TH101947A - Controllable-acting components And the method of producing the same substance - Google Patents

Abstract

DC60 (09/06/58) provides a controlled-acting compound containing a high concentration of the physiologically active substance, which inhibits overactive activity at an initial stage and provides a stable, sustained course of action. The controlled-acting compound consists of (1) the physiologically active substance or its salts in an amount of approximately 14% (w/w) to approximately 24% (w/w) depending on the weight of the total compounds, (2) hydroxyapthoeic acid selected from groups containing 3-hydroxy-2-naphthoic acid and 1-hydroxy-2-naphthoic acid or its salts, and (3) lactic acid polymer or its salts with a weight-average molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less, and the molar ratio of such hydroxyapthoeic acid is such that or salts of those substances in relation to the physiologically active substance, or salts of those substances, from 3:4 to 4:3. Revised Invention Summary 09/06/2015. Provide a controlled active compound with a high amount of the physiologically active substance, which inhibits the initial overactive effect and provides a stable, long-lasting rate of action. A controlled active compound consisting of (1) the physiologically active substance or salts of those substances in an amount of approximately 14% (weight/weight) to approximately 24% (weight/weight), depending on the weight of the total components, (2) hydroxyapthoic acid. (3) lactic acid polymers or salts of such substances with an average molecular weight of 15000 to 50000, in which the amount of polymer with a molecular weight of 5000 or less is approximately 5% by weight or less, in which the molar ratio of such hydroxyapthoic acid or such salts to such physiologically active substance Or salts of those substances, in a ratio of 3:4 to 4:3. ---------------------------------- Provide a controlled-acting mixture containing a high amount of the physiologically active substance, which inhibits the initial overactive effect and provides a stable, long-lasting rate of action. A controlled-acting mixture consisting of (1) the physiologically active substance or salts of those substances in an amount of approximately 14% (w/w) to approximately 24% (w/w) depending on the weight of the total mixture, (2) hydroxyapthoeic acid selected from groups containing 3-hydroxy-2-napthoeic acid and 1-hydroxy-2-napthoeic acid or salts of those substances, and (3) lactic acid polymer or salts of those substances with an average weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less, in which the ratio of The ratio of hydroxyapthoic acid, or its salts, to the physiologically active substance, or its salts, is from 3:4 to 4:3.

Claims (37)

Updated 9/6/2015 1. A controlled-acting compound consisting of a physiologically active substance or its salts, and a lactic acid polymer or salt of such substance with an average molecular weight of 15000 to 50000, where the amount of the polymer with a molecular weight of 5000 or less is 5% by weight or less, and where the compound does not contain hydroxyapthoic acid or its salts. 2. A controlled active ingredient pursuant to claim 1, comprising (1) the physiologically active substance or its salts in an amount of 3% (w/w) to 24% (w/w) depending on the weight of the total ingredient, and (2) a lactic acid polymer or its salts with a weight-average molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is 5% by weight or less. 3. Controlled active ingredient pursuant to claim 1 or 2, where lactic acid polymer contains 1.5% by weight or less of a polymer with a molecular weight of 3000 or less. 4. A controlled active ingredient pursuant to claim 1 or 2, where the lactic acid polymer contains 0.1% by weight or less of the polymer with a molecular weight of 1000 or less. 5. A controlled active ingredient pursuant to claim 1 or 2, where the lactic acid polymer has an average molecular weight of 15000 to 40000. 6. A controlled active ingredient pursuant to claim 1 or 2, in which the lactic acid polymer has an average molecular weight of 17000 to 26000. 7. A controlled active ingredient pursuant to claim 1 or 2, whereby the physiologically active substance is a physiologically active peptide. 8. Controlled active ingredient pursuant to claim 7, whereby the physiologically active substance is the LH-RH derivative. 9. A controlled active ingredient pursuant to claim paragraph 8, where the LH-RH derivative is a peptide of the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z [where Y represents DLeu, DAla, DTrp, DSer (tBU), D2Nal or DHis (ImBzl) and Z represents NH-C2H5 or Gly-NH2] or a salt of those substances. 10. A controlled active ingredient pursuant to claim 8, in which LH-RH derivatives or their salts are present in amounts ranging from 3% (w/w) to 24% (w/w) in the controlled active ingredient. 11. A controlled active ingredient pursuant to claim 1 or 2, which is an injectable component. 12. A method for the production of the controlled active ingredient pursuant to claim 1, which includes the removal of the solvent from the mixed solution of the physiologically active substance. or salts of those substances and lactic acid polymers or salts of those substances with an average molecular weight of 15000 to 50000, in which the amount of polymer with a molecular weight of 5000 or less is 5% by weight or less. 13. Drugs containing a controlled active ingredient according to claim 1 or 2. 14. Drugs for the prevention or treatment of prostate cancer, benign prostatic hyperplasia, endometriosis, uterine myoma, uterine phyroma, premenopause, menstrual pain, or breast cancer, or contraceptives containing a controlled active ingredient according to claim 8. 15. Drugs for the prevention of recurrence of breast cancer after surgery for premenopausal breast cancer, containing a controlled active ingredient according to claim 8. ----------------------------------------------------------------- 1. Controlled active mixtures containing (1) physiologically active substances or salts of those substances in an amount of approximately 14% (weight/weight) to approximately 24% (weight/weight), which depends on the weight of the total mixture, (2) hydroxyapthoeic acid selected from groups composed of 3-hydroxy-2-naphthoic acid and 1-hydroxy-2-naphthoic acid or salts of those substances, and (3) lactic acid polymers or salts of those substances with an average weight-weight molecular weight of 15000 to 50000, in which the amount of polymers with a molecular weight of 5000 or less is approximately 5% by weight or less, in which the molar ratio of such hydroxyapthoeic acid or salts of those substances to the physiologically active substance is or salts of those substances, i.e., from 3:4 to 4:3. 2. A controlled active compound under claim 1, in which the lactic acid polymer has an average molecular weight of 15000 to 50000. 3. A controlled active compound under claim 1, in which the physiologically active substance is an LH-RH derivative. 4. A controlled active compound under claim 3, in which the LH-RH derivative is a peptide of the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z [where Y represents DLeu, DAla, DTrp, DSer (tBu), D2Nal or DHis (lmBzl) and Z represents NH-C2H5 or Gly-NH2] or salts of those substances. 5. A controlled active compound under claim 1, in which the physiologically active substance... Or salts of those substances, i.e., LH-RH derivatives of the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-DLeu-Leu-Aeg-Pro-NH-C2H5, or acetate salts of those substances, and hydroxynaphthoic acid, i.e., 3-hydroxy-2-naphthoic acid or 1-hydroxy-2-naphthoic acid. 6. Drugs containing a controlled active ingredient mixture as per claim 1. 7. Drugs for the prevention or treatment of prostate cancer, benign prostatic hyperplasia, endometriosis, uterine myoma, uterine fibroma, precocious puberty, dysmenorrhea, or breast cancer, or contraceptives containing a controlled active ingredient mixture as per claim 3. 8. Substances for the prevention of breast cancer recurrence after surgery for premenopausal breast cancer, which contain a controlled active ingredient mixture as per claim 3. With a long-acting combination of substances as per patent claim 3. 9. A method for the prevention or treatment of prostate cancer, benign prostatic hyperplasia, endometriosis, uterine myoma, uterine fibroma, precocious puberty, menstrual pain, or breast cancer, or a method of contraception which includes the administration of a controlled combination of substances as per patent claim 3 in a dose that is effective in mammals. 10. A method for the prevention of recurrence of breast cancer after surgery for premenopausal breast cancer which includes the administration of a long-acting combination of substances as per patent claim 3 in a dose that is effective in mammals. 11. A controlled-acting mixture comprising a physiologically active substance or its salts and a lactic acid polymer or its salts with an average molecular weight of 15,000 to 50,000, where the amount of the polymer with a molecular weight of 5,000 or less is approximately 5% by weight or less. 12. A controlled-acting mixture comprising a physiologically active substance or its salts, hydroxinaphthoic acid or its salts, and lactic acid polymer or its salts, with an average molecular weight of 15,000 to 50,000, where the amount of polymer with a molecular weight of 5,000 or less is approximately 5% by weight or less. 13. A controlled active mixture under claim 11, which includes (1) the physiologically active mixture or salts of such substances in an amount of approximately 3% (weight/weight) to approximately 24% (weight/weight) depending on the weight of the entire mixture, and (2) a lactic acid polymer or salts of such substances with an average weight-weight molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less. 14. A controlled active mixture pursuant to any one of the claims 11 through 13, in which the lactic acid polymer contains approximately 1.5% by weight or less of a polymer with a molecular weight of 3000 or less. 15. A controlled active mixture pursuant to any of the claims 11 through 13, in which the lactic acid polymer contains approximately 0.1% by weight or less of a polymer with a molecular weight of 1000 or less. 16. A controlled active mixture pursuant to any of the claims 11 through 15, in which the lactic acid polymer has an average molecular weight of 15000 to 40000. 17. A controlled active mixture pursuant to any of the claims 11 through 15, in which the lactic acid polymer has an average molecular weight of 17000 to 26000. 18. A controlled active mixture under claim 12, in which hydroxyapthoic acid is 3-hydroxy-2-naphthoic acid or 1-hydroxy-2-naphthoic acid. 19. A controlled active mixture under claim 11 or 13, whereby the physiologically active substance is a physiologically active peptide. 20. A controlled active mixture under claim 12, whereby the physiologically active substance is a physiologically active peptide. 21. A controlled active mixture under claim 19, whereby the physiologically active substance is the LH-RH derivative. 22. A controlled active mixture pursuant to claim paragraph 20, in which the physiologically active substance is the LH-RH derivative. 23. Controlled active mixtures under claim 21 or 22, in which the LH-RH derivative is a peptide of the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z [where Y represents DLeu, DAla, DTrp, DSer (tBu), D2Nal or DHis (lmBzl) and Z represents NH-C2H5 or Gly-NH2], or a salt of those substances. 24. A controlled active mixture pursuant to claim paragraph 21 containing LH-RH derivatives or their salts in an amount of 3% (weight/weight) to 24% (weight/weight) in the controlled active mixture. 25. A controlled active mixture pursuant to claim paragraph 22 in which the molar ratio of hydroxynaphthoic acid or its salts to LH-RH derivatives or their salts is from 3:4 to 4:3. 26. A controlled active mixture under claim 22 containing LH-RH derivatives or their salts in an amount of 14% (weight/weight) to 24% (weight/weight) in the controlled active mixture. 27. Controlled active mixtures under any of the claims 11 through 13, which are used for injectable medications. 28. A controlled method for the production of an active mixture in accordance with claim 11, which includes the removal of the solvent from a solution of a mixture of the physiologically active substance or its salts, and lactic acid polymer or its salts with an average molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less. 29. A method for the controlled production of an active mixture in accordance with claim 12, which includes the removal of solvents from a solution of a mixture of the physiologically active substance or its salts, hydroxinaphthoic acid or its salts, and lactic acid polymer or its salts, with an average molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less. 30. A method for the controlled production of the active mixture pursuant to claim paragraph 29, which involves the mixing and dispersion of the physiologically active substance or its salts into a solution of an organic solvent containing hydroxynaphthoic acid or its salts and a lactic acid polymer or its salts with an average molecular weight of 15000 to 50000, in which the amount of the polymer with a molecular weight of 5000 or less is approximately 5% by weight or less, and then the organic solvent is removed. 31. A method for the production of a controlled active mixture in accordance with claim 30, whereby the physiologically active substance or its salts is an aqueous solution containing the physiologically active substance or its salts. 32. The method of production according to claim 30, in which the salt of the physiologically active substance is a salt containing a free base or acid. 33. A drug containing a controlled active ingredient as provided by any of Claims 11 through 13. 34. Drugs that prevent or treat prostate cancer, benign prostatic hyperplasia, endometriosis, uterine myoma, uterine fibroma, precocious puberty, menstrual pain, or breast cancer, or contraceptives containing a controlled active ingredient as per patent claim 21 or 22. 35. A substance for the prevention of breast cancer recurrence after surgery for premenopausal breast cancer, consisting of a controlled active ingredient mixture as per patent claim 21 or 22. 36. Methods of preventing or treating prostate cancer, benign prostatic hyperplasia, endometriosis, uterine myoma, uterine fibroma, precocious puberty, menstrual pain, or breast cancer, or methods of contraception which include the administration of a controlled active ingredient for mammals as per claim 21 or 22 in doses that are effective in mammals. 37. A method for preventing recurrence of breast cancer after surgery for premenopausal breast cancer, comprising the administration of a controlled, mammalian-effective combination of substances as per claim 21 or 22, in mammalian-effective doses.