Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-05-31
2002-10-15
Reamer, James H. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S456000
Reexamination Certificate
active
06465436
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to methods of treating alcohol intoxication and alcohol abuse with an extract from the Kudzu plant,
Puararia lobata.
Ethyl alcohol is the most widely used psychoactive drug in the world. Alcohol abuse and alcohol related diseases represent a serious threat to human health and pose major medical, social, and economic problems. In the United States alone, an estimated 10% of the population is affected by alcoholism. The problems associated with alcohol abuse are very costly, both to the individuals affected and to society at large. The physical, social and psychological harm which can result from alcohol abuse and dependence, such as fetal alcohol syndrome, cirrhosis of the liver, alcohol-related accidental death, homicide, suicide, etc., can be devastating. Thus, there remains a strong need to develop safe and effective therapeutic agents for treating alcohol abuse and dependence.
As public awareness of the problems associated with alcohol abuse has increased in recent years, greater efforts have been devoted to the development of treatments for alcoholism. Much of the current research in this area has focused on methods for treating the effects of alcohol withdrawal through the clinical use of various drugs, such as benzodiazepines and the antidipsotropic agent disulfuram (ANTABUSE™). Recent research has also led to the development of new therapeutic agents which suppress alcohol drinking in humans. For instance, dopamine agonists and antagonists, serotonergic agents, glutamate antagonists, opiate antagonists, ALDH inhibitors, and calcium blockers have been reported to reduce self administration of alcohol in alcoholic humans and alcohol-preferring rats (Banys, 1988; Lawrin et al., 1986; McBride et al., 1989; Naranjo et al., 1990; Rezvani et al., 1990, 1991; Sellers et al., 1992). Also, naltrexone (REVIA™), an opioid receptor antagonist, when combined with psychotherapy, has shown encouraging results in several clinical trials (Berg et al., 1990; O'Malley et al., 1992a,b; Volpicelli et al., 1990, 1992). Unfortunately, many of these current drug treatments are toxic, exhibit low efficacy and patient compliance, have many adverse side effect, and are unsuitable for use with adolescents and pregnant women. Thus, despite these recent advancements, developing effective treatments for alcohol dependence remains a challenging goal.
Since ancient times, Chinese herbalists have known of the medicinal value of the Kudzu plant,
Pueraria lobata.
Radix Puerariae (RP), a related herb in the same family, has long been used in traditional Chinese medicine as a treatment for alcohol intoxication. Although it has been a part of Chinese medicine for over 2000 years, only recently have attempts been made to purify, identify, and classify the active ingredients of RP. Research has shown that RP is a complex mixture having a multitude of components, not all of which have been identified. In addition to starch, some of the major constituents of RP include puerarin, daidzein, daidzin, genistein, 6,7-dimethoxycoumarin, formononetin, &bgr;-sitosterol, allantoin, and 5-methylhydantoin.
Recently, Keung and Vallee demonstrated that daidzin and daidzein were the active herbal components isolated from RP that suppressed alcohol intake in Syrian Golden hamsters (Keung and Vallee, 1993a; 1993b; Keung et al., 1995). Daidzein also decreases blood alcohol levels and shortens sleep time induced by alcohol (Xie et al., 1994). Daidzin and daidzein are potent human ALDH-1 inhibitors (Keung et al., 1993a,b), and in U.S. Pat. No. 5,204,369, Vallee et al disclose the use of daidzin as a selective inhibitor of ALDH-1 for the treatment of alcohol dependence.
U.S. Pat. No. 5,783,189 reports that comprehensive fractionation studies on
Pueraria lobata
yielded five isoflavonoids which are primarily responsible for the alcohol consumption suppressing activity of herbal medicines derived from
Pueraria lobata.
Daidzin and daidzein were among the five, as well as puerarin, 3′-methoxypuerarin, and mirificin.
SUMMARY OF THE INVENTION
The invention features pharmaceutical compositions for treating alcohol dependence and intoxication which contains a kudzu extract that includes, by weight, (i) 20-40% puerarin; (ii) 3-10% daidzein; and (iii) 1-5% daidzin, in a pharmaceutically acceptable carrier. Preferably, the composition contains, by weight, 25% puerarin, 5% daidzein and 2.5% daidzin. The pharmaceutical compositions of the invention are preferably adapted for oral ingestion.
These pharmaceutical compositions are useful for the treatment of alcohol dependence and alcohol intoxication. The methods and compositions of the invention are nontoxic, very efficacious, present few, if any, side effects, and can be safely used with pregnant women and adolescents.
Other features and advantages of the invention will be apparent from the following detailed description of the preferred embodiments thereof and from the claims.
REFERENCES:
patent: 5204369 (1993-04-01), Vallee et al.
patent: 5547671 (1996-08-01), Duthinh
patent: 5624910 (1997-04-01), Vallee et al.
patent: 5783189 (1998-07-01), Pei et al.
patent: 5886028 (1999-03-01), Vallee et al.
patent: 6121010 (2000-09-01), Vallee et al.
patent: 6255497 (2001-07-01), Vallee et al.
Lin et al (I), Am. J. Clin. Nurt., vol. 68, pp. 1512S-5s. 1998.*
Keung et al, Proc. Natl. Acad. Sci. USA, vol. 93, pp. 4284-4288, Apr. 1996.*
Lin et al (II), Alcohol Clin. Exp. Res, vol. 20, #4, pp. 659-663 (abstract), Jun. 1996.*
Keung and Vallee, “Daidzin and Daidzein Suppress Free-Choice Ethanol Intake by Syrian Golden Hamsters,”Proc. Natl. Acad. Sci. USA90:10008-10012 (1993).
Keung and Vallee, “Therapeutic Lessons from Traditional Oriental Medicine to Contemporary Occidental Pharmacology,”EXS71:371-381 (1994).
Keung et al., “Daidzin Suppresses Ethanol Consumption by Syrian Golden Hamsters without Blocking Acetaldehyde Metabolism,”Proc. Natl. Acad. Sci. USA92:8990-8993 (1995).
Keung et al., “Potentiation of the Bioavailability of Daidzin by an Extract ofRadix Puerariae,” Proc. Natl. Acad. Sci. USA93:4284-4288 (1996).
Keung et al., “Daidzin Inhibits Mitochondrial Aldehyde Dehydrogenase and Suppresses Ethanol Intake of Syrian Golden Hamsters,”Proc. Natl. Acad. Sci. USA94:1675-1679 (1997).
Keung and Vallee, “Daidzin and its Antidipsotropic Analogs Inhibit Serotonin and Dopamine Metabolism in Isolated Mitochondria,”Proc. Natl. Acad. Sci. USA95:2198-2203 (1998).
Keung and Vallee, “Kudzu Root: An Ancient Chinese Source of Modern Antidipsotropic Agents,”Phytochemistry47:499-506 (1998).
“Kudzu Extract Shows Potential for Moderating Alcohol Abuse,”Am. J. Hosp. Pharm.51:750 (1994).
Overstreet et al., “Suppression of Alcohol Intake After Administration of Chinese Herbal Medicine, NPI-028, and its Derivatives,”Alcohol. Clin. Exp. Res.20:221-227 (1996).
Rezvani et al., “Chinese Herbal Medicine NPI-028 Reduces Alcohol Intake without Inducing Taste Aversion,”Alcohol. Clin. Exp. Res.19:15A (Abstract) (1995).
Shebak and Rindone, “A Pilot Study Exploring the Effect of Kudzu Root on the Drinking Habits of Patients with Chronic Alcoholism,”J. Altern. Complement. Med.6:45-48 (2000).
Xie et al., “Daidzin, an Antioxidant Isoflavonoid, Decreases Blood Alcohol Levels and Shortens Sleep Time Induced by Ethanol Intoxication,”Alcohol. Clin. Exp. Res.18:1443-1447 (1994).
Lee David
Lukas Scott
Clark & Elbing LLP
McLean Hospital
Reamer James H.
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