RU2482872C1 - Pharmaceutical composition in form of capsule possessing antiviral, anti-inflammatory, antimicrobial and immunomodulatory action - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and concerns a pharmaceutical composition in the form of a capsule either acid-resistant, or with an acid-resistant coating containing recombinant interferon specified from alpha, beta, gamma recombinant interferon; a stabiliser of the biological, physical and chemical properties specified in low-molecular polyvinylpyrrolidone, macrogol 400-12000, propylene glycol, hydroxypropyl methylcellulose; a stabiliser of microbial contamination resistance specified in dexamethasone, diflorazone, boric acid, phospholipids, cyclodextrins, calcium stearate, and/or magnesium stearate, a thickly-forming base specified in hydrophilic, lipophilic, hydrophilic-lipophilic bases.

EFFECT: invention provides a higher therapeutic effect and prolonged shelf life.

3 cl, 4 ex

Description

The invention relates to medicine and the pharmaceutical industry and relates to a composition having antiviral, anti-inflammatory, antimicrobial and immunomodulatory effects for the prevention and treatment of hepatitis, acute respiratory viral infections, influenza, herpes, cancer.

Known pharmaceutical composition in the form of a capsule containing acetylphthalyl cellulose, which in the presence of a cytokine and target additives is subjected to colloidal microgranulation with the formation of the final product of the fibrous structure with inclusions of cytokine and target additives. A known dietary supplement as a cytokine may contain recombinant α-interferon. Moreover, the amount of cellulose acetate is 30-80 wt.%. Known biologically active food supplement may be tablets, granules, capsules (patent RU No. 2129394, 04/27/1999, A23L 1/305, 1/29, A61K 9/22, 38/21).

The closest in technical essence and the achieved result is a pharmaceutical composition in the form of a capsule having antiviral and antimicrobial action, which is a mixture for forming the contents of the capsule containing recombinant human interferon-α, swelling substance and target additives. The specified composition contains a hydrophilic conglomerate of recombinant human interferon-α adsorbed by polyethylene glycol 4000-6000, polyglucin and a structural agent selected from the range of: maltose, mannitol, glucose, fructose, with a particle size of not more than 250 microns, not exceeding the average particle size of the swelling and dispersing substances , swelling and dispersing substance selected from the series: cellulose, methyl cellulose, acetylphthalyl cellulose, sodium carboxymethyl cellulose, croscarmellose sodium, sodium starch glycolate, mixture l sodium starch glycolate and carboxymethyl cellulose, crospovidone, cross-linked carboxymethyl starch, with a particle size of not more than 300 microns, and a target additive with a particle size of not more than 250 microns, not exceeding the average particle size of the swelling and dispersing substance, with the following components in 1, 0 g of composition:

Human recombinant interferon-α 10000-3000000 ME Polyethylene glycol 4000-6000 0.0001-0.5 Polyglukin 0.001-0.1 Structure former 0.01-0.8 Swelling and dispersing agent 0.001-0.1 Target supplement Rest

(Patent RU No. 2292907 C1, A61K 38/19, A61K 9/20, 2007).

Known compositions do not provide increased bioavailability of recombinant human interferon due to its stabilization with discrete swelling and uniform dispersion of the composition in an aqueous medium.

The objective of the invention is to develop a pharmaceutical composition in the form of a capsule, which provides increased bioavailability and stability of recombinant interferon containing recombinant interferon and a stabilizer of biological, physico-chemical properties and a stabilizer of resistance to microbial contamination, which ensures the delivery of the claimed drug to the gastrointestinal fluids that regulates the release of the drug and its retention in the stomach for a long period.

The technical result obtained by using the invention is expressed in the high therapeutic effect of the claimed pharmaceutical composition with a long shelf life, which has antiviral, anti-inflammatory, antimicrobial and immunomodulating effects for the prevention and treatment of hepatitis, acute respiratory viral infections, influenza, herpes, oncological diseases, and also helps to reduce the time recovery in 2 times compared with the prototype, thanks to the qualitative and quantitative selection of ingredients, including recall incentive.

To achieve the technical result, a pharmaceutical composition in the form of a capsule having antiviral, anti-inflammatory, antimicrobial and immunomodulating effects, containing recombinant interferon as a biologically active component and a consistently forming base, is characterized in that it contains a stabilizer of biological, physicochemical properties selected from groups: low molecular weight polyvinylpyrrolidone, macrogol 400-12000, propylene glycol, hydroxypropylmethyl cellulose, contains stabil microbial contamination resistance mash selected from the group: dexamethasone, diflorazone, boric acid, additionally the composition contains phospholipids, cyclodextrins, calcium stearate and / or magnesium stearate, and as a consistently forming base, the composition contains a base selected from the group: hydrophilic, lipophilic , hydrophilic-lipophilic base, in the following ratio of components in wt.%:

recombinant interferon, ME 500-10000000 stabilizer of biological, physico-chemical properties 0.0001-0.5 microbial contamination resistance stabilizer 0.0001-0.1 phospholipids 0.001-0.5 cyclodextrins 0.001-0.5 calcium stearate 0.001-0.1 and / or magnesium stearate 0.001-0.1 consistent base rest

The composition contains recombinant interferon selected from the group: alpha, beta, gamma recombinant interferon.

The capsule is made acid-resistant or with an acid-resistant coating.

The analysis of the prior art by the applicants, including a search by patent and scientific and technical sources of information and identification of sources containing information about analogues of the claimed pharmaceutical composition, allowed us to establish that the applicants did not find an analogue characterized by signs that were identical (identical) to all the essential features of the claimed composition.

The definition from the list of identified analogues of the prototype allowed us to identify a set of essential in relation to the perceived technical result of the distinguishing features in the claimed composition set forth in the claims.

Therefore, the claimed pharmaceutical composition meets the criterion of "novelty."

To verify the compliance of the claimed pharmaceutical composition, the applicants conducted an additional search for known solutions in order to identify signs that match the distinctive features of the claimed invention from the prototype.

The search results showed that the composition of the claimed pharmaceutical composition does not follow explicitly from the prior art as determined by the applicants, the effect of the transformations provided for by the essential features of the claimed invention on the achievement of a technical result is not revealed.

Therefore, the claimed invention meets the criterion of "inventive step".

The criteria of the invention "industrial applicability" is confirmed by the fact that the proposed pharmaceutical composition having antiviral, anti-inflammatory, antimicrobial and immunomodulatory effects, can be successfully used for the treatment and prevention of hepatitis, acute respiratory viral infections, influenza, herpes, oncological diseases. Due to the high stability of the composition, the pharmaceutical composition is suitable for industrial production in the form of a finished drug and meets the requirements of the Pharmacopoeia.

The invention is illustrated by the following examples.

Example 1

Alpha-recombinant interferon, low molecular weight polyvinylpyrrolidone, dexamethasone, phospholipids, cyclodextrins, calcium stearate are mixed, and a hydrophilic base is used as a consistently forming base. The composition is used in the manufacture of capsules. The mass of the contents of one capsule averages 480 mg with the content of active components and excipients. Capsules are coated with an acid resistant coating.

These components are taken in the following ratio of components in wt.%:

Options one 2 3 alpha recombinant interferon, ME 500 100,000 10,000,000 low molecular weight polyvinylpyrrolidone 0.0001 0.001 0.5 dexamethasone 0.0001 0.001 0.1 phospholipids 0.001 0.01 0.5 cyclodextrins 0.001 0.01 0.5 calcium stearate 0.001 0.01 0.1 hydrophilic base the rest is up to 100

Example 2

Beta-recombinant interferon, macrogol 400, diphlorazone, phospholipids, cyclodextrins, magnesium stearate are mixed, and a lipophilic base as a consistently forming base. The composition is used in the manufacture of capsules. Capsules are coated with an acid resistant coating. These components are taken in the following ratio of components in wt.%:

Options one 2 3 beta recombinant interferon, ME 500 100,000 10,000,000 macrogol 400 0.0001 0.001 0.5 diphlorazone 0.0001 0.001 0.1 phospholipids 0.001 0.01 0.5 cyclodextrins 0.001 0.01 0.5 calcium stearate 0.001 0.01 0.1 lipophilic base the rest is up to 100

Example 3

Gamma-recombinant interferon, macrogol 12000, boric acid, phospholipids, cyclodextrins, calcium stearate and magnesium stearate are mixed, and a hydrophilic-lipophilic base as a consistently forming base. The composition is used in the manufacture of capsules. Capsules are coated with an acid resistant coating. These components are taken in the following ratio of components in wt.%:

Options one 2 3 gamma recombinant interferon, ME 500 100,000 10,000,000 macrogol 1200 0.0001 0.001 0.5 boric acid 0.0001 0.001 0.1 phospholipids 0.001 0.01 0.5 cyclodextrins 0.001 0.01 0.5 calcium stearate and magnesium stearate 0.001 0.01 0.1 hydrophilic lipophilic base the rest is up to 100

Example 4

Alpha and beta recombinant interferon, propylene glycol, boric acid, phospholipids, cyclodextrins, calcium stearate are mixed, and a hydrophilic base as a consistently forming base. The composition is used in the manufacture of acid resistant capsules. These components are taken in the following ratio of components in wt.%:

Options one 2 3 alpha and beta recombinant interferon, ME 500 100,000 10,000,000 propylene glycol 0.0001 0.001 0.5 boric acid 0.0001 0.001 0.1 phospholipids 0.001 0.01 0.5 cyclodextrins 0.001 0.01 0.5 calcium stearate 0.001 0.01 0.1 hydrophilic base the rest is up to 100

As a result of the studies, conglomerates were first obtained from the components of the above pharmaceutical composition with hydrophilic, lipophilic and hydrophilic-lipophilic bases, the combination of which in capsules when used provides increased bioavailability of recombinant interferon due to its stabilization and preservation of antiviral, anti-inflammatory, antimicrobial and immunomodulating activity. Checking the stability of the composition was carried out after 12 months and after 24 months. The contents of each capsule was checked for compliance with the requirements of the pharmacopoeia of GF X1, issue 1, 2. 10 capsules of each composition were tested. All values of the indicators corresponded to the declared composition. Capsules and their contents retained their original color and compliance with the requirements of the Global Fund X1, issue 2, p.143.

Test methods for the composition in experimental studies confirm the above about the therapeutic effect. Experimental studies were carried out using influenza infection on outbred white mice weighing 18-22 g. Based on the obtained experimental data, it was found that the antiviral effect of the test samples over the duration of the incubation period confirms the conclusion about the high anti-influenza activity of the studied compositions.

Thus, the proposed pharmaceutical composition provides a high therapeutic effect with pronounced antiviral, anti-inflammatory, antimicrobial and immunomodulating activity for the prevention and treatment of hepatitis, acute respiratory viral infections, influenza, herpes, oncological diseases, which helps to reduce the recovery time.

Claims (3)

1. A pharmaceutical composition in the form of a capsule having antiviral, anti-inflammatory, antimicrobial and immunomodulating effects, containing recombinant interferon as a biologically active component and a consistently forming base, characterized in that the composition contains a stabilizer of biological, physicochemical properties selected from the group: low molecular weight polyvinylpyrrolidone, macrogol 400-12000, propylene glycol, hydroxypropyl methylcellulose, contains a microbial resistance stabilizer a group selected from the group: dexamethasone, diphlorazone, boric acid, the composition further comprises phospholipids, cyclodextrins, calcium stearate and / or magnesium stearate, and as a consistently forming base, the composition contains a base selected from the group: hydrophilic, lipophilic, hydrophilic-lipophilic basis in the following ratio of components, wt.%:
recombinant interferon, ME 500-10000000 stabilizer of biological, physico-chemical properties 0.0001-0.5 microbial contamination resistance stabilizer 0.0001-0.1 phospholipids 0.001-0.5 cyclodextrins 0.001-0.5 calcium stearate and / or 0.001-0.1 magnesium stearate 0.001-0.1 consistent base rest 2. The composition according to claim 1, characterized in that it contains recombinant interferon selected from the group: alpha, beta, gamma recombinant interferon. 3. The composition according to claim 1, characterized in that the capsule is made acid-resistant or with an acid-resistant coating.