RU2561036C1 - Powder-like pharmaceutical composition and method of its obtaining - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: method of obtaining powder-like pharmaceutical composition consists in the fact that carbon dioxide and ammonia are passed through liquid fraction 2 of Dorogov stimulant antiseptic. Obtained paste-like product is mixed with powder-like sorbent and dried. Powder-like pharmaceutical composition, obtained by claimed method, contains (in wt %): DSA-2 with concentration degree 1.5-5.0-10.0-30.0, powder-like sorbent - 30.0-75.0, carbon-ammonium salts - 2.0-10.0, water - the remaining part. Claimed group of inventions makes it possible to obtain powder-like pharmaceutical composition, in which concentrated form of DSA-2 preserves all its properties of liquid form of DSA-2. Obtained powder-like pharmaceutical composition can be applied for production of medications in form of pills, boluses, mixtures with vitamins, as well as for production of forages and premixes for animals and birds.

EFFECT: reduction of therapeutic doses of medication and simplification of its storage process.

8 cl, 5 ex

Description

The group of inventions relates to the field of the pharmaceutical industry, in particular to a powdered pharmaceutical composition and a method for its preparation.

A well-known pharmaceutical composition is the antiseptic stimulator Dorogov fraction 2 (hereinafter - ASD-2), which is a unique natural complex of substances that affect almost all systems of a living organism. Because the preparation is obtained by dry sublimation of meat and bone meal in the form of an intensely colored liquid containing up to 75% water, and sublimation provides a gradual breakdown of organic substances to low molecular weight components, which in their structure are similar to metabolites of cell metabolism, ASD-2 has neither species nor organ specificity . ASD-2 has a stimulating effect on biochemical processes associated with the biological function of active sulfhydryl groups, and helps to intensify the metabolism of carbohydrates, lipids and proteins (Kiryutkin G. et al. Revival of the drug ASD. Animal husbandry of Russia, 2004, No. 10, p. 46 or Kiryutkin G.V. et al. Revival of the drug ASD.Internet address: http://www.areal-medical.ru/?action=stati).

The drug has been widely and successfully used in veterinary medicine for over 50 years.

ASD-2 has a multilateral effect on the body. It intensifies the metabolism, accelerates oxidative processes, increases the reserve alkalinity in the blood, which contributes to the normalization of metabolism in the tissues, improves digestion and absorption of nutrients. The drug causes an improvement in the functional state of the mechanisms of natural resistance, enhances tissue regeneration processes, stimulates immunogenesis, as a result of which resistance to adverse effects, including infectious diseases, is increased (SU 1729505 A1, 04/30/1992, RU 2005135207 A, 05/10/2007, RU 2159116 C, 11.20.2000).

ASD-2 is also allowed for medical use as a means for external use in the treatment of a number of human skin diseases, such as eczema, neurodermatitis, sycosis, etc., as well as an anti-inflammatory drug (Toropova N.P., Sinyavskaya O.A. Eczema and atopic dermatitis in children. Experimental therapy. M., 1993, p.336-339).

Currently, it is known to use ASD-2 as a means of activation therapy (immunomodulator), an antitumor, antiallergic agent, in the treatment of diseases of the heart, liver, nervous system, as well as an antibacterial drug with a wide spectrum of action (SU 1729505 A1, 04/30/1992, RU 2099068 C1, 12.20.1997, RU 2159116 C1, 11.20.2000, RU 2308956 C2, 10.27.2007. Antiseptic - Dorogov stimulant. Internet address: http://otherreferats.allbest.ru/medicine/00050099).

ASD-2 was first obtained by A.V. Dorogov (VIEV) in 1948. The essence of the method for the preparation of ASD is the thermal decomposition of meat and bone meal at a temperature of 300 to 500 ° C. In this case, volatile fractions are captured and cooled. Then the resulting two layers of liquid are separated. The upper layer (oil) is the ASD-3 fraction, the lower layer (water) is the ASD-2 fraction. The ASD-2 fraction is then purified from unwanted impurities by filtration through an asbestos filter (see SU 130857 A, 08.28.1962).

A known method of producing ASD-2 from meat and bone meal containing at least 55% protein. The decomposition of meat and bone meal is carried out at a temperature of from 150 to 450 ° C with a step range of 100 ° C and holding for at least 3 hours at temperatures of 250, 350 and 450 ° C (Abramov V.E. et al. Determination of quality indicators of the drug ASD-2. Veterinary Medicine, 2004, No. 9, pp. 13-16 or Drug ASD. History and current status, 12/12/2008. Internet address: http://www.novorossia.org/obshestvo/383-preparat-asd.-istoriia- i-sovremenrioe-sostoj ...).

However, the pharmaceutical composition obtained by known methods contains a large amount of water - up to 80%, and therefore, when using it is necessary to use high doses of the drug. In addition, during storage, in some cases, sediment appears in ASD-2, which makes it difficult to use the drug as a complete solution in veterinary and medical practice.

There is also a method for producing the adaptogenic preparation Dorogov of fraction 4 and fraction 5, which consists in the fact that after filtering the liquid fraction ASD-2, it is distilled by heating to from 60 ° C to 140 ° C, achieving a decrease in volume to 5-12% of the initial volume , and at the output, the adaptogenic drug Dorogova fraction 4 (APD-f4) is obtained in the form of a thick black mass, odorless with pH≤6. At the third stage, the obtained fraction 4 is taken as a basis, which is cooled to 0 ° С, then slowly heated, sublimating in the temperature range 0-375 ° С until a clear liquid is obtained from dark brown to black, with a light, faint smell and density close to the unit soluble in water, alcohol and other liquids, which is a fraction of 5-APD-f5 (see RU 2012120581 A, 11.27.2013).

This method allows you to get the product almost odorless, however, it is also a liquid and during storage is exposed to adverse factors.

Known methods for producing various modifications of the Dorogov antiseptic stimulator - ASDK-1-7, namely, that the ASD-2 fraction is treated with an inorganic or organic acid (RU 98109868 A, 03/10/2000) or the ASD-2 fraction is ionized in the cathode zone of the ionizer or negative charges through an intermediate charge carrier (RU 98109721 A, 03/10/2000);

However, the above sources of information do not contain information about the quality of the resulting product, its composition and properties.

A known method of obtaining a stable form of ASD-2, which consists in the fact that ASD-2 is mixed with alcohol, and then the resulting azeotropic mixture is evaporated under vacuum (RU 2494750 C1, 10/10/2013). The resulting product contains no more than 66% water; during the entire storage period, no precipitate was observed in it. However, the decrease in water concentration amounted to only 11% of the initial content of 75%, which is a relatively insignificant value, and the need to use flammable solvents and high vacuum severely limits the practical implementation of the method.

Methods for the preparation of pharmaceutical compositions based on ASD-2 in powder form are currently unknown.

The objective of the invention in terms of a method for producing a pharmaceutical composition is to obtain a preparation in powder form, which would ensure the concentration of the complex of active substances in the preparation without changing the composition of the product while reducing the amount of water in it.

The problem is solved in that according to the invention, carbon dioxide and ammonia are passed through the liquid fraction 2 of the antiseptic agent of the Dorogov stimulator, after which the resulting pasty product is mixed with a powdered sorbent and dried.

The problem is also solved by the fact that carbon dioxide and ammonia are passed through the liquid fraction 2 of the antiseptic stimulator Dorogov sequentially or simultaneously.

It is advisable to pass carbon dioxide and ammonia through fraction 2 of the antiseptic stimulator Dorogov in the amount of 0.1-1.2 g per 1 g of water removed.

In this case, the process is conducted at a temperature of -10 ° C - + 15 ° C.

The problem is also solved by the fact that the pasty product is mixed with a powdered sorbent in a ratio of 3: 1-14: 1.

It is advisable to mix the pasty product with a powdered sorbent at a temperature of from -10 ° C to + 15 ° C.

It is also advisable to dry the mixture of the pasty product with the powdered sorbent at a temperature not exceeding 40 ° C.

It is advisable to use aerosil, or polysorb, or white coal, or other types of enterosorbents as a powdered sorbent.

The technical result obtained from the implementation of the claimed invention in terms of the method consists in the fact that the proposed method allows for the first time to obtain a powdered pharmaceutical composition, each mass unit of which contains the whole complex of organic and inorganic substances of the initial drug ASD-2 in a concentrated form, which will reduce therapeutic doses of the drug and simplify the process of its storage.

It is known from the prior art that ASD-2 is used in veterinary medicine and medicine both as an independent drug (see Instructions for the use of the drug ASD fraction 2. Approved by the Department of Veterinary Medicine of the Russian Federation on September 14, 2007) and as part of compositions for various purposes (see e.g. RU 2089197 C1, 09/10/1997, RU 2361579 C1, 07/20/2009, RU 2368391 C1, 09/27/2009, RU 2404728 C1, 11/27/2010).

The objective of the invention in terms of the composition is the creation of a powdered product based on concentrated ASD-2.

The problem is solved in that the powdered pharmaceutical composition according to the invention is obtained as described above and contains ASD-2 with a degree of concentration of 1.5-5.0, a powdered sorbent, carbon ammonium salts and water, in the following ratio of ingredients (in wt.%):

ASD-2 with a degree concentration of 1.5-5.0 10-30 Powder sorbent 30-75 Coal ammonium salts 2-10 Water rest

The problem is also solved by the fact that the composition as a powdered sorbent contains aerosil, or polysorb, or white coal, or other types of enterosorbents.

In addition, the task is solved in that the composition can be used for the manufacture of medicines and feed for animals and birds, namely for the manufacture of tablets, boluses, mixtures with vitamins, as well as premixes for animals and birds.

The technical result obtained as a result of the implementation of the invention in terms of the pharmaceutical composition is that the obtained preparation retains all the properties of the liquid form of ASD-2, but contains no more than 28% moisture, which can significantly reduce the therapeutic dose of the drug, as well as simplify its process storage.

The group of inventions is characterized by the following examples of implementation, which, however, do not limit the scope of the claims of the applicant.

Example 1

Take the ASD-2 liquid fraction in an amount of 100 ml weighing 110 g. The amount of water in the selected ASD-2 liquid fraction is determined. The amount of water is 82.8 g. Carbon dioxide in an amount of 0.7 g and ammonia in an amount of 0.3 g for each gram of “bound water” are successively passed in portions through the ASD-2 liquid fraction. Due to the transmission of carbon dioxide and ammonia, free water and an essential part of the liquid form of ASD-2 “binds” to the constituent molecules of carbon ammonium salts - ammonium bicarbonate NH ₂ HCO ₃ and ammonium carbonate (NH ₄ ) ₂ CO ₃ .

The process is carried out at a temperature of + 3 ° C until the formation of a stable pasty product with a total weight of 150 g. The resulting pasty product is mixed with aerosil. At the same time, Aerosil is added to the pasty product in an amount of 20 g. The resulting wet mixture is dried at a temperature of 20 ° C until the loss of powder in the mass ceases. 54 g of preparation are obtained in which the concentration of ASD-2 is 2.03. The resulting preparation has the following composition (in wt.%):

ASD-2 with a degree concentration 2.03 27.0 Aerosil 37.0 Coal ammonium salts 9.0 Water 27.0

Example 2

We took 500 ml of liquid ASD-2 weighing 545 g with a water content of 400 g, and at a temperature of -10 ° C for three cycles, we sequentially dosed ammonia and carbon dioxide in equal portions in a total amount of 150 g and 200 g, respectively. The resulting mixture was mixed. The result was a paste-like substance with a total mass of 865 g.

100 g of polysorb was added to 865 g of the obtained paste-like substance and mixed again until a moist mass of a uniform brownish tint was obtained for about 90 minutes. As a result, 907 g of the mass was unloaded from the mixer, which was sent for drying at a temperature of 35 ° C. After 72 hours, the loss of powder mass stopped. The degree of concentration of ASD-2 in this drug is 4.22. The total weight of the drug was 155 g.

The composition of the obtained drug according to the analysis was (in wt.%):

ASD-2 with a degree concentration 4.22 19.0 Polysorb 61.0 Coal ammonium salts 5,0 Water 15.0

Example 3

The ASD-2 liquid fraction was taken in an amount of 500 ml weighing 550 g. The amount of water in the selected ASD-2 liquid fraction is 400 g. 150 g of carbon dioxide and 200 g of ammonia are simultaneously passed through the liquid fraction of ASD-2. The resulting paste in an amount of 860 g was placed in a mixer, powdered white coal in an amount of 200 g was added thereto, after which the mixture was stirred until a wet mass of a uniform brownish tint was obtained for about 120 minutes. After mixing, 1010 g of the mass was discharged from the mixer, which was sent for drying at a temperature of 35 ° C. After 40 hours, the loss of mass of the sample stopped. The total weight of the drug was 265 g, while the degree of concentration of ASD-2 in it was 2.44.

The composition of the obtained drug according to the analysis was (in wt.%):

ASD-2 with a degree concentration 2.44 11.0 White coal 74.0 Coal ammonium salts 4.0 Water 11.0

Example 4

15 liters of ASD-2 weighing 16.5 kg were loaded into the reactor. The water content is 75% or 12.4 kg. For 10 hours, with the stirrer running, first ammonia was fed into the apparatus, in total 9.0 kg, and then carbon dioxide, 6.0 kg. After the introduction of ammonia and carbon dioxide, the reaction mass was kept under stirring for 3 hours and a temperature of + 15 ° C. After mixing, 29.0 kg of paste was unloaded from the mixer.

The resulting paste in an amount of 29.0 kg was placed in a mixer, Aerosil was added there in an amount of 2.5 kg. The resulting mixture was stirred until a wet mass of a uniform brownish tint was obtained for about 90 minutes. After mixing, 30.2 kg of wet mass was discharged from the mixer.

The resulting wet mass was dried at a temperature of 35 ° C with periodic stirring. After 72 hours, the loss of powder mass stopped. The final mass of the sample was 3930 g, in which the degree of concentration of ASD-2 was 3.8.

The composition of the drug according to the analysis was (in wt.%):

ASD-2 with a degree concentration 3.8 19.0 Aerosil 63.0 Coal ammonium salts 4.0 Water 14.0

Example 5

15 liters of ASD-2 weighing 16.5 kg were loaded into the reactor. The water content in the ASD-2 liquid fraction is 75% or 12.4 kg. Within 10 hours, with the mixer operating, simultaneously through two independent inputs ammonia was supplied to the apparatus - only 9.0 kg and carbon dioxide - only 6.0 kg. The temperature of the reaction mass in the apparatus was maintained no higher than + 12 ° C. After completion of the 3-hour exposure, 30.0 kg of paste was unloaded from the reactor.

The resulting paste in an amount of 30.0 kg was placed in a mixer, and polysorb in an amount of 2.5 kg was added thereto. The resulting mixture was stirred until a wet mass of a uniform brownish tint was obtained for about 90 minutes. After mixing, 32.3 kg of wet mass were unloaded from the mixer.

The resulting wet mass was dried at a temperature of 39 ° C. During the drying process, the mass was periodically mixed. After 60 hours, the loss of powder mass stopped. The final mass of the sample was 3600 kg. The degree of concentration of ASD-2 in this sample is 4.6.

The composition of the drug according to the analysis was (in wt.%):

ASD-2 with a degree Concentration 4.6 22.0 Polysorb 68.0 Coal ammonium salts 2.0 Water 8.0

In powder pharmaceutical compositions obtained in Examples 1-5, to authenticate the SDA-2 compliance of the NMR spectra of hydrogen protons H ¹ (nuclear (proton) magnetic resonance PMR) test samples and reference samples (see. VE Abramov, V . I. Abdrakhmanov, OA Dorogova and others. On the issue of determining the quality indicators of the drug Antiseptic Dorogov Stimulator ASD-2. Veterinary Medicine, 2004, No. 9, pp. 13-16).

All samples of the powdered pharmaceutical composition obtained in examples 1-5 were subjected to the following tests:

- the analyzed sample weighing 10-20 g was suspended in distilled water at a ratio of 1: 5; after which the suspension was filtered on a vacuum filter;

- the aqueous extract was analyzed for authenticity by PMR and the content of carbon ammonium salts. Under the condition of preliminary calibration of aqueous extracts of ASD-2 powders with a known content of active substances, the density or refractive index was determined in the aqueous extracts of the analyzed samples.

Correspondence of the PMR spectrum of the analyzed sample to the reference one while confirming the necessary density or refractive index of the aqueous extracts allows us to unambiguously determine both the authenticity of the DV of the preparation and reliably estimate its amount in powder;

- the wet powder remaining on the filter was dried in a muffle furnace, which makes it possible to uniquely determine the amount of filler in the powder.

The degree of concentration of ASD-2 (N) was determined by calculation by the ratio:

N = M _ASD-2 / M _powder ,

Where

M _ASD-2 - the initial mass of the liquid fraction ASD-2 taken for processing;

M _powder - the mass of the powder form of the drug obtained by processing the liquid form of ASD-2.

As a result of the tests, it was found that in all samples of the obtained powdered pharmaceutical composition, the ASD-2 fully complies with the requirements of the reference drugs both in the PMR spectra and in the amount of DW in the powder.

Thus, the claimed group of inventions allows to obtain a powdered pharmaceutical composition containing ASD-2 with a degree of concentration of 1.5-5.0, which retains all the properties of the liquid form of ASD-2. In addition, a powdered pharmaceutical composition obtained by the claimed method allows to reduce therapeutic doses of the drug and simplify the process of its storage. The obtained powdered pharmaceutical composition can be used for the manufacture of medicines in the form of tablets, boluses, mixtures with vitamins, as well as for the manufacture of feed and premixes for animals and birds.

Claims (8)

1. A method of obtaining a powdered pharmaceutical composition, which consists in passing carbon dioxide and ammonia in an amount of 0.1-1.2 g per 1 g of water to be removed at a temperature of -10 ° С- + 15 ° through a liquid fraction 2 of an antiseptic agent of the Dorogov stimulator C, after which the resulting pasty product is mixed with a powdered sorbent in a ratio of 3: 1-14: 1 at a temperature of -10 ° С- + 15 ° С and dried at a temperature of no higher than 40 ° С. 2. The method according to p. 1, characterized in that carbon dioxide and ammonia are passed through fraction 2 of the Dorogov stimulator antiseptic sequentially or simultaneously. 3. The method according to claim 1, characterized in that as a powdered sorbent use Aerosil, or Polysorb, or white coal. 4. Powdered pharmaceutical composition obtained by the method according to any one of paragraphs. 1-3, characterized in that it contains (in wt.%):
ASD-2 with a degree concentration of 1.5-5.0 10.0-30.0 Powder sorbent 30.0-75.0 Coal ammonium salts 2.0-10.0 Water the rest, but not more than 28 5. A powdered pharmaceutical composition according to claim 4, characterized in that the powder sorbent contains Aerosil, or Polysorb, or white coal. 6. A powdered pharmaceutical composition according to claim 5, characterized in that it is intended for the manufacture of medicines and feed for animals and birds. 7. A powdered pharmaceutical composition according to claim 6, characterized in that it is intended for the manufacture of tablets, boluses, mixtures with vitamins. 8. The powdered pharmaceutical composition according to claim 7, characterized in that it is intended for the manufacture of premixes for animals and birds.