Claims
- 1. A sustained and controlled release composition consisting essentially of microspheres of biodegradable polymeric material which incorporate therein a water-insoluble salt of a medicamentous peptide substance having the formula (I):
- Ac-D-Nal-D-pClPhe-R.sup.3 -Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH.sub.2(I)
- wherein R.sup.3 is D-Pal or D-Trp.
- 2. Composition according to claim 1, wherein the water-insoluble peptide is a pamoate, tannate, stearate or palmitate.
- 3. Composition according to claim 1, wherein the biodegradable polymeric material is a polylactide, a polyglycolide or a copolymer of lactic and glycolic acids.
- 4. Composition according to claim 1, wherein the copolymer of lactic and glycolic acids is a copolymer of L- or D,L-lactic acid containing from 45 to 90% (molar) of lactic acid units and respectively 55 to 10% (molar) of glycolic acid units.
- 5. Composition according to one of claims 1 in the form of microspheres of a 75:25 (molar %) copolymer of lactic and glycolic acids, including at least 5% in weight of the pamoate salt of a peptide of formula (I).
- 6. A sustained and controlled release composition consisting essentially of micropheres of a biodegradable polymeric material which incorporate therein a water-insoluble salt of a medicamentous peptide substance having the formula (I):
- Ac-D-Nal-D-pClPhe-R.sub.3 -Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH.sub.2(I)
- wherein R.sup.3 is D-Pal or D-Trp, said composition prepared by process comprising the steps of:
- a) converting a water-soluble peptide salt of formula (I) into a water-insoluble peptide salt;
- b) suspending said water-insoluble peptide salt in an organic medium containing the biodegradable polymeric material in the dissolved state to afford an organic suspension;
- c) dispersing said organic suspension in an aqueous medium which forms the continuous phase of the resulting emulsion, said aqueous medium consisting essentially of water;
- d) transferring said emulsion into an excess of an aqueous medium; and
- e) separating microspheres thus obtained from the liquid phase, said microspheres containing a pharmaceutically effective amount between about 5-20% by weight of said water-insoluble peptide salt.
- 7. Composition according to claim 1, wherein before the transfer of the oil-in-water emulsion into an excess of aqueous medium, a partial evaporation of the organic solvent forming the oil phase is carried out.
- 8. Composition according to claim 1, wherein the water-insoluble peptide salt is a pamoate, a tannate, a stearate or a palmitate.
- 9. Composition according to one of claim 1, wherein the biodegradable polymeric material is a polylactide, a polyglycolide, or a copolymer of lactic and glycolic acids.
- 10. Composition according to claim 1, wherein the copolymer of lactic and glycolic acids is a copolymer of L- or D,L-lactic acid containing from 45 to 90% (molar) of lactic acid units and respectively 55 to 10% (molar) of glycolic acid units.
- 11. Process according to claim 6, wherein the water-insoluble peptide salt is present in the microspheres in an amount of from about 5% by weight.
- 12. The composition of claim 6, wherein said aqueous medium additionally contains a surfactant.
- 13. A sustained and controlled release composition consisting essentially of microspheres of a biodegradable polymeric material which incorporate therein a water-insoluble salt of a medicamentous peptide substance, said water-insoluble salt having a water solubility less than or equal to 0.1 mg/ml at 25.degree. C., said peptide substance having the formula (I):
- Ac-D-NAl-D-pClPhe-R.sup.3 -Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH.sub.2(I),
- wherein R.sup.3 is D-Pal or D-Trp and said biodegradable polymeric material being a polylactide, a polyglycolide, or a copolymer of lactic and glycolic acids, said composition prepared by a process comprising the steps of:
- a) converting a water-soluble peptide salt of formula (I) into a water-insoluble peptide salt;
- b) suspending said water-insoluble peptide salt in an organic medium containing the biodegradable polymeric material in the dissolved state to afford an organic suspension;
- c) dispersing said organic suspension in an aqueous medium which forms the continuous phase of the resulting emulsion, said aqueous medium consisting essentially of water and a surfactant;
- d) transferring said emulsion into an excess of an aqueous medium; and
- e) separating microspheres thus obtained from the liquid phase, said microspheres containing a pharmaceutically effective amount between about 5-20% by weight of said water-insoluble peptide salt.
- 14. The composition of claim 13, wherein said copolymer of lactic and glycolic acids is a copolymer of L- or D,L-lactic acid containing from 45 to 90% (molar) of lactic acid units and respectively 55 to 10% (molar) of glycolic acid units.
Priority Claims (1)
Number |
Date |
Country |
Kind |
02178/91 |
Jul 1991 |
CHX |
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Parent Case Info
This is a continuation of application Ser. No. 07/915,490, filed Jul. 16, 1992, now abandoned.
US Referenced Citations (13)
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WOX |
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Entry |
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Continuations (1)
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Number |
Date |
Country |
Parent |
915490 |
Jul 1992 |
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