the immunogenic conjugate acts to prevent conception during the period from about 6 weeks after administration until the LHRH antibodies formed in response to the conjugate are metabolized, generally about 0.5-2 years.

Abstract: A decapeptide of the formula:N-Ac-A.sup.1 -A.sup.2 -A.sup.3 -SER.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -A.sup.9 -A.sup.10,wherein each A.sup.1, A.sup.2, and A.sup.3, independently, is D-.beta.-Nal, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl); A.sup.5 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl); A.sup.6 is D-Lys, D-Arg, .beta.-Nal, D-.beta.-Nal, D-Trp, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl) or D-lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl group); A.sup.7 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, C.sub.2 F.sub.5, or C.sub.1-3 alkyl), cyclohexyala, or Trp; A.sup.8 is Arg, Lys, or Lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl croup); A.sup.9 is Pro; and A.sup.10 is D-Ala-NH.sub.2, Gly-NH.sub.2, D-Ser, or D-Ser-NH.sub.2 ; provided that at least one of A.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formulap Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D ABu (.alpha.-aminobutyric acid), D Phe, D SEr, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D SEr (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D TRp, Trp, 2-methyl Ala, D Tyr, .epsilon.-lauryl-D Lys, .alpha.

Abstract: A method of inducing or increasing ovulation in female animals which method includes administering to the animal an effective amount of a ruminant follicle-stimulating hormone, (as hereinbefore defined).

Abstract: A technique has been developed to cause a mammal to generate antibodies which will bind to its native GnRH thus suppressing the mammal's fertility. The technique involves vaccinating a mammal with a novel conjugate of an immuno stimulating carrier and a novel GnRH analogue. The analogue is substantially identical to the natural GnRH which is common to all mammals except that one or more of the normally occurring amino acids of this decapeptide have been replaced by an amino acid with a more reactive side group. A favored technique is to utilize an analogue containing cysteine which, of course, has as a sulfhydryl side group. This analogue may then be conjugated to a large protein carrier using a heterobifunctional agent carrying a group reactive with carboxyl or amino groups and a group reactive with sulfhydryl groups. This conjugate then forms the immunogen base for a vaccine which may also contain art recognized adjuvants.

Abstract: A 28,000-dalton protein with FSH-releasing activity is isolated from porcine follicular fluid in a multi-step procedure including gel filtration, ion exchange chromatography and several reverse-phase high-performance liquid chromatography steps. The 28 kD protein promotes secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system, exhibiting an EC.sub.50 of 0.5 ng/ml. These peptides are dimers of inhibin .beta.-chains of mammals, and homodimers or heterodimers of the .beta..sub.A and .beta..sub.B chains are biologically active to regulate fertility of various mammalian species, including humans.

Abstract: Microcapsules are advantageously produced with high take-up of a water-soluble drug by preparing a W/O emulsion composed of a water-soluble drug-containing solution as the inner aqueous phase and a polymer-containing solution as the oil phase, dispersing said emulsion in an aqueous phase and subjecting the resulting W/O/W emulsion to an in-water drying, wherein the viscosity of the W/O emulsion used in preparing the W/O/W emulsion is adjusted to about 150 to about 10,000 centipoises.

Abstract: The present invention relates to novel gonadoliberine analogues of formula IGlp-His-Trp-Ser-X-W-Leu-Arg-Pro-Y (I)whereinX is Phe-, Tyr (3,5-.sup.3 H) or 3,5-dibromo-tyrosyl,W is Asu or Asp OR, wherein R is alkyl having 1 to 6 carbon atoms or phenyl or phenyl (alkyl having 1 to 4 carbon atoms), which latter two groups may optionally be substituted by nitro or one or more halogen atoms, andY is glycinamide, aza-glycinamide or alkylamino having 1 to 4 carbon atoms,and acid-addition salts thereof, processes for preparing the same and pharmaceutical compositions comprising the same.The novel compounds have an influence on the sexual processes.

Abstract: A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

Abstract: A decapeptide of the formula:N-Ac-A.sup.1 -A.sup.2 -A.sup.3 -Ser-A.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -A.sup.9, wherein each A.sup.1, A.sup.2, and A.sup.3, independently, is D-.beta.-Nal, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl), D-Trp, D-benzothienyl (2)-Ala, or D-benzothienyl (1)-Ala; A.sup.4 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl), Tyr, Lys, Arg, Leu, Trp, or Nal; A.sup.5 is D-Lys, D-Tyr, D-Arg, D-Phe, D-.beta.-Nal, D-Trp, D-homo-Arg, D-diethyl-homo-Arg, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl), or D-Lys-.epsilon.-NH-R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group); A.sub.6 is Leu, .beta.-Nal, p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, C.sub.2 F.sub.5, C.sub.1-3 alkyl), or Trp; A.sup.7 is Arg, Lys, or Lys .epsilon.-NH-R (where R is H, a branched or straight chain C.sub.1 -C.sub.6 alkyl group, or an aryl group); A.sub.8 is Pro; and A.sup.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependent mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formulap Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, E-lauryl -D Lys, E-dextran-D Lys, (c) Z is NH-cyclopropyl-or NH-Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Othu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH.

Abstract: Antagonist analogs of luteinizing hormone-releasing hormone (LHRH) having N-alkylated basic amino acid residues at the 8 position, 8 and 6 positions, 8 and 5 positions, and 8, 6 and 5 positions, having high antiovulatory activity and low histamine release activity, and their use in regulating the release of gonadatropic hormones from the pituitary gland of mannals.

Abstract: The antagonistic effect of the releasing hormone of LH and FSH or of one of its synthetic analogues selected from the group(pyro) Glu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2(pyro) Glu-His-Trp-Ser-Tyr-D-Phe-Leu-Arg-Pro-Gly-NH.sub.2and(pyro) Glu-His-Trp-D-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHR.sup.1(R.sup.1 being an alkyl group). On hormone-dependent diseases can be increased by coating such compounds by micro-encapsulation or by matrix formation with a copolymer of a lactide and a glycolide. The initial stimulating effect of the above-mentioned compounds is increased by this coating, with about 23 to 50% of the active principle of the analog being released within about 1-5 days after injection to a human, with the remainder released over a period of between about 3 weeks and two months.

Abstract: Synthetic nona- and decapeptide LHRH antagonist analogs are disclosed, having a sterically hindered guanidino-substituted arginyl or homoarginyl residue at position 8, with no arginyl substituent at position 6.

Abstract: The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans.The compounds of this invention are represented by the formulaX-R.sup.1 -R.sup.2 -R.sup.3 -Ser-Tyr-R.sup.6 -Leu-Arg-Pro-R.sup.10 -NH.sub.2whereinX is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms,R.sup.1 is D- or L-Pro, D- or L- .DELTA. .sup.3 -Pro, D-Phe, D-Phe(4-H1), D-Ser, D-Thr, D-Ala, D-Nal (1) or D-Nal (2),R.sup.2 is D-Phe or D-Phe(4-H1)R.sup.3 is D-Trp, D-Phe, D-Pal, D-Nal(1) or D-Nal (2),R.sup.6 is D-Cit, D-Hci, D-Cit(Q) or D-Hci(Q) andR.sup.

Abstract: A hormone composition for producing superovulation in cattle. The composition has a particular ratio of follicle stimulating hormone (FSH) and luteinizing hormone (LH) which produces an optimum superovulation response in cattle. The composition can be produced from animal pituitary glands or by recombinant DNA procedures.

Abstract: A method of treatment of breast cancer in susceptible animals whose ovarian hormonal secretions were previously blocked by surgical or chemical means, e.g., by use of an LH-RH agonist, e.g., [D-Trp.sup.6, des-Gly-NH.sub.2.sup.10 ]LH-RH ethylamide with a combination therapy comprising administering an antiandrogen, e.g., flutamide and an antiestrogen, e.g., Tamoxifen, pharmaceutical compositions useful for such treatment and two and three component pharmaceutical kits containing such compositions are disclosed.

Abstract: A method of treatment of breast cancer in susceptible animals whose ovarian hormonal secretions are blocked by surgical or chemical means, e.g., by use of an LH-RH agonist, e.g., [D-Trp.sup.6, des-Gly-NH.sub.2.sup.10 ]LH-RH ethylamide with a therapy comprising administering an antiandrogen, e.g., flutamide and an optionally, an inhibitor of adrenal sex steroid biosynthesis e.g., aminoglutethimide, pharmaceutical compositions useful for such treatment and two, four and five component pharmaceutical kits containing such compositions are disclosed.

Abstract: This invention is directed to a method for assessing hypothalamic function and anterior pituitary hormone function comprising administering 14-hydroxydihydronormorphinone derivatives to a patient in an amount sufficient to stimulate the secretion of anterior pituitary hormones in said patient and assessing the level of secreted hormone.

Abstract: This invention is directed to a delivery system and a method useful for preventing pregnancy in female mammals by administering an LHRH composition. The method comprises administering during the entire follicular phase of the menstrual cycle, beginning at the time of menses, an LHRH composition and sufficient levels of an estrogenic steroid to counteract the possibility of side effects which may develop during prolonged therepy with LHRH. Following the follicular phase, at the beginning of the luteal phase, and for the entire course of the luteal phase, the LHRH/estrogenic steroid combination administered during the follicular phase, in combination with a physiological amount of progestational steroid, is administered.The delivery system comprises means for administering the LHRH composition, estrogenic steroid and progestational steroid.

Abstract: Birds are induced to molt by administering them a LHRH receptor ligand. One preferred ligand for administration is the LHRH agonist [D-Trp.sup.6 ] LHRH. Suitable subjects for treatment are laying hens which are at or near the end of their egg laying cycle, which can be induced to molt and returned to egg production by the method provided.

Abstract: A combination therapy for treatment of selected sex steroid dependent cancers in susceptible warm-blooded animals comprising administering to such animals whose hormone output of their testes or ovaries, respectively, is blocked a therapeutically effective amount of an antiandrogen and/or an antiestrogen and/or at least one inhibitor of sex steroid biosynthesis or pharmaceutical compositions thereof wherein the selected sex steroid dependent cancer are, for example, testicular cancer, ovarian cancer, renal cancer or uterine cancer is disclosed.

Abstract: The invention relates to novel gonadoliberin nonapeptide ethylamide or decapeptide amide derivatives of the general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -X.sub.2 -X.sub.3 -Pro-X.sub.4 (I)whereinX.sub.1 stands for a 2-aminobenzoic or 3-aminobenzoic acid group;X.sub.2 stands for a leucyl, tryptophyl or phenylalanyl group;X.sub.3 means an arginyl, leucyl or glutaminyl group; andX.sub.4 represents a glycylamide or ethylamide group, as well as their acid addition salts and pharmaceutical presparations containing these compounds. Further on, the invention relates to a process for preparing these compounds and preparations.The gonadoliberin derivatives of the invention can more effectively be used for reproduction biological purposes as compared to the derivatives known so far.

Abstract: The invention relates to a process for producing sexual products suitable for natural or artificial fertilization from mammalia through controlling the activity of their sexual organs in their pre- and post-natal lives, during their infancy, puberty and mature state and, in a given case, to produce offsprings from them as well as to increase several times the production of sexual products to a level far above that typical of the life's performance of the species. According to the invention the mammalia are treated at least once and at most 60 times with a compound of general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -X.sub.2 -X.sub.3 -Pro-X.sub.4, (I)whereinX.sub.1 means a glycil-group or any other natural or synthetic D-aminoacid group,X.sub.2 means an L-aminoacid-group with a side chain of an alkyl-, phenyl, or triptophyl group containing 1-4 carbon atoms,X.sub.3 means an L-aminoacid group having a side chain of an alkyl group with 1-4 carbon atoms or an alkanoyl-amide group of 2-4 carbon atoms andX.sub.

Abstract: The invention relates to a process for increasing the sexual activity of birds and useful domestic mammals and for preparing spermatozoa suitable to their propagation. The process of the invention comprises treating sexually mature male birds or useful domestic mammals at least twice and at most four times with 0.1 to 5 .mu.g/kg of body weight of a compound of the general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -Leu-Arg-Pro-X.sub.4 (I)whereinX.sub.1 stands for a glycyl group, a natural or synthetic aminoacid or aminoacid derivative of D configuration, an -Asp-Q group of L configuration, wherein Q is attached to the .alpha.-carbonyl moiety of the aspartyl group and represents a C.sub.1-5 alkylamide, an arylamide, a C.sub.1-4 alkoxy or a benzyloxy group; andX.sub.4 stands for a glycylamide or a C.sub.1-4 alkylamide group,while keeping a pause of at least 30 hours and at most 72 hours between the consecutive treatments.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formulap Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.beta.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, .epsilon.lauryl -D Lys, .epsilon.

Abstract: Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure: Ac-.beta.-D-NAL-R.sub.2 -D-3PAL-Ser-Arg-R.sub.6 -Leu-Arg-Pro-R.sub.10 wherein R.sub.2 is Cl-D-Phe, F-D-Phe, NO.sub.2 -D-Phe, Br-D-Phe, 3,4Cl.sub.2 -D-Phe or C.alpha.Me-Cl-D-Phe; R.sub.6 is D-3PAL, D-Trp, For-D-Trp, NO.sub.2 -D-Trp, (imBzl)D-His, D-Tyr or .beta.-D-NAL; and R.sub.10 is Gly-NH.sub.2, NHCH.sub.2 CH.sub.3, NHNHCONH.sub.2 or D-Ala-NH.sub.2.

Abstract: A protein moiety having a molecular weight of from 12,000 to 15,000 inhibits aromatase levels, stimulates 3.beta.-ol dehydrogenase levels and modulates the formation of mature ova substantially independently of steroidal sex hormones. The moiety may be isolated from follicular effluent or produced by granulosa cell cultures.

Abstract: A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of peptide of the formulap Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I)wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.- aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), d Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, .epsilon.-lauryl -D Lys, .epsilon.

Abstract: Incorporation of a ketomethylene or a hydroxyethylene group in place of the amide linking group between the Pro.sup.9 and Gly.sup.10 residues of LHRH and its analogs improves the oral activity of LHRH or its analogs.

Abstract: Synthetic nonapeptide and decapeptide LHRH antagonist analogues having a halo lower alkyl guanadino-substituted amino acyl residue at position six are disclosed herein.