GB2184352A - Compositions containing fructose - Google Patents

Abstract

Use of fructose as a sweetener e.g. in cough/cold preparations alleviates problems associated with diabetics' use of these types of preparations.

Description

SPECIFICATION Sucrose-free formulations The relief of cold symptoms in diabetic patients can present several unique problems. Many of these patients have adverse reactions to the sugar and/or antihistamines used in conventional preparations. In addition, when diabetics are ill, they often experience one or more symptoms of hyperglycemia.

These and other related problems have underscored the need for "sugar-free" or "sucrosefree" preparations which could be consumed by diabetics for the relief of various symptoms, and in particular those associated with coughs and colds.

It has been discovered that fructose, or fruit sugar, a naturally occurring sweetening agent, can be substituted for all other conventionally used sweeteners in cold preparations.

The invention relates to medicaments containing fructose as a principal or sole sweetener.

Thus it is directed to compositions which consist essentially of a pharmaceutically active ingredient and fructose. Furthermore, it relates to a process for minimizing the glycemic response to cough/cold formulations by employing fructose as a sweetener therein.

Fructose, or fruit sugar, is a naturally occurring substance. It is commercially available and is readily obtained via the enzymatic conversion of sucrose.

Depending upon the conditions under which it is used, it can be as sweet or sweeter than sucrose. Generally, it has been found to be sweeter than sucrose when cold or under acidic conditions, e.g., in acidic solutions.

In a controlled diabetic, fructose can have the sweetness of sucrose, but does not produce the rise in blood sugar that sucrose or glucose would produce. In a poorly controlled diabetic, fructose can elicit a significant rise in blood sugar levels because of its rapid conversion to free glucose in the liver.

The term "controlled" diabetic means a diabetic whose blood glucose levels are maintained under 180-200 mg/dl through diet, exercise, medication and self-monitoring. Note that a poorly controlled diabetic cannot be equated with one who is ill with hyperglycemia. A poorly controlled diabetic would, in fact, have hyperglycemic symptoms for a prolonged period of time and would experience other complications.

The value of fructose as a component of a sweetener for a medicament or pharmaceutical preparation for diabetics appears to stem from the way in which it is metabolized. Apparently, fructose does not depend upon insulin for its initial metabolism. Furthermore, there tends to be less of an insulin secretory response to fructose than the responses typically evoked by sucrose or glucose. It follows, then, that fructose can be metabolized by patients who have difficulty metabolizing glucose due to impaired insulin secretions.

Fructose-containing formulations compare favorably with other "sugar-free" preparations on the market. Substances such as saccharin, sugar alcohols, corn syrup, and glycerin are conventionally used. For the most part, these offer no advantages over fructose. Corn syrup, technically a glucose syrup, has no place in the diabetic diet. While there are some high fructose corn syrups, they generally contain a large enough percentage of glucose to render them useless.

Saccharin, a non-caloric artificial sweetener, has been on the market but has suspected carcinogenicity. It is 375 times as sweet as sucrose but has a metallic aftertaste.

The sugar alcohols such as sorbitol, mannitol and xylitol are absorbed at a slower rate than glucose. Their ingestion results in a small post-meal rise in blood glucose but a delayed hyperglycemic response if the patient has an insulin lack. These sugar alcohols are also suspected of causing many of the diabetic's complications, such as retinopathy, by creating osmotic abnormalities in cells.

Their side effects are also a drawback. Mannitol and sorbitol can cause gas and bloating with ingestion of as little as 10 grams and diarrhea with 20 grams. Xylitol usage has been limited since it was linked to the development of tumors.

Aspartame, a synthetic sweetener composed of the amino acids L-aspartic acid and L-phenylalanine, is unstabie at high temperatures and in solution. The solution instability depends upon temperature and acidity. These problems would result in a product with a very short shelf life. In addition, aspartame is suspected of causing lesions in the hypothalamus.

When used in accordance with the invention, fructose will generally be present in pharmaceutical preparations in amounts suitabie to produce good tasting formulations which can be ingested by diabetics with minimal, if any, unpleasant side effects.

Suitable quantities of fructose to be employed in medicaments, such as cough and/or cold preparations will range from about 30 to about 60 w/v%, preferably about 45 to about 55 w/v%, based on total composition weight. It is preferred that fructose be the only sweetener present in the preparation.

The medicaments or therapeutic formulations in which the sweetener of the invention is employed are generally conventional pharmaceutical preparations, preferably preparations to alle viate cough and/or cold symptoms.

Typically cough/cold remedies contain one or more ingredients which mediate the body's natural reactions to the common cold, to allergens, or to other cough-promoting conditions.

These reactions include coughing, sneezing, headache, and the like.

The active ingredients in such preparations are generally antihistamines, cough suppressants, anti-allergens, antitussives, expectorants, decongestants, and the like. Typical expectorants include guaifenesin, terpin hydrate, and ammonium chloride. Guaifenesin is preferred. Mixtures of active ingredients are operable.

While emphasis has been placed on cough and cold preparations, it should be kept in mind that, in general, any pharmaceutically- or phsiologically- active substance can be combined with the sweetener of this invention. It should be appreciated that the invention is also useful in formulations such as vitamin preparations, laxatives, etc. In short, any medicinally active substance which can be combined with a fructose-containing sweetener can be employed in the preparations of the invention.

Furthermore, while diabetics are particularly troubled with the conditions set out hereinbefore, it should be recognized that fructose-sweetened preparations are useful-in the administration of preparations to other individuals as well, particularly when medical considerations dictate such administration.

When carriers are employed such as liquid and/or solid vehicles for administration of the subject compositions, they are generally present in pharmaceutically acceptable quantities. Such quantities can vary greatly. For purposes of illustration, from which the skilled artisan can extrapolate, it is suggested that pharmaceutically acceptable carriers be present in the preparations of the invention in quantities ranging from about 35 w/v% to about 65 w/v%, based in total composition weight. Water-containing carriers are preferred.

It is preferred that the formulations of the invention to be administered in liquid form. However, solid dosage forms, e.g., lozenges or cough drops, have been contemplated.

Optionally, formulations produced in accordance with the invention can contain minor amounts of various conventional additives. Preservatives, e.g., sodium benzoate and the like may be present in amounts of up to about 2 w/v%.

EXAMPLES Example I A prototype formulation was prepared using a cough/cold formulation, but replacing all its sweetening agents with fructose syrup.

This formulation is administered in 2 teaspoon dosages every 4 hours.

Table I Actives/ Actives/ fructose fructose Ingredient Per 100 ml per 5 ml per dose Guaifenesin 1.000 g 0.05 g 100 mg Diphenhy dramine HCI 0.225 g 0.01275 g 25.5 mg Glycerin, USP 6.25 ml Sodium Citrate 1.000 g Citric Acid 0.200 g Fructose, USP crystalline 50 g 2.5 g 5 g Purified Water qs. to 100 ml Example II Another formulation which has been prepared and used with comparable results is shown in Table II.

Table II Guaifenesin 1.000 g Diphenhydramine, USP 0.255 g Glycerin, USP 6.250 ml Sodium Citrate, Hydrous USP 1.000 g Citric Acid, Anhydrous USP 0.200 g Fructose, powdered (2% silicon dioxide) 50.000 g Sodium Carboxymethylcellulose 1.200 g Menthol, USP 0.010 9 Purified Water, USP qs. to 100 ml Examples Ill-IV. Other formulations contemplated are given in Tables Ill, IV, and V.

Table 111 Guaifenesin 1.000 g Diphenhydramine HCl 0.225 g Glycerin, USP 7.000 ml Sodium Citrate, Hydrous USP 1.000 g Citric Acid, Anhydrous USP 0.200 g Fructose, USP crystalline 50.000 g Purified Water, USP qs. to 100 ml Table IV Terpin Hydrate 0.625 g Diphenhydramine, USP 0.255 g Glycerin, USP 6.000 ml Sodium Citrate, Hydrous USP 1.000 ml Citric Acid, Anhydrous USP 0.200 g Fructose, USP crystalline 45.000 g Purified Water, USP qs. to 100 ml Table V Ammonium Chloride USP 2.500 g Diphenhydramine HCI 0.255 g Glycerin, USP 8.000 ml Sodium Citrate, Hydrous USP 1.000 ml Citric Acid, Anhydrous USP 0.200 g Fructose, USP crystalline 45.000 g Purified Water, USP qs. to 100 ml Reasonable variations, such as those which would occur to a skilled artisan, can be made herein without departing from the scope of the invention.

Claims (12)

1. A composition consisting essentially of a pharmaceutically active ingredient and fructose.

2. The composition of claim 1 wherein the active ingredient assists in the suppression of symptoms due to colds.

3. The composition of claim 2 wherein the composition contains a cough suppressant.

4. The composition of claim 3 containing from about 30 to about 60 weight percent fructose.

5. The composition of claim 4 in combination with at least one pharmaceutically acceptable carrier.

6. A process for suppressing the insulin response of diabetic patients to a pharmaceutical preparation comprising use of fructose in the sweetener for the preparation.

7. The process of claim 6 comprising using from about 30 to about 60 weight percent fructose in the preparation.

8. The process of claim 7 wherein fructose is the only sweetener for the preparation.

9. The process of claim 6 wherein fructose is the only sweetener for the preparation.

10. A composition comprising a pharmaceutically active agent and fructose.

11. A composition comprising fructose and a pharmaceutically active agent and being- free of sucrose.

12. A composition substantially as hereinbefore described with reference to the accompanying examples.

12. For use in a method of treating colds, a composition comprising a pharmaceutically active agent and fructose.

13. A composition substantially as hereinbefore described with reference to the accompanying examples.

CLAIMS Amendments to the claims have been filed, and have the following effect: New claims have been filed as follows: New claims 1-12 inclusive filed on 15 April 1986 supersede Claims 1-13 inclusive originally filed.

1. A composition consisting essentially of a cough suppressant and fructose.

2. The composition of claim 1 containing from about 30 to about 60 weight percent fructose.

3. The composition of claim 1 or 2 in combination with at least one pharmaceutically acceptable carrier.

4. A composition according to claim 1, 2 or 3, in liquid form.

5. A process for suppressing the insulin response to diabetic patients to a pharmaceutical preparation comprising use of fructose for the sweetener in the preparation.

6. The process of claim 5 comprising using from about 30 to 60 weight percent fructose in the preparation.

7. The process of claim 5 or 6, wherein fructose is the only sweetener for the preparation.

8. For use in the suppression of insulin response to a pharmaceutical preparation by a diabetic patent, fructose as the sweetener for said preparation.

9. A composition comprising a cough suppressant and fructose.

10. A composition comprising fructose and a cough suppressant and being free of sucrose.

11. For use in a method of treating colds, a composition comprising a cough suppressant and fructose.