Hepatoprotective agent

 

The invention relates to the creation of hepatoprotective funds. The tool is made in the form of solution for injection contains essential phospholipids, benzyl alcohol, deoxycholic acid, sodium chloride, sodium hydroxide, Riboflavin,-tocopherol, ethanol and water for injection at a specific ratio of ingredients. The tool is non-toxic and with the introduction does not cause significant changes in the activity of enzymes, concentration of hemoglobin, the number of platelets and leukocytes. 3 tab., 2 Il.

The invention relates to medicine and relates to integrated product in the form of a solution for injection that contains essential phospholipids, active beginning which are of natural origin diglyceride esters holinesterzoy acids and unsaturated fatty acids: linoleic, linolenic and oleic.

Known made in Germany " product “Essentiale” (Handbook Vidal, ed. 2. - M., 1996, p. B-816; Mashkovsky M. D. Drugs, ed. 12. - M., 1993, T. II, S. 52). It comes in the form of capsules and solution for injection in ampoules of 5 ml In injection form in one ampoule contains essential phospholipids 250 mg, pyridoxine of the invention is to provide on the basis of essential phospholipids domestic drug hepatoprotective activity in injectable dosage form. Due to the qualitative and quantitative selection of ingredients, the drug is non-toxic, with the introduction in therapeutic doses does not cause statistically significant changes in the activity of the enzymes alanine, aspartokinase and alkaline phosphatase, hemoglobin concentrations, in number of platelets and leukocytes.

To solve the problem proposed hepatoprotective agent in the form of a solution for injection that contains essential phospholipids, benzyl alcohol, deoxycholic acid, sodium chloride, sodium hydroxide, Riboflavin,-tocopherol, ethanol 96and water for injection. The product contains these ingredients in the following ratio, wt.%:

3-Phosphatidyl)choline from soybean,

containing 93% (3-phosphatidyl)choline 4,5-5,5

Benzyl alcohol 0,8-1,0

Deoxycholic acid 2,0-2,6

Sodium chloride of 0.2-0.3

Sodium hydroxide of 0.2-0.3

Riboflavin 0,009-0,011

-Tocopherol 0,013-0,02

Ethanol 960,25-0,4

Water for injection Else

An example of obtaining injectable solution essential phospholipids

In one ampoule (5 ml) contains mg:

3-Phosphatidyl)choline from soybean,

sociatry hydroxide 11,5

Riboflavin 0,5

-Tocopherol 0,75

Ethanol 9616,304

Water for injection 5 ml

To prepare 1 l of the drug 700 ml of water for injection is heated to a temperature of 45±5C and saturated with nitrogen. Download and dissolve 2.4 g of sodium chloride. Download 23 g deoxycholic acid after stirring the obtained white suspension. To the suspension under stirring was added 1 M solution of sodium hydroxide to dissolve deoxycholic acid, the pH value is of 8.8 ą 0.2. The consumption of 1 M solution of sodium hydroxide of about 60 ml.

In a clear colorless solution at a temperature of 455With loads estimated number of essential phospholipids and stirred until a homogeneous suspension is yellow.

After adding 9 g of benzyl alcohol and mixing receive clear solution is light yellow in color.

Add 0.1 g of Riboflavin and stirred until complete dissolution getting the solution bright yellow color with greenish light, which is then cooled with stirring to a temperature of 20±2C.

Estimated number

After filtration through a filter Millipore” with a pore size of 22 μm get a clear solution, which is subjected to sterilizing filtration and poured in a stream of nitrogen in a sealed dark glass.

A comparative study of the proposed drug and the drug “Essentiale N” - solution for injection in ampoules of 5 ml manufactured by “Rhone Poulenc Rorer (Germany), series 18541.

The active substance of the drug “Essentiale N” - essential phospholipids (EPL substance) - are the main elements in the structure of cell membrane and cell organelles liver. In the body of the EPL have a normalizing effect on the metabolism of lipids, proteins and detoxification function of the liver; restore and preserve the cellular structure of the liver and phospholipidosis enzymatic system; inhibit the formation of connective tissue in the liver.

“Essentiale N” is used in fatty degeneration of the liver of various etiology, acute and chronic hepatitis, liver cirrhosis, hepatic coma, radiation syndrome, toxemia of pregnancy, poisoning, drug and alcohol poisoning liver, N. the absorption of drugs held on spectrophotometer Ultrospec II” manufactured by LKB Biochrom. Drugs were diluted with distilled water in the ratio of 1:3.5, and the resulting solution was filtered through filter Millipore” with a pore size of 0.45 ám.

In Fig.1 presents an overview of the absorption spectrum of a solution of the reference preparation, shot in the wavelength interval from 300 to 550 nm. There are two distinct absorption: one at 370 nm (0,72 units of optical density), the other at 443 nm (0,73 units of optical density).

In Fig.2 shows the absorption spectrum of the solution of the proposed drug, shot in the same wavelength interval. Here also there are two peaks of absorption at the same values of wavelengths, as shown in Fig.1.

Spectra of the drugs are similar in location of the peaks of maximum absorption, which indicates the identity of the active substances in solutions of drugs.

Spent the determination of acute toxicity of drugs. For this outbred white mice were injected in the tail vein at 0.5 ml of appropriately diluted offer drug or drug comparison. Dose that was administered the drugs, was 400, 500, 600, 700, 800, and 900 mg/kg observation of the mice was performed within two weeks after a single injection of drugs.

As the proposed drug and the comparator drug in the introduction II. At doses exceeding 500 mg/kg, was observed convulsions - first tonic, with further increase of the dose - generalized clinico-tonic. The death of animals occurred due to respiratory arrest.

For the proposed drug value LD50amounted to 634±65 mg/kg, compared to a drug 667±70 mg/kg

Subacute toxicity of the drugs studied in outbred white rats weighing 180-220 g Drugs in the amount of 1 ml was injected into the tail vein of animals. Based on the fact that therapeutic dose is 40 mg/kg, and ten times therapeutic dose is 400 mg/kg, laboratory animals were divided into five groups:

- group 1 - 10 times the proposed dose of the drug,

- group 2 - the proposed therapeutic dose of the drug; and

- group 3 - to 10-fold dose of the comparator drug;

- group 4 - therapeutic dose of the comparator drug;

- group 5 - intact animals (saline solution).

The drugs were administered to rats for 14 days. The degree of intoxication was assessed by the General condition of the animal, condition of coat, the change in the number of uriasi, defecation, salivation, the onset of tremor, seizures, changes in frequency and rhythm of the breath.

After okonchan the kidneys, liver, spleen, thymus and brain for histological analysis and blood samples for determination of biochemical and haematological parameters.

In table.1 presents the results of biochemical blood analysis laboratory animals. Between the results obtained for the proposed drug and drug comparisons, significant differences are not observed neither in the introduction of therapeutic doses, nor with the introduction of 10-fold dose of drugs. There is no difference from the data obtained in control animals.

The results of hematological analysis are given in table.2. They are practically the same in all groups of animals, including the control.

In response to the introduction of drugs in both the studied doses were not changed and WBC blood of laboratory animals (PL.3).

Histological examination in the definition of subacute toxicity showed that the introduction of therapeutic doses of the proposed product and reference product was not observed pronounced pathological changes in the studied organs of animals, including gastric mucosa. Defining characteristics of the microscopic structure of the liver, kidneys, thymus, spleen, brain tissue SOS with the introduction of 10-fold therapeutic dose comparison.

Studies conducted after the introduction of 10-times the proposed therapeutic dose of the drug showed that the macroscopic structure of the liver, kidneys, thymus, spleen, brain tissue and the mucous membrane of the stomach corresponds to that found in control animals.

Microscopic examination showed the following:

Liver. Without visible changes, clearly expressed the typical delicatest structure. There are single-celled infiltration along the portal tracts in the parenchyma. Separate Central and Podmoskovye Vienna testirovanie and filled with blood. There were areas with increased capillary pattern, clearly visible endothelial cells.

The buds. In General, histoarchitecture body is not different from that in the control group of animals. Cortical substance presents vascular glomeruli and tubules of the nephron. The capsule is adherent to the parenchyma of the organ. Major vascular highway preserved, the walls of blood vessels intact. The brain substance is represented by the rays of the collecting tubes, the longitudinal and transverse sections of the loops of the nephron. The epithelial lining of the tubules without pathological changes. There were areas with focal small cell lung infiltrates.

The thymus. Without Wulai and prevails over the brain. In the medulla is found mainly small thymocytes and peripheral crust liberally infiltrated large and medium thymocytes. Capillaries places testirovanie and crownpointe.

The spleen. A typical structure, the capsule is well developed and contains fibrous components. The white pulp is detected in the form of periarterial clutch and primary lymph follicles. The boundary between red and white pulp is soft. The red pulp is enhanced by the sinusoidal dilation structures and explicit content of erythrocyte mass.

The brain. The bark has five distinct layers with a characteristic shape and size of cells. Width, customlocale layers, cytoarchitectonic, state basophilic substance are OK.

Due to the fact that solutions of the drugs were injected into the tail vein of animals, local irritating action of the preparations was assessed by the state of the epithelium of the tail. Using binocular lenses conducted a visual inspection of the place of introduction of the solution in order to detect hematomas, violation of the integrity of the epithelium and the presence of ulcerative lesions. In all groups of laboratory animals were marked by single hematoma, and their number is not depended on the dose of the drug.

revealed was not.

The histological pattern uncut tails in the control group of animals typical. Muscles dyed, cartilage education are clearly structured, the vessels are well developed. Veins are moderately dilated.

In groups of animals, which have introduced the proposed drug and the comparator drug in both doses, the histological pattern without the expressed pathology, cytoarchitectonic the introduction of drugs is the same as in the control.

Claims

1. Hepatoprotective agent, characterized in that it is a solution for injection and contains 3-phosphatidyl)choline from soybean, containing 93% 3-phosphatidyl)choline chloride, benzyl alcohol, deoxycholic acid, sodium chloride, sodium hydroxide, Riboflavin,-tocopherol, ethanol 96and water for injection in the following ratio of ingredients, wt.%:

3-Phosphatidyl)choline from soybean, containing 93% (3-phosphatidyl)choline 4,5-5,5

Benzyl alcohol 0,8-1,0

Deoxycholic acid 2,0-2,6

Sodium chloride of 0.2-0.3

Sodium hydroxide of 0.2-0.3

Riboflavin 0,ECCI Else

 

Same patents:

The invention relates to the creation of a group of drugs vitamin b and lidocaine combined drug, analgesic, improves blood circulation, stimulates the regeneration of nerve tissue and antiallergic

The invention relates to the field of pharmaceutical industry and relates to a method and composition containing acetylcholine

The invention relates to medicine, in particular to pharmacy
The invention relates to the field of medicine and relates to a liquid dosage form of naltrexone, intended for internal use
The invention relates to medicine and AIDS, based on piracetam, affect the Central nervous system
The invention relates to the field of pharmaceutical industry

The invention relates to the field of medicine and concerns sedative medicinal composition of soft steps, including for Pediatrics

The invention relates to medicine, namely to the means for treatment based on blood, and can be used in the treatment of patients with defects in epithelial tissues of different etiology

The invention relates to pharmacy and medicine and relates to a medicinal product for the treatment of opium addiction
The invention relates to medicine, in particular to gynecology, and can be used to treat patients with ovarian cancer stage III - IV

The invention relates to medicine, namely to medicines for the treatment of skin cancer and precancerous skin diseases

The invention relates to new derivatives of phospholipids, namely alkylphosphates or ALCOHOLATES, kalinovy residue which is part of a heterocyclic ring, the method of obtaining a class of these compounds, as well as to medicines and the way to obtain medicines that contain compounds as biologically active substances

The invention relates to the field of pharmaceutical industry and relates to an aqueous solution containing bile acid, and method of its production

The invention relates to medicine, namely to the adhesive polymer matrix applied to the device for percutaneous introduction of progestogenic, and this matrix is composed of a single layer (2) or the following sequential layers: if necessary, layer (1), called anchoring, formed of silicone polymer; a layer (2) formed of silicone polymer enriched Trimegestone and/or one or more pharmaceutically acceptable derivatives and, if necessary, a plasticizer; if necessary, the layer (3), called adhesive formed of silicone polymer

The invention relates to biology, can be used in medicine and concerns the stimulation of meiosis of germ cells in mammals

The invention relates to biology, and further can be used in medicine and for the stimulation of meiosis of germ cells in mammals

The invention relates to derivatives of 16-hydroxy-11-(substituted phenyl)-östra-4,9-diene corresponding to the formula I, where R1- C1-6- alkyl, triflate or phenyl, where the phenyl group is optionally substituted by one or more substituents selected from cyano, halogen and C1-4-alkyl, R2is hydrogen or carboxy-1-oxo-C1-6-alkyl; R3is hydrogen, halogen or1-6- alkyl, optionally substituted by one or more1-6-alkoxy, R4is hydrogen or C1-6-alkyl, and X, O or NOH; or their pharmaceutically acceptable salts or MES; describes the methods for their preparation and the pharmaceutical composition is intended for use in medical therapy particularly for the treatment or prevention glucocorticoidavoid diseases or symptoms

The invention relates to steroids Sterol number of General formula I, where R1and R2independently selected from the group comprising hydrogen and unbranched or branched C1-C6-alkyl; R3selected from the group including hydrogen, methylene, hydroxy, oxo, =NOR26where R26represents hydrogen and hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or R3together with R9or R14designate an additional bond between the carbon atoms that are associated with R3and R9or R14; R4selected from the group comprising hydrogen and oxo, or R4together with R13designate an additional bond between the carbon atoms that are associated with R4and R13; R5selected from the group comprising hydrogen and hydroxy, or R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6; R6represents hydrogen or R6together with R5designate an additional bond between the carbon atoms that are associated with R6and R5or R14; R9represents hydrogen or R9together with R3or R10denote dobavlaet hydrogen or R10together with R9designate an additional bond between the carbon atoms that are associated with R10and R9; R11selected from the group comprising hydroxy, acyloxy, oxo, = NOR28where R28represents hydrogen, halogen, or R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R12; R12represents hydrogen or R12together with R11designate an additional bond between the carbon atoms that are associated with R12and R11; R13represents hydrogen or R13together with R4or R14designate an additional bond between the carbon atoms that are associated with R13and R4or R14; R14represents hydrogen or R14together with R3, R6or R13designates an additional bond between the carbon atoms that are associated with R14and R3or R6or R13; R15is hydrogen; R16selected from the group comprising hydrogen, hydroxy, oxo or16together with R17designate an additional bond between the carbon atoms that are associated with R16and R17; R17represents hydrogen or hydroxy, or R1716; R18and R19represent hydrogen; R25selected from the group including hydrogen, and C1-C4-alkyl; a represents a carbon atom or a nitrogen atom; when a represents a carbon atom, R7selected from the group including hydrogen, hydroxy and fluorine, and8selected from the group including hydrogen, C1-C4-alkyl, methylene, and halogen, or R7together with R8designate an additional bond between the carbon atoms that are associated with R7and R8; R20is1-C4-alkyl; R21selected from the group including1-C4-alkyl, C1-C4-hydroxyalkyl,1-C4-halogenated containing up to three halogen atoms; when a represents a nitrogen atom, R7denotes a lone pair of electrons, and R8selected from the group comprising hydrogen and oxo; R20and R21are1-C4-alkyl with the proviso that the compound of General formula (I) does not have any cumulated double bonds and with the additional condition that the connection is not one of the known compounds cholestenone
Up!