HK1171245B - Alcoholic compositions having a lowered risk of acetaldehydemia - Google Patents

Abstract

The present invention provides beverages and pharmaceutical compositions containing a deuterated alcohol according to Formula 1, and provides methods for their manufacture and use. The compositions of the invention are expected to ameliorate some of the negative side effects associated with the consumption of alcohol, such as hangover and facial flushing.

Description

Ethanol composition with reduced risk of acetaldehydemia

Technical Field

The present invention relates generally to compositions and methods for reducing side effects associated with the consumption of ethanol. The invention more particularly relates to beverages and pharmaceutical compositions comprising deuterated alcohols, and uses thereof.

Cross Reference to Related Applications

The present application claims benefit of priority from united states provisional patent application series No. 61/274,875 filed on 8/21/2009, united states provisional patent application series No. 61/280,860 filed on 11/9/2009, and united states provisional patent application series No. 61/283,524 filed on 12/4/2009, in accordance with 35u.s.c. § 119 (e). The disclosures of these applications are incorporated herein by reference.

Background

Ethanol is the major psychoactive component in alcoholic beverages (alcoholic beverages), which are usually consumed with the specific intent of experiencing some effect of ethanol on the central nervous system. These effects decrease over the course of several hours, as ethanol is gradually metabolized by the body into a common metabolite, acetyl-coa, and an energy source.

The metabolism of ethanol in humans is a two-step process (equation 1) mediated by the enzymes Alcohol Dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Unfortunately, acetaldehyde, an intermediate metabolite of ethanol, is toxic, mutagenic, and carcinogenic to consumers.

(equation 1)

As can be seen from equation 1, the rate (k) of the reaction when the ALDH catalyzes₂) Not high enough to keep up with the ADH-catalyzed dehydrogenation of ethanol (k)₁) Acetaldehyde will accumulate. High acute concentrations of acetaldehyde in the body (acetaldehy mia) can lead to undesirable effects such as cardiovascular complications, drowsiness, nausea, headache, asthma and facial flushing, while chronic acetaldehy can lead to cirrhosis of the liver and esophageal cancer. Another undesirable result of acute acetaldehyde toxicity well known to people with alcohol addiction is hangover (hangover). A hangover person will experience dizziness, fatigue, headache, nausea, muscle pain, vomiting, sensitivity to bright light, or sensitivity to noise, and most often a combination of these adverse symptoms, for a period of time, typically 12 to 36 hours.

Acetaldehyde is recognized as the chief culprit in hangover and ethanol-induced facial flushing, and is also a major suspect for ethanol-related cancers, see below. Glyoxemia can occur as a result of large ethanol consumption, resulting in saturation of ALDH activity, or in the presence of abnormally high ADH activity or insufficient ALDH activity (k in equation 1)₁>>k₂) Small or moderate consumption of ethanol. Genetic defects in both enzyme systems are known to cause glyoxemia-related syndromes (D.W.Crabb, M.Matsumoto, D.Chang, M.You, Proc.Nutr.Soc.2004,63: 49-63).

For example, individuals with inactivated or ineffective acetaldehyde dehydrogenase (ALDH) experience a small number of acetatemia-associated facial flushes after drinking alcohol or after administration of an ethanol-containing pharmaceutical composition. (S.Harada, D.P.Agarwal, H.W.Goedde, Lancet.1981,2: 982) inhibition of ALDH by the drug disulfiramSimilar sensitivity occurs in humans with the present normally functioning enzymes. In both cases, there is k in equation 1₂So that acetaldehyde is not cleared from the blood as quickly as it is formed, thereby bringing its concentration to toxic levels. This type of sensitivity to ethanol-induced flushing is generally associated with the ALDH2 x 2 allele; having the ALDH2 x 2 allele also enhances the risk of esophageal cancer in drinkers. (T.Yokoyama et al, Cancer epidemic, Biomarkers)&Prevention 2003,12:1227-1233）

Another way in which ethanol consumption can lead to glyoxemia is the excessively rapid metabolism of ethanol (i.e., by increasing k in equation 1)₁). Several studies have shown that the presence of the ALDH2 x 2 allele which encodes an excessively active form of alcohol dehydrogenase (W.F. Bosron, T.K. Li, Hepatology,19866: 502-510) also contributes to the susceptibility to ethanol flushing and esophageal cancer (A.Shibuya et al, hum. Genet.1989,82: 14-16; T.Takeshita et al, hum. Genet.1996,97: 409-413; WJ.Chen et al, alcohol. Clin. Exp. Res.1998,22: 1048-1052; A.Yokoyama et al, alcohol. Clin. Exp. Res.1999,23: 1705-1710).

From the earliest hangover, efforts were made to find effective methods of treating the unpleasant physical effects of excessive ethanol consumption. Consumption of additional ethanol is the oldest remedy; the expression "drunkenness (hai of the Dog)" comes from the studios anshenius in the 4 th century prior to greek, e.c. brewer, Dictionary of Phrase and Fable, 1898. While this may temporarily alleviate the symptoms of acetaldehydemia and alcohol withdrawal, pain is only delayed and damage may be compounded. Other proposed effective interventions include various foods, vitamins, dietary supplements, exercise and drugs. Compounds intended to sequester acetaldehyde in vivo have been designed and evaluated (see, e.g., h.t. nagasawa et al, j.med. chem.1987,30: 1373-. Despite the enormous folk and anecdotal treasury, none of these methods have been shown to be effective in clinical trials. (M.H.Pittler et al, BMJ, 2005,331: 1515-)

The ethanol-induced flushing response (sometimes referred to as "asian flushing" due to the relatively large incidence in asian descent) is a set of symptoms experienced by people with abnormalities in ethanol metabolism-related enzymes. When affected people consume ethanol, there is a rapid accumulation of acetaldehyde in their systems due to acetaldehyde dehydrogenase deficiency and/or excessive alcohol dehydrogenase activity. This accumulation causes erythema (reddening due to capillary dilation) in the face, neck and shoulders of the person; the person may also experience nausea, headache, dizziness, and increased pulse rate. These sensations are sufficiently difficult that affected individuals often refrain from drinking alcohol at all and may discourage their use of ethanol-containing drugs. The pharmaceutical workers wishing to solve this problem have to forego the favorable physical properties of ethanol, its low cost and relative safety. There remains a need for compositions and methods that reliably address the problem of ethanol-induced flushing for hangover.

The deuterium isotope effect is a well-known phenomenon in the field of enzymology and pharmacodynamics. The primary isotopic effect can be particularly large, and deuterium substitution of enzymatically removed hydrogen can slow the rate of substrate metabolism in vivo by a factor of two or three. In particular, it is well recognized that deuteration of a substrate can reduce the concentration of metabolites in vivo by slowing the rate of metabolism. An early and appropriate example was the effect of deuteration of the N-methyl group of morphine: in vivo metabolism is slowed by about two-fold, lowering blood levels of pharmacologically active metabolites and causing a corresponding decrease in analgesic potency (C.Elison et al, Science,1961, 1078-1079).

Deuterated drugs are the subject of a number of patent applications. U.S. patent No. 5,223,269 to Liepins describes methods and compositions for treating hypertension. U.S. patent No. 5,838,375 to Furminger describes a pharmaceutical composition comprising a biological agent and D2O to improve the stability of the agent. U.S. patent No. 5,895,660 to Hoffmann describes deuterated drugs for transdermal applications. Us patent No. 6,376,531 describes deuterated drugs for the treatment of psychotic disorders. The contents of these patents are incorporated by reference in their entirety into this document for all purposes.

The hydrogen atom at C-1 in ethanol is enantiomerically ectopic; conventionally, oxygen and C-1 carbon and C-2 carbon define a plane that divides the surrounding space, and the hydrogen remaining in the "Si" half space is designated as H (Si) or H_Si. The hydrogen in the "Re" half space is designated H (Re) or H_Re. In the case of ethanol, an alternative nomenclature would be H_ReDesignated as "pre-R" hydrogen, and reacting H_SiDesignated as "pre S". The absolute stereochemistry is shown below:

h of ethanol during oxidation by mammalian alcohol dehydrogenase_ReIs stereospecifically removed and transferred to the enzyme cofactor NAD, while at the same time abstracting the hydroxyl protons. This produces the product acetaldehyde, in which H is present_SiIs retained as hydrogen of the aldehyde.

Notably, despite thousands of years of effort directed to mitigating the unpleasant effects of excess ethanol consumption, as well as recent attempts to alleviate problems associated with the administration of ethanol-containing pharmaceutical formulations, there remains a need for compositions and methods that effectively address these problems.

Summary of The Invention

The present invention provides an ethanol composition (alcoholic composition), such as a beverage or pharmaceutical formulation, wherein at least 5 mole percent of the ethanol in the composition is deuterated ethanol, wherein H is_ReIs deuterium, as shown in formula 1.

Formula 1

Should be understood as being in the formulaIn 1, and in all other structures represented herein, each atom designated "H" without a superscript may independently be hydrogen: (¹H) Or deuterium (²H) In that respect Term "²H "and" D "are used interchangeably to specifically refer to deuterium.

The present invention also provides methods of increasing the time period between consumption of an ethanol beverage and reaching a peak blood level of ethanol, and methods of delaying the onset of ethanol-induced symptoms associated with consumption of an ethanol beverage, including consumption of a deuterated ethanol-containing ethanol beverage. The invention also provides methods of ameliorating glyoxemia and its symptoms comprising consuming the ethanol-containing beverages and pharmaceutical compositions of the invention.

Brief Description of Drawings

Fig. 1 shows the time course of blood ethanol levels in human subjects after administration of common beverage ethanol (° c) and 1, 1-dideuterol ethanol (■).

Detailed Description

The present invention makes use of the surprising finding that the absorption rate of orally administered ethanol in human subjects is significantly reduced if the ethanol is deuterated (figure 1). The blood peak concentration of ethanol, which is usually reached 20-30 minutes after ingestion, is delayed to 1-2 hours after ingestion and the peak concentration is reduced by 15-20%. (the biochemical basis of this unexpected sensitivity to molecular weight is currently unknown). The peak acetaldehyde blood level is also delayed and reduced because the rate of oxidation by alcohol dehydrogenase varies with the concentration of ethanol.

The invention provides ethanol compositions, such as beverages or pharmaceutical formulations, wherein at least 5 mole percent of the ethanol in the composition is deuterated ethanol, wherein H_ReIs deuterium, as shown in formula 1:

formula 1

As noted above, each atom designated "H" may independently be hydrogen: (a)¹H) Or deuterium (²H) In that respect Specific examples of suitable deuterated alcohols include, but are not limited to: ethanol-1-D (formula 2), ethanol-1, 1-D₂(formula 3), ethanol-1, 2-D₂(formula 4) and ethanol-D₅（CD₃CD₂OH). The enantiomer of ethanol-1-D illustrated in formula 2 may be present in the compositions of the present invention.

Formula 2, formula 3, formula 4

In an successively more preferred embodiment, the composition comprises ethanol, wherein at least 15 mole percent, 30 mole percent, 50 mole percent, 75 mole percent, or 95 mole percent of the ethanol is deuterated ethanol according to formula 1.

In a further embodiment, the invention also makes use of the fact that: removal of H from ethanol by alcohol dehydrogenase_ReSubject to a substantial first order deuterium isotope effect. Specifically, H is removed by alcohol dehydrogenase_ReDeuterium in position (²H) Specific light hydrogen (¹H) Two to four times slower. This effect is thoroughly demonstrated in vitro (B.V.Plapp.et al, J.biol.chem.1973,248: 3470; Lundquist et al, Alcohol Clin.exp.Res.1986,10 (suppl.6): 69S-72S; J.O.Winberg et al, biochem.mol.biol.int.1993,31: 651-658) and in vivo (S.E.Damgaard, Biochemistry 1981,20: 5662-.

Having greater than normal levels of alcohol dehydrogenase activity and thus having an alcohol effect due to the effect of the first-order deuterium isotopeThe flushing-prone individual should be metabolized to H as compared to him or her after consuming the ethanol composition of the invention_ReThe deuterated alcohols of formula 1 are metabolized at a significantly lower rate than alcohols having natural isotopic abundance. K in equation 1 arises from kinetic isotope effects₁So that the rate at which the individual produces acetaldehyde in the body is shifted back to the rate observed in normal individuals. The result should be a reduced level of acetaldehyde in the individual's system, and a corresponding reduction in the severity of the symptoms of acetaldehydemia (such as hangover and ethanol-induced flushing). In ethanol in H_ReThe greater the proportion of deuterium, the greater the reduction in acetaldehyde concentration in blood is expected.

The reduction in blood levels of acetaldehyde should be particularly significant if the individual is able to metabolize the ADH produced acetaldehyde at a rate that prevents accumulation of aldehydes. The metabolism of acetaldehyde to acetate is performed by aldehyde dehydrogenase (ALDH) and to some extent by cytochrome P450. Some ALDH enzymes exhibit deuterium isotope effects when acted upon certain substrates such as benzaldehyde (M.Scharschmidt et al, Biochemistry 1984,23: 5471-. On the other hand, sheep liver ALDH is on acetaldehyde-1-d (CH)₃CDO) showed no isotopic effect (GJ. Hart and F.M.Dickinson, biochem. J.1978,175: 899-908) and horse liver ALDH in the presence of p-propanal-1-d (CH)₃CH₂CDO) showed no isotopic effect (R.I.Feldman and H.Weiner, J.biol.chem.1972,247: 267-272). To avoid any possible reduction in ALDH activity, H in the compound of formula 1_SiWith little or no deuterium and correspondingly little CH generation₃CDO or no CH production₃CDO may be desirable. It is to be understood, however, that the process according to the invention is carried out by reacting in ethanol H_ReThe provision of deuterium to reduce acetaldehyde concentration in vivo should reduce the symptoms of glyoxemia and H_SiRegardless of the isotopic composition.

It will be appreciated that consumption of the compositions of the invention in place of an equivalent amount of prior art beverages and pharmaceutical formulations should result in slower in vivo acetaldehyde formation, with a reduction in the symptoms of acetaldehydemia, even in individuals not suffering from an enzyme abnormality. The slower metabolism of deuterated alcohols of the present invention, combined with the extended time to peak blood alcohol concentration, should reduce the amount of ethanol required to produce a given psychopharmacological effect. Thus, the beverages of the present invention can be made with lower ethanol content than equivalent prior art beverages without being perceived by the consumer as "weaker" or less potent, and they should produce a more constant and prolonged effect, and a less pronounced initial effect. In particular, the beverage of the present invention can be drunk on an empty stomach with less risk of sudden drunkenness.

Conversely, pharmaceutical compositions can be produced having higher ethanol concentrations and greater solvency than prior art compositions without increasing the side effects caused by acetaldehyde. The greater solvency enables the production of more concentrated formulations with savings and convenience.

The present invention thus provides methods of avoiding or reducing the severity of ethanol-induced acetaldehydemia, hangover and facial flushing by providing and/or consuming the ethanol beverages and pharmaceutical compositions of the present invention.

The present invention also provides a method of making an alcoholic beverage. The method comprises the step of adding deuterated ethanol according to formula 1 to a beverage in an amount sufficient to produce an ethanol beverage comprising water and ethanol as follows: wherein at least 5 mole percent of the ethanol is deuterated ethanol according to formula 1. In further embodiments, the deuterated ethanol according to formula 1 is added in an amount sufficient to produce an ethanol beverage comprising water and ethanol as follows: wherein at least 15 mole percent, 30 mole percent, 50 mole percent, 75 mole percent, or 95 mole percent of the ethanol is deuterated ethanol according to formula 1.

The invention also provides a method for manufacturing the ethanol pharmaceutical composition. The method includes the step of combining an Active Pharmaceutical Ingredient (API) with a deuterated ethanol according to formula 1 in an amount sufficient to produce a composition comprising: wherein at least 5 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1. In another embodimentIn an amount sufficient to produce a composition comprising: wherein at least 15 mole percent, 30 mole percent, 50 mole percent, 75 mole percent, or 95 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1. Pharmaceutically acceptable excipients can be introduced or mixed with the deuterated ethanol and/or API before or after the combining step. In this document, the use of "H" refers to any isotopically composed species of hydrogen atoms, i.e.¹H、²H, or¹H、²Any combination of H in any ratio. "D" or "²The use of H "specifically refers to deuterium isotopes. Unless otherwise indicated, the percentages by weight ratios described herein are percentages by weight.

"ethanol (Alcohol)" refers to ethanol (ethanol).

"bocop beverage (alcopop)" refers to certain flavored alcoholic beverages, including: malt beverages supplemented with various fruit juices or other flavorings; alcoholic beverages (e.g., wine cooler) to which ingredients such as fruit juices or other flavorings have been added; and beverages containing distilled ethanol and additional ingredients such as fruit juices or other flavorings.

"near sake (almost sake)" refers to sake infused with a fruity flavor. An example of "near Sake" is Hana flavored Sake produced by Takara Sake.

"brewed liquor (awamori)" means distilled spirits derived from long grain rice, typically produced from okinawa.

"Baijiu" refers to distilled spirit made from sorghum, wheat or glutinous rice. It typically has an ethanol content of about 60%.

"beer" refers to an alcoholic beverage produced by brewing and fermentation of starch derived primarily from grains (e.g., malted barley, wheat, corn, and rice). The ethanol content of beer is typically in the range of one percent to six percent.

Ethanol beverageBy "drink" is meant a liquid suitable for human consumption comprising ethanol, water and at least one further component which is a sweetener, a flavour enhancer or a fragrance, or the like (conner) derived from the brewing or fermentation composition from which the beverage is produced. The amount of ethanol is at least 1% by weight. In various other embodiments of the present invention, the amount of ethanol is at least 2%, 5%, 10%, 20% or 40% by weight. In the context of this document, "deuterated ethanol" refers to an ethanol having at least one deuterium atom and corresponding to formula 1. Deuterated alcohols are commercial items sold by suppliers such as CDN Isotopes, inc, Pointe-Claire, Quebec, Canada, and methods of making such compounds are well known to those skilled in the art. At H_ReEthanol in which the position is stereospecifically deuterated is known (see Damgaard et al, Biochemistry, 198120: 5662-9 and references therein), whereas racemic ethanol-1-d is readily accessible by use of BD₃Or NaBD₄Reducing acetaldehyde to obtain. Non-specific hydrogen-deuterium exchange reactions are mentioned and/or discussed in U.S. patent No. 7,517,990, which is incorporated by reference in its entirety into this document for all purposes and in particular for the purpose of disclosing methods for deuterium incorporation. By D₂Gas hydrogenation of vinyl esters (e.g., vinyl acetate), followed by hydrolysis, will provide in H_ReEthanol-l, 2-D with at least 50% D in position₂(ii) a The proportion of D at this location can be increased, if desired, by using an asymmetric hydrogenation catalyst (see, e.g., GJ. Clarkson et al, Tetrahedron: Asymmetry,2004,15: 1787-.

In the context of ethanol metabolism, "enzymatic abnormality" refers to a decrease in aldehyde dehydrogenase levels or an increase in alcohol dehydrogenase activity levels, or both, resulting in higher than normal acetaldehyde levels in the affected human. Although this is most often the result of allelic variation of the gene encoding the enzyme, other reasons, such as, for example, misregulation of gene expression (misregulation), are also encompassed by the present invention.

Reference herein to a method of "avoiding" symptoms of acetaldehyde haemia or "reducing" the severity of symptoms of acetaldehyde intoxication is to be understood as referring to the avoidance or reduction of symptoms relative to those which would be experienced with an equivalent dose of non-deuterated components.

"fermentation by-products" refers to non-ethanol compounds produced as a result of starch fermentation.

"Korea vodka (han)" refers to a liquid made of barley vodka that is distilled several times and mixed with polished rice (polished rice). It was not diluted with water.

By "pharmaceutical composition" is meant a liquid composition suitable for administration to a human comprising an active pharmaceutical ingredient, ethanol and optionally water and/or other pharmaceutically acceptable excipients.

"sake" refers to an ethanol-based beverage produced by multiple, parallel fermentations of fine rice. There are two basic types of sake: common sake (futsu-shu), which is often referred to as "regular sake" (for example); the special name wine (tokutei meisho), which is a top-grade sake often referred to as "special designation sake". The brewed sake (Honjozo-shu), the pure rice brewed sake (Junmai-shu) and the Yin brewed sake (Ginjo-shu) are top-grade sake categories. The brewed sake comprises a processing step of adding a small amount of brewer's ethanol to the sake prior to pressing. Pure rice wine or pure rice wine is prepared from rice, water and Aspergillus (Aspergillus oryzae) simply; saccharomyces cerevisiae or other additives are not included in the production process. The Yiniangqing wine is prepared from rice processed to 60% or less of the original weight.

"shochu (shochu)" means a distilled spirit made from barley, sweet potato, sucrose or rice. It typically has an ethanol content of 25% or higher.

"korean shochu (soju)" means a distilled spirit traditionally made from rice with an ethanol content ranging from 25% to 45%. In some varieties, the manufacturing process includes fermenting potatoes, barley, wheat, sweet potatoes, or cassava in place of rice.

"spirit (spirit)" refers to an alcoholic beverage produced by fermentation of starch and subsequent distillation. Starch is typically obtained from a variety of natural sources (e.g., agave, potato, sugar beet, unmalted grain), and spirits typically have an ethanol content of greater than twenty percent. The term includes liquor spirits such as vodka, qin, whiskey, rye, cognac, brandy, bourbon, rum, tequila, and the like.

"wine" refers to an alcoholic beverage produced by fermentation of sugars and starches derived primarily from fruit (e.g., grapes). The alcohol content of wine is typically in the range of nine to sixteen percent. Also included within this term are high wine (strained wine) with higher ethanol content.

Composition comprising a metal oxide and a metal oxide

The compositions of the present invention are beverages and pharmaceutical formulations comprising deuterated alcohols according to formula 1. Typically, the composition comprises between 0.25% and 60.0% by weight of deuterated ethanol.

In the case where the beverage is a pop beverage, it typically includes between 0.25% and 20.0% deuterated ethanol. Oftentimes, the beverage includes between 0.5% and 15.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 15.0%; 2.0% to 15.0%; 3.0% to 15.0%; 4.0% to 15.0%; 4.0% to 14.0%; 4.0% to 13.0%; 4.0% to 12.0%; 4.0% to 11.0%; 4.0% to 10.0%; 4.0% to 9.0%; and 4.0% to 8.0%.

In the case where the beverage is beer, it typically includes between 0.25% and 15.0% deuterated ethanol. Oftentimes, the beverage includes between 0.5% and 12.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 12.0%; 2.0% to 12.0%; 3.0% to 12.0%; 3.0% to 11.0%; 3.0% to 10.0%; 3.0% to 9.0%; 3.0% to 8.0%; 3.0% to 7.0%; and 3.0% to 6.0%.

In the case of the beverage being a wine, it typically comprises between 0.25% and 15.0% deuterated ethanol. Oftentimes, the beverage includes between 0.5% and 12.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 12.0%; 2.0% to 12.0%; 3.0% to 12.0%; 4.0% to 12.0%; 5.0% to 12.0%; 6.0% to 12.0%; 3.0% to 11.0%; 3.0% to 10.0%; 3.0% to 9.0%; 3.0% to 8.0%; 3.0% to 7.0%; and 3.0% to 6.0%.

In case the beverage is a spirit, it typically comprises between 20.0% and 60.0% deuterated ethanol. Oftentimes, the beverage includes between 25.0% and 50.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 20.0% to 50.0%; 20.0% to 45.0%; 20.0% to 40.0%; 20.0% to 35.0%; and 20.0% to 30.0%.

In the case where the beverage is sake, it typically comprises between 0.25% and 20.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 17.5% deuterated ethanol. In certain instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 15.0%; 1.0% to 12.5%; 1.5% to 10.0%; 2.0% to 10.0%; and 2.5% to 10.0%.

In the case of a beverage that is a brewed wine, it typically includes between 0.25% and 35.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 30.0% deuterated ethanol. In certain instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 27.5%; 1.5% to 25.0%; 2.0% to 20.0%; 2.5% to 17.5%; and 2.5% to 15.0%.

In the case where the beverage is white spirit, it typically comprises between 0.25% and 65.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 60.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 55.0%; 1.5% to 50.0%; 2.0% to 45.0%; 2.5% to 40.0%; 3.0% to 35.0%; and 3.5% to 30.0%.

In the case where the beverage is vodka in korea, it typically includes between 0.25% and 55.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 50.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 45.0%; 1.5% to 40.0%; 2.0% to 35.0%; 2.5% to 30.0%; and 3.0% to 25.0%.

In the case where the beverage is a japanese distilled liquor, it typically includes between 0.25% and 35.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 30.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 25.0%; 1.5% to 22.5%; 2.0% to 20.0%; 2.5% to 17.5%; 3.0% to 15.0%; and 3.5% to 12.5%.

In case the beverage is korean shochu, it generally includes between 0.25% and 50.0% of deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 45.0% of the deuterated compound. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 40.0%; 1.5% to 35.0%; 2.0% to 30.0%; 2.5% to 25.0%; and 2.5% to 20.0%.

In the case where the beverage is near sake, it typically includes between 0.25% and 12.0% deuterated ethanol. Oftentimes, the beverage includes between 0.25% and 11.0% deuterated ethanol. In particular instances, the beverage can include deuterated alcohols in any of the following ranges: 1.0% to 10.0%; 1.5% to 9.0%; 2.0% to 8.0%; 2.5% to 7.5%; 3.0% to 7.0%; and 3.5% to 6.0%.

Various beverages include mixtures of non-deuterated alcohols and deuterated alcohols of formula 1, typically in ratios ranging from 1/10 to 10/1. Non-deuterated ethanol can be obtained, for example, from a composition derived from fermentation, brewing and fermentation, and/or fermentation and subsequent distillation.

For example, in the case where the beverage is a pop beverage containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the ratio by weight of the deuterated ethanol to non-deuterated ethanol mixture include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a beer containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a wine containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a spirit containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is sake containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a brewed wine containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a white spirit containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is korean vodka containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a japanese shochu containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is korean shochu containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

In the case where the beverage is a near sake containing deuterated ethanol and non-deuterated ethanol, non-limiting examples of the weight ratio of the mixture of deuterated ethanol and non-deuterated ethanol include: 1/10, respectively; 1/9, respectively; 1/8, respectively; 1/7, respectively; 1/6, respectively; 1/5, respectively; 1/4, respectively; 1/3, respectively; 1/2, respectively; 1/1, respectively; 2/1, respectively; 3/1, respectively; 4/1, respectively; 5/1, respectively; 6/1, respectively; 7/1, respectively; 8/1, respectively; 9/1, respectively; and 10/1.

Examples

By way of illustration, representative examples of various beverages according to the present invention are provided below.

Example 1

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 100 percent.

Percentage of non-deuterated ethanol: 0 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 2

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 90 percent.

Percentage of non-deuterated ethanol: 10 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 3

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 80 percent.

Percentage of non-deuterated ethanol: 20 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 4

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 70 percent.

Percentage of non-deuterated ethanol: 30 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 5

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 60 percent.

Percentage of non-deuterated ethanol: 40 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 6

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 50 percent.

Percentage of non-deuterated ethanol: 50 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 7

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 40 percent.

Percentage of non-deuterated ethanol: 60 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 8

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 30 percent.

Percentage of non-deuterated ethanol: 70 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 9

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 20 percent.

Percentage of non-deuterated ethanol: 80 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 10

Beverage type: a pop beverage.

Total ethanol content (deuterated and non-deuterated alcohols): 4.0% to 8.0%.

Percentage of deuterated ethanol: 10 percent.

Percentage of non-deuterated ethanol: 90 percent.

Other components: water; a sugar; fruit juice and/or soda.

Example 11

The pharmaceutical composition comprises: aromatic Elixir (Aromatic Elixir), united states pharmacopeia.

Total ethanol content (deuterated and non-deuterated alcohols): 22 percent.

Percentage of deuterated ethanol: 90 percent.

Percentage of non-deuterated ethanol: 10 percent.

Other components: water, sugar, orange oil, lemon oil, coriander oil, and anise oil.

By way of example, the following pharmaceutical compositions may be manufactured essentially as currently known in the art, but with the deuterated ethanol of formula 1 replacing 50% to 100% of the total ethanol in the composition:

method of producing a composite material

The present invention provides a method of making an alcoholic beverage. The method comprises the step of adding deuterated ethanol according to formula 1 to an alcoholic beverage, a non-alcoholic beverage, or a beverage low in ethanol in an amount sufficient to produce a beverage comprising water and ethanol as follows: wherein at least 5 mole percent of the ethanol is deuterated ethanol according to formula 1. In another embodiment, deuterated ethanol according to formula 1 is added in an amount sufficient to produce a beverage comprising water and ethanol as follows: wherein at least 15 mole percent of the ethanol is deuterated ethanol according to formula 1. In another embodiment, deuterated ethanol according to formula 1 is added in an amount sufficient to produce a beverage comprising water and ethanol as follows: wherein at least 30 mole percent of the ethanol is deuterated ethanol according to formula 1. In another embodiment, deuterated ethanol according to formula 1 is added in an amount sufficient to produce a beverage comprising water and ethanol as follows: wherein 50 to 100 mole percent of the ethanol is deuterated ethanol according to formula 1.

The invention also provides a method for manufacturing the ethanol pharmaceutical composition. The method comprises the step of adding deuterated ethanol according to formula 1 to the active pharmaceutical ingredient in an amount sufficient to produce a pharmaceutical composition, after all other ingredients have been added: wherein at least 5 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1. In another embodiment, the deuterated ethanol according to formula 1 is added in an amount sufficient to produce a pharmaceutical composition as follows: wherein at least 15 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1. In another embodiment, the deuterated ethanol according to formula 1 is added in an amount sufficient to produce a pharmaceutical composition as follows: wherein at least 30 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1. In another embodiment, the deuterated ethanol according to formula 1 is added in an amount sufficient to produce a pharmaceutical composition as follows: wherein 50 to 100 mole percent of the ethanol in the composition is deuterated ethanol according to formula 1.

Practitioners of the present invention will appreciate that the benefits of increasing the mole fraction of deuterated ethanol will be obtained at correspondingly high costs, and that the beneficial use of the present invention in commercially sold products necessarily results in a tradeoff between benefit and cost.

The beverage according to the invention is generally made by adding one or more deuterated alcohols to the other ingredients. In the example of example 6 above, for example, one can mix together appropriate amounts of fruit juice, water, sugar, and non-deuterated ethanol (e.g., malt liquor or vodka), then add the deuterated ethanol in the correct amount required for the beverage to contain 4% to 8% ethanol and 50% ethanol to be deuterated ethanol.

Beer and wine beverages are generally manufactured by adding a suitable amount of deuterated ethanol of formula 1 to beer or wine having a reduced alcohol content. For example, if a beer is desired with a 6% ethanol content, one would obtain a reduced ethanol content beer (e.g., a 3.2% non-deuterated ethanol containing beer) or a non-ethanol beer, and add deuterated ethanol in an amount such that the total ethanol content (i.e., deuterated ethanol plus non-deuterated ethanol) is 6%.

Spirits with a variety of ethanol contents are available. As with beer and wine, one can make a spirit beverage according to the invention by: deuterated ethanol is added to spirits having less than the desired amount of ethanol-for example, deuterated ethanol is added such that the total ethanol content of the spirits is increased from 20% (non-deuterated) ethanol to 40%.

Sake, brewed wine, white spirit, korean vodka, japanese distilled spirit, korean distilled spirit and "near sake" beverage according to the present invention are preferably manufactured by adding an appropriate amount of deuterated ethanol of formula 1 to ethanol-reduced form beverage. For example, if sake is desired to have 15% ethanol content, one can obtain an ethanol-reduced sake and add deuterated ethanol according to formula 1 in an amount such that the total ethanol content (deuterated ethanol plus non-deuterated ethanol) is 15%. Examples of suitable reduced ethanol sake include, but are not limited to: sparkling sake (sparkling sake) such as POOCHI^TM(Junmai spark Sake, SuehiroSake Brewery (Tohoku, Fukushima), ethanol content 7.5%), TANZAN JAPON^TM(Junmai Sparkling Sake, Tanzan Shuzo (Kinki, Kyoto), ethanol content 8.0%), HANA AWAKA^TM(Junmai Sparkling Sake, Ozeki Corporation (Kinki, Hyogo), ethanol content 7.0%), and SAWASAWAWA^TM(Junmai Sparkling Sake, Choryo (Kinki, Nara), ethanol content 8.0-9.0%).

Methods for making reduced alcohol beers and wines are also well known to those of ordinary skill in the art. Non-alcoholic and "light" beers are particularly well known commercial products. A related description of the production of low-ethanol beer is presented in U.S. patent publication No. 20070116801 and references therein; a description of the production of low ethanol wine is presented in U.S. Pat. No. 4,681,767 and references therein. These patent documents are incorporated by reference in their entirety into this document for all purposes.

Methods for making reduced ethanol sake are also well known to those of ordinary skill in the art. A related description of the production of Low ethanol Sake is presented in "Development of Low Alcohol Sake" Onko Chishin,2004, pages 58-62.

Methods for producing Low ethanol Beverages with general applicability are discussed in U.S. patent No. 4,612,196 ("Preparation of Low Alcohol Beverages by reverse Osmosis"), which is incorporated by reference in its entirety for all purposes.

The present invention provides a method of reducing the severity of hangover in a person being served an alcoholic beverage by a practitioner. The method comprises providing to the person an alcoholic beverage comprising water and ethanol as follows: wherein at least 5 mole percent of the ethanol is deuterated ethanol according to formula 1.

In another embodiment, the present invention provides a method of reducing ethanol-induced facial flushing symptoms in a human being served an ethanol beverage by a practitioner. The method comprises providing to the person an alcoholic beverage comprising water and ethanol as follows: wherein at least 5 mole percent of the ethanol is deuterated ethanol according to formula 1. It is expected that the drinking beverages of the present invention provide a reduction in the consumer's objectionable physical effects associated with acetaldehydemia compared to the effects of drinking an equivalent amount of a beverage in which all of the ethanol in the beverage is non-deuterated ethanol. This is especially true after consumption of such beverages to the extent that they typically cause hangover. Consumption of the beverage of the invention should generally reduce one or more hangover symptoms by at least 3%, as measured by standardized scales in human or animal models. Non-limiting symptoms associated with hangover include dizziness, fatigue, headache, nausea, muscle pain, vomiting, sensitivity to bright light and sensitivity to noise. Animal models associated with such symptoms are described in r.d. prediger et al, "Activation of adenosine A1receptors and metabolism-like stimulation of adenosine ethanol with dry (human) in mice (Activation of adenosine A1receptor reduces anxiety-like behavior in mice during acute abstinence (hangover) —" Neuropsychopharmacology,2006,31(10): 2210-2220; becker, "Animal Models of Alcohol Withdraw. (Animal model for Alcohol Withdrawal)" Alcohol Research & Health,2000,24(2): 105-.

Consumption of the beverage according to the invention reduces one or more hangover symptoms by at least 5%, 7.5% or 10.0%, depending on the relative deuterium content and the total amount of ethanol consumed. In favorable cases, such consumption reduces symptoms by at least 15.0%, 20.0%, or 25.0%.

Consumption of the beverage according to the invention should furthermore reduce one or more symptoms of ethanol flushing by at least 5%, as measured by standardized scales in human or animal models. Non-limiting symptoms associated with ethanol flashes include skin redness, nausea, headache, dizziness, and increased pulse rate. Suitable methods for measuring Flushing are described, for example, in A.K. Kawata et al, "Flushing Assetment tool (FAST): psychological properties of pathological properties of a new measure of assessing Flushing symptoms and Clinical impact of niacin therapy," Clinical Drug Investigation,2009,29(4): 215-.

Depending on the relative deuterium content and total amount of ethanol consumed, and depending on the genotype and phenotype of the individual, consumption of the beverages and pharmaceutical compositions of the present invention may reduce one or more symptoms of ethanol flushing by at least 5.0%, 7.5%, or 10.0%. In favorable cases, such consumption reduces symptoms by at least 15.0%, 20.0%, or 25.0%.

The compositions of the present invention provide a novel method of marketing ethanol-containing beverages. In one method, a beverage is communicated to a consumer that includes a particular amount of ethanol. Also communicating to the consumer that ethanol in the beverage will provide less of an objectionable physical impact than a typical beverage that includes a specific amount of ethanol. The beverage comprises water and at least 1.0% deuterated ethanol according to formula 1.

The target consumer of the present method may be a person who wishes to reduce the harmful side effects of hangover; may be a person with an abnormality in an enzyme associated with alcohol metabolism; or may be a person focusing on different aspects of the ethanol-containing beverage. The compositions sold according to the present methods include any of the compositions encompassed by this document.

Experiment of

The subject was a 52 year old white man, 154kg, with no known abnormalities in ethanol metabolism. Experiments were performed after overnight fasting. 1, 1-dideuteroethanol, 99 atomic% D (CDN Isotops; Quebec, Canada) (70mL) was diluted to 500mL with orange juice and the resulting beverage was consumed by the subject over a five minute process. Rinse the mouth and palate with orange juice and then use a commercial breath analyzer (AlcoHAWK) every 10 minutes^TMPro, Q3 Innovations inc., independency, Iowa, u.s.a.) were repeated three times to obtain data points. A control experiment used 175mL of commercial vodka (80 strength standard (proof); 40% ethanol), but was otherwise identical.

Fig. 1 presents the measured blood level as a function of time. Each data point in the graph is the average of three measurements taken at each time point. The substantially equal areas under the curve indicate that the analyzer is equally sensitive to normal ethanol and deuterated ethanol.

The results from the control experiments were qualitatively similar to those reported by previous workers (see, e.g., Milne et al, am. J. Clin. Nutr.,1987,46: 688-693). However, as is evident from fig. 1, the absorption of deuterated ethanol is greatly retarded and the clearance rate is reduced relative to ethanol having a natural isotopic abundance.

Many modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.

Claims (47)

1. An ethanol beverage comprising water and ethanol, wherein at least 5 mole percent of the ethanol is deuterated ethanol having the formula

Wherein each H independently can be hydrogen or deuterium and the beverage is suitable for human consumption.

2. The ethanol beverage of claim 1, wherein at least 5 mole percent of the ethanol is deuterated ethanol having the formula

3. The ethanol beverage of claim 1, wherein at least 5 mole percent of the ethanol is deuterated ethanol having the formula

4. The ethanol beverage of claim 1, wherein at least 5 mole percent of the ethanol is deuterated ethanol having the formula

5. The ethanol beverage of claim 1, wherein at least 5 mole percent of the ethanol is of the formula CD₃CD₂Deuterated ethanol of OH.

6. The ethanol beverage of claim 1, wherein at least 15 mole percent of ethanol is the deuterated ethanol.

7. The ethanol beverage of claim 6, wherein at least 30 mole percent of ethanol is the deuterated ethanol.

8. The ethanol beverage of claim 7, wherein at least 50 mole percent of ethanol is the deuterated ethanol.

9. The ethanol beverage of claim 8, wherein at least 75 mole percent of ethanol is the deuterated ethanol.

10. The ethanol beverage of claim 9, wherein at least 95 mole percent of ethanol is the deuterated ethanol.

11. A method of making an alcoholic beverage as claimed in claim 1, the method comprising the step of adding to the beverage a deuterated alcohol having the formula

Wherein each H may independently be hydrogen or deuterium.

12. The method of claim 11, wherein the deuterated ethanol has the formula

13. The method of claim 11, wherein the deuterated ethanol has the formula

14. The method of claim 11, wherein the deuterated ethanol has the formula

15. The method of claim 11, wherein the deuterated ethanol has the formula CD₃CD₂OH。

16. A pharmaceutical composition comprising an active pharmaceutical ingredient and ethanol, wherein at least 5 mole percent of the ethanol is deuterated ethanol having the formula

Wherein each H may independently be hydrogen or deuterium.

17. The pharmaceutical composition of claim 16, wherein at least 5 mole percent of ethanol is deuterated ethanol having the formula

18. The pharmaceutical composition of claim 16, wherein at least 5 mole percent of ethanol is deuterated ethanol having the formula

19. The pharmaceutical composition of claim 16, wherein at least 5 mole percent of ethanol is deuterated ethanol having the formula

20. The pharmaceutical composition of claim 16, wherein at least 5 mole percent of the ethanol is of the formula CD₃CD₂Deuterated ethanol of OH.

21. The pharmaceutical composition of claim 16, wherein at least 15 mole percent of ethanol is the deuterated ethanol.

22. The pharmaceutical composition of claim 21, wherein at least 30 mole percent of ethanol is the deuterated ethanol.

23. The pharmaceutical composition of claim 22, wherein at least 50 mole percent of ethanol is the deuterated ethanol.

24. The pharmaceutical composition of claim 23, wherein at least 75 mole percent of the ethanol is the deuterated ethanol.

25. The pharmaceutical composition of claim 24, wherein at least 95 mole percent of ethanol is the deuterated ethanol.

26. A method of making the pharmaceutical composition of claim 16, the method comprising the step of combining an active pharmaceutical ingredient with a deuterated ethanol having the formula in an amount sufficient to produce a composition wherein at least 5 mole percent of the ethanol in the composition is the deuterated ethanol

Wherein each H may independently be hydrogen or deuterium.

27. The method of claim 26, wherein the deuterated ethanol has the formula

28. The method of claim 26, wherein the deuterated ethanol has the formula

29. The method of claim 26, wherein the deuterated ethanol has the formula

30. The method of claim 26, wherein the deuterated ethanol has the formula CD₃CD₂OH。

31. The ethanol beverage of claim 1, wherein 0.25 to 60% by weight of the ethanol beverage is deuterated ethanol.

32. The alcoholic beverage of claim 31, further comprising: additional components suitable for said alcoholic beverage.

33. The alcoholic beverage of claim 31, further comprising: a sweetener.

34. The alcoholic beverage of claim 31, further comprising: a flavoring agent.

35. The alcoholic beverage of claim 31, further comprising: and (3) a perfume.

36. The alcoholic beverage of claim 31, further comprising: the same class of substances derived from the brewing or fermented composition from which the beverage is produced.

37. The ethanol beverage of claim 1, wherein 1% to 40% by weight of the ethanol beverage is ethanol.

38. The alcoholic beverage of claim 37, further comprising: additional components suitable for said alcoholic beverage.

39. The alcoholic beverage of claim 37, further comprising: a sweetener.

40. The alcoholic beverage of claim 37, further comprising: a flavoring agent.

41. The alcoholic beverage of claim 37, further comprising: and (3) a perfume.

42. The alcoholic beverage of claim 37, further comprising: the same class of substances derived from the brewing or fermented composition from which the beverage is produced.

43. The alcoholic beverage of claim 1, further comprising: additional components suitable for said alcoholic beverage.

44. The alcoholic beverage of claim 1, further comprising: a sweetener.

45. The alcoholic beverage of claim 1, further comprising: a flavoring agent.

46. The alcoholic beverage of claim 1, further comprising: and (3) a perfume.

47. The alcoholic beverage of claim 1, further comprising: the same class of substances derived from the brewing or fermented composition from which the beverage is produced.