Antiviral agent

 

(57) Abstract:

Antiviral agent contains, wt%: as the active substance 1-phenyl-2,3-dimethyl-4-iteration-5 50-70, as pharmaceutically acceptable excipients starch 10-30, glucose crystalline hydrated 10-19, salt of stearic acid of 0.1 to 1.0, low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600 2,0-4,0. Preferably the tool is made in the form of tablets. New antiviral agent stable when stored for a long time (not less than 3 years), has improved strength characteristics, easily releases the active substance 1-phenyl-2,3-dimethyl-4-iteration-5, characterized by high bioavailability and pharmacological activity. 2 C.p. f-crystals, 1 table.

The invention relates to the field of medicine and is suitable for the treatment and prevention of viral diseases.

The tool has anti-inflammatory, immunostimulant and interferogram properties. It is an active inducer of alpha - and beta-interferon, significantly stimulates cellular and humoral immunity. Stabilizes the biological membrane and inhibits entry of the virus into the cell.

The creation of a pharmaceutically acceptable, effective drugs for prompt and effective treatment and prevention of tick-borne encephalitis is relevant in connection with the expansion of the spread of the virus - encephalitogen mite growth is infected with tick-borne encephalitis virus.

In practical medicine use specific immunoglobulin and serum for the prevention and treatment of viral encephalitis (Viral and bacterial drugs. Tomsk, 1989, S. 134-138). However, apart from the fact that the drug does not have sufficient activity, as an injectable preparation, it is not adapted for an affordable and wide prevention population.

Due to the fact that the disease tick-borne encephalitis is directly connected with the places of distribution encephalitogen mite, and it is basically far from medical centers, forests, suburban areas, the most convenient dosage form for emergency treatment and prevention of tick-borne encephalitis, including acute respiratory infections, yavlyaetsya tick-borne encephalitis, induced in the experiment (RF patent 2025126 And 61 To 31 /41).

4-Yodantipirin, like most substances of medicines has no ability to direct pelletizing. Therefore, to create stable for a long time, meet pharmacopoeial requirements of the pharmaceutical form, you must enter the excipients in amounts determined pharmaceutical and therapeutic usefulness.

Closest to the claimed invention is a solid dosage form 4-yodanthipirina made in the form of tablets, which is used for the prevention and treatment of tick-borne encephalitis, containing as active principle 1-phenyl-2,3-dimethyl-4-iteration-5, as well as pharmaceutical additives, potato starch, glucose crystalline hydrate, magnesium stearate (RF patent 2141826), which is approved for medical use as therapeutic and prophylactic health Ministry for 316 from 13.08.96, registration 96/316/5.

However, the tool has a number of disadvantages: slow release of the active substance (72% in 45 minutes), the instability of the tablet, which essentially limits the shelf life (2 the concentration of the active compounds in the body and thus is not reached emergency therapeutic effect.

Thus, it is important to establish a stable antiviral agents on the basis of 1-phenyl-2,3-dimethyl-4-iteration-5, intended for oral administration in the form of a solid dosage form of the pharmacologically sufficient dosed release of the active principle.

The technical result obtained by implementing the present invention, is the following: a new antiviral agent intended for oral administration in the form of solid dosage forms, stably for a long time (not less than 3 years), has improved strength characteristics, increased the rate of decay of her body and the release of active substance from the pharmaceutical composition.

This technical result is achieved by the fact that the proposed antiviral drug containing as an active substance 1-phenyl-2,3-dimethyl-4-iteration-5 and as pharmaceutically acceptable auxiliary substances, starch, glucose crystalline hydrated, as salts of stearic acid, magnesium stearate, further comprises a low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600 in the following ratio Kai hydrate - 10-18

Low-molecular polyvinylpyrrolidone with an average molecular weight 2600-16000 - 2-4

Salt of stearic acid, and 0.1 - 1

The claimed ratio of 1-phenyl-2,3-dimethyl-4-iteration-5 and auxiliary substances is best found experimentally and ensures compliance with the modern requirements of quality tools and requirements of the global Fund XI.

It is known the use of low-molecular polyvinylpyrrolidone, amorphous linear polymer, in medicine as a blood substitute with detoxification properties, in the pharmaceutical industry for the prolongation of the action of certain drugs (e.g. penicillin), as a binder and/or stabilizer in the manufacture of medicines (such as acyclovir).

Adding polyvinylpyrrolidone leads to an increase in the strength of solid dosage forms, but also worsens the performance raspadaemosti.

For controlled release of drugs as a binder filler most commonly used methylcellulose, sodium carboxymethyl cellulose. This group functional fillers include starch, which is about the offering conditions for the ingress of fluid.

However, the application as disintegrator only starch in the preparation of solid dosage forms antiviral agents with active ingredient 1-phenyl-2,3-dimethyl-4-iteration-5 indicators disintegration, solubility, strength or are at the limit, or at a lower level requirements GF XI.

Experimentally selected ratios of ingredients polyvinylpyrrolidone in combination with the active ingredient, starch and salt of stearic acid was suddenly possible to achieve improved and most balanced scorecard quality solid drugs in terms of "strength", "solubility", "raspadaemost" - the release of drugs, "shelf life", which allowed us to solve the problem.

As a salt of stearic acid can be used stearates of calcium, magnesium, zinc. It is preferable to use magnesium stearate.

Failure of selected components and their relationships is not possible to achieve the required quality solid dosage forms such as antiviral agents.

The method of obtaining the claimed antiviral agent containing 1-phenyl-2,3-dimethyl-4-iteratio is -5 with glucose crystalline hydrate, starch and an aqueous solution of low molecular weight polyvinylpyrrolidone, drying, dry granulation, powder and tableting.

The invention is illustrated by the following examples.

Example 1.

20 g (50 wt.%) ground 1-phenyl-2,3-dimethyl-4-iteration-5, 12.0 g (30 wt. %) of sifted potato starch, 6.0 g (15 wt.%) glucose crystalline hydrated sifted mix and moisturize 8.00 g of 20% or 1.6 g based on 100% of the basic substance (4 wt.%) a solution of low molecular weight polyvinylpyrrolidone, stirred for 5-10 minutes to evenly distribute the moisture. The mixture is dried to 2% residual moisture. This is followed by granulation and dry dusting granulate 0.4 g (1 wt.%) the stearate. The resulting mixture tabletirujut. Get 38,6 g tablets average weight 0,161 g, corresponding to the requirements of the pharmaceutical agent.

Example 2.

18.51 g (62.5 wt.%) ground 1-phenyl-2,3-dimethyl-4-iteration-5, to 4.81 g (16,25 wt.%) potato starch sifted, lower than the 5.37 g (18,10 wt. %) glucose crystalline hydrated sifted mix and moisturize 4,63 g of 20% or 0,93 g based on 100% of the basic substance (3 wt.%) the solution of low-molecular polyvinyle is. This is followed by granulation and dry dusting granulate 0.04 g (1 wt. %) stearate. The resulting mixture tabletirujut. Get tablets that meet the requirements of the pharmaceutical agent.

Example 3.

51,49 g (65 wt.%) ground 1-phenyl-2,3-dimethyl-4-iteration-5, 17 and 19 g (21,7 wt.%) potato starch sifted, a 7.92 g (10 wt.%) glucose crystalline hydrated sifted mix and moisturize 5.31g 20% or 2,37 g based on 100% of the basic substance (4 wt.%) a solution of low molecular weight polyvinylpyrrolidone, stirred for 5-10 minutes to evenly distribute the moisture. The mixture is dried to 2% residual moisture. This is followed by granulation and dry dusting granulate 0.24 g (0.3 wt.%) the stearate. The resulting mixture tabletirujut. Get tablets that meet the requirements of the pharmaceutical agent.

Example 4.

100 g (70 wt. %) ground 1-phenyl-2,3-dimethyl-4-iteration-5, of 14.28 g (10 wt.%) potato starch sifted, 25,71 g (18.0 wt.%) glucose crystalline hydrated sifted mix and moisturize 14,30 g of 20% or 2.86 g based on 100% of the basic substance (2 wt.%) a solution of low molecular weight polyvinylpyrrolidone, mix 5-10 mine is podravanje dry granulate 0.14 g (0.1 wt.%) the stearate. The resulting mixture tabletirujut. Get tablets that meet the requirements of the pharmaceutical agent.

Example 5.

100 g (62.5 wt.%) 1-phenyl-2,3-dimethyl-4-iteration-5 grind, 19,43 g of 8.5 wt. % of potato starch or of 0.68 g based on 100% of the basic substance, 28.8 g (18 wt.%) glucose crystalline hydrated sifted mix and moisturize 26 g of 3.5% (0.56 wt.%) starch paste. The mixture is dried to 2% residual moisture. This is followed by granulation and dry dusting granulate mixture of starch 7.5 g and calcium stearate is 0.8, the resulting mixture tabletirujut. The obtained tablets are rough to the touch. The quality indicators at extremes GF XI or do not meet the requirements of the global Fund XI in terms of quality: "appearance", "raspadaemost" and "dissolution".

The influence of the ratio of the ingredients of examples on the quality of the finished dosage form (tablets) are illustrated in the table.

From the examples show that the introduction of low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600 allowed in combination starch, salt of stearic acid to improve the pharmacokinetic properties of antivirals jodan is Preferable to apply a low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600.

So raspadaemost tablets with the stated ratio of ingredients was not more than 4 minutes. The rapid disintegration of the claimed composition, and high rates of release of active ingredient after 45 minutes on Wednesday dissolution becomes more than 90% of 1-phenyl-2,3-dimethyl-4-iteration-5, which has significantly improved emergency therapeutic effect. Reducing the amount of starch reduces the strength of the tablets, the heterogeneity of the granules and tablets, high abrasion. The increase in the number of starch significantly slows down the release of the active substance. Reducing or increasing the number of glucose crystalline hydrate leads to the violation of the requirements of the global Fund XI, issue 2, page 154.

Thus, the proposed antiviral agent containing as main active substance 1-phenyl-2,3-dimethyl-4-iteration-5 and the stated ratio of the components is pharmacologically and pharmaceutically appropriate.

Sources of information

1. Viral and bacterial drugs. Tomsk, 1989, S. 134-138.

2. VFS 42-2777-96. The Ministry of health of the Russian Federation for 316 from 13.08.96, registration 96/316/5.

3. RF patent 2025126, a 61 K 31/41, 1986

4. Patent of the Russian Federation 2 141826, the containing as active substance 1-phenyl-2,3-dimethyl-4-iteration-5 and as pharmaceutically acceptable auxiliary substances - starch, glucose crystalline hydrated salt and stearic acid, wherein the tool further comprises a low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600, in the following ratio of ingredients, wt. %:

1-Phenyl-2,3-dimethyl-4-iteration-5 - 50-70

Starch - 10-30

Glucose crystalline hydrate - 10-19

Low-molecular polyvinylpyrrolidone with an average molecular weight 2600-12600 - 2,0-4,0

Salt of stearic acid - 0,1-1,0

2. Antiviral agent under item 1, characterized in that salts of stearic acid contains magnesium stearate.

3. Antiviral agent under item 1 or 2, characterized in that it is made in the form of tablets.

 

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