EA011243B1 - Composition having nootropic properties and method for preparing thereof - Google Patents

Abstract

The invention relates to medicine, in particular to pharmacology and can be used for manufacturing an agent having nootropic properties. A method for preparing a composition based on calcium homopantothenate having nootropic properties is characterized in that the calcium homopantothenate is dissolved in heated to 20-40°C water so as to produce solution with concentration 400-600 g/l, the calcium homopantothenate solution is cooled to 15-35°C and added to cooled to 40-60°C sugar syrup. Wherein the composition having nootropic properties comprises the calcium homopantothenate and saccharose with the following component ratio: the calcium homopantothenate 8-12 g, the saccharose 75-78 g., water up to 100 ml. The storage life of the composition is 3 years, it has good organoleptic properties, simple in the production, it has no potential carcinogens in its composition.

Description

The invention relates to medicine, more specifically to the pharmaceutical industry and can be used in industrial technology for the production of agents with nootropic properties.

Known Nootropic agent Pantogam® - calcium salt of homopantothenic acid (M. D. Mashkovsky “Medicines”, thirteenth edition, Kharkov, “Torsing”, 1997, p. 114). The drug is prescribed for children with mental disability (mental retardation and oligophrenia), as well as with delayed speech development. The drug is indicated as part of complex therapy or, in some cases, on its own for the treatment of children suffering from epilepsy. Adult pantogas are prescribed in combination with anticonvulsants for epilepsy with mental retardation. The drug is also used for urination disorders in children and adults (enuresis and daytime urinary incontinence).

The disadvantage is that it is available only in the form of tablets of 0.25 and 0.5 g at a daily dose for children of 0.75-3 g, depending on age and diagnosis. Since the drug is taken by children from 2 months to 15 years, then, given the medical indications of the drug, it may be difficult to enter the desired dose for children of younger, and sometimes older.

Known nootropic agent (VI Patent No. 2177783, publ. 2002.01.10), which is a syrup containing 5-20% pantogam, glycerin, sorbitol, citric acid, aspartame, aromatic essence, sodium benzoate, water in a certain ratio.

In this invention, the drug is calcium homopantothenate (Pantogam®), to improve the taste of which sorbitol syrup is used, as well as the sweetener aspartame and citric acid. The syrup preservative is sodium benzoate; An additional 25-35% glycerol is added.

The disadvantage of this invention is a complex method for producing syrup, due to its multicomponent nature, which does not guarantee the storage of precipitations of both chemical nature and microbial mass during storage. Recently, for a number of components included in the syrup, data have appeared on their undesirable use in food and pharmaceutical products.

First of all, this refers to aspartame (Mogaib 8oyi1b s1 a1. “Akrabate shbiseb 1utrbota8 aib 1eiket1a§ ίη gab.” Eig. 1oiso1, νο1.10, p.2, 2005), which consists of two amino acids - phenylalanine and asparagine, combined between themselves a molecule of methyl alcohol. Aspartame in the body breaks down into its constituent components and methanol, which at a temperature> 30 ° C turns into formaldehyde, a class A carcinogen. As of 2004, ΕΌΑ had already received> 1000 complaints about aspartame, which makes up 80% of all complaints about food additives. In this regard, the use of aspartame in food and medicine intended for children under 4 years of age is prohibited in all European states.

Another undesirable component is the preservative E 211 - sodium benzoate, which is an expectorant. It is introduced into Pantogam syrup as a bactericidal and antifungal agent, which is conditionally approved in Russia, but is prohibited in several European countries. This drug causes allergic reactions, it is forbidden to use for asthmatics and people sensitive to aspirin. In the body, aspartame can react with vitamin C, resulting in the formation of benzene - a powerful carcinogen.

It should also be noted that a low concentration of sorbitol (it is not possible to increase the concentration of sorbitol, because the laxative effect is manifested) does not allow to obtain satisfactory organoleptic parameters of the syrup - the bitter taste of calcium homopantothenate due to the presence of calcium ions is felt in the syrup.

The objective of the present invention is to develop a medicinal product (syrup) based on calcium homopantothenate, devoid of the disadvantages of known funds, and a method for its preparation.

The technical result of the invention is that the created composition has a shelf life of 3 years, has good taste (organoleptic characteristics, bitter taste is absent) and ease of manufacture, there are no potential carcinogens in the composition.

The problem is solved as follows.

The production method consists in carrying out the technology in two stages. At the first stage, with stirring and heating to 20-40 ° C, calcium homopantothenate is dissolved in purified or distilled water in order to obtain a solution with a concentration of 400-600 g / l, sugar syrup is prepared separately from sugar (sucrose in the form of crystals). At the second stage, the previously prepared calcium homopantothenate solution is introduced into the prepared syrup, mixed until a homogeneous syrup is obtained and adjusted to the required volume with water.

A method of obtaining the proposed composition is illustrated by the following example.

In 1.3 l of water heated to 20-40 ° C, 1.0 kg of calcium homopantothenate is dissolved with stirring. Separately, they prepare sugar syrup in water. In 3.4 l of water heated to a temperature of 70-90 ° C, 7.7 kg of sucrose in the form of crystals are dissolved with stirring. In the obtained sugar syrup, cooled to 40-60 ° C, the previously prepared calcium homopantothenate solution is slowly introduced (20-40 min), adjusted to 10 L with water. A sweet taste syrup with a sucrose concentration of 830 is obtained.

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930 g / l and a concentration of calcium homopantothenate 400-600 g / l, which can be used as a nootropic agent.

Another object is a composition (syrup) having nootropic properties, based on calcium homopantothenate, obtained as described above, in the following ratio of starting components, g:

calcium homopantothenate 8-12 sucrose 75.0 - 78.0 water to 100 ml

The product has a density of 1.27 ± 0.05 g / l at a temperature of 20 ° C.

The resulting composition was analyzed for a number of indicators in comparison with the analogue - Pantogam syrup. One of the important indicators of syrups is their organoleptic properties. The results of these studies are given in table. one.

Table 1. Organoleptic properties of the proposed composition and 10% Pantogam syrup

Name

Pantogam

Sweetness

The presence of a sweet taste

Aftertaste

Bittersweet unpleasant

taste

Pure sweet

The proposed syrup is pleasant

As follows from the data given in table. 1, the claimed composition in organoleptic properties surpasses the analogue - the drug "Pantogam" (syrup).

At the same time, studies were conducted on the stability of calcium homopantothenate in the composition of the claimed composition. The concentration was determined by the direct method using an ion-selective electrode according to a calibration graph. The results are shown in table. 2.

Table 2. The concentration of calcium homopantothenate in samples of the claimed composition during storage

Sample No. The concentration of calcium homopantothenate,% After manufacturing In 6 months After 12 months In 24 of the month After 36 months Experienced 01.04 series 8.05 7.95 8.00 7.90 7.95 Experimental Series 02.04 10.00 10.00 10.10 10.05 10.00 Experienced 03.04 series 12,20 12.10 12.05 12.10 12.00

As follows from the table. 2, calcium homopantothenate was stable during storage for three years of observation, remaining transparent.

At the same time, a comparative study of the microbiological purity of the claimed suspension was carried out in comparison with the analogue - Pantogam syrup. The results are presented in table. 3.

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Table 3. The results of microbiological control of homopantothenic acid syrups

Microbiological characteristics resulting from storage through 0 6 months 12 months 24 months 36 months Experienced 01.04 series 20-25 purely purely PURELY 1 out of 10 vials PURELY Experienced 02.04 series 20-25 purely PURELY purely purely purely Experienced 03.04 series 20-25 PURELY purely purely purely 1 out of 10 bottles, conc. 10' Experienced Pantogam recipe series 20-25 PURELY Sediment in 3 of 10 bottles Sowing put. In 4 out of 10 vials -10 ² 6 vials:> 10 ' Not watched Not watched Commercial drug Pantogam from a pharmacy * Seoia 290407 20-25 purely White filament fluid Not watched Not watched Not watched 300407 Series 20-25 purely Liquid with suspension and filamentary fibers Not watched Not watched Not watched Seoia 090207 20-25 purely Liquid with suspension and filamentary fibers Not watched! · Not watched Not watched

* Federal Service Data - Roszdravnadzor

As follows from the table. 3, the claimed composition withstands long-term (up to three years) storage under normal conditions, which is ensured by the formulation changed in relation to the analogue - it is necessary to introduce> 60% sucrose to achieve a preserving and sterilizing effect. The use of 20% sorbitol in combination with a preservative sodium benzoate provides guaranteed purity of the drug only when stored for up to 1.5 years, which is 2 times less than the shelf life of the proposed drug, which is unacceptable for further use in the manufacture of medicines.

A comparative analysis of the bioavailability of Pantogam syrup and the claimed composition in experiments on rats was also conducted. Due to the fact that according to available data pantogues in the body are not metabolized and excreted unchanged, with 67.5% excreted by the kidneys, the content of homopantothenic acid in the urine was studied. It was found that in the urine of rats that took the same dose of Pantogam syrup and the claimed composition, the same concentration of calcium homopantothenate was found, which indicates that the relative bioavailability of the two Pantogam syrups and the claimed composition is almost the same.

Thus, on the basis of the data presented, it can be stated that the proposed composition of calcium homopantothenate, while preserving the pharmacological properties at the analogue level, has significantly better operational properties, a long shelf life, which is extremely important for the pharmaceutical market, simpler manufacturing technology and simple formulation. in which there are no potentially dangerous preservatives and sweeteners.

Claims (4)

1. A method of obtaining a composition having nootropic properties based on calcium homopantothenate, characterized in that the calcium homopantothenate is dissolved in water heated to 20-40 ° C in order to obtain a solution with a concentration of 400-600 g / l, the calcium homopantothenate solution is cooled to 15 -35 ° C and injected into a sugar syrup cooled to a temperature of 40-60 ° C. 2. The method of obtaining the composition according to claim 1, characterized in that the concentration of sugar syrup is 830-930 g / L. 3. The method of obtaining the composition according to claim 1, characterized in that the ratio of the volume of the solution of calcium homopantothenate and the volume of sugar syrup is 1: 4. 4. A composition having nootropic properties containing calcium homopantothenate, characterized in that it additionally contains sucrose in the following ratio of components, g: calcium homopantothenate 8-12, sucrose 75.0-78.0, water up to 100 ml.