Abstract: The present invention relates to a lyophilization process for preparing a teverelix-TFA lyophilizate, said process comprises the following steps: a) providing a lyophilization suspension by mixing teverelix and trifluoroacetate at a molar ratio sufficient for providing a microcrystalline teverelix-TFA suspension without formation of a gel, and b) lyophilizating the lyophilization suspension, thereby providing a teverelix-TFA lyophilizate. The process provides the possibility of obtaining a “pure” teverelix-TFA lyophilizate i.e. without any undesirable residues in the composition.

Abstract: An approach combining immune-based therapies with focused radiation, including stereotactic radiation, to treat cancers is disclosed. The use of focused radiation primes the immune system in a similar manner to vaccines to augment immune-based therapies and can counteract the suppressive effects of a tumor. The combination of focused radiation and immune-based therapies, including administration of at least one immunotherapeutic agent, improves survival compared to each therapy alone and can, in some cases, lead to a durable cure. Accordingly, focused radiation can be an adjuvant for immune-based therapies for treating cancers.

Abstract: A method for producing a microcapsule powder includes a concentration step. In the concentration step, an aqueous dispersion of a microcapsule is supplied into a cyclone, and the aqueous dispersion is then concentrated. The concentration step includes an aqueous dispersion-supplying step and a concentrated dispersion-recovering step. In the aqueous dispersion-supplying step, the aqueous dispersion is supplied into a cylindrical member inlet. In the concentrated dispersion-recovering step, a microcapsule dispersion is recovered. The microcapsule dispersion is discharged through a conical member outlet.

Abstract: A method for synchronizing ovulation in sows and gilts without heat detection by a single injection of hormones is disclosed. A hormone, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), analogues, derivatives, agonists or combinations thereof is administered to an open sow post weaning at a specific time to stimulate ovulation of mature responsive follicles. The sow is then bred without heat detection at a specific subsequent timed interval after injection with hormone, with one or two artificial or natural breedings. In gilts, the hormone is injected at a timed interval from onset of estrus or at a specific timed interval following Prostaglandin F2a for those gilts which have been held in a state of pseudopregnancy.

Abstract: LHRH analogues and LHRH antagonists for use in the treatment or prophylaxis of hormone-dependent cancers, in particular prostate cancer, prostate carcinoma and/or advanced prostate carcinoma, by administering an initial dose of an LHRH analogue over a first period sufficient to effect hormonal castration, then administering a maintenance dose of an LHRH antagonist over a second period, the dose being insufficient to achieve and/or maintain hormonal castration.

Abstract: The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein at least one bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Abstract: A method of treating or preventing an ovary-related syndrome associated with infertility in a subject in need thereof is provided. The method comprising administering to the subject a pharmaceutical composition comprising an active ingredient consisting of pigment epithelium-derived factor (PEDF) and a pharmaceutically acceptable carrier, thereby treating or preventing the ovary-related syndrome associated with infertility in the subject.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: A method, for synchronizing ovulation in sows and gilts by a single injection of hormones is disclosed. A hormone, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), analogues, derivatives, agonists or combinations thereof is administered to an open sow post weaning at a specific time to stimulate ovulation of mature responsive follicles. The sow is then bred, without heat detection, at a specific subsequent timed interval after injection with hormone, with one or two artificial or natural breedings. In gilts, the hormone is injected at a timed interval from onset of estrus or at a specific timed interval following Prostaglandin F2a for those gilts which have been held in a state of pseudopregnancy.

Abstract: Methods are directed to the treatment of subjects with prostate cancer, in particular those with castration resistant prostate cancer, with glucocorticoid receptor antagonists. The prostate cancer may be one that has become resistant to androgen deprivation therapy, for example, by increase in glucocorticoid receptor expression and/or activity.

Abstract: A method for synchronizing ovulation in sows and gilts by a single injection of hormones is disclosed. A hormone, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), analogs, derivatives, agonists or combinations thereof is administered to an open sow post weaning at a specific time to stimulate ovulation of mature responsive follicles. The sow is then bred, without heat detection, at a specific subsequent timed interval after injection with hormone, with one or two artificial or natural breedings. In gilts, the hormone is injected at a timed interval from onset of estrus or at a specific timed interval following Prostaglandin F2a for those gilts which have been held in a state of pseudopregnancy.

Abstract: This invention provides a production method for a solid sustained-release preparation, characterized in that a sustained-release preparation (a sustained-release preparation suspension) is freeze-dried in a freeze-drying container whose inner face is partially or totally coated with an ice layer or water-repelling base material.

Abstract: Drug delivery devices (e.g., polymeric vaginal rings) and related methods of manufacture and treatment are disclosed herein. In some embodiments, a manufacturing process for drug delivery devices is disclosed that includes a compounding extrusion process and an injection molding process. The various manufacturing parameters associated with these processes can be optimized to produce a drug delivery device with a favorable release profile and other characteristics. In particular, reducing the energy introduced into the system during manufacture can unexpectedly result in drug delivery devices with improved release profiles, especially in the case of large molecule drugs or in devices with a relatively low drug loading or drug particle size.

Abstract: LHRH analogs and LHRH antagonists for use in the treatment or prophylaxis of hormone-dependent cancers, in particular prostate cancer, prostate carcinoma and/or advanced prostate carcinoma, by administering an initial dose of an LHRH analog over a first period sufficient to effect hormonal castration, then administering a maintenance dose of an LHRH antagonist over a second period, the dose being insufficient to achieve and/or maintain hormonal castration.

Abstract: The present invention relates to compositions forming a low viscosity mixture of: a. at least one diacyl glycerol and/or at least one tocopherol; b. at least one phospholipid component comprising phospholipids having i. polar head groups comprising more than 50% phosphatidyl ethanolamine, and ii. two acyl chains each independently having 16 to 20 carbons wherein at least one acyl chain has at least one unsaturation in the carbon chain, and there are no more than four unsaturations over two carbon chains; c. at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein optionally at least one bioactive agent is dissolved or dispersed in the low viscosity mixture; and wherein the pre-formulation forms, or is capable of forming, at least one non-lamellar liquid crystalline phase structure upon contact with an aqueous fluid.

Abstract: The present invention relates to a continuous process for preparing microspheres and microspheres prepared thereby, and in particular, a process for preparing microspheres comprising steps of injecting a first emulsion and a second emulsion at the same time to form microspheres instantaneously, applying high pressure to the microspheres formed, and injecting the microspheres into an agitator, wherein the steps can be carried out continuously, and microspheres prepared thereby. When microspheres are prepared using the method of the present invention, scale variables, which have been the biggest disadvantage in existing preparation methods of microspheres, can be significantly reduced, drug encapsulation efficiency can be improved, and small and uniform particles can be obtained.

Abstract: The present invention provides a constant release copolymer composition adapted for use in a controlled release formulation for a bioactive agent, such as a formulation adapted for implantation within a patient's body tissues as a depot to release the agent over a period of time, wherein the copolymer provides a substantially constant rate of release of the bioactive agent over the time period for which the depot persists in the body tissues. The copolymer includes a PLG copolymer and a PLG oligomer of about 5-10 kDa average molecular weight, which can lack free carboxylic acid groups. When the PLG copolymer is a low burst copolymer, the constant release copolymer composition is a low burst, constant release copolymer composition adapted for implantation in the body tissues of a mammal, wherein a substantially constant rate of release of the bioactive agent is achieved.

Abstract: A new microsphere formulation (composition) for controlled- or sustained-release delivery of therapeutic ingredient(s), mainly peptides and proteins not over 10K in molecular weight, comprises at least a therapeutic ingredient, a helping agent (such as PH sensitive agent whose solubility is a function of pH) and a biodegradable polymer. The therapeutic ingredient(s) and the helping agent are in the form of fine particles, less than 1O um in diameter, encapsulated in the polymer which forms the microsphere matrix. A method for preparing the composition comprises a step of in-situ precipitating the therapeutic ingredient(s) and the helping agent to the fine particles and successive steps for forming the microspheres. Such a microsphere formulation offers a well-controlled release profile for prolonged period and encapsulation efficiency over 95%.

Abstract: The present invention relates to a method of preparing microspheres by using a polymer having a sol-gel transition property and microspheres prepared thereby, and more particularly, to a method of preparing microspheres by using a polymer having a sol-gel transition property and microspheres prepared thereby capable of preventing a solvent in a polymer solution for a carrier from being rapidly diffused to the aqueous medium before formation of the microspheres to reduce porosity of the microspheres and reduce surface roughness of the microspheres in order to obtain microspheres having a sphere shape, and increasing an encapsulation ratio of a bioactive substance, by using a polymer having a sol-gel transition property as a surfactant included in an aqueous medium into which a primary emulsion is injected and gelating a secondary emulsion formed after injecting the primary emulsion using the sol-gel transition property of the polymer used as the surfactant.

Abstract: The invention relates to fusion constructs, methods of using fusion constructs and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies.

Abstract: Described herein is the androgen receptor modulator of formula (I) in the treatment of prostate cancer in combination with other therapeutic options and in the treatment of diseases or conditions that are amenable to treatment with the androgen receptor modulator, as well as pharmaceutical compositions and medicaments that include such compound.

Abstract: The invention relates to a therapeutic device for the delivery of therapeutic agents, e.g. a peptide such as leuprolide, via the vagina to a female mammal. In some embodiments, the invention also relates to methods for the treatment of obesity and eating disorders, diabetes, multiple sclerosis (MS), endometriosis, uterine fibroids, polycystic ovarian disease, various cancers such as breast cancer, acne, hirsutism, microbial or fungal or viral infections such as bacterial vaginosis or AIDS/HIV, and chronic diseases using a disclosed vaginal device.

Abstract: A softgel of NLKJ for the treatment of prostate diseases, comprising 0.05-1.0 g of NLKJ and 0.05-1.5 mg of an antioxidant, said NLKJ having the following physicochemical parameter: acid value<0.56, iodine value 95.0-107.00, saponification value 185.00-195.00, specific gravity 0.914-0.918 (20° C.), and refractive index 1.470-1.475 (20° C.). The inhibition of the softgel of NLKJ on the growth of prostate cancer in combination with the injection of Lupron is stronger than that of each of them used alone.

Abstract: Provided are methods and assays for cancer cell classification, cancer prognosis and treatment based on the isolation of circulating tumor cells and the characterization of their nuclear organization and telomere signatures.

Abstract: The present invention provides a sterile solution comprising leuprolide acetate in a pharmaceutically acceptable vehicle, wherein solution is present as a reservoir in a multiple dose pen injection device, the device being adapted to subcutaneously inject a portion of the said reservoir in a single daily dose and further being adapted to provide multiple portions of solution said while the reservoir remains sterile.

Abstract: A method for synchronizing ovulation in sows and gilts by a single injection of hormones is disclosed. A hormone, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), analogues, derivatives, agonists or combinations thereof is administered to an open sow post weaning at a specific time to stimulate ovulation of mature responsive follicles. The sow is then bred, without heat detection, at a specific subsequent timed interval after injection with hormone, with one or two artificial or natural breedings. In gilts, the hormone is injected at a timed interval from onset of estrus or at a specific timed interval following Prostaglandin F2a for those gilts which have been held in a state of pseudopregnancy.

Abstract: Disclosed herein are naphthoquinone analogs, such as plumbagin, pharmaceutical compositions that include naphthoquinone analogs, such as plumbagin, and methods of treating diseases and/or conditions such as cancer with naphthoquinone analogs, such as plumbagin. Also included are combination therapies wherein a naphthoquinone analog, such as plumbagin, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.

Abstract: A fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic and a counter-ion of a strong proton donor in water, wherein the peptide or peptidomimetic and counter-ion are present in amounts and at a molar ratio sufficient to form the suspension upon mixing and without formation of a gel. Also, lyophilized compositions that include a dried suspension, methods of making the lyophilized composition, methods of preparing the suspension, and sustained release formulations prepared by the methods.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: The invention relates to methods and compositions for inhibiting metastasis, such as by inhibiting FOXC2 expression or activity. The invention further relates to methods of prognosticating, diagnosing, and assisting in the diagnosis of metastasis in an individual, or of determining the metastatic potential of a tumor. The invention further relates to methods of identifying agents which inhibit metastasis.

Abstract: The present invention provides methods of forming a solid, biodegradable implant in-situ in a body by administering a liquid pharmaceutical composition comprising an effective amount of a biocompatible, water-insoluble, biodegradable polymer and an effective amount of a therapeutic peptide covalently modified with one or more lipophilic or amphiphilic moieties, which are dissolved or dispersed in a biocompatible, water-soluble organic solvent. This invention also provides related compositions and methods.

Abstract: The present invention relates to a method for the prophylaxis or treatment of a subject for flushing, wherein a pharmaceutical agent having LHRH antagonistic activity is administered to said subject at a dosage of less than 15 ?g/kg/day. The present invention also relates to a pharmaceutical agent having LHRH antagonistic activity for use in the prophylaxis or treatment of a subject for flushing, wherein the pharmaceutical agent having LHRH antagonistic activity is administered to said subject at a dosage of less than 15 ?g/kg/day. The flushing is preferably postmenopausal flushing or perimenopausal flushing.

Abstract: The invention relates to a fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic and a counter-ion of a strong proton donor in water, wherein the peptide or peptidomimetic and counter-ion are present in amounts and at a molar ratio sufficient to form the suspension upon mixing and without formation of a gel. The invention also relates to lyophilized compositions that include a dried suspension, methods of making the lyophilized composition, methods of preparing the suspension, and sustained release formulations prepared by the methods.

Abstract: The invention relates to a therapeutic device for the delivery of therapeutic agents, e.g. a peptide such as leuprolide, via the vagina to a female mammal. In some embodiments, the invention also relates to methods for the treatment of obesity and eating disorders, diabetes, multiple sclerosis (MS), endometriosis, uterine fibroids, polycystic ovarian disease, various cancers such as breast cancer, acne, hirsutism, microbial or fungal or viral infections such as bacterial vaginosis or AIDS/HIV, and chronic diseases using a disclosed vaginal device.

Abstract: The present invention relates to biocompatible oligomer-polymer compositions for the in situ formation of implants, wherein the implants release a bioactive agent, a metabolite, or a prodrug thereof, at a controlled rate. The sustained release delivery system includes a flowable composition containing a bioactive agent, a metabolite, or a prodrug thereof, and an implant containing a bioactive agent, a metabolite, or a prodrug thereof. The flowable composition may be injected into tissue whereupon it coagulates to become the solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, a biocompatible end-capped oligomeric liquid, and a bioactive agent, a metabolite, or a prodrug thereof.

Abstract: A method of treatment and/or prevention of cancer comprises administering agents which cause increased intracellular granularity in cancer cells, at least in an amount sufficient to inhibit proliferation of such cells and preferably in an amount sufficient to lead to cancer cell death. The method is particularly directed to refractory cancer, particularly hormone refractory prostate cancer. The agents identified cause increased intracellular granularity in the cancer cells, and also convert adherent cancer cells to non-adherent cancer cells, leading to cancer cell death. Using the present invention, cancer cells undergo increased intracellular granularity at relatively low agent concentrations, while also inhibiting cell proliferation. Increased concentrations lead to conversion of adherent cancer cells to non-adherent cancer cells, then to cell death.

Abstract: Disclosed are drug delivery systems for the delivery of small molecule and macromolecular drugs. More particularly, disclosed are substituted analogs of 3,6-di(alkyl-4 aminobutyl)-2,5-diketopiperazine (which may also be referred to DKP), their use in the formulation of both small molecule and macromolecular drugs including therapeutic, prophylactic and diagnostic agents, stabilizing agents and systems for their delivery.

Abstract: A sustained release apparatus including at least one sustained release mini-implant or pellet; the or each mini-implant or pellet including: a sustained release support material; and a pharmaceutical composition including a Luteinising Hormone Releasing Hormone (HLRH) agonist and/or antagonist component the size and/or number and/or payload of mini-implant(s) or pellet(s) providing, release of LHRH agonist and/or antagonist at, or above, a desired threshold level for treatment of a selected indication, the apparatus providing approximately zero order release of the LHRH agonist and/or antagonist.

Abstract: This invention provides a production method for a solid sustained-release preparation, characterized in that a sustained-release preparation (a sustained-release preparation suspension) is freeze-dried in a freeze-drying container whose inner face is partially or totally coated with an ice layer or water-repelling base material.

Abstract: Compositions which act synergistically to inhibit the growth of cancer cells and methods of use thereof are disclosed.

Abstract: The present invention relates to a method for slowing, preventing or delaying senescence or treating or preventing a disease associated with senescence by administering a therapeutically effective amount of at least one physiological agent that decreases or regulates the blood level, production, function or activity of LH or FSH, or that decreases or regulates the production or activity of activin, or that increases or regulates the blood level, production, function, or activity of inhibin or follistatin.