MXPA00001214A - Chromium/biotin treatment of type ii diabetes - Google Patents

Abstract

A method for treating Type II diabetes by administering to an affected individual a combination of chromic tripicolinate and biotin. The two compounds are administered orally or parenterally at in daily dosages which provide between 50 and 1,000 mg of chromium and between 25 mg and 200 mg biotin, the amounts of chromium and biotin being selected together to provide a greater than additive effect.

Description

CHROME / BIOTINE TREATMENT OF DIABETES OF TYPE II Field of the Invention The present invention relates to the treatment of diabetes (Type II) not dependent on insulin, in an adult. More specifically, the invention relates to the treatment of Type II diabetes by the administration of chromic picolinate and biotin.

Background of the invention It is known that diabetes mellitus affects at least 10 million Americans and millions more may not know that they have the disease. In the form of this disease known as Type II diabetes, not dependent on insulin, or attacking adults (as opposed to juvenile or Type I diabetes), the pancreas often continues to secrete normal amounts of insulin. However, this insulin is not effective in preventing the symptoms of diabetes, which include hyalglycemia, altered carbohydrate metabolism, glucose tolerance, and decreased insulin sensitivity. These symptoms, if left untreated, often lead to severe complications. The current drugs used to manage Type II diabetes are found in two classes of compounds: biguanides and sulfonylureas. Biguanides, for example metformin, are thought to prevent excessive gluconeogenesis. Sulfonylureas, for example tolbutamide and gluburide, decrease plasma glucose primarily by stimulating insulin secretion, by increasing the effects of insulin in some target tissues and by inhibiting hepatic glucose synthesis. U.S. Patent No. 4,315,927 discloses that when the selected essential metals are administered to mammals, such as exogenously synthesized coordination complexes, of picolinic acid, they are available directly by absorption, without competition from other metals. These complexes are safe, cheap, biocompatible and easy to produce. U.S. Patent No. 5,087,623 describes the administration of chromic tripicolinate for the treatment of Type II diabetes, in doses that deliver between 50 and 500 μg of chromium. In E.U.A. The recommended daily dose for chromium is 50 to 200 μg. Although there is a small decrease in glycosylated hemoglobin, an accurate indicator of blood glucose levels, it was observed, the value of 10.4% obtained after the treatment of chromic tripicolinate is still within the diabetic range. International Patent Application No. PCT / US96 / 06493 discloses the administration of high ("super-nutritional") doses of chromium (1,000 to 10,000 μg / day) to individuals with Type II diabetes. Individuals who received 1,000 μg of chromium per day, such as chromic tripicolinate, exhibited a 30% decrease in glycosylated hemoglobin and a similar reduction in fasting and table-top glucose levels. Biotin is a prosthetic group for a number of carboxylation reactions, the most notable being the pivurate carboxylase, which is involved in gluconeogenesis and the replenishment of the citric acid cycle, and the acetyl CoA carboxylase, which plays a role in the biosynthesis of the fatty acid. The recommended, safe and adequate daily administration of biotin is 100 to 300 μg, although no side effects or toxicities were noted in previous clinical studies with oral administration of up to 200 mg daily (Mock et al., In Present Knowledge in Nutrition, seventh edition, Ziegler ,. et al, Eds., ILSI Press, Washington, DC, 1996, pages 220-235). The supernutritional doses of biotin have shown to have a therapeutic utility in diabetes. High doses, oral or parenteral, of biotin have been shown to improve oral glucose tolerance in diabetic KK monkeys (Reddi et al., Life Sci., 42: 1323-1330, 1988), rats made diabetic by injection with Streptozotocin (Zhang et al., 16th International Nutrition Congress, Montreal, 1977, excerpt book, p.264) and pre-diabetic Tokushima Otsuka Long-Evans rats (Zhang et al., "Nutr. Sci. Vi taminol 42: 517-526, 1996). In a clinical study, Coggeshall et al., (Ann. NY Acad. Sci., 1 -. 381-392, 1985) demonstrated that an oral daily dose of biotin of 16 mg decreases fasting plasma glucose levels in Type I diabetics, where insulin injections have been temporarily discontinued. Maebashi et al (J. Clin. Biochem. Nutr. 14: 211-218, 1993) showed that the administration of 3 mg of biotin per day to diabetics of < Type II, poorly controlled, resulted in enhanced pancreatic beta cell functions, as evidenced by the fact that fasting insulin levels did not decline in subjects treated with biotin, despite the acute decline in glucose levels. There is a constant need for effective treatments for Type II diabetes. The present invention addresses this need by the provision of a safe, inexpensive, drug-free therapeutic agent.

SUMMARY OF THE INVENTION One embodiment of the present invention is a method for reducing hyperglycemia and stabilizing the level of serum glucose, which comprises administering to an individual in need, between 50 and 1,000 micrograms per day of chromium such as tripicolinate. of synthetic chromium, in combination with between about 25 μg and 200 mg per day of biotin, the amounts of the chromic tripicolate and the botin being selected together to provide greater effect than the additive. Preferably, the amount of chromium administered as the synthetic chromic tripicolinate is between 500 and 1,000 micrograms per day. Advantageously, the amount of botin administered per day is between mg and 100 mg. in one aspect of this preferred embodiment, the chromic tripicolinate is a pharmaceutically acceptable carrier. In another aspect of the preferred embodiment, the biotin is in a pharmaceutically acceptable carrier. Preferably, biotin is administered orally. Advantageously, chromic tripicolinate is administered orally. Preferably, the chromic tripicolinate is administered parenterally. In another aspect of this preferred embodiment, biotin is administered parenterally. The present invention also provides a pharmaceutical composition comprising chromium as a synthetic chromic tripicolinate and biotin, in which the ratio of chromium to biotin is between 2: 1 and 1: 200 (w / w), the amounts of chromic tripicolinate and biotin are selected together to provide a greater effect than the additive. Another embodiment of the invention is the use of synthetic chromic tricicoline in an amount that provides between about 50 and 1,000 micrograms per day of chromium, in combination with about 25 μg to 200 mg per day of biotin, to reduce hypergj.ucem .ia and stabilize the level of serum glucose in an individual. Preferably, the synthetic chromic tripicolinate supplies between about 500 and 1,000 micrograms of chromium per day. Advantageously, biotin is present in an amount between about 1 and 100 mg. In one aspect of this preferred embodiment, chromic tripicolinate and biotin are in a pharmaceutically acceptable carrier, Detailed Description of the Preferred Modes The present invention includes the discovery that chromium doses of the highest RDA amount up to five times that amount, administered in the form of chromic picolinate, combined with low and high doses of biotin, promote the reduction Significant in blood glucose levels and stabilize blood glucose levels in individuals with Type II diabetes. This reduction is markedly greater than that expected when any component is administered sclo, thus indicating a synergistic effect.

The synthesis of chromic picolinates is described in U.S. Pat. No.5, 087, 623. Fl chromic tripicolinate and biotin are commercially available from food stores, drug stores and other commercial sources. In order to reduce the requirements of insulin and / or diabetic drugs and reduce the various important risk factors, associated with Type II diabetes, it is anticipated that the dose range of chromium, associated with a patient, in the form of chromic tripicolinate, will be between about 50 and 1,000 μg / day. In a preferred embodiment, this amount will be between about 500 and 1,000 μg / day. With respect to the biotin component of this combination therapy, the preferred daily dose is between about 25 and 200 mg. More preferably, the daily dose of biotin is between about 1 mg and 100 mg. For oral administration, chromic picolinatos and biotin can be supplied as tablets, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs. The compositions intended for oral use can be prepared according to any method known in the art of manufacturing pharmaceutically acceptable compositions and these compositions can contain one or more of the following agents: sweeteners, flavoring agents, coloring agents and condoms Flavor agents and sweeteners will increase the acceptability of the preparation. The raleas containing the chromic tripicolinate in admixture with pharmaceutically acceptable, non-toxic excipients, suitable for the manufacture of tablets, are acceptable. Pharmaceutically acceptable means that the agent must be acceptable in the sense of being compatible with the other ingredients of the formulation (as well as not harming the patient). Such excipients include inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate.; granulation and disintegration agents, such as corn starch or alginic acid; binding agents, such as starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques, to delay disintegration and absorption in the gastrointestinal tract and thus provide a sustained action for a prolonged period of time. For example, a material that delays the time of action, such as glycerol monostearate or glyceryl distearate, alone or with a wax may be employed. Formulations for oral use may also be as hard gelatin capsules, in which the active ingredient is mixed with an inert solid diluent, for example calcium carbonate or phosphate, or kaolin, or as soft gelatin capsules, wherein the Active ingredient is mixed with water or an oily medium, such as peanut oil, liquid paraffin or olive oil. The aqueous suspensions may contain the chromic tripicolinate complex of the invention, in admixture with excipients, suitable for the manufacture thereof. These excipients include suspending agents, dispersing agents or humectants, one or more preservatives, color, or flavoring agents and one or more sweetening agents, such as sucrose or saccharin. Oil suspensions can be formulated by suspending the active ingredient in a vegetable oil, such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil, such as liquid paraffin. The oil suspension may contain a thickening agent, such as hard paraffin wax or cetyl alcohol. Sweetening agents, such as those noted above, and flavoring agents, can be added to give a pleasant oral preparation. These compositions are preserved by adding an antioxidant, such as ascorbic acid. Dispersible powders and granules of the invention, suitable for the preparation of an aqueous suspension by the addition of water, supply the active ingredient in admixture with a dispersing or wetting agent, a suspending agent and one or more preservatives. They may contain additional excipients, for example sweetening, flavoring and coloring agents. The syrups and elixirs can be formulated with sweetening agents, such as glycerol, sorbitol or sucrose. These formulations may also contain an emollient, a condom, a flavor or color agent. The preparations of chromic tripicolinate for parenteral administration may be in the form of a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to methods well known in the art, using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a diluent or solvent - non-toxic, parenterally acceptable, such as a solution of 1,3-butanediol. Suitable diluents include, for example, water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils can conventionally be used as a solvent or suspension medium. For this purpose, any soft fixed oil can be used, which includes synthetic mono and diglycerides. In addition, fatty acids, such as oleic acid, can be similarly used in the preparation of injectable preparations.

The pharmaceutical compositions can also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, such as olive oil or arachis oil, a mineral oil, such as liquid paraffin, or a mixture thereof. Suitable emulsifying agents include naturally occurring gums, such as acacia gum naturally occurring tragacanth phosphatides, such as soy lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan monooleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening or flavoring agents. The amount of the chromic tripicolinate / biotin that can be combined with the carrier material, in order to produce a single dose form, will vary depending on the host treated and the particular mode of administration. The above description of the invention was pointed out only to help understand the invention. It will be understood that variations of the invention, which include all equivalents now known or later developed, will be considered as within the scope of the invention, which is limited only by the following claims.

Claims (14)

1. CLAIMS 1. A method to reduce hyperglycemia and stabilize the level of serum glucose, this method comprises administering to an individual who needs it, between about 5 and 1,000 micrograms per day of chrom, or, as the synthetic chromic tripicolinate, in combination with between about 25 μg and 200 mg per day of biotin, in which the amounts of chromic tripicolinate and biotin are selected together to provide a greater effect of the additive effect.
2. 2. The method of claim 1, which comprises administering between about 500 and 1,000 micrograms per day of chromium, such as synthetic chromic tripicolinate.
3. 3. The method of claim 1, which comprises administering between about 1 mg and 100 mg of biotin per day.
4. 4. The method of claim 1, wherein the chromic tripicolinate is in a pharmaceutically acceptable carrier.
5. 5. The method of claim 1, wherein the biotin is in a carrier that is pharmaceutically acceptable.
6. 6 The method of claim 1, wherein the chromic tripicolinate is administered orally.
7. 7. The method of claim 1, wherein the biotin is administered orally.
8. 8. The method of claim 1, wherein the chromic tripicolinate is administered parenterally.
9. 9. The method of claim 1, wherein the biotin is administered parenterally.
10. 10. A pharmaceutical composition, comprising chromium as the synthetic chromic tripicolinate, and biotin, wherein the ratio of chromium to biotin is between about 2: 1 and 1: 200 (w / w), in which the amounts of chromic tripicolinate and Biotin are selected together to provide an effect greater than the additive effect.
11. 11. The use of chromic tripicolinate in an amount that supplies between approximately 50 and 1,000 micrograms per day of chromium, in combination with between approximately 25 μg and 200 mg per day of biotin, to reduce hyperglycemia and stabilize the level of serum glucose in An individual .
12. 12. The use according to claim 11, wherein the synthetic chromic tripicolinate supplies between about 500 and 1,000 micrograms of chromium per day.
13. 13. The use according to claim 11, wherein the biotin is present in an amount between about 1 mg and 00 mg.
14. 14. The use according to claim 11, wherein the chromic tripicolinate and the biotm are in a pharmaceutically acceptable carrier.