WO2005034973A1

WO2005034973A1 - Capsulated herbal composition as auxilary medicament against diabetes mellitus type (i) and (ii)

Info

Publication number: WO2005034973A1
Application number: PCT/HR2004/000033
Authority: WO
Inventors: Vladimir Leko
Original assignee: Vladimir Leko
Priority date: 2003-10-10
Filing date: 2004-10-04
Publication date: 2005-04-21
Also published as: HRP20030816A2; HRP20030816B1; EP1675604A1

Abstract

Subject matter of this application is obtaining of active principle and pharmaceutical preparation from herbal mixture comprising following dried and ground ingredients: plant of centaury (Centaurii umbellatum, Gentianaceae) 10-15% by weight (wt.) root of dandelion (Teraxacum officinale, Asteraceae) 6-12 % by wt. fruit of juniper (Juniperi communis L, Cupresaceae) 5-8 % by wt. plant of nettle (Urticae dioica L, Urticaceae) 5-10 % by wt. root of nettle (Urticae dioica L, Urticaceae) 5-10 % by wt. root of chicory (Cichorium intybus L, Cichoriaceae) 12- 20 % by wt. leaf of black mulberry (Morus nigra L, Moraceae) 5-10 % by wt. flower of yarrow (Achilleae millefolium L, Asteraceae) 2-5 % by wt. leaf of bilberry (Vaccinium myrtillus L, Ericaceae) 4-10 % by wt. pod of beans (Phaseolus vulgaris L, Fabaceae) 10-20 % by wt. and root of valerian (Valeriana officinalis L, Valerianaceae) 5-10 % by wt wherein each percentage refers to the total mass of the dried ingredients in the composition, at room temperature, extraction of this mixture in a covered container at the room temperature and pressure for 28 days, decantation of upper layer, filtration of lower layer comprising increasing the density of the herbal mixture by whirling spray granulation with spraying with gas under pressure 1-3 barr, through 30-40 minutes, with provision that temperature of anhydrous gas has to be at least 10° C higher than entering temperature of tincture.

Description

CAPSULATED HERBAL COMPOSITION AS AUXLLARY MEDICAMENT AGAINST DIABETES MELLITUS TYPE (I) AND (II)

FIELD WHICH THE INVENTION REFERS TO

This invention refers to the field of pharmacy, and more closely, it refers to the medicament against diabetes mellitus type I and II, and even more precisely, it refers to the medicament against diabetes mellitus type based on a herbal composition as an active substance.

According to the International Classification of Patents, the subject invention is marked with the classification symbol A 61 K 35/78- Medical preparations containing substances or products of their reactions with undefined composition, whereby substances from herbs are in question.

TEHNICAL PROBLEMS

A technical problem, the solution of which is disclosed in this patent application, consists in finding cheaper and simplier way of obtaining and optimisation of proces of production substance that is disclosed within patent application with publication No. WO 99/55351. Unexpectitly, obtained composition has shown improved efficiency in treatment of diabetes mellitus type II in comparation with composition described in aforsaid patent application. Also surprisigly, in contrast to composition dislosed in WO 99/55351, according to present invention obtained composition has biological activity against diabetes mellitus type I as well.

STATE OF THE ART

Process for production active substance that can be used in treatment of diabetes mellitus type II from herbal composition was disclosed by patent application WO 99/55351. In the same patent application pharmaceutical preparation that comprises active substance, natural microcelullose, natural zeolite, monosaccharide and Mg state in following portions 16,7 : 22,2 : 50,0 : 9,7 : 1,4 was disclosed. DETAILED DESCRIPTION OF INVENTION

Process of production of an active substance according to the patent application WO

99/55351 comprises evaporation in the vacuum in the timely linear temperature gradient, following with, by liquid air, freezing of evaporated suspension on -186°C, with lyophilization as last step in process. It was been found that amount of obtained active substance substantially vary with small variation of timely linear temperature gradient substantially. Further, freezing of evaporated suspension on -186°C causes quality problems (namely obtained active substance in hygroscopic) and cost of production final product becomes unexpectedly high. Finally, implementetion of high pressures can cause plastic deformation of particles and deformation of intramolecular forces. As consequence biological activity can be damaged and quality fluctuation of final product, that was noticed, will be developed.

Except aforesaid, it was been noticed that zeolite as compound in pharmaceutical preperation disclosed in WO 99/55351 often comprises Pb2θs. Purification of zeolite from Pb2θ5 traces makes final product production cost higher.

Listed problems are removed by less aggressive method for preparation of active substance and pharmaceutical preparation and by change of carrier, punila and other auxiliary substances. Namely, zeolite was changed by root of chicory, and instead of natural miccrocellulose in pharmaceutical preparation, according to the invention, pulvis powder of herbal composition described in patent application WO 99/55351 was charged.

With this elements all aforsaid problems of invention disclosed in cited application are removed.

Above that, unexpectidlly was found, in test on volontires, 7- 10% better biological activity of preparation obtained on way that was dislosed in present invention.

According to this invention active substance is obtained from extract made from herbal composition that comprises following usitnjeni and dried ingredients:

plant of centaury (Centaurii umbellatum, Gentianaceae) 10-15% by weight (wt.) root of dandelion (Teraxacum officinale, Asteraceae) 6-12 % by wt. fruit of juniper (Juniperi communis L., Cupresaceae) 5-8% by wt. plant of nettle (Urticae dioidca L, Urticaceae) 5- 10% by wt. root of nettle (Urticae dioica L, Urticaceae) 5-10% by wt. root of chicory (Cichorium intybus L, Cichoriaceae) 12-20% by wt. leaf of black mulberry (Morus nigra L, Moraceae) 5- 10% by wt. flower of yarrow (Achilleae millefolium L, Asteraceae) 2-5% by wt. leaf of bilberry (Vaccinium myrtillus L, Ericaceae) 4-10% by wt. pod of beans (Phaseolus vulgaris L, Fabaceae) 10-20% by wt. and root of valerian (Valeriana ojficinalis L, Valerianaceae) 5-10% by wt. wherein each percentage refers to the total mass of the dried ingredients in the composition.

According to the invention, the active substance from the herbal composition is obtained in the following way: the herbal composition which is made of dried and ground to 40±5 mesh ingredients is to be covered in 60% ethanol at the room temperature. For the purpose of extraction, the mixture is left to rest for 28 days in a covered container, at the room temperature and pressure. The herbal tincture is then obtained by decanting the liquid above the sediment. The alcoholic tincture obtained in that way was exposed to whirling spray granulation, with spraying with anhydrous gas under pressure 1-3 barr, during 30-40 minutes. Temperature of gas is at least 10°C higher than entering temperature of the tincture. Gas was provided by two-phase nozzle. Entering tempeature of tincture is, in prefe ed embodyment of the invention, 25 ± 5° C, and temperature of the gas is 48 ± 3° C. Gas used for spraying can be oxigen.

Active substance obtained by aforesaid process has to be mixed, until homogeneous mixture, with pulvis powder of herbal composition, root of chicory and Mg-stearate to for obtaining pharmaceutical preparation.

Unexpectedly, it was been shown by comparative tests that on this way prepared pharmaceutical composition has 7- 10% better efficiency in lowering blood glucose level than preparation disclosed in patent application WO 99/55351. To conclude, with less aggressive process of obtaining and with change of zeolite with chicory root, and with change of natural microcellulosse with pulvis powder of mixture described within patent application WO 99/55351, as well as with grinding herbal mixture before treatment with 60% alcohol (ethanol) up to 40 ± 5 mesh pharmaceutical preparation with same active principle, but with improved biological activity for 7- 10 % in relation to preparation disclosed in previous application, was obtained.

Except described effect, it was been noticed that pharmaceutical preparation according to this invention can be used for treatment diabetes mellitus type I, as well.

DESCRIPTION OF ONE EMBODIMENT OF INVENTION

Described embodiment of invention that follows could not in any possible way act in direction to narrow subject matter of invention.

Steps needed for active principle preparation and for preparation of pharmaceutical preparation are as follows:

1) Adding 7,2 kg of 60% of ethyl alcohol to the each kg of herbal composition which consist of:

plant of centaury (Centaurii umbellatum, Gentianaceae) 10- 15% by weight (wt.) root of dandelion (Taraxacum officinale, Asteraceae) 6- 12 % by wt. fruit of juniper (Juniperi communis L, Cupresaceae) 5-8 % by wt. plant of nettle (Urticae dioica L, Urticaceae) 5-10 % by wt. root of nettle ( Urticae dioica L, Urticaceae) 5- 10 % by wt. root of chicory (Cichorium intybus L, Cichoriaceae) 12-20 % by wt. leaf of black mulberry (Morus nigra L, Moraceae) 5-10 % by wt. flower of yarrow (Achilleae millefolium L, Asteraceae) 2-5 % by wt. leaf of bilberry (Vaccinium myrtiϊlus L, Ericaceae) 4-10 % by wt. pod of beans (Phaseolus vulgaris L, Fabaceae) 10-20 % by wt. and root of valerian (Valeriana ojficinalis L, Valerianaceae) 5-10 % by wt. 2) The aforesaid mixture is left to rest for 28 days in a covered container, at the room temperature and pressure. The herbal tincture is then obtained by decanting the liquid above the sediment and filtration of lower layer. Yield is 63 weight %.

3) Obtained alcoholic tincture is entered to apparatus for whirling spray granulation on temperature of 25 ° C. In apparatus alcoholic tincture is to be sprayed with anhydrous air, which has a temperature around 48 ° C. Air was provided in the apparatus with two phase nozzle. In apparatus alcoholic tincture has to be increased in density for factor 5. Spaying with air is applied under pressure of 3 barr. All procedure can be done with WSG-GLATT-50. 282 mg of alcoholic extract produces 56,4 mg dried powder of active substance.

4) Active principle, pulvis powder of herbal mixture, chicory root and Mg- stearate are mixed in weight ratio 16,7 : 37,0 : 45,0 : 1,3 until homogenous mixture. Obtained homogenous mixture is capsulated in gelatinize capsule.

According to the preferred embodiment of invention capsules can consist 200 mg or 480 mg pharmaceutical preparation described above.

In 200 mg capsule we have:

Active principle 33 mg

Pulvis powder 74 mg

Chicory root -90 mg

Mg-stearate 3 mg

In 480 mg capsule we have:

Active principle 79 mg

Pulvis powder 37 mg

Chicory root 216 mg

Mg- stearate 7 mg WAY OF DOSING AND APPLICATION

For diabetes mellitus type II:

1.) In case that a person suffering from diabetes mellitus type II has the glucose level from 4,5 to 7 mmol L, the therapy of one 200 mg capsule twice a day is recommended.

2.) In case that a person suffering from diabetes mellitus type II has the glucose level from 7 to 10 mmol/L, the therapy of one 480 mg capsule twice a day is recommended.

3.) In case that a person suffering from diabetes mellitus type II has the glucose level above 10 mmol/1, the therapy of one 480 mg capsule three time a day is recommended.

For diabetes mellitus type II:

1.) Children younger than 10 years have to take one time a day one 200 mg capsule. 2.) Children older than 10 years have to take one 200 mg capsule twice a day. 3.) Adults that have glucose level above 10 mmol/L have to take one 480 mg capsule once a day. 4.) Adults that have glucose level above 10 mmol/L have to take one 480 mg capsule once or twice a day. 5.) Person suffering from diabetes with insulin resistence need to take capsules as described from 1 to 4. In case of disorders connected with diabetes mellitus: 1.) In case of high cholesterol, therapy of one 200 mg capsule twice a day is recommended. 2.) In case of high triglycerides, therapy of one 480 mg twice a day is recommended.

Claims

1. Process for obtaining of an active substance from: tincture produced by adding 7.21 1 60% ethanol to the each kg of the herbal composition which consist of ground and dried ingredients: plant of centaury (Centaurii umbellatum, Gentianaceae) 10-15% by weight (wt.) root of dandelion (Taraxacum officinale, Asteraceae) 6-12% by wt. fruit of juniper (Juniperi communis L, Cupresaceae) 5-8% by wt. plant of nettle (Urticae dioica L, Urticaceae) 5-10% by wt. root of nettle ( Urticae dioica L, Urticaceae) 5-10% by wt. root of chicory (Cichori m intybus L, Cichoriaceae) 12-20% by wt. leaf of black mulberry (Morus nigra L, Moraceae) 5-10% by wt. flower of yarrow (Achillea millefolium L, Asteraceae) 2-5% by wt. leaf of bilberry (Vaccinium myrtillus L, Ericaceae) 4-10% by wt. pod of beans (Phaseolus vulgaris L, Fabaceae) 10-20% by wt. and root of valerian (Valeriana officinalis L, Valerianaceae) 5-10% by wt. wherein each percentage refers to the total mass of the dried ingredients in the composition, at room temperature, extraction of this mixture in a covered container at the room temperature and pressure for 28 days, decantation of upper layer, filtration of lower layer comprising increasing the density of the herbal mixture by whirling spray granulation with spraying with gas under pressure 1-3 barr, through 30-40 minutes, with provision that temperature of anhydrous gas has to be least 10°C higher than entering temperature of tincture.

2. Process according to the claim 1 characterited by fact that anhydrous air is anhydrous gas for spraying tincture.

3. Process according to the claim 2, characterized by the fact that air is entered in apparatus by two phase nozzle.

4. Process according to the claim 1, characterized by the fact that entering temperature of tincture is 25 ± 5°C.

5. Process according to the claim 1, characterized by the fact that temperature of anhydrous air is 48 ±3°C.

6. Process according to the claim 1, characterized by the fact that density of tincture is to be increased by factor 5.

7. Process according to the claim 1, characterized by the fact that herbal mixture come in process ground on 40±5 mesh.

8. Pharmaceutical preparation comprising active principle obtained according to the claim 1, pulvis powder of herbal mixture, root of chicory and Mg stearate in following weight ratio 16,7 : 37,0 : 0.45: 1,3.

9. Process of obtaining of pharmaceutical composition comprising mixing active principle obtained according to the claim 1, pulvis powder of herbal mixture, chicory root and Mg- stearate until homogenous mixture, and capsulation that mixture in gelatinous capsule.

10. Use of pharmaceutical preparation according to the claim 7, characterized by the factthat it is used for production medicament against diabetes mellitus type I.