Treatment of damaged bone marrow and dosage units therefor

• US 4,938,949 A
• Filed: 09/12/1988
• Issued: 07/03/1990
• Est. Priority Date: 09/12/1988
• Status: Expired due to Term

• Current Assignee: University of Rochester Rochester New York 14627 A Not-For-Profit Corporation of New York
• Original Assignee: University of York
• Inventors: Schmalbach, Therese K., Borch, Richard F.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Henley, III, Raymond J.
• Application Number:
  US07/243,405
• Time in Patent Office: 659 Days
• Field of Search: 424/10, 514/476
• US Class Current: 514/476
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

Various types of biological treatments, including antineoplastic treatments with antineoplastic drugs, can result in damage to the blood-forming function of the bone marrow. This damage can be reversed, at least to some degree, with an effective amount (preferably an extremely low dose) of a pharmaceutically acceptable dithiocarbamic compound, including a compound of the formula R₁ R₂ NCSSM or R₁ R₂ NCSS--SCSNR³ R⁴, wherein R¹, R², R³, and R⁴ are the same or different aliphatic or cycloaliphatic or heterocycloaliphatic groups, unsubstituted or substituted by hydroxyl, or one of R¹ and R² and one of R³ and R⁴ can be H, or R¹ and R² or R³ and R⁴, taken together with the N atom upon which the pair of R groups is substituted, can be a 5- or 6-member N-heterocyclic ring which is aliphatic or aliphatic interrupted by a ring oxygen or second ring nitrogen, and M is H or one equivalent of a pharmaceutically acceptable cation, in which case the rest of the molecule is negatively charged. The dosage in mammals can range from about 0.001 to 30 mg/kg of body weight. For larger mammals, including humans, a typical dosage unit is less than 10 mg/kg, e.g. <3 mg/kg. The dosage unit can be dissolved in a suitable pharmaceutically acceptable carrier (e.g. an aqueous medium) and is then preferably administered intravenously within 8 hours of the administration of the agent which can cause bone marrow damage. The extremely low dosages particularly preferred in this invention do not cause any significant side effects.

Claims

1. A process for the treatment of myelosuppression resulting from a toxic side effect of a cytotoxic streptomyces-produced antibiotic derivative administered to a human, said process comprising administering about 0.01-10 mg/kg of body weight of said human, of a compound of the formula:

##STR8## wherein M⁺ is a pharmaceutically acceptable cation, and R¹ and R² are the same or different and represent C₁ -C₆ lower aliphatic or hydroxy-substituted lower aliphatic groups.

2. The process of claim 1 wherein the antibiotic derivative is doxorubicin hydrochloride.