RU2246934C2 - Periphery blood circulation improving remedy - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention provides topical blood circulation improving remedy containing simultaneously nitroglycerine and aminophylline. Remedy can be provided in the form of emulsion, gel, or ointment, which are administered 1-2 times a day.

EFFECT: strengthened blood circulation activation effect, which is prolonged to 24 hours.

5 cl, 9 ex

Description

The invention relates to medicine and can be used in the treatment of peripheral circulatory disorders.

Due to the fact that peripheral circulatory disorders are extremely common in clinical practice, especially with chronic diseases of the heart, blood vessels of the brain and extremities, diabetes mellitus (diabetic foot), multiple sclerosis, etc., many agents that activate peripheral blood flow are known. In the clinic, drugs such as nitrosorbide, nicotinic acid, cavinton, trental, dibazole, etc. are widely used for this purpose (M.D. Mashkovsky. Medicines, vol. 1, M .: Medicine 2000). However, these drugs are used rassorbatively and, due to their pharmacokinetics, they do not create the proper and long-term concentration in spasm vessels, which weakens and shortens the effect.

In this regard, in our work, we set the task to create a tool for local use with the goal of local activation of peripheral circulation.

Actovegin (or solcoseryl) is a topical agent that improves peripheral blood circulation. However, the effect of this drug even in the conditions of intravenous administration develops only after 20 minutes (Register of medicines in Russia. Encyclopedia of medicines, 7th edition, 2000). In addition, the drug is not characterized by the authenticity of the chemical composition. It is obtained from the blood of healthy dairy calves. Raw materials are thus expensive and scarce. Its production in Russian conditions is difficult, especially in connection with a pronounced tendency to reduce the number of livestock. Recently, similar difficulties have been encountered abroad in connection with the mass infection of cattle with the virus of mad cow disease. Therefore, this drug is not optimal for wide clinical use.

We have shown that nitroglycerin and aminophylline in dosage forms for local action gives a quick activation effect of peripheral circulation. The duration of this effect is up to 24 hours, which will allow the use of an emulsion (ointment, gel) only 1 to 2 times a day.

We included nitroglycerin in the composition of this product due to the fact that it is rapidly absorbed from the skin surface, expanding blood vessels at the site of application, which allows accelerating the resorption of aminophylline. The mechanism of the vasodilating action of nitroglycerin is associated with the generation of cyclic GMF (guanosine monophosphate). Eufillin blocks the phosphodiesterase of c-GMF and enhances the local effect of nitroglycerin (N. A. Fedorov, M. G. Radulovatsky, G. E. Chekhovich. Cyclic nucleotides and their analogues in medicine, 1990). When absorbed into the general bloodstream, aminophylline (like other xanthine derivatives) removes the undesirable effect of nitroglycerin on cerebral circulation, leading to the disappearance of the headache sensation noted by some patients. (B.E. Votchal. Essays on Clinical Pharmacology. M .: Medicine, 1965). By activating the heart, it enhances blood circulation.

Examples of the use of drugs to improve peripheral circulation.

Example 1

Preparation of the emulsion.

To prepare the oil solution, 186 g of vaseline oil was taken, 2 g of nitroglycerin were dissolved in it. To prepare the aqueous solution, 542 g of distilled water was taken and 60 g of aminophylline and 90 g of ethyl alcohol were dissolved in it. Then they took 120 g of emulsion wax and an oil solution of nitroglycerin, loaded into the reactor. The resulting mixture was heated to 80 ° C until the emulsion wax completely melted and a homogeneous mixture was formed.

Then, a previously prepared aqueous solution of aminophylline and ethyl alcohol was poured into the solution. The mixture was thoroughly mixed to obtain an emulsion. The resulting emulsion was slowly cooled and a preservative was added.

Example 2

Preparation of the emulsion.

To prepare the oil solution, 100 g of vaseline oil was taken and 0.3 g of nitroglycerin was dissolved in it. To prepare the aqueous solution, 779.7 g of distilled water was taken and 30 g of aminophylline and 40 g of ethyl alcohol were dissolved in it.

Then they took 50 g of emulsion wax and an oil solution of nitroglycerin, loaded into the reactor. The resulting mixture was heated to 80 ° C until the emulsion wax completely melted and a homogeneous mixture formed.

Then, a previously prepared aqueous solution of aminophylline and ethyl alcohol was poured into the solution. The mixture was thoroughly mixed to obtain an emulsion. The resulting emulsion was slowly cooled and a preservative was added.

Example 3

The preparation of the gel.

2 g of nitroglycerin were dissolved in 30 g of liquid paraffin and a solution of 60 g of aminophylline, 20 g of ethyl alcohol and 868 g of distilled water was added, then 20 g of polymethyl methacrylate was added. The resulting mixture was kept at 80 ° C and stirred for 40 minutes. The resulting gel was slowly cooled and a preservative added.

Example 4

An emulsion prepared as in Example 2 at a dose of 10 mg was applied in a uniform thin layer to the rabbit's auricle. On visual examination after 3 minutes there was an increase in the contour of the vascular pattern. Blood flow rate was determined by the volume of blood flowing from the marginal vein of the ear for 1 min. Before applying the emulsion, 2 ml / min flowed out, 5 minutes after applying 4.2 ml. When examining the rabbit’s auricle on a thermal imager, a temperature increase of 2 degrees was detected over the entire surface of the rabbit’s auricle.

Example 5

Preparation of ointment.

2 g of nitroglycerin were mixed with 10 g of ethyl alcohol and 60 g of aminophylline with 10 g of ethyl alcohol, 258 g of distilled water was added. Then added 5 g of borax, 45 g of beeswax and 110 g of lanolin. Thoroughly mixed. Heated to 80 ° C until a homogeneous mixture.

Example 6

An emulsion prepared as in Example 1 at a dose of 10 mg was applied in a uniform thin layer to the rabbit's auricle. A visual examination after 5 minutes resulted in an increase in the contour of the vascular pattern. Blood flow rate was determined as in example 4. Before applying the emulsion, it was 2.2 ml / min, 5 minutes after applying 3.1 ml / min. When examining the rabbit’s auricle on a thermal imager, a temperature increase of 1 degree was detected over the entire surface of the rabbit’s auricle.

Example 7

The gel, prepared as in example 1, at a dose of 10 mg was applied in a uniform thin layer on the auricle of a rabbit. On visual examination after 3 minutes there was an increase in the contour of the vascular pattern. The blood flow rate, determined as in Example 4, was before application of the gel 2.0 ml / min, after application of the gel 3.8 ml / min. When examining the rabbit’s auricle on a thermal imager, a temperature increase of 2 degrees was detected over the entire surface of the rabbit’s auricle.

Example 8

Patient B, 65 years old, suffering from diabetes mellitus and trophic ulcers on the lower leg, ointment was applied to the upper 1/3 of the thigh on both sides. After 10 minutes, the patient noted an increase in body temperature to 34-35.7 ° C in the hip area on both sides and an increase in body temperature to 34 ° C (at 30.1 ° C before application).

After 20 minutes, the patient can see an increase in the temperature increase zone already on both sides. The patient continued to be treated with ointment, and on the third day of treatment, the formation of a dry crust on a trophic ulcer was noticed, and on the 7th day the trophic ulcer healed.

Example 9

Patient A, 54 years old, suffering from diabetic angiopathy, was applied an emulsion with a thin layer around the wrist. Research was conducted on a thermal imager. Before applying the ointment, the temperature reaction is 28 ° C and is noted only on the back of the hand, the phalanges of the fingers are not visible due to severe pathology in the patient.

5 minutes after applying the emulsion, we noted an increase in temperature to 30 ° C in the center of the palm and the appearance of a temperature reaction on the phalanges of the fingers 26 ° C.

30 minutes after applying the emulsion, an increase in temperature occurred over the entire surface of the palm from 26 to 30 ° C.

After 1 hour, the entire surface of the palm from the center to the fingertips was warm and there was a uniform increase in temperature to 31.3 ° C. This effect lasted 10 hours with a single application of the emulsion.

Claims (5)

1. Means for improving peripheral circulation of local action, characterized in that it contains nitroglycerin, aminophylline and target additives in the following ratio of components, g: Nitroglycerin 0.3-2.0 Eufillin 30.0-60.0 Target additives Up to 1000.0 2. The tool according to claim 1, characterized in that it can be made in the form of an emulsion, gel, ointment. 3. The tool according to claim 1, made in the form of an emulsion, as target additives contains liquid paraffin, emulsion wax, distilled water and ethyl alcohol. 4. The tool according to claim 1, made in the form of a gel, as target additives contains liquid paraffin, ethyl alcohol, distilled water, polymethyl methacrylate. 5. The tool according to claim 1, made in the form of an ointment, as the target additives contains ethyl alcohol, distilled water, borax, beeswax lanolin.