ACTIVE SUBSTANCE

TECHNICAL FIELD

The present invention relates to pharmaceutical compositions comprising ursodeoxycholic acid as active substance.

PRIOR ART

Ursodeoxycholic acid (Formula I) is a gall acid formed naturally in the body. The chemical formula of ursodeoxycholic acid is C24 I40O4 and the chemical structure thereof is 3alpha,7beta-Dihydroxy-5beta-colan-24-oic acid and the molecular weight thereof is 392.6 g/mole. Ursodeoxycholic acid is crystallized powder which has white color or a color similar to white color. Practically, it does not dissolve in water, it freely dissolves in alcohol and glacial acetic acid and it less dissolves in chloroform and it slightly dissolves in ether.

Formula I

Gall acids form the basic component of gall and they are synthesized from cholesterol in liver and they are responsible for carrying and absorption of oil in diet and vitamins which dissolve in oil. The gall acids synthesized in liver are named as primary gall acids (colic acid and cenodeoxycolic acid). Gall acids are released to intestine in gall. By means of the hydroxylation of primary gall acids in the intestine by the intestinal bacteria, secondary gall acids (deoxycolic acid and litholic acid) are formed. Ursodeoxycholic acid (UDCA) is formed as a result of 7b epimerization of cenodeoxycolic acid in the intestine and forms 1 -3% of gall acid pool. A big part of gall acids is absorbed through terminal ileum and carried again to the liver and excreted to the gall. This is called entero-hepatic circulation. Gall acids are conjugated with glycine and taurine in the plasma or are provided in a bonded manner with the plasma proteins and intra-cellular proteins, and the free form is under 5%. Since more than 5% of gall acids are in free form, toxicity occurs. Bonding of hydroxyl group in different positions and in different numbers with the cholesterol determines that the gall acid is hydrophobic or hydrophilic. Hydrophobicity is responsible for toxicity. The hydrophobicity characteristic exists in respectively decreasing amounts in lithocolic acid, deoxycolic acid, cenodeoxycolic acid, colic acid and ursodeoxycholic acid. Gall acids are used in diseases of duodenogastric reflux and gall stone for a long time. In the recent times, as the pharmacological characteristics of gall acids are examined and as related studies are made, the role of gall acids in the treatment of colestatic liver diseases which has auto-immune component has been shown and gall acids have been used frequently in a clinical manner.

Ursodeoxycholic acid is a gall acid which is naturally produced in the body. In patients whose gall bladder functions are active, ursodeoxycholic acid is used for melting non-radio-opaque cholesterol gall stones and for melting stone fragments which occur after gall stone fragmentation. Ursodeoxycholic acid can also be effective in treatment of cystic fibrosis associated with hepatobiliary disease in babies and children; it is used for eliminating liver functions and disease symptoms in primary biliary cirrhosis (I. and II. period).

Ursodeoxycholic acid exists in small amounts in normal human gall and suppresses hepatic synthesis and excretion of cholesterol and absorption through the intestines. Thus, it shows its effect by decreasing cholesterol excretion from the liver and by decreasing cholesterol ingredient of both gall and gall stones depending on decreasing fractional absorption of cholesterol through the intestines. In order to observe the effect thereof against gall stones, it must be used for months, and in some patients, gall stones may not dissolve completely. In pharmaceutical compositions comprising ursodeoxycholic acid which need long duration usage, formulations must be developed which will increase compliancy of the patient to this long-duration treatment.

As a result, because of all of the abovementioned problems, an improvement is required in the related technical field. BRIEF DESCRIPTION OF THE INVENTION

The present invention relates to pharmaceutical compositions comprising ursodeoxycholic acid, for eliminating the above mentioned disadvantages and for bringing new advantages to the related technical field.

An object of the present invention is to provide pharmaceutical compositions comprising 750 mg ursodeoxycholic acid in unit dose.

In order to realize the abovementioned objects and the objects which are to be deducted from the detailed description below, the present invention relates to pharmaceutical compositions comprising 750 mg ursodeoxycholic acid. Thus, by means of said dose amount which does not exist in the known are, the patients will not have to use two different tablets, for instance, 250 mg and 500 mg, and the compliancy of the patients to the treatment will increase. This is going to indirectly increase the chance of healing in patients. Moreover, by means of this, the number of tablets in the package decreases and easiness is provided in the packaging process.

A preferred embodiment of the present invention relates to pharmaceutical compositions comprising binder, dispersant, lubricant besides 750 mg ursodeoxycholic acid.

A preferred embodiment of the present invention relates to pharmaceutical compositions comprising Povidon K30, microcrystalline cellulose, crospovidon, talc and magnesium stearate besides 750 mg ursodeoxycholic acid.

An embodiment of the present invention relates to pharmaceutical compositions comprising Povidon K30 between 1 -10%, microcrystalline cellulose between 5-30%, crospovidon between 1 -5%, talc between 1 -5% and magnesium stearate between 0.2-5% by weight proportion in total tablet weight besides 750 mg ursodeoxycholic acid.

In a particularly preferred application of the present invention, the subject matter pharmaceutical composition comprises 750 mg ursodeoxycholic acid, 40.50 mg Povidon K30, 195 mg microcrystalline cellulose, 34.50 mg crospovidon, 15 mg talc and 15 mg magnesium stearate.

In a preferred embodiment of the present invention, the subject matter pharmaceutical compositions can be in dosage forms which are suitable for oral intake, for instance, can be in tablet, capsule, oral drop, effervescent tablet form. In a particularly preferred embodiment of the present invention, the subject matter pharmaceutical compositions are in tablet form.

Pharmaceutical compositions, prepared in tablet form according to the present invention and comprising 750 mg ursodeoxycholic acid in unit dose, can be coated by means of a suitable coating solution.

When the subject matter pharmaceutical compositions are prepared in tablet form, they can have a notched form. Thus, the patient can easily take half-dose drug when required.

From another perspective, the present invention relates to pharmaceutical compositions comprising 750 mg ursodeoxycholic acid in unit dose for usage in cirrhosis treatment, in melting of gall stones, in treatment of pregnancy intra-hepatic cholestasis, in treatment of hepatobiliary diseases associated with cystic fibrosis or in elimination of the symptoms resulting from these diseases.

From another perspective, the present invention relates to usage of pharmaceutical compositions comprising 750 mg ursodeoxycholic acid in preparation of a drug to be used in cirrhosis treatment, in melting of gall stones, in treatment of pregnancy intra-hepatic cholestasis, in treatment of hepatobiliary diseases associated with cystic fibrosis or in elimination of the symptoms resulting from these diseases.

DETAILED DESCRIPTION OF THE INVENTION

In this detailed description, the subject matter pharmaceutical compositions comprising 750 mg ursodeoxycholic acid in unit dose is explained with references to examples without forming any restrictive effect only in order to make the subject more understandable.

Example 1 : Recipe for pharmaceutical compositions comprising 750 mg ursodeoxycholic acid in unit dose

Example 2: Results of In Vitro Dissolving Speed

250 mg and 500 mg tablet formulas are used as reference, which exist in the known state of the art, in the in vitro dissolution tests realized, since in the world, there is no tablet which comprises the subject matter 750 mg ursodeoxycholic acid. Said dissolution tests have been realized by means of“multiple doses” study.

The protection scope of the present invention is set forth in the annexed claims and cannot be restricted to the illustrative disclosures given above, under the detailed description. It is because a person skilled in the relevant art can obviously produce similar embodiments under the light of the foregoing disclosures, without departing from the main principles of the present invention.