LT6473B - Pharmaceutical composition of syrup form with multiple hepatoprotective effect - Google Patents

Abstract

The present invention relates to the pharmaceutical compositions of syrup form with multiple hepetoprotective effect. The components of the pharmaceutical composition in the syrup form are (in mass percent):@Beet root juice 19,84 - 24,00;@Genuine marigold seed extract 10,37 - 12,55;@Artichoke leaf extract 7,67 - 9,27;@L-ornithine hydrochloride 1,35 - 1,64;@Choline bitartrate 0,72 - 0,87;@Fructose 31,57 - 38,19;@Cleaned water 13,76 -16,64;@Excipients 4,92 - 5,97.

Description

The present invention relates to a pharmaceutical composition in the form of a syrup with multiple hepatoprotective effects comprising biologically active substances (plant materials and amino acids). The resulting pharmaceutical composition restores impaired hepatocyte function, detoxifies the liver and can therefore be used to improve liver function, for the prevention and treatment of liver disease, either as monotherapy or in combination with other agents and medications for treating the liver.

Liver inflammation is one of the most common gastrointestinal diseases. Liver pathology can be caused by smoking, alcohol, drugs, viruses and other infections or metabolic diseases. In about 10% of cases, hepatitis becomes chronic and patients may develop liver fibrosis, cirrhosis and even hepatocellular carcinoma.

Plant extracts have a hepatoprotective effect and are effective throughout the course of liver pathology from infection to recovery. Some natural substances block the ability of the virus to penetrate into liver cells, plant extracts inhibit viral replication and suppress levels of inflammatory markers, stop carcinogenic processes in the liver, and so on. [Kuntz E., et al. Hepatology Principles and Practice. Berlin: Springer Verlag. 2002, p. 825. ISBN 3540-42161-0].

There is reason to believe that natural substances can affect the health of patients with hepatitis. Some plants have long been used in folk medicine, as well as in the production of functional foods and biologically active dietary supplements. However, based on scientific publications such as the US National Library of Medicine (PubMed.gov) and the situation on the EU market, biologically active substances of plant origin are more often used as monoproducts or in blends for traditional Chinese medicine with efficacy and safety not sufficiently investigated.

In vivo studies in animals have shown the hepatoprotective effect of the active ingredient of Silybum marianum (Silybum marianum), an active ingredient of silymarin, in hepatic toxicity [Kropacova et al., Radiats Biol. Radioecol. 38.3 (1998) p. 411-415],

Artichoke leaf extract (Cynara scolymus) promotes biliary excretion [Kirchhoff R., et al. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994, Vol 1, p. 107-115], exhibiting a diuretic and hepatic stimulatory effect [Adzet T., et al. Action of an artichoke extract against CCI4-induced heptotoxicity in rats. Actą Pharm Jugosl. 1987, Vol 37, p. 183-187]. Several in vitro and in vivo studies have demonstrated the antioxidant and hepatoprotective properties of artichoke leaf extract and its active components in resisting hepatocellular damage caused by various hepatotoxins such as CCU and alcohol [Maros T., et al. Extract of Wolverine der Cynara scolymus for Regeneration der Rattenleber. Arzneimittelforschung. 1968, Vol 18, p. 884-886].

Beet root juice (Beta vulgaris) reduces viscous viscosity, increases bile flow [Kane E. Managing Menopause Naturally: Before, During and Forever. United States, 2004. p. 101-103], beet root juice has potent antioxidant properties, reduces DNA damage and mitochondrial hepatocyte damage [Han J., et al. Betanin attenuates paraquat-induced livertoxicity through a mitochondrial pathway. Food and Chemical Toxicology. August 2014, Vol 70, p. 100-106],

Choline preserves the structural integrity of cell membranes, facilitates cell membrane cell synthesis, promotes the synthesis of signaling molecules, and reduces the deposition of low-density lipoproteins on hepatocytes [Kohlmeier, et al. Genetic variation of folate-mediated one-carbon transfer pathway viability predicts susceptibility to choline deficiency in humans. Proc Natl Acad Sci USA 2005, Vol 102 (44), p. 16025-16030].

Ornithine provides the urea cycle, creating a direct detoxification function for the body by removing nitrogen (ammonia) from the body. [McGuire J.P., et al. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency. Dis Model Mech. February 2014; Vol 7 (2), p. 205-213. doi: 10.1241 /dmm.013003]. Even small amounts of ammonia are toxic and it is necessary to maintain the urea cycle within normal limits [Sidhu S.S. L-ornithine L-aspartate in Overt Hepatic Encephalopathy. January 2013; Rose C., et al. L-Ornithine-L-aspartate lovvers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. December 30, 2003].

Known dry pharmaceutical composition for the treatment of the gastrointestinal tract (in tablet form) [VV0200703090] includes dry artichoke extract (Cynara scolymus), dry chilli extract (Peumus boldo), dry marshmallow seed extract (Silybum marianum), .

However, the known pharmaceutical composition does not exhibit an effective hepatoprotective effect and is not convenient to use since some patients find it difficult to swallow the tablets and do not start immediately after swallowing the tablets.

The pharmaceutical composition according to the invention comprising artichoke leaf extract (Cynara scolymus), choline bitartrate, true mocha seed extract (Silybum marianum) is in the form of a syrup and further comprises beet root juice (Beta vulgaris), L-ornithine hydrochloride, purified water, fructose. , excipients, at a percentage by weight of components:

beet root juice 19.84-24.00; true dandelion seed extract 10.37 - 12.55; artichoke leaf extract 7.67 - 9.27; Of L-ornithine hydrochloride 1.35-1.64; choline bitartrate 0.72 - 0.87; fructose 31.57-38.19; of purified water 13.76-16.64; excipients 4.92-5.97.

The plant substances detoxify the body, but indirectly by improving urine output or stimulating the production and flow of bile. Ornithine (L-ornithine hydrochloride), which is added to the pharmaceutical composition, is an amino acid that directly detoxifies the body biochemically inside the liver (through the biochemical processes of the hepatocytes). Beetroot juice added also has a direct positive effect on liver tissue. Choline bitartrate improves the membrane structure of hepatocytes and creates a regenerative function. The experimentally selected composition of the pharmaceutical composition, with the active components having various types of action, produces a multiplicity of hepatoprotective effects.

As excipients, citric acid, thickener xanthan gum, sweetener steviol glycosides, sweeteners sodium benzoate and potassium sorbate may be added to the pharmaceutical composition in the following percentages by weight:

citric acid xanthan gum steviol glycosides sodium benzoate potassium sorbate

3.25-3.93;

1.35-1.64;

0.14-0.16;

0.09-0.11;

0.09-0.11.

In addition, the combination of the active ingredients and excipients in the composition is experimentally selected so that the syrup retains microbiological stability over a long period. The syrup is easy to use and works immediately after a few minutes.

An embodiment of the present invention is described in the example.

A pharmaceutical composition having multiple hepatoprotective effects comprises the components at the following percentages by weight of the components:

beet root juice (Beta vulgaria L.) 22.00;

true dandelion seed extract (Silybum marianum) (70% ethyl alcohol) 11.50; artichoke leaf extract (Cynara scolymus) (70% ethyl alcohol) 8.50; L-ornithine hydrochloride 1.50;

choline bitartrate 0.80;

fructose 35.00;

purified water 15.25;

citric acid 3.60;

xanthan gum (thickener) 1.50;

steviol glycosides (sweetener) sodium benzoate (preservative) potassium sorbate (preservative)

0.15;

0.10;

0.10.

The proposed syrup-shaped pharmaceutical composition is prepared as follows.

Extract of true dandelion seed and artichoke leaves are obtained by maceration in stainless steel extractors using a water / ethanol mixture, 30:70 by volume, as solvent. The resulting extracts were filtered.

In the reactor, citric acid, xanthan gum, fructose, steviol glycosides, sodium benzoate and potassium sorbate are added to the purified water according to the formulation and heated to 78-83 ° C with continuous stirring. The solution is kept at this temperature for 45-60 minutes until a viscous homogeneous liquid is obtained. Adds beet root juice, pasteurizes for 10-15 minutes. The resulting mixture is cooled down to 25-30 ° C, added with true dandelion seed and artichoke leaf extracts according to recipe. Mix thoroughly until smooth. Then, L-ornithine hydrochloride and choline bitartrate are added, one after the other, according to the formula, with stirring for 10 minutes. The mixture is homogenized for 15 minutes. The product is placed in a container, bottled, sealed, labeled and packaged.

A syrup test batch (25 kg) was produced.

Samples were taken from the reactor for microbiological testing. The quality and stability tests were repeated twice, after the test batch was produced and after two months. The results of the quality and stability tests of the syrup described in the example are summarized in Table 1.

As the results meet the requirements of the Regulation, it is concluded that the technological process developed ensures the microbiological stability of the syrup.

Table

Results of the quality and stability tests of the syrup described in the example

Organoleptic characteristics Taste Sweet and sour, with beet juice and existing components aftertaste Appearance Dark red, syrupy liquid The smell Characteristic aroma of beet juice used

Presence of particulate matter Homogeneous viscous liquid without sediment Physico-chemical indicators Content BAV,% 3.4-3.6 pH 4.4-4.7 Density in g / cm ³ 1.15-1.20 Volume of ethyl alcohol,% ~ 12.0-14.0 Microbiological indicators The initial result After two months General amount of micro-organisms, KW / 1g * <1x10 ¹ <1x10 ¹ Yeast and mold, KW / 1g ** <1x10 ¹ <1x10 ¹

* Ph.Eu.2.6.12.p.

Claims (2)

DEFINITION OF INVENTION A pharmaceutical composition having a multifunctional effect of a hepatoprotector comprising artichoke leaf extract, choline bitartrate and true cornflower seed extract, characterized in that it is in the form of a syrup, further comprising beet root juice, L-orintin hydrochloride, purified water, fructose and excipients. for the following components by weight: beet root juice 19.84-24.00; true dandelion seed extract 10.37-12.55; artichoke leaf extract 7.67-9.27; Of L-ornithine hydrochloride 1.35-1.64; choline bitartrate 0.72 - 0.87; fructose 31.57-38.19; of purified water 13.76-16.64; excipients 4.92 - 5.97. 2. A pharmaceutical composition according to claim 1, wherein the excipients include citric acid, a xanthan gum thickener, steviol glycosides sweetener, sodium benzoate preservative, and potassium sorbate at the following percentages by weight: citric acid 3.25 - 3.93; xanthan gum 1.35-1.64; steviol glycosides 0.14-0.16; of sodium benzoate 0.09-0.11; of potassium sorbate 0.09-0.11.