Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1995-06-06
1999-05-11
Venkat, Jyothsna
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
264 41, 4284022, A61K9/66
Patent
active
059026049
ABSTRACT:
This invention provides an aqueous/t-butanol solvent-system, facile reconstitute, submicron-reconsitiute preliposome-lyophilaye and method of its preparation and use.
In one embodiment this entails a modified method for the preparation of a submicron and stable liposome formulation of the non-cross-resistant anthracycline Annamycin is described. The optimal lipid composition was DMPC:DMPG at a 7:3 molar ratio and the optimal lipid:drug weight ratio 50:1. The selected formulation is a preliposome lyophilized powder that contains the phospholipids, Annamycin, and 1.7 mg Tween 20 per mg of Annamycin. The liposome suspension is obtained on the day of use by adding normal saline at 37.degree. C. (1 ml per mg Annamycin) and hand-shaking for one minute. The presence of Tween 20 is essential in shortening the reconstitution step (from >2 hours to 1 minute), avoiding the early formation of free drug crystals, and reducing the median particle size (from 1.5 .mu.m to 0.15-0.20 .mu.m) without destruction of the liposome vesicles. The chemical stability of the preliposome powder at room temperature was >3 months and the chemical and physical stability of the liposome suspension at room temperature >24 hours. The in vitro cytotoxicity of the formulation was equivalent to that prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the liposome size of lyophilized liposome formulations of lipophilic drugs.
REFERENCES:
patent: 4201773 (1980-05-01), Horton et al.
patent: 4311712 (1982-01-01), Evans et al.
patent: 4522803 (1985-06-01), Lenk et al.
patent: 4537882 (1985-08-01), Horton et al.
patent: 4558579 (1985-12-01), Fountain et al.
patent: 4812312 (1989-03-01), Lopez-Berestein
patent: 4855090 (1989-08-01), Wallach
patent: 4863739 (1989-09-01), Perez-Soler et al.
patent: 4911928 (1990-03-01), Wallach
patent: 4950432 (1990-08-01), Mehta et al.
patent: 4975282 (1990-12-01), Cullis et al.
patent: 4999199 (1991-03-01), Anaissie et al.
patent: 5032404 (1991-07-01), Lopez-Berestein
patent: 5132290 (1992-07-01), Priebe et al.
patent: 5178875 (1993-01-01), Lenk et al.
Japanese Abstract, JP 62-93615 A (Nippon Oils & Fats Co. Ltd.), Oct. 21, 1994.
Perez-Soler et al, "Anthracycline Antibiotics with High Liposome Entrapment: Structural Features and Biological Activity," Cancer Research 50: 4260-4266 (Jul. 15, 1990).
Zou et al, "Antitumor Activity of Free and Liposome-entrapped Annamycin, A Lipophilic Anthracycline Antibiotic with Non-Cross-Resistance Properties," Cancer Research 54:1479-1484 (Mar. 15, 1994).
McCutcheon's "Emulsifiers & Detergents," vol. 1, p. 201, North American Edition (1993).
Kronberg et al, "Preparation and Evaluation of Sterically Stabilized Liposomes: Colloidal Stability, Serum Stability, Macrophage Uptake, and Toxicity," J. Pharm. Sci. 79(8):667-671 (1990).
Singer et al, "Time- and Dose-dependent Changes in Ejection Fraction Determined by Radionuclide Angiography After Anthracycline Therapy," Cancer Treatm. Rep., 62(6):945-948 (1978).
Herman et al, "Prevention of Chronic Doxorubicin Cardiotoxicity in Beagles by Liposomal Encapsulation," Cancer Res. 43:5427-5432 (1983).
Rahman et al, "A Phase I Clincical Trial and Pharmacokinetic Evaluation of Liposome-Encapsulated Doxorubicin," J. Clin. Oncol. 8:1093-1100 (1990).
Gabizon et al, "Prolonged Circulation Time and Enhanced Accumulation in Malignant Exudates of Doxurubicin Encapsulated in Polyethylene-glycol Coated Liposomes," Cancer Research 54:987-992 (1994).
Thierry et al, "Effect of Liposomes on P-glycoprotein Function in Multi-drug Resistent Cells," Biochem. Biophys. Res. Comm. 187:1098-1105 (1992).
Rahman et al, "Liposome-mediated Modulation of Multidrug Resistance in Human HL-60 Leukemia Cells," J. Natl. Cancer Inst. 84:1909-1914 (1992).
Mayer et al, "Influence of Vesicle Size, Lipid Composition, and Drug-to-Lipid Ratio on the Biological Activity of Liposomal Doxurubicin in Mice," Cancer Research 49:4922-5930 (1989).
Acton et al, "Intensely Potent Morpholinyl Anthracyclines," J. Med. Chem. 27:638-645 (1984).
Priebe et al, "Removal of the Basic Center From Doxurubicin Partially Overcomes Multidrug Resistance and Decreases Cardiotoxicity," Anticancer Drugs 4:37-48 (1993).
Barbieri et al, "Chemical and Biological Characterization of 4'-iodo-4'-deoxydoxorubicin," Cancer Research 47:4001-4006 (1987).
Perez-Soler et al, "Cellular Pharmacology of the Partially Non-Cross-Resistent Anthracycline Annamycin Entrapped in Liposomes in KB and KB-VI Cells," Cancer Research 34:109-118 (1994).
Perez-Soler et al, "Phase I Clinical and Pharmacology Study of Lipsome-Entrapped Cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane-platinum (II)," Cancer Research 50:4254-4259 (1990).
Murray et al, "Phase I Trial of Liposomal Muramyl Tripeptide Phosphati-dylethanolamine in Cancer Patients," J. Clin. Oncol. 7:1915-1925 (1989).
Zou et al, "Organ Distribution and Tumor Uptake of Annamycin, A New Anthracycline Derivative with High Affinity for Lipid Membranes, Entrapped in Multilamellar Vesicles," Cancer Chemother. Pharmacol. 32: 190-196 (1993).
Zou et al, "Quantitative Analysis of the Lipophilic Doxurubicin Analogue Annamycin in Plasma and Tissue Samples by Reverse-Phase Chromatography," J. Pharmaceutical Sci., 82(11):1151-1154 (1993).
Gu et al, "Study on the Polyphase Liposomes -- A New Dosage Form for Anti-tumor Drugs. I Antitumor Activity Screening of Polyphase Liposome 139 and Others," Chinese Herb Medicine, 13(4):13-19 (1982).
Zou et al, "Stability and Some Other Important Physical Properties of Polysaccarides Polyphase Liposome (PPL)," Acta Pharmaceutica Sinicia, 24(1):58-62 (1989).
Young et al, "The Anthracycline Antineoplastic Drugs," N. Engl. J. Med., 305(3):139-153 (1981).
Pazdur et al, "Phase I Trial of Taxotere: Five-Day Schedule," J. Natl. Cancer Inst. 84:1781-1788 (1992).
Perez-Soler Roman
Priebe Waldemar
Zou Yiyu
Board of Regents , The University of Texas System
Venkat Jyothsna
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