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Method to reduce the physiologic effects of drugs on mammals

a technology of physiologic effects and drugs, applied in the field of reducing the physiologic effects of drugs on mammals, can solve the problems that the replacement drug methadone itself is addictive, and achieve the effects of reducing the physiologic effect of drugs, and reducing the toxicity of drugs

Inactive Publication Date: 2008-03-13
ANARCO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention is about using a drug-conjugated immunogen to induce antibodies that can reduce the physiological effects of a drug. This can help prevent or treat drug abuse by reducing the toxicity and effects of the drug. The method can also be used to reduce the toxicity of anti-neoplastic drugs and provide a slow in vivo release of drugs. Overall, this invention provides a useful tool for drug treatment programs."

Problems solved by technology

Heroin addiction is sometimes treated with methadone therapy to permit gradual withdrawal, however, the replacement drug methadone is itself addictive.

Method used

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  • Method to reduce the physiologic effects of drugs on mammals

Examples

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example 1

Preparation of a Benzoylecgonine-Conjugated Immunogen

[0023] To form a conjugate between benzoylecgonine, a cocaine derivative, and sheep albumin, 5 mg of sheep albumin was conjugated to 1 mg of benzoylecgonine using 100 mg of EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl, Pierce Chemical Company, Catalog No. 22980) in 1 ml of 0.1 M MES buffer (2-(N-morpholino)ethanesulfonic acid) at pH 4.5 for four hours at 50° C. The mixture was dialyzed against water for two days at room temperature using a 1,000 m.w. cutoff dialysis tubing. Approximately 5 mg of the benzoylecgonine-albumin conjugated immunogen (COALB) in a volume of 1.5 ml was recovered and used in the subsequent studies.

[0024] Similarly, conjugates of benzoylecgonine to mannan or lipopolysaccharide were formed by dissolving 10 mg of mannan (Sigma Chemical Co. IM7504) or Salmonella typhosa lipopolysaccharide (Sigma Chemical Co. #L6386) in 0.1 M sodium carbonate buffer, pH 10.7, to which 10 mg of cyanobromide (CNBr) was...

example 2

Conjugation of Benzoylecgonine to Diphtheria Toxin

[0025] Similarly benzoylecgonine can be coupled to other carrier molecules such as Diphtheria Toxin. In this example, 5 mg. of Diphtheria toxin (Sigma D7544) is dissolved in 0.9 ml of 0.1M MES (pH 4.5) to which is added 1 mg. of benzoylecgonine dissolved in a volume of 0.05 ml. 0.1M MES (pH 4.5) and to which 10 mg. EDC in 0.05 ml of 0.1 M MES (pH 4.5) is added. This coupling reaction is performed at 50° C. for four hours then the mixture is dialyzed against water or PBS using a 1000 molecular weight cut-off dialysis membrane or purified by passing the mixture over an gel filtration column. The recovered conjugate can then be used as drug-conjugated immunogen.

example 3

Preparation of Anti-Neoplastic-Conjugated Immunogens

[0026] Anti-neoplastic drugs, or other highly toxic drugs, may be directly coupled to carrier molecules as a method to lower the toxicity of the drug and to provide controlled release or degradation of the drug. For example, methotrexate can also be coupled to albumin, diphtheria toxoid, tetanus toxoid, and modified polysaccharide as described above. In this example, 5 mg. of a carrier molecule, which has amine groups for binding, such as tetanus toxoid, is coupled to 1 mg. of methotrexate in 0.9 ml of 0.1M MES (pH 4.5) to which is added 10 mg. of EDC dissolved in 0.1 ml of 0.1M MES (pH 4.5). The mixture is allowed to couple the anti-neoplastic, or other toxic substance, to the carrier molecule—tetanus toxoid in this example—for four hours at 50° C. after which the drug-conjugated immunogen is purified by dialyzing against water or a buffered solution, such as PBS, or is purified by column filtration or by High Pressure Liquid Chr...

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Abstract

A method to reduce the physiologic effects of drugs in vivo by inducing specific anti-drug antibodies using drugs conjugated to carrier molecules so as to reduce a drug's toxicity and its physiologic effects upon the recipient. This method includes the treatment and prophylactic prevention of drug abuse, specifically for cocaine and nicotine, and to help reduce the toxic effects of drugs, such as anti-neoplastics.

Description

FIELD OF THE INVENTION [0001] This invention relates to a method for reducing the physiologic effects of drugs on mammals in vivo. Specifically, the method of this invention consists of inducing specific anti-drug antibodies in mammals with immunogens consisting of a drug conjugated to a carrier molecule. More particularly, the method of this invention consists of generating antibodies towards addictive substances—particularly cocaine and nicotine—such that the physiologic effects of such addictive substances are reduced. As a result, toxicity to such addictive substances is dramatically lowered in those mammals which have been treated with the immunogens prior to introduction of the addictive substance. In addition, mammals can be afforded prophylactic protection from such addictive substances by the administration of the drug-conjugated immunogen prior to introduction of the addictive substance. BACKGROUND OF THE INVENTION [0002] The National Institute of Drug Abuse National House...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/385A61K47/48A61P25/30A61P37/02
CPCA61K39/0013A61K47/4823A61K2039/6081A61K2039/6037A61K47/4833A61K47/61A61K47/646A61P25/26A61P25/30A61P37/02Y02A50/30
Inventor BOHANNON, ROBERT C.
Owner ANARCO
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