CA1238577A - Weight control drug - Google Patents

Abstract

Abstract Of The Disclosure There is disclosed a method for the treatment of a host animal, including man, to prevent or reduce the ability of the host animal to metabolize D-sugars as a means for weight control. The method comprises periodic-ally administering to the host animal an amount of a non-metabolizable L-sugar sufficient to block at least a portion of the receptor sites on the enzymes which are responsible for metabolizing D-sugars.

Description

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WEIGHT CONTROL COMPOSITION
This invention relates to a method for the treatment of a host animal, including man, to prevent or reduce the ability of the host animal to metabolize D-5 sugars thereby permitting control of its weigh-t, by the use of a weight control composition.
U.S. Patent No. 4,262,032 to Levin discloses non-fattening sweeteners based on the use of certain L-hexose monosaccharides in food stuffs and beverages.
Such usage depends on a one to one substitution of an h-hexose for its counterpart normal sugar, the two isomers bein~ of equal sweetness and bulk. The invention replaces caloric sugar with non-caloric sugar for its desired effect. The denial of calories is no greater than the amount of available calories replaced by ~he L-hexose. Disadvantages of this method are (1) a laxa-tive effect imposes limits on the daily per capita consumption of L-sugars; (2) the exposure of users to potential health hazards of consuming relatively large quantities of L-sugars; t3) the high cost of L-sugars also militates against their high-dose usage such as would be required in soft drinks or baked goods.
An article entitled "Metabolism of L-Sorbose in the Rat and the Effect of the Intestinal Microflora on its Utilization both in the Rat and in the Human" by Wursch et al in Nutritlon and Metabolism, Volume 23, No.
3, pp. 145-155 (1979) discloses that when L-sorbose is administered orally to rats it is not initially metabo-lized. However, within a matter of days, the L-sorbose, a naturally occurring L-sugar, is metabolized. Wursch et al found the same delayed and adapted metabolism occurs when L-sorbose is administered to human intestinal flora.
Thus, any attempt to utilize this phenomenon as a method for weight control would become ineffectual for the individual within a matter of several days. In "The Effects of a Sorbose-Sucrose Diet on Experimental Caries and Body Weight Gains", H.R. Muhlemann tZahnheilk. 860 1339-1345, 1976) reported that L-sorbose depressed the ~l~3~35

- 2 -body weight gain of rats. However, large amounts of L-sorbose had to be given to achieve the effect. This is consistent with the Wursch et al findings that 70-75% of the L-sorbose is metabolized by adapted animals and microorganisms. The adaptability of host animals and their intestinal flora again makes it impractical to use this method for body weight control.
T~le present invention is based upon the surpri-sing discovery that non-metabolizable L-sugars can be used as weight control agents. Accordingly, the present inven-tion provides a weight control composition comprising a non-metabolizable L-sugar.
The present invention also includes a method for the treatment of a host animal, including man, to prevent or reduce the ability of the host animal to metabolize D-sugars. It is based on three innovations: ~l) the use of non-naturally occurring L-sugars which, as taught by Levin in U.5. Patent No. 4,262,032, are non-metaboliz-able; (2) the utilization of temporal binding by L-sugars 20 4f natural sugar enzyme sites in host animals and intes-tinal flora to preclude binding absorption of natural sugars; and (3) constraining the administration of L-sugars to small amounts over protracted periods (with respect to the displacement o intestinal microflora) to preclude or minimize to relative insignificance the adaptation, if any, of the flora to the unnatural L-sugars without which adaptation the host animal cannot assimilate the L-sugars.
The method comprises periodically administering to the host animal an amount of a non-metabolizable L-sugar sufficient to block at least a portion of the receptor sites on the enzymes which are responsible for metabolizing D-sugars. Far leqs quantities of L-sugar are required than in the practice of V.S. Patent No.
4,262,032 to prevent uptake of larger amounts of normal sugars. Continuous administration of large quantities of non-met,abolizable materials such as L-sugars produces a laxative effect, an effect which is avoided by he " ~23~577

- 3/4 -practice of this invention. Further, since the L-sugars are non-metabolizable, they are unlike L-sorbose describ-ed by Wursch et al, which is slowly metabolized and, hence, does not block the en2ymes which are responsible for metabolizing D-sugars long enough to be effective.
Any non-metabolizable L-sugar may be used in accordance with this invention such as the L-hexose monosaccharides disclosed in U.S. Patent No. 4,262,032, i.e., L-glucose, L-allose, L-fructo~e, L-gulose, L-galac-tose, L-altrose, L-idose, L-talose, L-tagatose and L-psicose. Other L-sugars which may be used include aldoses: L-mannose, L-ribose, L-xylose, L-lyxose, L-erythrose and L-threose; deoxyaldoses, e.g., L-rhamnose and L-fucose; and ketoses: L-altroheptulose, L-manno-heptulose, L-ribulose, L-xylulose and L-erythrulose.
In accordance with this invention, a small amount of L-sugar, typically from about 1 to 30 mg per kg of body weight per day, or about 100 to 3000 mg/220 lb.
person, is taken periodically, regularly or irregularly, as a pill, in solution or in any other suitable form or preparation for oral ingestion. The L-sugar may be used alone or along with common pharmaceutically acceptable additives, i.e., with an inert diluent or with an as-similable edible carrier. The orally ingestable prepara-tion of L-sugar may also contain the following: a binder such as gum tragacanth, acacia, corn starch or gelatin; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and/or a flavoring agent such as peppermint, oil of wintergreen or cherry flavoring. When the dosaye unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier. Various other materials may be present as coatings or to other-wise modify the physical form of the dosage unit. Of course, any material used in preparing any dosage unit form of the L-sugar should be pharmaceutically pure and substalntially non-toxic in the amounts employed. In addition, the L-sugar may be incorporated into sustained-release preparations and formulations.

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~23~ 7 The period of use and dosa~e are determined experimentally. This will allow the user to consume otherwise ~attening food stuffs containing D-sugars with the effect of rejectiny all, or a substantial portion, of the caloric sugars thus preventing weight gain or other undesirable effects associated with the metabolism of D-sugars. The enzymes which metaholize D-sugars initial-ly accept the corresponding L-sugars which, not being metabolizable, remain fixed on enzyme receptor sites.
This constitutes competitive inhibition and may be expected to continue for up to 24 hours. Thus, in accordance with this invention, L-sugars are supplied to the enzyme receptor sites so that the receptor sites are not available to initiate the metabolism of subsequently arriving D-sugars. The D-sugars thus are not actively absorbed into the system and the rejected D-sugars are relatively quickly excreted from the body without adding to the caloric budget of the individual. After a period of time, typically about one day, the L-sugar molecules are dislodged from the enzyme sites, thereby leaving the enæyme again free to catalyze the metabolism of D-sugar molecules, or again to be hlocked by an L-sugar if administered.
The practice of this invention depends upon (1) individual and/or statistical determination of the period of enzyme blockage to be achieved; (2) the ratio of L-sugar molecules ingested-to-enzyme sites blocked; and (3) the percent oE total enzyme sites required to be blocked to achieve the desired degree of control of caloric uptake from consumption of foods and beverages contalning or liberating D-sugars. By the practice of this invention, the upta]ce of caloric sugars can be moderated to the extent desired or entirely prevented, on a day-to-day basis, by the user through taking amounts of L-sugar prescribed by his physician after appropriate tests.

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This invention provides a ready, conven:ient, pleasant and safe way to control weight and sugar metabo-lism for healthy and diseased persons. The advantages of this invention are: It provides a simple, non-demanding means for controlling sugar uptake and body weight. The weight and calorie control method is highly tunable to personal metabolic needs and desires. The method of this invention is also immediately responsive to changes in regimen. The method can be terminated within any given period, e.g., 24 hours, by merely stopping the periodic intake of the L-sugar(s). The results are achieved without altering the taste of foods. The desired effects are obtained without any adverse appetite depression or any impact on dietary habits, gustatorial pleasure, preferences or quantities of food or drink consumed. In the sense that the L-sugars are chemically identical to their familiar counterparts, no chemically alien sub-stances are introduced into the diet. The results are achieved by short-term blockage of metabolic enzyme sites, thereby requiring very small quantitles of the L-sugar(s) which thus produce an amplification effect.
No toxic or other side effect is known to occur. Upon termination of the treatment, no residual metabolic ePfect remains.

25The following examples i.llustrate the practice of this invention:

EXAMP~F 1 An obese person fin~s it difficult to lose weight through voluntary control of caloric intake, but wishes to do so for health and esthetic reasons. He goes to his physic:ian who examines him and recommends loss of weight to be achieved by reducing the normal avera~e

4,000 calorie daily intake of his patient to 2,000 calories. The physician has the patient record his food , .~ .

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3~577 intake over a week's period and analysis of the record shows that, o~ the confirmed 4,0no calorie daily intake~
the amount contributed by sugars and foods which hydro-lyze to fructose and glucose upon in~estion constitutes 2,50~ calories. The physician then refers to charts developed for the purpose of previous human experimental use and prescribes indicated daily amounts of L-fructose and/or L-glucose to be taken by the patient, in the ~orm of pill, powder, liquid or in any suitable vehicle, separately or with food and drink. The daily amounts are selected from the chart based on the patient's weight, caloric intake, sex, age, metabolic rate, activities, desired rate of weight loss and other factors determined by the physician. The amount and combination of L-fruc-tose and L-glucose selected for the patient should reduce his caloric intake by blocking uptake of 2,000 calories of the 2,500 normally ohtained through the D-fructose and D-glucose routes. The physician asks the patient to return after two days, or other appropriate time, for a check-up, including, but not limited to metabolic rate.
If necessary, the physician will adjust the prescribed dailv amounts of L-~ructose and L-glucose. He will then resort to weekly checks which will include weight moni-toring and he will "titrate" the L-sugar dosage to achieve the desired loss of weight rate. When the patient's target weight i8 achieved, the physician will review the case history and refer to other experimental data. Based on this total information, he will prescribe a maintenance mixture of L-fructose and L-glucose ~or the patient's daily use which is designed to maintain the desired weight without the inconvenience and difficulty o~ requiring the patient to alter his normal, preferred dietary intake. Of course, the physician may elect to reduce the caloric inta]ce in more steps than described above should he think it preferred practice. Each step would be performed in the same manner as explained.

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Example 2 A patient suffering from diabetes mellitus cannot assimilate the amount of sugar she normally consumes daily, resulting in a danger to her health. ~ler physician performs glucose tolerance and other tests to determine a safe level of sugar intake for her. In the same manner described in Example 1, the physician pre-scribes daily amounts of L-sugars to control her normal metabolic uptake to the safe limit. This dose is then maintained and checked at intervals for any required adjustment in response to metabolic or dietary changes.

Example 3 In planning a vacation, a person wishes to orient towards good restaurants and heavy eating, but is concerned about gaining weight. He goes to his physician and, together, they plan a calorie schedule. As in Example 1, a calculated amount of L-sugar(s) is prescrib-ed for use by the patient during his eating spree. Upon his return from vacation, the patient visits his physi-cian for a check-up and for any calorie absorption control adjustment required to maintain or achieve target weight, or to end the program if the proper weight has been maintained.

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Claims (7)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A weight control composition comprising a non-metabolizable L-sugar.

2. A composition as defined in claim 1 in the form of a pill.

3. A composition as defined in claim 1 in the form of a solution.

4. A composition as defined in claim 1 provided in a form for administration of from 1 to 30 mg per kg of body weight per day.

5. A weight control composition comprising a non-metabolizable L-sugar and a pharmaceutically-acceptable additive.

6. The composition of claim 5 wherein said additive is an inert diluent.

7. The composition of claim 5 wherein said additive is an assimilable edible carrier.