Long-acting oxytocin analogues for the treatment and prevention of breast cancer and psychiatric disorders

Abstract

Methods and compositions are provided for prophylaxis and treatment of breast cancer involving administration of a therapeutically effective amount of carbetocin and/or other long-acting oxytocin analogues. 1-Butanoic acid-2-(O-methyl-L-tyrosine)-1-carbaoxytocin (carbetocin) and/or other long-acting oxytocin analogues are formulated with a pharmaceutically acceptable carrier and administered in an amount sufficient to inhibit initiation or growth of breast cancer in the patient. The carbetocin and/or other long-acting oxytocin analogues may also be formulated with a pharmaceutically acceptable carrier and administered in an amount sufficient to treat, prevent or alleviate the symptoms of a psychiatric disorder in the patient. Carbetocin may be administered prophylactically or to treat existing conditions in patients by a variety of administration modes, including intramuscular, intravenous, intranasal, intrapulmonary, subcutaneous, parenteral, oral, or transdermal delivery methods and formulations. Preferably, the carbetocin is administered to a mucosal surface of the patient via intranasal delivery. For this purpose, pharmaceutical compositions are provided for intranasal delivery that incorporate carbetocin in a powder or aqueous formulation for intranasal delivery.

1 - 12 . Cancelled.  
     
     
         13 . A method of prophylaxis or treatment of a psychiatric disorder in a mammalian patient comprising administering to said patient a therapeutically effective amount of one or more compound(s) selected from the group consisting of carbetocin and other long-acting oxytocin analogues in a pharmaceutically acceptable carrier sufficient to alleviate an obsessive-compulsive behavior of said disorder in said patient.  
     
     
         14 . The method of  claim 13 , wherein said psychiatric disorder is obsessive compulsive disorder, Praeder Willi syndrome or autism.  
     
     
         15 . The method of  claim 13 , wherein said one or more oxytocin analogue(s) comprises carbetocin.  
     
     
         16 . The method of  claim 13 , wherein said one or more oxytocin analogue(s) is/are administered to said patient by a mode of administration selected from intramuscular, intravenous, intranasal, intrapulmonary, subcutaneous, parenteral, oral, and transdermal delivery.  
     
     
         17 . The method of  claim 16 , wherein said one or more oxytocin analogue(s) is/are administered to said patient intranasally.  
     
     
         18 . The method of  claim 16 , wherein said one or more oxytocin analogue(s) is/are formulated in said carrier for intranasal or intrapulmonary administration.  
     
     
         19 . The method of  claim 18 , wherein said one or more oxytocin analogue(s) is/are formulated in a powder or aqueous formulation for intranasal delivery.  
     
     
         20 . The method of  claim 19 , wherein said one or more oxytocin analogue(s) is/are combined in an aqueous formulation with one or more excipients selected from the group consisting of nonoxynol-9, laureth-9, poloxamer-124, octoxynol-9, lauramide DEA, chlorobutanol, glycerol, citric acid, sodium phosphate, methyl paraben, propyl paraben, sorbitol, sodium chloride, and/or sodium acetate for intranasal delivery.  
     
     
         21 . The method of  claim 19 , wherein said carbetocin is formulated with a nonionic surfactant and polysorbate-80 in an aqueous formulation for intranasal delivery.  
     
     
         22 . The method of  claim 13 , wherein said one or more oxytocin analogue(s) is/are administered daily in a dose of at least one microgram.  
     
     
         23 . The method of  claim 13 , wherein said one or more oxytocin analogue(s) is/are administered daily in an intranasal formulation.  
     
     
         24 . The method of  claim 13 , further comprising administering a selective serotonin reuptake inhibitor or serotonin reuptake inhibitor to said patient in an amount sufficient to alleviate an obsessive-compulsive behavior in said patient.  
     
     
         25 . The method of  claim 24 , wherein said one or more oxytocin analogue(s) is/are and said selective serotonin reuptake inhibitor are administered simultaneously as a mixture.  
     
     
         26 . A pharmaceutical composition for prophylaxis or treatment of breast cancer in a mammalian patient comprising a therapeutically effective amount of one or more oxytocin analogue(s) selected from the group consisting of carbetocin and other long-acting oxytoc in analogues in a pharmaceutically acceptable carrier, wherein said composition is sufficient to inhibit initiation or growth of breast cancer in said patent.  
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein said one or more oxytocin analogue(s) comprises carbetocin.  
     
     
         28 . The pharmaceutical composition of  claim 26 , wherein said one or more oxytocin analogue(s) is/are formulated in said carrier for intranasal or intrapulmonary administration.  
     
     
         29 . The pharmaceutical composition of  claim 26 , wherein said one or more oxytocin analogue(s) is/are formulated in a powder or aqueous formulation for intranasal delivery.  
     
     
         30 . The pharmaceutical composition of  claim 26 , wherein said one or more oxytocin analogue(s) is/are combined in an aqueous formulation with one or more excipients selected fron the group consisting of nonoxynol-9, laureth-9, poloxamer-124, oxtoxynol-9, lauramide DEA, chlorobutanol, glycerol, citric acid, sodium phosphate, methyl paraben, propyl paraben, sorbitol, sodium chloride, and/or sodium acetate for intranasal delivery.  
     
     
         31 . The pharmaceutical composition of  claim 26 , prepared in a unit dosage form containing at least one microgram of said one or more oxytocin analogue(s).  
     
     
         32 . The pharmaceutical composition of  claim 26 , further comprising tamoxifen and/or raloxifen in an amount sufficient to inhibit initiation or growth of estrogen-dependent breast cancer in said patient.  
     
     
         33 . A medicament suspension or powder for nasal administration to treat or prevent breast cancer comprising carbetocin and a powder of one or more cation exchange resins and/or one or more absorbent resins.  
     
     
         34 . A pharmaceutical composition for prophylaxis or treatment of a psychiatric disorder in a mammalian patient comprising a therapeutically effective amount of one or more oxytocin analogue(s) selected from the group consisting of carbetocin and other long-acting oxytocin analogues in a pharmaceutically acceptable carrier, wherein said composition is sufficient to alleviate at least one symptom of said psychiatric disorder in said patient.  
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein said one or more oxytocin analogue(s) comprises carbetocin.  
     
     
         36 . The pharmaceutical composition of  claim 34 , wherein said one or more oxytocin analogue(s) is/are formulated in said carrier for intranasal or intrapulmonary administration.  
     
     
         37 . The pharmaceutical composition of  claim 34 , wherein said one or more oxytocin analogue(s) is/are formulated in a powder or aqueous formulation for intranasal delivery.  
     
     
         38 . The pharmaceutical composition of  claim 34 , further comprising a selective serotonin reuptake inhibitor or serotonin reuptake inhibitor.  
     
     
         39 . A method for treatment of breast cancer in a mammalian patient comprising administering to said patient a therapeutically effective amount of one or more compound(s) selected from the group consisting of carbetocin and other long-acting oxytocin analogues in a pharmaceutically acceptable carrier sufficient to inhibit growth of breast cancer in said patient.  
     
     
         40 . The method of  claim 39 , wherein said one or more oxytocin analogue(s) comprises carbetocin.  
     
     
         41 . The method of  claim 39 , wherein said one or more oxytocin analogue(s) is/are administered to said patient by a mode of administration selected from intramuscular, intravenous, intranasal, intrapulmonary, subcutaneous, parenteral, oral, or transdermal delivery.  
     
     
         42 . The method of  claim 41 , wherein said one or more oxytocin analogue(s) is/are administered to said patient intranasally.  
     
     
         43 . The method of  claim 41 , wherein said one or more oxytocin analogue(s) is/are formulated in said carrier for intranasal or intrapulmonary administration.  
     
     
         44 . The method of  claim 43 , wherein said one or more oxytocin analogue(s) is/are formulated in a powder or aqueous formulation for intranasal delivery.  
     
     
         45 . The method of  claim 44 , wherein said one or more oxytocin analogue(s) is/are combined in an aqueous formulation with one or more excipients selected from the group consisting of nonoxynol-9, laureth-9, poloxamer-124, octoxynol-9, lauramide DEA, chlorobutanol, glycerol, citric acid, sodium phosphate, methyl paraben, propyl paraben, sorbitol, sodium chloride, and/or sodium acetate for intranasal delivery.  
     
     
         46 . The method of  claim 44 , wherein said carbetocin is formulated with a nonionic surfactant and polysorbate-80 in an aqueous formulation for intranasal delivery.  
     
     
         47 . The method of  claim 39 , wherein said one or more oxytocin analogue(s) is/are administered in a dose of at least one microgram.  
     
     
         48 . The method of  claim 39 , wherein said one or more oxytocin analogue(s) is/are administered daily in an intranasal formulation.  
     
     
         49 . The method of  claim 39 , further comprising administering tamoxifen and/or raloxifen to said patient in an amount sufficient to inhibit growth of estrogen-dependent breast cancer in said patient.  
     
     
         50 . The method of  claim 49 , wherein said one or more oxytocin analogue(s) and said tamoxifen and/or raloxifene are administered simultaneously as a mixture.