Drug treatments for multiple sclerosis

 

(57) Abstract:

The invention relates to medicine, namely to the production of medicines on the basis of [N-methyl-N -/ D-glyukopiranozil/ammonium-9-one-10-Il/acetate] -cycloferon, and can be used for the treatment of multiple sclerosis. The objective of the invention is to create high quality, effective, low-toxic, versatile tools for the treatment of multiple sclerosis. The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances used, the compound N-methyl-N/a, Dr. glyukopiranozil/ammonium-2-acridin-9-one-10-Il/acetate, and the solvent is water in the following ratio, wt.%:

active substance - 18,0-22,5

water - the rest

5 table.

The invention relates to medicine, namely to the production of medicines on the basis of [N-methyl-N -/ D-glyukopiranozil/ammonium-2-/acridin-9-one-10-Il/acetate] -cycloferon (application trademark N 93006831/50 from 24.03.93), and can be used for the treatment of multiple sclerosis.

Known parenteral form of the medicinal product based on the chemical analogue of cycloferon replaced acridinone composition:

as active substances substituted acridine sodium salt of 10-carboxymethyl-9-acridone structural formula

,

surfactant,

sodium hydroxide,

the water solvent.

The tool has not been used for the treatment of multiple sclerosis.

Known means at the specified prototype has the following disadvantages: strong irritating and painful action, due to the high pH (9); the risk of necrosis and gemokoagulyatsii; insufficient concentration of the active substance (55 mg/ml (5%), which requires an increase in the volume of injectate for the manifestation of therapeutic effect (up to 10 ml or more).

In order to reduce pain effect with the drug we were trying stabilization specified in the prototype dosage forms extended in the Pharmacopoeia by means of, for example, buffers, complexing agents.

During the experiment, we tried to reduce the pH of the dosage form below 8, but this has not led to a positive result.

At pH below 8 there was a gradual precipitation of greenexpo acid, which testifies to the impossibility of soy just used glucocorticosteroid hormones (prednisolone, triamcinolone, dexamethasone) (1,2). In order to reduce the side effects of hormonal therapy at the same time appoint etemity.

In remission for patients with signs of immunodeficiency appoint Immunostimulants gamma globulin, levamisole, fractional blood transfusion and blood substitutes, preparations of thymus: fluorouracil (timesin), thymalin, taktivin and symptomatic treatment (1,2).

The objective of the invention to create high quality, effective, low-toxic, versatile tools for the treatment of multiple sclerosis.

The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances used, the compound N-methyl-N -/ D-glyukopiranozil/ammonium-2-/acridin-9-one-10-Il/acetate structural formula

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and as a solvent water in the following ratio, wt.

active substance 18,0-22,5

water the rest

Currently, biomedical experiments have shown that the effective daily therapeutic dose of cycloferon is 360-450 mg per person in a single dose. In accordance with the proposed therapeutic dose by the applicant was provideservices for vials with a volume of 1.2 and 5 ml, applied to produce the dosage form.

To obtain a parenteral dosage form, the applicant used a specified number of greenexpo acid and water for injections and different amounts allowed in the Pharmacopoeia of the N-methylglucamine.

Dosage form was obtained by the method described below.

The results of the studies are given in table. 1.

From table. 1 shows that when using N-methylglucamine less of 96.5 g dosage form is not stable: formed turbidity or precipitation during storage. When using N-methylglucamine more of 96.5 g of the solution has a pH above 9 and has a strong local irritant effect.

Thus, the optimal ratio of components is of 96.5 g of N-methylglucamine 125 g greenexpo acid in aqueous solution.

Taking into account the optimal ratio of components of the dosage form, the optimal therapeutic daily dose of 360-450 mg per person, single administration, as well as manufactured standard vials (1,2 and 5 ml) was obtained the optimal concentration of active substance in again the type of 18.0-22.5 wt.

The results of the surveys are large for a single injection. When using vials in 1 ml with a concentration of active substance 45% dosage form low-tech due to the high viscosity and gives infiltrates with parenteral administration of the drug.

In table. 3 shows the comparative characteristics of qualitative indicators of the claimed dosage forms and prototype structural entity.

As follows from the table. 3, the claimed medicinal product has the following advantages:

the complete absence of irritating and painful steps in injecting drug due to close to physiological pH (pH of blood 7,3);

in 5-20 times higher concentration of active substance in the solution, allowing to obtain a pronounced therapeutic effect with minimal amounts of administered drug;

the lack of biological impurities (chelating agents, components, buffer);

upon receipt of the dosage form does not require special equipment for sealing ampoules under inert gas.

A formulation was prepared as follows.

In chemical beaker with a capacity of 2 litres pour 1 liter of water for injection, load 193 g N methylglucamine, stir until dissolved and add the key bring the volume of the solution to 2 l with water for injection, filtered through Millipore and poured into ampoules and vials. The sealed ampoules and autoclave. Vials sealed with rubber stoppers, practicing aluminum caps and autoclave.

The results of biomedical research has been proved to be highly effective drugs in the treatment of multiple sclerosis.

Here is an example confirming therapeutic activity of the drug.

Patient K., 35 years. Diagnosis: multiple sclerosis (multiple sclerosis), spinal form. Sick since January 1987 (November 1986 flu). Disability group II the basic disease. Repeatedly examined and treated in the clinics of nervous diseases of the postgraduate Institute, military medical Academy. Kirov, Sbbmi them. Acad. Pavlov, surveyed all the specialists and all the usual and most modern methods (including NMR-tomography). Underwent a complete examination (at a famous clinic). Treated with hormones, answered, chimes, drugs thymus had no lasting effect. With 20.04. C., after thorough examination held exchange treatment drug cycloferon scheme:

first course: 1 injection of 8 ml of 22.5% solution, 3 days 4 ml 2But intramuscularly 20 ampoules of 2 ml of 22.5% solution of each.

On the background of the treatment was a clear improvement in clinical data as subjective improvement in mood, appearance of faith in the healing and objective change for the better the view, the reduction of the nystagmus, the appearance of previously absent abdominal reflexes, a significant reduction of muscle hypertonicity of the lower extremities, gait improvement, writing, speech). Clinical improvement was accompanied by a clear normalization of indices of laboratory examination of the patient (see table. 4, 5). When computed tomography (24.06) noted positive dynamics in comparison with a similar study from 13.03.93.

Thus, this example demonstrates positive therapeutic effect of the drug in multiple sclerosis and no side effects.

In addition, the drug significantly different (for the better) on the effect and mechanism of action of all the currently used tools.

Drug treatments for multiple sclerosis, containing the active substance and a solvent, characterized in that the active substance it contains the compound N-methyl-N-(,,D-glyukopiranozil)ammonium-2-(acridin-9-one-10-yl)acetate formula

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Water Ostalnoe

 

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