WO1995017199A1

WO1995017199A1 - Novel therapeutic carbohydrate blends useful for aiding sleep disorders

Info

Publication number: WO1995017199A1
Application number: PCT/US1994/014734
Authority: WO
Inventors: Judith J. Wurtman; Jeff L. Shear; Alvin Kershman
Original assignee: Walden Laboratories, Inc.
Priority date: 1993-12-22
Filing date: 1994-12-21
Publication date: 1995-06-29

Abstract

Novel therapeutic compositions comprising carbohydrate blends, processes for preparing such carbohydrate blends and methods of using the foregoing for general use as a sleep aid and relaxant and for assistance with sleep difficulties and disorders.

Description

NOVEL THERAPEUTIC CARBOHYDRATE BLENDS USEFUL FOR AIDING SLEEP DISORDERS

FIELD OF THE INVENTION The present invention generally relates to novel therapeutic compositions comprising carbohydrate blends, to processes for preparing such carbohydrate blends and to methods of using the foregoing for general use as a sleep aid and relaxant and for assistance with sleep difficulties and disorders.

BACKGROUND OF THE INVENTION Difficulty in falling asleep is a problem that afflicts some 70 million Americans. Such difficulties range from simply taking a while to fall asleep due to temporary lack of drowsiness or inability to relax, to more serious problems such as chronic insomnia. While many ideas exist as to what can help with this problem, effective solutions have been lacking.

There are numerous pharmaceuticals for sleep problems, both prescription and non-prescription. Examples of over-the-counter products such as Sominex (Diphenylhydramine) , Unisom (Diphenylhydramine) , Nytol (Diphenylhydramine) , and other brands. Examples of prescription drugs include Doral (Quazepam) , Prosom (Estazolam) , and Halcion (Triazolam) . However, these products may be of limited effectiveness or have side effect problems.

Often, therefore, sufferers of sleep problems will use natural remedies such as dietary supplements and other herbal products, including teas, or such common solutions as warm milk. Unfortunately, these natural solutions are limited in effectiveness or have never been clinically proven as effective. 1 In 1989, a large number of Americans began using supplements of the amino acid L-tryptophan as a sleep aid. This was the result of clinical studies indicating that increasing the amount of tryptophan in the blood relative to other large neutral amino acids (T:LNAA) induced sleep. Unfortunately, contaminants in one batch of imported tryptophan led to a number of deaths and permanent serious medical conditions of the central nervous system. As a result, L-tryptophan supplements are no longer sold in the U.S.

The invention is related to a carbohydrate blend that aids in relaxation and drowsiness, using the body's natural digestive process. Unlike pharmaceuticals, it does so without side effects or risk of dependency, and unlike natural remedies is proven effective in clinical tests.

SUMMARY OF THE INVENTION The present invention is directed generally to novel therapeutic compositions comprising carbohydrate blends, to methods of using same for the general use as a sleep aid and relaxant and for assistance with sleep difficulties and disorders, and to processes for preparing said carbohydrate blends.

Specifically, in one embodiment, the present invention is directed to therapeutic compositions comprising novel blends of carbohydrates, such as but not limited to dextrose, galactose, and mixtures thereof. Preferably, said therapeutic compositions include carbohydrate blends comprising novel mixtures of dextrose and galactose, in ratios of about 10:1 to 1:1 respectively. Still more preferred are compositions comprising carbohydrate blends of dextrose and galactose in ratios of about 6:1 to 1:1. Specifically preferred is a composition comprising a carbohydrate blend of dextrose and galactose in a ratio of about 5:1.

Preferably, said carbohydrate blends are in the form of a solution comprising dextrose, galactose and water. More preferably, the solution comprises about 5 mL of water to 1 gram of carbohydrate. More preferably, the solution further comprises an acidulant to maintain a therapeutically effective pH. Such acidulants include but are not limited to adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid. Preferred are solutions with a pH of less than 5. Most preferred is a solution comprising 60g total carbohydrate comprised of 50g dextrose and lOg galactose, 280 mL water and malic acid to maintain the solution at a pH of 2. Another embodiment of the invention is directed to methods of using said therapeutic compositions, effective as inducers of drowsiness for the general use as a sleep aid and relaxant and for assistance with sleep difficulties and disorders comprising administering such novel compositions to subjects in need of said treatment. A further embodiment of the invention is a process for the production of novel carbohydrate blends for use in said therapeutic composition. Said process comprises the steps of hydrolysing lactose, crystallizing the products, drying the products and adjusting the ratio of dextrose to galactose by adding anhydrous dextrose. More preferred is the process wherein the hydrolysing step comprises acid or lactase enzymatic hydrolysis. Also more preferred is the process wherein the crystallization step comprises selectively and separately crystallizing the products dextrose and galactose or crystallizing both dextrose and galactose together.

These and other aspects of the invention will become more apparent from the following detailed description.

DETAILED DESCRIPTION OF THE INVENTION

SUBSTITUTE SHffi (RULE 26) The present invention is generally directed to pharmaceutical compositions comprising a carbohydrate blend, preferably in the form of a solution, for general use as a sleep aid and relaxant and for assistance with sleep difficulties and disorders. The phrase "carbohydrate blend", as used herein and in the claims, refers to a mixture of carbohydrates including but not limited to dextrose, galactose, and mixtures thereof. In a preferred embodiment of the invention, the carbohydrate blend is dextrose and galactose in ratios of 10:1 to 1:1. More preferably the ratio of dextrose to galactose is from about 6:1 to 1:1. Specifically preferred is the ratio 5:1 dextrose to galactose. The choice of a particular ratio will depend upon several factors such as the weight of the individual, the rate of effect the carbohydrates have on the subject and the nature of the sleep disorder or the manner in which the carbohydrate blend is used. The term "solution" as used herein and in the claims, refers to mixtures of carbohydrate blends of dextrose and galactose in water. The term "water", as used herein, includes distilled, deionized or tap water. The term "dextrose" as used herein and in the claims reflects to glucose or polymers thereof. Preferred is a solution further comprising an acidulant to maintain a therapeutically effective pH. The term "acidulant" as used herein, includes acids which can maintain the pH of the solution at less than 5. Such acids include but are not limited to adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid. Preferred is the acidulant malic acid. The phrase "therapeutically effective" as used herein and in the claims refers to that amount of carbohydrate blend necessary to administer to a subject to induce the desired effect of drowsiness. The therapeutic compositions of this invention can be administered as general use as a sleep aid and relaxant and for assistance with sleep -difficulties and disorders by any means that produces contact of the active agent with the agent's site of action in the body of a mammal. They can be administered by any conventional means available for use in conjunction with therapeutic agents. They can be administered alone, but generally administered with a carrier selected on the basis of the chosen route of administration and standard therapeutic practice.

The dosage administered will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired. Dosage forms (compositions suitable for administration) contain from about 20g - lOOg of active ingredient per unit. In these therapeutic compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.

The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, and powders if taken together with a suitable amount of water, or in liquid dosage forms, such as elixirs, syrups, and suspensions. It can also be administered parenterally, in sterile liquid dosage forms.

Gelatin capsules contain the active ingredient and other powdered carriers, such as cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

Various colorings and flavorings can be employed in any dosage form to improve the taste of the therapeutic composition to increase patient acceptance, and to make it more palatable. Such flavorings can include but are not limited to artificial or real: chocolate, vanilla, strawberry, coffee, banana, orange, etc. In general, water, a suitable oil, saline, and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a suitable stabilizing agents, and if necessary, buffer substances. Anti-oxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. Suitable carriers are described in Remington's Pharmaceutical Sciences. Mack Publishing Company, a standard reference text in this field.

Further, the therapeutic compositions can also be prepared in the form of a food-stuff. Such forms include, but are not limited to: a cold or hot liquid or powdered beverage, soup, pudding, wafer, a snack bar, cookies, cakes, breakfast cereal form, frozen hard or soft dessert format, fruit roll-up, gummy confection, pasta form, chewable tablets, solid food or confection bars, or other snack, etc.

Another embodiment is the process for the preparation of carbohydrate blends comprising dextrose and galactose. Lactose is comprised of 50% dextrose and 50% galactose. In order to obtain a pure form of either of the carbohydrates, lactose must be broken down into its integral parts. Currently, galactose is only available when lactose is digested. In addition to the monosaccharide derived from the digested disaccharide lactose, there is also protein and fats which may interfere with the ability of galactose and dextrose to induce drowsiness or function as a night time sleep aid. Therefore, it is preferred that specific methods be employed to obtain the monosaccharide in the purest form available.

The present invention is further described in the following examples. These examples are not to be construed as limiting the scope of the appended claims.

EXAMPLE 1 Lactose was acid hydrolyzed and in a selective crystallization process galactose was crystallized separate from dextrose and dried. Dry galactose was then mixed with dry anhydrous dextrose in the proper proportion with additional flavors and acidulant.

EXAMPLE 2 Lactose was acid hydrolyzed into dextrose and galactose with both sugars crystallized out together. The mix was then dried, resulting in a 50/50 blend of dextrose to galactose. To the 50/50 blend was added additional dextrose to meet the appropriate ratio required when rehydrated for consumption plus flavor and acidulants.

EXAMPLE 3 Lactose in solution was treated with the enzyme lactase, which resulted in the hydrolysis of lactose into dextrose and galactose. The mixture was then dried, forming crystals of galactose and dextrose at a ratio of 50/50, or the material was concentrated. crystallized and then dried. The 50/50 blend was then mixed with additional dextrose and acidulants so that when rehydrated, will result in the proper ratio for treatment. Another reason for following the prescribed methods set out in Examples 1-3 above is that many individuals cannot digest lactose. Therefore, it is necessary to provide galactose and dextrose already in solution and without the presence of other interfering factors such as protein and fat. In this preferred embodiment, the benefit of sleep inducement is optimized.

EXAMPLE 4 In a controlled double-blind study with 8 subjects, all subjects fell asleep after taking the product, while none fell asleep after taking control products or placebo. None of the subjects knew that the product could help them sleep. A composition was made containing 50g dextrose, lOg galactose, 280 mL water, and sufficient malic acid to maintain the pH of the solution pH of 2.

A composition of the present invention was administered to subjects each week for a period of four weeks. All subjects receiving said composition of the present invention fell into a deep sleep, whereas control compositions had no effect. The results show that compositions comprising a carbohydrate blend of the present invention are effective at inducing drowsiness, thereby are useful as therapeutic agents to aid in sleep disorders.

Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. The foregoing disclosure includes all of the information deemed necessary to enable those skilled in the art to practice the claimed invention. Because the cited references may provide further useful information these cited materials are hereby incorporated by reference in their entirety.

Claims

What is claimed is:

1. A composition for use in aiding sleep disorders comprising about 20-100g of a carbohydrate blend of dextrose and galactose in a solution, wherein the solution comprises a ratio of about 5 mL of water to about lg carbohydrate blend, that when administered to a subject will induce drowsiness.

2. A composition of claim 1, wherein the carbohydrate blend comprises a ratio of dextrose to galactose between about 10:1 to 1:1.

3. A composition of claim 2, wherein the carbohydrate blend comprises a ratio of dextrose to galactose between about 6:1 to 1:1.

4. A composition of claim 3, wherein the carbohydrate blend comprises a ratio of dextrose to galactose of about 5:1.

5. A composition of claim 1, wherein the solution further comprises an acidulant selected from the group: adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid to maintain a therapeutically effective pH.

6. A composition of claim 5, wherein the acidulant is malic acid.

7. A composition of claim 5, wherein the pH less than 5.

8. A composition of claim 7, wherein the pH is about 2.

9. The composition of claim 5 comprised of about 50g dextrose, about lOg galactose, about 280 mL water and malic acid to maintain the pH at about 2.

10. A method for aiding sleep disorders which comprises administering to a subject in need of such treatment a therapeutically effective amount of a composition comprising about 20-100g of a carbohydrate blend of dextrose and galactose in a solution, wherein - li ¬

the solution comprises a ratio of about 5 mL water to about lg carbohydrate blend.

11. A method of claim 10, wherein the carbohydrate blend comprises a ratio of dextrose to galactose between about 10:1 to 1:1.

12. A method of claim 11, wherein the carbohydrate blend comprises a ratio of dextrose to galactose between about 6:1 to 1:1.

13. A method of claim 12, wherein the carbohydrate blend comprises a ratio of dextrose to galactose of about 5:1.

14. A method of claim 10, wherein the solution further comprises an acidulant selected from the group: adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid to maintain a therapeutically effective pH.

15. A method of claim 14, wherein the acidulant is malic acid.

16. A method of claim 14, wherein the pH is less than 5.

17. A method of claim 16, wherein the pH is about 2.

18. The method of claim 14 wherein the composition is comprised of about 50g dextrose, about lOg galactose, about 280 mL water, and malic acid to maintain the pH at about 2.

19. A process for the preparation of a carbohydrate blend of dextrose and galactose comprising the steps of hydrolysing lactose, crystallizing the products, drying the products and adjusting the ratio of dextrose to galactose by adding anhydrous dextrose.

20. The process of claim 19 wherein the crystallization step further comprises selectively crystallizing the products, and obtaining separately crystallized galactose.

21. The process of claim 19 wherein the crystallization step further comprises crystallizing both dextrose and galactose together resulting in a 50/50 blend of dextrose and galactose.

22. The process of claim 19, wherein the hydrolysis step further comprises treatment of lactose by the enzyme lactase resulting in the hydrolysis of lactose into dextrose and galactose.

23. The process of claim 19, wherein the hydrolysis step further comprises acid hydrolysis.