Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-07-10
2003-10-14
Peselev, Elli (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
Reexamination Certificate
active
06632799
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a stable, injectable, ready-to-use solution of an antitumor anthracycline glycoside, e.g. doxorubicin (Adriamycin(®), to a process for preparing such a solution, and providing the same in a sealed container, and to a method for treating tumors by the use of the ready-to-use solution.
2. Description of the Related Art
The anthracycline glycoside compounds are a well known class of compounds in the antineoplastic group of agents, of which doxorubicin is a typical, and the most widely used, representative: Doxorubicin. Anticancer Antibiotics, Federico Arcamone, 1981, Publ: Academic Press, New York, N.Y.; Adriamycin Review, EROTC International Symposium, Brussels, May, 1974, edited by M. Staquet, Publ. Eur. Press Medikon, Ghent, Belg.; Results of Adriamycin Therapy, Adriamycin Symposium at Frankfurt/Main 1974 edited by M. Ghione, J. Fetzer and H. Maier, publ.: Springer, New York, N.Y.
In the past, solutions of anthracycline glycosides have been prepared and the stability thereof has been studied. However, results of these studies have been inconsistent, and no clear parameters have emerged for maintenance of a stable anthracycline glycoside, e.g., doxorubicin, solution. Bosanquet, in a recent article entitled “Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays,” (Cancer Chemother. Pharmacol. 1986, 17, 1-10) reviews the field of stability studies, with particular emphasis on doxorubicin (Adriamycin®). He points out that “very little can be categorically stated about the stability of adriamycin, and a very carefully designed study is urgently required to resolve these conflicting results.”
At present, anthracycline glycoside antitumor drugs, in particular, e.g., doxorubicin, are solely available in the form of lyophilized preparations, which need to be reconstituted before administration.
Both the manufacturing and the reconstitution of such preparations expose the involved personnel (workers, pharmacists, medical personnel, nurses) to risks of contamination which are particularly serious due to the toxicity of the antitumor substances.
Indeed, the Martindale Extra Pharmacopoeia 28th edition, page 175 left column, reports on adverse effects of antineoplastic drugs and recommends that “They must be handled with great care and contact with skin and eyes avoided; they should not be inhaled. Care must be taken to avoid extravasation since pain and tissue damage may ensue”.
Similarly, Scand. J. Work Environ Health vol. 10(2), pages 71-74 (1984), as well as articles in Chemistry Industry, Issue Jul. 4, 1983, page 488, and Drug-Topics-Medical-Economics-Co, Issue Feb. 7, 1983, page 99, report severe adverse effects observed in medical personnel exposed to use of cytostatic agents, including doxorubicin.
Even though the effect of long-term low-level exposure to such cytotoxic drugs is not yet completely known, there is certainly a hazard for those who regularly prepared and administer these substances in view of the fact that they are known mutagens and carcinogens in animals and implicated as carcinogens in man.
To administer a lyophilized preparation, double handling of the drug is required, the lyophilized cake having to be first reconstituted and then administered. Moreover, in some cases, the complete dissolution of the powder may require prolonged shaking because of solubilization problems. Reconstitution of a lyophilized cake or powder can result in formation of aerosol droplets which can be inhaled or can come into contact with skin or mucous membranes of those handling the solution.
SUMMARY OF THE INVENTION
As the risks connected with the manufacturing and the reconstitution of a lyophilized preparation would be highly reduced if a ready-to-use solution of the drug were available, the present inventors have developed a stable, therapeutically acceptable injectable solution of an anthracycline glycoside drug, e.g. doxorubicin, whose preparation and administration does not require either lyophilization or reconstitution.
According to the present invention, there is provided a stable, injectable, sterile, pyrogen-free, anthracycline glycoside solution which consists essentially of a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable solvent therefor, which has not been reconstituted from a lyophilizate, which has a pH of from 2.5 to 3.5 and which is preferably contained in a sealed glass container.
REFERENCES:
patent: 4109076 (1978-08-01), Henry et al.
patent: 4296105 (1981-10-01), Baurain et al.
patent: 4537593 (1985-08-01), Alchas
patent: 4564054 (1986-01-01), Gustavsson
patent: 4576211 (1986-03-01), Valentini et al.
patent: 4588403 (1986-05-01), Weiss et al.
patent: 4786281 (1988-11-01), Valentini et al.
patent: 1005760 (1977-02-01), None
patent: 1129344 (1982-08-01), None
patent: 1203482 (1986-04-01), None
patent: 35 36 896 (1986-04-01), None
patent: 401 896 (1990-12-01), None
patent: 2405957 (1979-05-01), None
patent: 2178311 (1987-02-01), None
The Interpharm International Dictionary of Biotechnology and Pharmaceutical Manufacturing,edited By Dean E. Snyder, Publisher Buffalo Grove, IL: Interpharm Press, Inc., 1992.
Merck Index, 10thedition, 1983, p. 499, Entry No. 3435.
Bosanquet, “Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays”,Cancer Chemotherapy and Pharmacology,vol. 17, 1986, pp. 1-10.
Rolf Kaltofen, Joachim Ziemann et al., Tabellenbuch Chemie, 12thedition, pp. 172, 181.
Yüksel, “Determination of Ceftriaxone in Aqueous Humour and Serum Samples by Differrential-pulse Adsorptive Stripping Voltammetry”,Analyst,vol. 119, 1994, pp. 1575-1577.
Falbe et al.,Rompp Chemie Lexikon,9thedition, Georg Thieme Verlag Stuttgart, New York, 1992, “Buffers”, pp. 3677-3678.
Mortimer,Chemie,3rdedition, Georg Thieme Verlag Stuttgart, New York, 1980, pp. 490-494.
Europaischez Arzneibuch, vol. III, 1979, p. 654 (English translation provided.).
Arcamone et al. (1972), “Structure and Physiochemical Properties of Adriamycin (Doxorubicin),” International Symposium on Adriamycin, Springer-Verlag, Berlin, pp. 9-22.
Beijnen, J.H. et al. (1985), “Aspects of the Chemical Stability of Doxorubicin and Seven Other Anthracyclines in Acidic Solution,”Pharmaceutisch Weekblad Scientific Edition,vol. 7, pp. 109-116.
German Patent Office Decision dated Oct. 8, 1996 (English translation attached) revoking Patent No. 3621844.
Wang and Kowal (1980), “Review of Excipients and pH's for Parenteral Products Used in the United States,”J. of the Parenteral Drug Association,vol. 14, p. 452-462.
Harris, Daniel C. (1995), “Quantitative Chemical Analysis,” 4thEdition, W.H. Freeman and Company.
Topics in Antibiotic Chemistry,2, 109-115, 1978.
Arcamone et al. (1969, “Adrimycin, 14-Hydroxydaunomycin, a New Antitumor Antibiotic fromS. Peucetius Var. Caesius,” Biotechnology and Bioengineering,vol. XI, pp. 1101-1110.
Despois et al. (1967), “Isolement D'un Nouvel Antibiotique Doue D'Activite Antitumorale: La Rubidomycine (13.057 R.P.) Identite De La Rubidomycine et de La Daunomycine,” Path. Biol., vol. 15, pp. 887-891.
Lokich et al. (1983), “constant Infusion Schedule for Adrimycin: A Phase I-II Clinical Trial of a 30-Day Schedule by Ambulatory Pump Delivery System,”J. Clinical Oncology,vol. 1, pp. 24-28.
Wasserman and Bundgaard (1983), “Kinetics of the Acid-Catalyzed Hydrolysis of Doxorubicin,”International J. Pharmaceutics,vol. 14, pp. 73-78.
Merck Index (1996), Mitoxantrone, 12thEdition, Entry 6303, p. 1064.
Martindale (1989), Mitotone,The Pharmaceutical Press,29thEdition, London, Entry 1852-x, pp. 643-645.
ABPI Data Sheet Compendium, 1994-1995, “Novantron Injection,” Lederle Laboratories, pp. 752-754.
Geigy Scientific Tables, vol. 3,Physical Chemistry Composition of Blood Hematology Somatometric Data8threvised and enlarged edition, Edited by C. Lentner, pp. 54-60.
Dorr (1979), “Incompatibilities with Parenteral Anticancer Drugs,”The American Journal of Intravenous Therapy,Feb./Ma
Bottoni Giuseppe
Confalonier Carlo
De Ponti Roberto
Gambini Luciano
Gatti Gaetano
McDonnell & Boehnen Hulbert & Berghoff
Peselev Elli
Pharmacia & Upjohn Company
LandOfFree
Injectable ready-to-use solutions containing an antitumor... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Injectable ready-to-use solutions containing an antitumor..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Injectable ready-to-use solutions containing an antitumor... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3134639