MXPA99007163A - Use of gastrointestinal lipase inhibitors - Google Patents

Abstract

The use of a gastrointestinal lipase inhibitor for the manufacture of oral medicaments for treating or preventing type II diabetes mellitus, and the medicaments thus manufactured.

Description

USE OF LIPASE GASTROINTESTINAL INHIBITORS Diabetes mellitus is a pathology characterized by an abnormality of glucose utilization and associated with an elevated blood glucose concentration. The most common form of diabetes mellitus is non-insulin dependent diabetes mellitus (NIDDM: Type II). More than 10 million people in the United States alone are affected with type II diabetes mellitus. The initial approach to treating obese patients affected with diabetes mellitus type II is weight reduction. Other types of treatment include oral hypoglycemia and insulin. See. Gregerman, MD, Section 10, Metabolic and Endocrinological Problems (Endocrinological and Metabolic Problems), Chapter 72. Diabetes Melitus, page 977-989. The invention relates to the use of an inhibitor • Gastrointestinal lipase for the manufacture of oral medications for the treatment or prevention of diabetes mellitus type II. The other aspect, the invention relates to an oral medication for the treatment or prevention of diabetes mellitus type II which is characterized in that it contains a gastrointestinal lipase inhibitor. The gastrointestinal lipase inhibitor is preferably tetrahydrolipstatin. Tetrahydrolipstatin, also known as REF .: 30845 orlistat, is a known compound, useful for the control or prevention of obesity and hyperlipidemia. See, North American Patent No. 4,598,0889 (equivalent to Argentine patent No. 233,709), issued on July 1, 1986, which also discloses processes for making tetrahydrolipstatin. Surprisingly it has now been known that a gastrointestinal inhibitor of lipase, preferably tetrahydrolipstatin, when administered orally is useful in the treatment and prevention of type II diabetes mellitus. Preferably, they are administered orally between 60 and 720 mg. per day of the gastrointestinal lipase inhibitor, in divided doses two or three times per day. The daily administration of a gastrointestinal lipase inhibitor to a subject preferably ranges from 180 to 360 mg, more preferably a subject is administered 360 mg. per day, preferably in divided doses, particularly two or three times per day. The subject is preferably an obese or overweight person, i.e., a human being with a Body Mass Index of 25 or more. Generally, it is preferred that the gastrointestinal lipase inhibitor be administered within the period of about one or two hours of ingestion of a meal containing fats. Generally, to prevent type II diabetes mellitus, it is preferred that the treatment be administered to 1) a person having a strong family history of type II diabetes mellitus and having a body table index of 25 or more; or 2) a person with impaired glucose tolerance and a body mass index of 25 or more. As used herein, the term "strong family history" means a person with at least one first-degree relative who has had type II diabetes mellitus. Generally, impaired glucose tolerance is diagnosed by an oral glucose tolerance test. Tetrahydrolipstatin can be administered to humans in conventional oral compositions, such as tablets, coated tablets, hard or soft gelatin capsules, emulsions or suspensions. Examples of carriers that can be used for coated tablets, dragees and hard capsules of gelatins include lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like. Suitable carriers for soft gelatine capsules are, for example, vegetable oil, waxes, fats, liquid and semi-solid polyols and the like. In addition, the pharmaceutical preparations may contain preservatives, solubilizers and stabilizing agents, moisturizing agents, emulsifying agents, sweetening agents, coloring agents, flavoring agents, salts for the variation of osmotic pressure, buffers, agents to be used for coating c er. antioxidants They themselves can also have other valuable therapeutic substances. The formulations can conveniently be presented in unit doses and can be prepared by any etatoac : ac in art rarmace tico. Preferably, tetrahydrolipstatin is administered according to the formulation of Example i.

Ahem 1 * Extracted during the process. Procedure 1. Combine tetrahydrolipstatin, microcrystalline cellulose and sodium starch glycolate in an appropriate mixer.

Granulate with a solution of polyvinylpyrrolid Pass granulation through an extruder and pass *; Q c C; 'go c-p ^ r' • '3 * "* -granules 4. Dry the granules at 30 ° C. 5. Add talc and mix c) Fill the hard gelatine capsules.

Example 2 Extracted during the process Procedure 1. Combine tetrahydrolipstatin, microcrystalline cellulose and sodium starch glycolate in an appropriate mixer. 2. Granulate with a solution of polyvinyl pyrrolidone and sodium lauryl sulfate in purified water. 3. Pass the granulation through extrudate and pass the extruder through a spheronizer to form lesion. - s. 4. Dry the granules at 3 CC. 5. Add talc and mix. 6. Fill the hard gelatine capsules.

Example 3 Extracted during the process Procedure 1. Combine tetrahydrolipstatin, lactose, microcrystalline cellulose and sodium starch glycolate in an appropriate mixer. 2. Granulate with a solution of polyvinylpyrrolidone and sodium lauryl sulfate in purified water. 3. Pass the granulation through an extruder and pass the extruder through a spheronizer to form the granules. 4. Dry the granules at 30 ° C. 5. Add talc and mix. 6. Fill the hard gelatine capsules.

EXAMPLE 4 Study of Patients with Diabetes Melitus Non-Insulin Dependent A double-blind, placebo-controlled study in 321 stabilized non-insulin-dependent diabetics was performed for one year. The results indicate that 30% of patients treated with tetrahydrolipstatin (120 mg three times per day) achieved at least a 5% reduction in baseline body weight, compared with 13% of patients controlled with placebo (p <0.001). Tetrahydrolipstatin also improved glycemic control in these patients, as evidenced statistically by significant reductions in hemoglobin levels Ale (improvement of 0.5% compared with placebo, p <0.001) and in doses of sulfonylureas. In this study, 43% of patients treated with tetrahydrolipstatin were able to reduce or discontinue their oral hypoglycemic medications compared to 29% of patients who received placebo, p < 0.01. The mean levels of the rapid glucose remained essentially unchanged compared to the baseline in the tetrahydrolipstatin group (-0.02 mmol / L), while there was an increase (+0.54 mmol / L) in the placebo group, p < 0.05. From the statistical point of view, there was a significant increase in total cholesterol, LDL-cholesterol, LDL / HDL ratio and triglycerides in the group treated with tetrahydrolipstatin compared with placebo.

EXAMPLE 5 Glucose Tolerance in Obese Patients Studies were conducted for two years, which included oral glucose tolerance tests in obese patients, whose baseline oral glucose tolerance test (PTGO) status was normal, impaired, or diabetic The progression of a PTGO was compared as a baseline, with a deteriorated or diabetic PTGO after two years of treatment with tetrahydrolipstatin (n = 242) (120 mg administered orally three times a day) or placebo (n = 201). ). After treatment with tetrahydrolipstatin, 0.0% and 6.2% of patients progressed from normal to diabetic and impaired, respectively, compared with 1.5% and 12.4% of the placebo treatment group, p < 0.01. In patients where they were found to have an impaired PTGO at the baseline, the percentage of patients who improved to normal or deteriorated until reaching a diabetic status: a s. .- .- j-. comparator, cor. treated patients: resente e cer.t nu i - < = rupos ce i a iei was sva. rp < 0.01 and ** p < 0.05, Fisher's exact test It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, from the manufacture of the objects to which it refers. Having described the invention as above, the content of the following is claimed as property.

Claims (4)

1. Use of a gastrointestinal lipase inhibitor for the manufacture of oral medications to treat and prevent diabetes mellitus type II.

2. The use according to claim 1, wherein the gastrointestinal lipase inhibitor is tetrahydrolipstatin.

3. An oral medication for the treatment or prevention of diabetes mellitus type II, characterized in that it contains an effective amount of a gastrointestinal lipase inhibitor.

4. An oral medication according to claim 3, characterized in that the gastrointestinal lipase inhibitor is tetrahydrolipstatin.