RU2599020C1 - Tableted drug based on the extract of alchemilla vulgaris - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to tableted drug for the treatment of syndrome of increased blood viscosity. Agent includes 6 wt% of thick extract of Alchemilla vulgaris, obtained by evaporation of alcoholic extract to a residual humidity of 25 %, 46.8 wt% of glucose, 46.8 wt% of lactose, 0.1 wt% of calcium stearate and 5 % aqueous solution of methylcellulose - the rest.

EFFECT: invention ensures production of tablets with high strength, high stability during storage and satisfying the requirements of the current pharmacopoeia.

1 cl, 2 tbl, 1 ex

Description

The invention relates to medicine, specifically to pharmaceutical technology, and for the creation of a preparation based on an extract of the common cuff, intended for the treatment of a complex of hemorheological disorders - a syndrome of high blood viscosity.

Currently, the most common occurrence of sudden death is due to various diseases of the cardiovascular system. An aggravating factor in cardiovascular diseases is the syndrome of increased blood viscosity (SPVK), which is a complex of changes in the rheological parameters of the blood.

Classical SPVC therapy has a relatively small arsenal of drugs that either selectively act on a specific pathogenesis link or have serious side effects. So, for example, often patients are shown synthetic drugs pentoxifylline, clopidogrel, dipyridamole, acetylsalicylic acid and its preparations (cardiomagnyl, magnecard, aspirin-cardio, etc.) (Mashkovsky M.D. Medicines / M.D. Mashkovsky. - M .: New wave, 2007 .-- 1206 p.).

Herbal medicines have less toxicity on the body compared to synthetic drugs and, with prolonged use, are usually devoid of pronounced side effects. The list of herbal remedies with hemorheological action is very limited, while they are the most promising in the complex treatment of diseases accompanied by SPVC. In addition, there is reliable evidence that flavonoids and extracts of flavonoid-containing plants have pronounced hemorheological activity under the conditions of a simulated SPVK (Plotnikov M. B. Medicines based on dikvertin / M. B. Plotnikov, N. A. Tyukavkina, T. M. Plotnikova. - Tomsk: Tomsk University Press, 2005. - 228 p.).

The need of medicine for natural products is not fully satisfied, the nomenclature and volume of offers on the herbal medicine market do not meet the needs of the population, whose growth has been noted in recent years.

For example, the following hemorheological medicines based on plant materials are known today: ginkgo biloba extract (patent RU No. 2367459, publ. 09/20/2009), liquid extract of Leuzea (patent RU No. 2138285, publ. 09/27/1999) , dry extract from the aerial part of chalcedony lichen (patent RU No. 2138284, publ. 09/27/1999), dry extract of Amur maaki (patent RU No. 2342944, publ. 10.01.2009), liquid red clover extract (patent RU No. 2279287, publ. 10.07.2006), dry extract of white melilot (patent RU No. 2471495, publ. 10.01.2013).

Conducted in the laboratory of pharmacology of blood circulation NIIIFiRM them. E.D. Goldberg's study of the hemorheological properties of extracts of a number of plants in Siberia showed that the cuff extract ordinary has a pronounced positive effect on the normalization of hemorheological properties of blood in cardiovascular pathology in rats (Plotnikov M. B. Hemorheological properties of extracts from some plants containing flavonoids / M. B. Plotnikov, A.A. Koltunov, O.I. Aliyev [et al.] // Plant Resources. - 1998. - T. 34, No. 1. - P. 87-91). The development of a medicinal herbal remedy based on a cuff extract effective in SPVC has been updated.

The closest analogue of the present invention is the developed granules and tablets based on the extract of the common cuff (Schetinin P.P. Obtaining granules and tablets based on the extract of the common cuff as an agent that limits the formation of the syndrome of increased blood viscosity / P.P. Schetinin, V.Yu. Andreeva, IM Smolyakova // Electronic Scientific and Educational Bulletin "Health and Education in the XXI Century." - 2011. - T. 13, No. 10. - P. 485-486).

The source discloses a composition that limits the formation of high blood viscosity syndrome and includes a thick extract of common cuff, sucrose, lactose and 5% aqueous solution of methylcellulose.

The disadvantage is that the known composition is difficult to tablet.

For the administration of the drug inside, especially with a long course of treatment, solid forms are most suitable. The tablet is one of the most convenient and technologically advanced forms of performing solid dosage forms of drugs, as it is produced by the factory, which means it is stable and retains the properties of the drug for a long time (Mashkovsky M.D. Medicines / M.D. Mashkovsky. - M .: New Wave, 2007 .-- 1206 p.).

An object of the invention is the creation of a dosage form based on an extractive complex isolated from an ordinary cuff that meets the requirements of the current State Pharmacopoeia. Tablets based on the extract of the ordinary cuff should have high strength, high stability during storage, while quickly disintegrating in the environment of the gastrointestinal tract.

The extract of the common cuff, like most of the substances of plant origin, does not have the ability to direct tableting. Therefore, to create a stable solid dosage form that meets all the requirements of the state pharmacopoeia, a technology for producing tablets by pressing previously obtained granules based on the extract of an ordinary cuff is proposed.

The problem is solved by developing a solid dosage form (tablets) based on the extract of the ordinary cuff with a residual moisture content of 25%, including glucose, lactose, calcium stearate and methyl cellulose solution in the ratio of components, wt. % respectively - 6; 46.8; 46.8; 0.1; 0.3.

The authors managed to obtain an active agent in the form of a thick mass that retains pharmacological properties, and to preserve the tablet hardness during manufacture by using a mixture of lactose and glucose as a diluent. The use of methylcellulose as a binder in the form of a solution in combination with the proposed diluent also allowed us to achieve our goal.

To obtain granules by wet granulation, 10 formulations were developed, which differed in the ratio of excipients. Each type of granule was examined according to quality parameters in accordance with the requirements of the current State Pharmacopoeia: fractional composition, humidity, disintegration time, abrasion resistance (Table 1).

In appearance, the granules had a rounded shape and uniform dark golden color. Prescriptions, which are included as a filler of microcrystalline cellulose (MCC), do not achieve a good result. Lactose and glucose prescriptions show good and excellent results. The use of starch mucus as a bonding agent impairs the hygroscopicity of the tablets, which can affect storage of the tablets, and also increases the risk of microbial contamination. The use of polyvinylpyrrolidone (PVP) significantly increased the disintegration time and the amount of dust fraction. Talc, as a moving substance, increased the force exerted on the ejection of tablets. Thus, the highest quality parameters showed copy No. 5 (Table 2).

The granular mass was then compressed on a manual hydraulic press in a tablet matrix using a punch with a diameter of 10 mm at a pressure of 90 MPa. The use of less pressure leads to a deterioration in the quality of the tablets. The use of more pressure does not improve the quality of the tablets. The following indicators served as criteria for optimizing the quality of the tablets: tablet breaking strength; tablet abrasion resistance; disintegration of tablets. The data obtained indicate a good quality of the tablets, if calcium stearate is used as an antifriction substance, as well as their compliance with the requirements of regulatory documents. Tablets according to the invention are obtained without cracks and chips, with smooth edges.

The technical result obtained by the implementation of the present invention is to achieve the required tablet quality, in particular, satisfactory strength, storage stability, the required release rate in the body, regardless of the activity of gastric and intestinal juices and intestinal motility. As a result, a technology was developed for manufacturing a solid dosage form based on an extractive complex isolated from an ordinary cuff that meets the requirements of the current State Pharmacopoeia. EFFECT: invention allows convenient dosage of a medicine upon use. In addition, the developed technology of tablets based on the extract of the ordinary cuff ensures uniform distribution of the extract in the tablet mass, its stability and good release of the active ingredient in a liquid medium.

The claimed technical solution proposes an original prescription of tablets based on a thick extract of a cuff ordinary, including a thick extract of a common cuff obtained by evaporation of an alcoholic extract to a residual moisture content of 25%, containing as an auxiliary lactose and 5% aqueous solution of methylcellulose. Additionally, as auxiliary substances, the product contains glucose and calcium stearate, in the following ratio, wt. %:

thick cuff extract 6 glucose 46.8 lactose 46.8 calcium stearate 0.1 5% aqueous solution of methyl cellulose the rest is up to 100

The optimal ratio of components to ensure the quality requirements of the dosage form is claimed.

Implementation example. The extract was obtained from the terrestrial part of the common cuff (Alchemilla vulgaris L.s.l.) by the method of multistage countercurrent extraction. As extractant used 40% ethanol. The liquid extract was evaporated by convective drying in a gentle mode until a thick viscous mass with a residual moisture content of 25% was formed (Smolyakova I.M.The development of a technology and methodology for standardizing cuff extract ordinary / I.M. Smolyakova, V.Yu. Andreeva, G.I. Kalinkina, P.P. Schetinin, S.N. Avdeenko // Chemical and Pharmaceutical Journal. - 2011. - V. 45, No. 11. - P. 27-30).

A mixture of sieved powders of glucose, lactose and a weighed portion of the thick extract is mixed with the addition of a solution of methylcellulose until the moisture is evenly distributed, granulated in a plant to obtain granulate through a 2 mm sieve, the granulate is dried by convective drying to a residual moisture content of 1.5-2%.

The granulate is dusted with calcium stearate and the mixture is tabletted at a pressure of 90 MPa. The resulting tablets with an average weight of 0.5 g fully satisfy the requirements for solid dosage forms. Standard methods of pharmacopeia research showed that the proposed tool provides speed (no more than 15 minutes) and uniformity of the release of the extract.

The above-described technology for the manufacture of tablets based on the extract of the ordinary cuff provides a product (tablet medicine) that meets the standards and requirements of the state pharmacopoeia for tablets: tablets do not crumble, have solid even edges, a smooth surface, and high strength. The developed composition of the tablets ensures that there is no sticking of the tablet mass on the equipment; also, in the manufacture of finished tablets, the loss of the active substance and the change in the mass ratio of the components with respect to the calculated one are minimized.

Information sources

1. Mashkovsky M.D. Medicines / M.D. Mashkovsky. - M .: New wave, 2007 .-- 1206 p.

2. Plotnikov M.B. Medicines based on dikvertin / M.B. Plotnikov, N.A. Tyukavkina, T.M. Plotnikova. - Tomsk: Publishing house of Tomsk University, 2005. - 228 p.

3. Plotnikov M.B. Hemorheological properties of extracts from some plants containing flavonoids / M.B. Plotnikov, AA. Koltunov, O.I. Aliev [et al.] // Plant resources. - 1998. - T. 34, No. 1. - S. 87-91.

4. Shchetinin P.P. Obtaining granules and tablets based on the extract of the cuff ordinary as a means of limiting the formation of high viscosity syndrome / P.P. Shchetinin, V.Yu. Andreeva, I.M. Smolyakova // Electronic Scientific and Educational Bulletin "Health and Education in the XXI Century". - 2011. - T. 13, No. 10. - S. 485-486 (prototype).

5. Smolyakova I.M. Development of technology and methods for standardizing the extract of the cuff ordinary / I.M. Smolyakova, V.Yu. Andreeva, G.I. Kalinkina, P.P. Schetinin, S.N. Avdeenko // Chemical and Pharmaceutical Journal. - 2011. - T. 45, No. 11. - S. 27-30.

Claims (1)

A tablet drug for the treatment of high blood viscosity syndrome, including a thick extract of the common cuff obtained by evaporation of an alcohol extract to a residual moisture of 25%, as well as lactose and methyl cellulose as excipients, characterized in that it additionally contains glucose and calcium stearate as excipients , in the following ratio of components, wt.%:
thick cuff extract 6 glucose 46.8 lactose 46.8 calcium stearate 0.1 5% aqueous solution of methyl cellulose the rest is up to 100