A method for producing a cationic liposomal preparation comprising a lipophilic active compound with physical and chemical stability during manufacturing, storing and reconstituting, and further a cationic liposomal preparation obtainable by this method as well as specific cationic liposomal prepara
A method for producing a cationic liposomal preparation comprising a lipophilic active compound with physical and chemical stability during manufacturing, storing and reconstituting, and further a cationic liposomal preparation obtainable by this method as well as specific cationic liposomal preparations as well as pharmaceutical compositions are disclosed.
대표청구항▼
1. A dehydrated preparation of a cationic liposomal composition, wherein the cationic liposomal composition has a pH of between about 3 and 7 and comprises a lipophilic active compound of at least about 0.1%, at least one cationic lipid of at least about 30 mol %, optionally at least one further amp
1. A dehydrated preparation of a cationic liposomal composition, wherein the cationic liposomal composition has a pH of between about 3 and 7 and comprises a lipophilic active compound of at least about 0.1%, at least one cationic lipid of at least about 30 mol %, optionally at least one further amphiphile of up to about 69.9 mol %, a lipophilic active compound of at least about 2 mol %, and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v). 2. The dehydrated preparation of claim 1, wherein the lipophilic active compound is a taxane. 3. The dehydrated preparation of claim 2, wherein the taxane is selected from the group consisting of paclitaxel, docetaxel, or a lipophilic derivative thereof. 4. The dehydrated preparation of claim 3, wherein the cationic liposomal composition comprises paclitaxel of about 2 mol % to about 5 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v) and optionally at least one further amphiphile of up to about 65 mol %. 5. The dehydrated preparation of claim 3, wherein the cationic liposomal composition comprises docetaxel of at least about 5 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v) and optionally at least one further amphiphile of up to about 65 mol %. 6. The dehydrated preparation of claim 3, wherein the cationic liposomal composition comprises succinyl-paclitaxel of at least about 5 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v) and optionally at least one further amphiphile of up to about 65 mol %. 7. The dehydrated preparation of claim 3, wherein the liposomal composition comprises liposomes having a positive zeta potential in about 0.05 M KCl solution at about pH 7.5 at room temperature. 8. The dehydrated preparation of claim 2, wherein the cationic liposomal composition comprises less than 5% degradation product of the taxane. 9. The dehydrated preparation of claim 4, wherein the liposomal composition comprises less than 5% degradation product of paclitaxel. 10. The dehydrated preparation of claim 9, wherein the liposomal composition comprises less than 5% of 7-Epi-Taxol or Baccatin III. 11. The dehydrated preparation of claim 2, wherein the stabilizing agent is in the range of about 5% (m/v) to about 15% (m/v). 12. The dehydrated preparation of claim 11, wherein the stabilizing agent is a sugar or an alcohol. 13. The dehydrated preparation of claim 12, wherein the sugar is trehalose. 14. A pharmaceutical composition comprising the dehydrated composition of claim 2 and a pharmaceutically acceptable carrier, diluent, and/or adjuvant. 15. A reconstituted cationic liposomal preparation, wherein the reconstituted cationic liposomal preparation comprises the dehydrated preparation of claim 2 reconstituted in an aqueous solution, wherein the aqueous solution has a pH of between about 3 and 7, and wherein the taxane is physically and chemically stable for at least about 12 hours at about 2° C. to about 8° C. or at least about 4 hours at ambient temperature. 16. The reconstituted cationic liposomal preparation of claim 15, wherein the reconstituted cationic liposomal preparation comprises liposomes with an average particle size of about 50 nm to about 400 nm, or about 100 nm to about 300 nm. 17. The reconstituted cationic liposomal preparation of claim 15, wherein the reconstituted cationic liposomal preparation comprises less than 5% degradation product of the taxane. 18. A pharmaceutical composition comprising the reconstituted cationic liposomal preparation of claim 15 and a pharmaceutically acceptable carrier, diluent, and/or adjuvant. 19. A reconstituted cationic liposomal preparation, wherein the reconstituted cationic liposomal preparation comprises the dehydrated preparation of claim 4 reconstituted in an aqueous solution, wherein the aqueous solution has a pH of between about 3 and 7, and wherein the paclitaxel is physically and chemically stable for at least about 12 hours at about 2° C. to about 8° C. or at least about 4 hours at ambient temperature. 20. The reconstituted cationic liposomal preparation of claim 19, wherein the reconstituted cationic liposomal preparation comprises liposomes with an average particle size of about 50 nm to about 400 nm, or about 100 nm to about 300 nm. 21. The reconstituted cationic liposomal preparation of claim 19, wherein the reconstituted liposomal composition comprises less than 5% degradation product of paclitaxel. 22. The reconstituted cationic liposomal preparation of claim 21, wherein the reconstituted liposomal composition comprises less than 5% of 7-Epi-Taxol or Baccatin III. 23. A pharmaceutical composition comprising the reconstituted cationic liposomal preparation of claim 19 and a pharmaceutically acceptable carrier, diluent, and/or adjuvant. 24. A reconstituted cationic liposomal preparation, wherein the reconstituted cationic liposomal preparation comprises the dehydrated preparation of claim 1 reconstituted in an aqueous solution, wherein the aqueous solution has a pH of between about 3 and 7, and wherein the lipophilic active compound is physically and chemically stable for at least about 12 hours at about 2° C. to about 8° C. or at least about 4 hours at ambient temperature. 25. A pharmaceutical composition comprising the reconstituted cationic liposomal preparation of claim 24 and a pharmaceutically acceptable carrier, diluent, and/or adjuvant. 26. A pharmaceutical composition comprising the dehydrated preparation of cationic liposomal composition of claim 1.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (18)
McDonald,Donald M.; McLean,John W.; Thurston,O. Gavin, Cationic liposome delivery of taxanes to angiogenic blood vessels.
Rahman Aquilur (Gaithersburg MD) Rafaeloff Rafael (Tel-Aviv MD ILX) Husain Syed R. (Gaithersburg MD), Liposome encapsulated taxol and a method of using the same.
Rahman Aquilur (Gaithersburg MD) Rafaeloff Rafael (Tel-Aviv ILX) Husain Syed Rafat (Gaithersburg MD), Liposome encapsulated toxol and a method of using the same.
Janoff Andrew S. (Yardley PA) Cullis Pieter R. (Vancouver CAX) Bally Marcel B. (Vancouver CAX) Fountain Michael W. (Griggstown NJ) Ginsberg Richard S. (Monroe NJ) Hope Michael J. (Vancouver CAX) Madd, Method of dehydrating liposomes using protective sugars.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.