RU2571071C2 - Agent with albumin and propolis extract, exhibiting reparative activity in anaemias of various genesis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to an agent in the form of a suppository applicable for treating hemorrhagic anaemia, which contains as active substances albumin and 10% ethanolic propolis extract, type A solid fat, Lutrol F68 in certain proportions.

EFFECT: agent provides oncotic, colloidal blood pressure recovery in treating hemorrhagic anaemia, exhibits reparative, anti-inflammatory, spasmolytic, antibacterial action with constant-rate release of the active substances; it is easy to use by patients independently.

2 cl, 2 dwg, 3 tbl, 6 ex

Description

The present invention relates to medicine, namely to pharmacy, and relates to the development of agents in the form of medical suppositories containing albumin and propolis extract, and can be used in the complex treatment of hemorrhagic anemia.

The well-known drug albumin, manufactured under various trade names - the drug "Plazbumin 20" - a 20% solution for infusion in bottles of 20 g in 100 ml, produced by Talekris Bioteralutiks Inc. USA.

Albumin preparations known are Albumin Postab dry, Albumin Dessau, Donor albumin, placental albumin, Human albumin, Zelnab, Postab, Uman albumin in the form of infusion solutions - 5%, 20%, 25%. Albumin is obtained by fractionating blood, plasma, placenta, blood serum from healthy donors. The therapeutic effect of albumin is due to its physiological functions - high oncotic activity [http://www.piluli.com.ua/notes.php?lek=21028]. The main active ingredient is albumin, a plasma substitute, a natural protein, and a blood product. It is part of the human protein fraction. In human plasma in a healthy state, albumin constitutes 60% of all protein proteins. Albumin contains 20 amino acids. It is synthesized in the liver. The main task of albumin is to maintain oncotic colloidal blood pressure. Solutions of the drug are prepared from the placenta, blood plasma by fractionation. Albumin is a clear liquid, the color of which varies from light brown to yellow [http://medside.ru/albumin-drug].

Albumin is effectively used to correct hypoalbuminemia of various etiologies, restore oncotic, colloidal blood pressure, impaired hemodynamics (central, peripheral), water-electrolyte balance, improves the absorption of drugs, has a detoxifying effect. Albumin transports and binds fatty acids, pigments, drugs, metal ions, and inactivates toxins.

Known composition for the treatment of wounds and burns, which contains a stimulator of reparative processes - etaden, targeted additives - etonium and trimecaine, and a base, which is used as a water-polyethylene oxide solution, glycerol-polyethylene oxide solution and an emulsion base of the type "oil-in-water" [patent RU 2164133, 2001].

Known wound healing coating for the treatment of burns, which is made in the form of a plate based on collagen and contains propolis extract concentrated in the following ratio of components, wt.%: Propolis extract concentrated 1.0-2.0, collagen - the rest, may additionally contain 40% - aqueous solution of alfalfa seed in the amount of 1.3-1.5% [patent RU 2231368, 2004].

A drug with albumin and propolis extract is known for the treatment of burn diseases in the form of an ointment containing dry albumin and alcohol propolis extract, and as an ointment base, medical vaseline, pentol and purified water, in the following ratio, wt.%: Dry albumin 10; alcohol propolis extract 5; medical vaseline 38; pentol 2; purified water to 100, additionally containing a preservative (mixture of nipagin and nipazole 7: 3) 0.1 [patent RU 2381804, 2010].

Known means Ferroplex, containing as active substance iron sulfate and ascorbic acid in the amount of 50 mg and 30 mg in the form of dragees. Ferroplex is used in the treatment of anemia of various origins (hypochromic anemia, chronic gastritis, the condition after resection of the stomach, acute and chronic bleeding, peptic ulcer of the stomach and duodenum) [http://www.vidal.ru/poisk_preparatov/ferroplex_14861.htm].

The closest analogue of the invention is the drug Propolis suppositories 0.1 No. 5. Composition: 1 suppository contains, as an active substance, a phenolic hydrophobic preparation of propolis, in terms of 50%, the content of the amount of phenolic compounds is 0.1 g, and dimethyl sulfoxide, propylene glycol, and solid fat as excipients [http: //www.lekhim. ua / products / propolis.html].

The objective of the invention is the expansion of the arsenal of funds for the treatment of hemorrhagic anemia with reparative activity and restoration of oncotic, colloidal blood pressure.

EFFECT: obtaining a new medicinal product in the form of rectal suppositories with reparative activity, providing restoration of oncotic, colloidal blood pressure during hemorrhagic anemia.

The specified technical result is achieved in that the agent in the form of a suppository used to treat hemorrhagic anemia, containing propolis as an active substance and solid fat as an auxiliary substance, according to the invention additionally contains albumin as an active substance, and contains 10% as propolis propolis alcohol extract, and as an auxiliary substance additionally contains lutrol F68, in the following ratio of components, g per 1 suppository:

Albumen 0.05 Propolis Extract 10% Alcohol 0.3 Type A solid fat 2.0 Loutrol F 68 0.2

In this case, ethyl alcohol 70% is used as a solvent to obtain a 10% alcohol extract of propolis.

The invention is illustrated by the following drawings: figure 1 shows the dynamics of the release of albumin from suppositories; figure 2 - the content of cerulloplasmin in the blood of rats, where 1 - intact animals, 2 - control, 3 - received albumin intraperitoneally, 4 - received albumin with propolis extract in the form of suppositories.

All components that make up the product are approved for medical use.

Dry albumin placental VFS 42-1104-81.

Propolis TU GOST 28886-90. The introduction of alcohol propolis extract in combination with albumin into the suppository composition of the drug increases tissue regeneration, has antimicrobial activity, and contributes to the manifestation of the analgesic, hemostatic, immunomodulating, reparative effect of the dosage form.

Type A solid fat - VFS 42-3466-97 is a solid confectionery fat based on plasticized salomas.

Lutrol F 68 BASF (Germany) 9003-11-6. Lutrol® F 68 is a hydrophilic polymer, a block copolymer of polyoxyethylene polyoxypropylene, available in granular form with an average particle size of about 1000 microns, while non-crystalline active ingredients have a particle size in the range of 20-200 microns. One of the physical ways to increase the solubility of the active ingredient is to increase its surface area by micronization. Another method is the use of solubilizers, such as surfactant polymers - poloxamers.

In the available scientific, medical and patent literature, information about the popularity of rectal suppositories containing albumin and propolis alcohol extract as active substances, and solid fat type A and lutrol F68 as a basis, was not found for a certain ratio of components. Thus, the claimed invention meets the criterion of "novelty."

As a result of experimental studies, it was found that the proposed suppositories have high bioavailability and a number of advantages: they have a satisfactory appearance, are homogeneous. The composition of the suppository base contributes to the rapid and further prolonged release of the active substances: albumin and propolis extract. Giving the drug the form of suppositories provides convenience and hygiene of use, storage stability. Due to the introduction of albumin in the composition of the drug in combination with propolis extract, suppositories have a wide range of biological and therapeutic activity: they have a regenerating effect, restore the oncotic, colloidal blood pressure during hemorrhagic anemia, have an antioxidant effect in combination with anti-inflammatory, analgesic and antibacterial effects. In addition, suppositories have a uniform release of active substances, are convenient for patients to use on their own. In addition to the manifestation of known properties, each component of the claimed composition in the aggregate enhances its effect, which is explained, obviously, by the effect of their synergism. Thus, the claimed invention meets the criterion of "inventive step".

Example 1. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; Type A solid fat 2.0 g; emulsifier T2 0.2 g

In a porcelain evaporation cup, the emulsifier T2 and type A solid fat are fused at a temperature of 50-60 ° C, transferred to a heated mortar, the calculated amount of albumin and alcohol propolis extract are added in portions to a semi-cooled suppository base (39-42 ° C), continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 9 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1%, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 1 and table 2, composition 1).

Example 2. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; Type A solid fat 2.0 g; emulsifier twin-80 0.2 g

In a porcelain evaporation cup, the Tween-80 emulsifier and solid fat (type A) are fused at a temperature of 50-60 ° C, transferred to a heated mortar, a calculated amount of albumin and alcohol propolis extract are added in portions to a semi-cooled suppository base (39-42 ° C), and continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 9 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1%, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 2 and table 2, composition 2).

Example 3. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; Type A solid fat 2.0 g; Lutrol F68 0.1 g; Cremophor RH-40 0.1 g

In a porcelain evaporation cup, type A solid fat, cremophor RH-40 and lutrol F68 are fused at a temperature of 50-60 ° C, transferred to a heated mortar, a calculated amount of albumin and alcohol propolis extract are added in portions to a semi-cooled suppository base (39-42 ° C), and continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 11 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1%, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 3 and table 2, composition 3).

Example 4. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; Type A solid fat 2.0 g; Cremophor RH-40 0.2 g.

In a porcelain evaporation cup, type A solid fat, cremophor RH-40 is fused at a temperature of 50-60 ° C, transferred to a heated mortar, a calculated amount of albumin and alcohol propolis extract are added in portions to a semi-cooled suppository base (39-42 ° C), and continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 11 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 4 and table 2, composition 4).

Example 5. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; solid fat (type A) 2.0 g; emulsifier T2 0.1 g; emulsifier twin-80 0.1 g

In a porcelain evaporation cup, a T2 emulsifier, Tween-80 emulsifier and type A solid fat are fused at a temperature of 50-60 ° C, transferred to a heated mortar, a calculated amount of albumin and alcohol propolis extract are added in portions in a semi-cooled suppository base (39-42 ° C), and continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 9 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1%, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 5 and table 2, composition 5).

Example 6. Composition per 1 suppository: albumin 0.05 g; propolis extract 10% alcohol 0.3 g; Type A solid fat 2.0 g; Lutrol F68 0.2 g.

In a porcelain evaporation cup, solid fat (type A) and lutrol F68 are fused at a temperature of 50-60 ° C, transferred to a heated mortar, a calculated amount of albumin and alcohol propolis extract are added in portions to a semi-cooled suppository base (39-42 ° C), and continuously triturated. In prepared (pre-chilled and lubricated with liquid paraffin) suppository forms the mass is poured, cooled in the refrigerator at a temperature of 3-5 ° C for 20 minutes, after which the quality of the suppository is evaluated by appearance, elasticity, uniformity, solubility. The resulting suppositories are of regular shape, solid and uniform. The total dissolution time is 11 minutes. The determination of pharmaceutical availability was carried out by agar diffusion using a solution of ninhydrin 1%, which was introduced into agar in an amount of 5%. The effect of excipients on the release of albumin is noted (table 1, composition 6 and table 2, composition 6).

The effect of suppositories with albumin on the relief of the effects of experimental hemorrhagic anemia in rats was studied. There were 5 animals in each group. After six hemorrhages, rats developed acute anemia, manifested in a decrease in hemoglobin concentration to 61% of the initial level, and the level of serum iron decreased by 3 times. For 5 days, albumin was administered intraperitoneally to rats at a dose of 10 mg / day for infusions and suppositories with the same amount of albumin and propolis extract. The results of the experiment showed that, starting from the 7th day, there is an increase in hemoglobin up to 91% (with the introduction of the infusion solution) and 95% with the introduction of suppositories. In the control group, on the 7th day, the hemoglobin level was 65%, and on 14 - 72%. The serum ferroxidase activity of ceruloplasmin, reduced by the 5th blood loss, was restored to the initial level only in rats treated with albumin (table 3, figure 2).

Ceruloplasmin - the main copper proteide, has ferrooxidase activity due to the fact that it catalyzes the oxidation of Fe2 + to Fe3 +.

A sharp violation of copper metabolism is observed with anemia, when its concentration in the blood increases significantly with a decrease in the content of deposited copper in the liver tissue. Copper in combination with cobalt, like ceruloplasmin itself, is a valuable drug for the treatment of hypochromic anemia in children, as well as anemia from blood loss and chronic anemia in women. In some cases, the occurrence and development of anemia is associated with a lack of copper in food. In this case, a very noticeable depletion of copper in the liver and an increase in the concentration of this element in the blood are usually noted.

From the above examples it is seen that the composition described in example 6 is optimal from the point of view of ease of use, high release of active substances and at the same time the effect of prolongation.

Obtaining the proposed suppositories is easily feasible, and when using them, the specified technical result is achieved. Thus, the claimed invention meets the criterion of "industrial applicability".

Claims (2)

1. The drug is in the form of a suppository, used to treat hemorrhagic anemia, containing propolis as an active substance and solid fat as an auxiliary substance, characterized in that it additionally contains albumin as an active substance, and as propolis contains 10% alcohol extract propolis, and as an auxiliary substance additionally contains lutrol F68, in the following ratio of components, g per 1 suppository:
Albumen 0.05 Propolis Extract 10% Alcohol 0.3 Type A solid fat 2.0 Loutrol F 68 0.2 2. The tool according to p. 1, characterized in that as a solvent to obtain a 10% alcoholic extract of propolis use ethyl alcohol 70%.

Images