Abstract: Methods for treating uterine fibroids, endometriosis, adenomyosis, or heavy menstrual bleeding in a subject, which include administering to the subject from 10 mg to 60 mg per day of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N?-methoxyurea, and from 0.01 mg to 5 mg per day of a hormone replacement medicament. The present disclosure has methods for reducing menstrual bleeding in a subject, reducing bone mineral density loss in a subject caused by administering a GnRH antagonist to the subject, suppressing sex hormones in a subject, reducing vasomotor symptoms or hot flashes in a subject, and reducing symptoms of decreased libido in a subject having uterine fibroids, endometriosis, or adenomyosis.

Abstract: The invention provides therapeutic methods and kits for treating a glioma using a particular dosing regimen of the organonitro compound ABDNAZ, radiation therapy, and one of temozolomide, irinotecan, or bevacizumab.

Abstract: The invention provides therapeutic methods and kits for treating a glioma using a particular dosing regimen of the organonitro compound ABDNAZ, radiation therapy, and one of temozolomide, irinotecan, or bevacizumab.

Abstract: The invention provides therapeutic methods and kits for treating a glioma using a particular dosing regimen of the organonitro compound ABDNAZ, radiation therapy, and one of temozolomide, irinotecan, or bevacizumab.

Abstract: The invention relates to pharmaceutical compositions suitable for parenteral administration comprising, peptides in the form of acetate, gluconate, glucuronate, lactate, citrate, ascorbate, benzoate or phosphate salts in dissolved or dispersed form and at least one of the acids for forming the salts in free acid form.

Abstract: A method for preventing aggregation of an LHRH antagonist in a pharmaceutical composition. The method comprises combining the LHRH antagonist in the form of an acetate, gluconate, glucuronate, lactate, citrate, ascorbate, benzoate or phosphate salt and at least one of the acids for forming the salts in free acid form.

Abstract: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.

Abstract: A bioabsorbable release-sustaining pharmaceutical formulation using a biodegradable release-sustaining base material which can prevent an effective component drug from being released too rapidly just after administration of the formulation and then allow continued release of the drug for at least one month at a defined rate, is provided. For the biodegradable release-sustaining base material, a lactic acid-glycolic acid copolymer (PLGA) with an adjusted distribution in molecular weight is used.

Abstract: The present invention relates to the treatment of dementia and neurodegenerative diseases like Alzheimer's disease with intermediate doses of LHRH antagonists which do not cause a castration. A preferred LHRH antagonist is cetrorelix.

Abstract: A lyophilizate, method of preparation, and use of the lyophilizate for gonad protection is described. The lyophilizate comprises cetrorelix dissolved in 30% (v/v) acetic acid, transferred to water, and freeze-dried.

Abstract: A method of spherifying a sustained release ionic conjugate which contains a free carboxyl group-containing polymer and a free amino group-containing drug which are ionically bonded to each other.

Abstract: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.

Abstract: Methods to inhibit hot flashes or gynaecomastia in a subject are provided. In the methods of the invention, an LHRH antagonist is administered to a subject in need of treatment for hot flashes or gynaecomastia such that hot flashes or gynaecomastia are inhibited in the subject. In a particularly preferred embodiment, the invention provides a method for inhibiting menopause-related hot flashes in which an LHRH antagonist is administered to a subject in need of treatment for menopause-related hot flashes such that the hot flashes are inhibited in the subject.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptide and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptide in a small volume and for delivery of a pharmaceutically active peptide for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptide of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

Abstract: An agent for cancer immunotherapy with independent use, containing bacterial components as an active ingredient, which induces cancer patients to exhibit immune responsiveness, as indicated by the increase of interferon-&ggr; and CD28 markers in peripheral blood, when administered to an immuno-competent patient intracutaneously.

Abstract: A composition for enteral administration having a non-ionic vegetable oil GIT absorption enhancer capable of increasing the enteral absorbability of drugs, especially oral absorbability of hydrophilic and macromolecular drugs. The non-ionic vegetable oil GIT absorption enhancer, particularly Babassu oil or a derivative thereof, is capable of enhancing the uptake of a drug from the gastrointestinal tract so as to allow therapeutically effective amounts of the drug to be transported across the GIT of an animal such as a human without significant toxic side effects.

Abstract: Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.

Abstract: Methods and articles of manufacture are provided for the long-term prevention of clinical symptoms and signs produced by endometriosis. Such methods and articles of manufacture involve the continuous coadministration of low doses of an estrogen agent and a progestin agent to maintain an induced state of oligomenorrhea or amenorrhea in an afflicted woman.

Abstract: Disclosed is a sustained release pharmaceutical composition. The composition includes a polyester containing a free COOH group ionically conjugated with a bioactive polypeptide comprising at least one effective ionogenic amine, wherein at least 50% by weight of the polypeptide present in the composition is ionically conjugated to the polyester.

Abstract: Peptides are provided which have improved duration of GnRH antagonistic properties. These antagonists may be used to regulate fertility and to treat steroid-dependent tumors and for other short-term and long-term treatment indications. These antagonists have a derivative of aminoPhe or its equivalent in the 5- or the 5- and 6-positions. This derivative is modified so as to contain a carbamoyl group or heterocycle, including a urea moiety, in its side chain. Decapeptides having the formula: Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(L-hydroorotyl)-D-4Amf(Q2)-Leu-Lys(isopropyl)-Pro-Xaa10, wherein Q2 is Cbm or MeCbm and Xaa10 is D-Ala-ol or Ala-ol are particularly effective and continue to exhibit very substantial suppression of LH secretion at 96 hours following injection.

Abstract: The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

Abstract: Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.

Abstract: The invention relates to a diagnostic composition for improving the effectiveness of hysteroscopy, characterized in that it contains an LH-RH antagonist, in particular cetrorelix. The composition is envisaged for use prior to hysteroscopy and/or for preparation for surgery, specifically in a single dose of between 0.1 and 2 mg/kg.However, the composition can also be administered, for use prior to hysteroscopy and/or for preparation for surgery, in a multiple dose of between 0.01 and 0.5 mg/kg, preferably spread over 1-14 days. The composition is furthermore suitable for use in hysteroscopy in combination with the subsequent treatment of pathological conditions of the uterus such as myoma and endometrial hyperplasia.

Abstract: This invention relates to novel salts composed of a cation derived from a peptide containing at least one basic group and an anion derived from a carboxy-terminated polyester, processes for the manufacture of such salts, and the use of such salts in the manufacture of extended release pharmaceutical compositions. The salts of the invention possess a variety of properties which are useful in the formulation of extended release pharmaceutical compositions, whether the salts are in pure form or are in admixture with either an excess of the peptide in its free, unbound form or an excess of the free polyester.

Abstract: Described are LHRH-antagonistic and bombesin-antagonistic nona- and decapeptides suitable for use in the preparation of a drug for the treatment of AIDS and ARC as well as for use in the preparation of an immunostimulation drug.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptide and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptide in a small volume and for delivery of a pharmaceutically active peptide for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptide of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

Abstract: The invention concerns a liquid gonadotropin-containing formulation characterised in that the formulation comprises a gonadotropin and stabilising amounts of a polycarboxylic acid or a salt thereof and of a thioether compound. The particular proteins (e.g. LH, TSH, FSH, or HCG) are in admixture with the particular stabilizers in an aqueous solution. The preparations contain a sufficient amount of the polycarboxylic acid or a salt thereof, preferably sodium citrate, and a sufficient amount of the thioether compound, preferably methionine, to stabilize the protein. The preparations preferably also include a nonreducing disaccharide like sucrose, and a non-ionic surfactant.

Abstract: Peptides are provided which have improved duration of GnRH antagonistic properties. These antagonists may be used to regulate fertility and to treat steroid-dependent tumors and for other short-term and long-term treatment indications. These antagonists have a derivative of aminoPhe or its equivalent in the 5- and/or 6-positions. This derivative contains a carbamoyl group or a heterocycle including a urea in its side chain. Particularly effective decapeptides, which continue to exhibit very substantial suppression of LH secretion at 96 hours following injection, have the formulae: Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(hydroorotyl)-D-4Aph(acetyl)-Leu-Lys(isopr opyl)-Pro-D-Ala-NH.sub.2, and Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(hydroorotyl)-D-4Amf(Q.sub.2)-Leu-Lys(isop ropyl)-Pro-D-Ala-NH.sub.2, wherein Q.sub.2 is Cbm or MeCbm.

Abstract: This invention relates to novel salts composed of a cation derived from a peptide containing at least one basic group and an anion derived from a carboxy-terminated polyester, processes for the manufacture of such salts, and the use of such salts in the manufacture of extended release pharmaceutical compositions. The salts of the invention possess a variety of properties which are useful in the formulation of extended release pharmaceutical compositions, whether the salts are in pure form or are in admixture with either an excess of the peptide in its free, unbound form or an excess of the free polyester.

Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.

Abstract: Disclosed is a sustained release pharmaceutical composition. The composition includes a polyester containing a free COOH group ionically conjugated with a bioactive polypeptide comprising at least one effective ionogenic amine, wherein at least 50% by weight of the polypeptide present in the composition is ionically conjugated to the polyester.

Abstract: The present invention provides a uniform dispersion in aqueous medium of droplets comprising: (a) a core comprising water, a non-toxic C.sub.2 -C.sub.5 alkanol, a water-soluble drug, and a surfactant, and (b) a coating surrounding the core comprising one or more pharmaceutically acceptable oils. The compositions of the present invention are particularly useful for the oral delivery of therapeutic agents because of their potential for taste masking, prolonged action, and protection of the drug against the external environment and enzyme entrapment.

Abstract: Invitro incubation of primate embryos in the presence of gonadotrophin releasor hormone (GnRH) results in enhanced chorionic gonadotrophin production associated with increased survival and attachment of the embryos. Treatment of invitro fertilized embryos with GnRH can be used to improve implantation. Agonists of GnRH reduce attachment competence of embryos and are thereby useful as post-fertilization contraceptives.

Abstract: A method is provided for the design and synthesis of Leuteinizing Hormone Releasing Hormone (LHRH) antagonists having exact amino acid sequences and containing 5-100 amino acids. This method can be used to produce peptides useful in treating disorders of the reproductive endocrine system, including endometriosis, precocious puberty, prostate cancer and breast cancer. Additionally, peptides produced by this method can be used as contraceptives for either males or females. Peptides produced by this method can further be employed in the diagnosis and treatment of infertility.

Abstract: Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.

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: Peptides which include unnatural amino acids and which either promote or inhibit 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 and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. 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.

Abstract: A method of treating prostate cancer in warm-blooded animals comprising administering to warm-blooded animals an effective amount of a peptide of Formula I and an anti-androgen.

Abstract: A growth such as a tumor, hypertrophied tissue or cyst is biopsied or more completely excised subsequent to the administration of an effective amount of a gonadotropin releasing hormone analog or other inhibitor of ovarian steroid production or action.

Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.

Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.

Abstract: A composition including a polyester containing one or more free COOH groups ionically conjugated with a bioactive polypeptide comprising at least one effective ionogenic amine, wherein the polyester contains a member selected from the group of L-lactic acid, D-lactic acid, DL-lactic acid, .epsilon.-caprolactone, p-dioxanone, .epsilon.-caprolic acid, alkylene oxalate, cycloalkylene oxalate, alkylene succinate, .beta.-hydroxybutyrate, substituted or unsubstituted trimethylene carbonate, 1,5-dioxopan-2-one, 1,4-dioxepan-2-one, glycolide, glycolic acid, L-lactide, D-lactide, DL-lactide, meso-lactide, and any optically active isomers, racemates or copolymers thereof, and at least 50%, by weight, of the polypeptide present in the composition is ionically conjugated to said polyester.

Abstract: For application during the treatment of benign and malign tumour diseases, the product according to the invention containing the initial dose of Cetrorelix acetate and one or more maintenance doses of Cetrorelix acetate, Cetrorelix embonate or a slow-release form of Cetrorelix, is used as a combination preparation for treatment to be administered at specific time intervals.

Abstract: Novel peptide hormones which influence the release of gonadotropins by the pituitary gland in fish are disclosed. Methods in which such peptides may be administered to fish to control their reproduction are also described. Furthermore, novel isolated cDNA encoding the precursor of the novel gonadotropin-releasing hormone is disclosed. The use of such cDNA in controlling the gonadal development and spawning of fish is also described.

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: A method for preventing conception in mammals wherein a composition containing (1) free LHRH or its analog and (2) an immunogenic conjugate between LHRH or its analog and a carrier protein is administered to the mammals 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 growth such as a tumor, hypertrophied tissue or cyst is biopsied or more completely excised subsequent to the administration of an effective amount of a gonadotropin releasing hormone analog or other inhibitor of ovarian steroid production or action.