Therapeutical agent "forinit-gel" for treatment and prevention of cardiovascular disease

FIELD: pharmaceutical chemistry.

SUBSTANCE: agent contains active components foridonum (3.00-6.00%) and isosorbide dinitrate (3.00-6.00%) with pharmaceutically acceptable gel base. The latter is composed of thickener, non-aqueous hydrophilic solvents, hydrophobic solvents, preservative, neutralization agent, emulsifier, and purified water.

EFFECT: increased bioavailability of active components and reduced or suppressed negative side effects such as locally irritating effects.

9 cl, 3 tbl, 14 ex

 

The invention relates to medicine and pharmaceutical industry, in particular to the creation, production and application of funds in the form of gels for the treatment of cardiovascular diseases.

Known drug cardiovascular actions Nitrosorbid" in the form of tablets containing 0.05, 0.01 and 0.02 g of active substance nitrosorbid (the isosorbide dinitrate treatment or 1,4,3,6-dianhydro-D-sorbitol, the dinitrate treatment). Used as antianginal funds with chronic coronary insufficiency. With long-term use "Nitrosorbid" observed the development of tolerance and you need to increase doses and frequency of administration. In addition, there is often a headache, dizziness and low blood pressure (1).

It is known for the treatment of cardiovascular diseases "Ointment "Nitro", which contains 2% nitroglycerin ointment and the basis, including paraffin, cetanol, oksipropil-cellulose, vaseline. Ointment relates to long-acting drugs (the effect is manifested in 30-40 minutes and lasts for 2-5 hours) and was appointed as an additional tool for the prevention of angina attacks in conjunction with nitrates, which are used orally (2).

Known drug cardiovascular actions "Cardice" in the form of tablets containing the e 20, 40 and 60 mg of isosorbide dinitrate, and in the form of a retard capsules containing 120 mg of the active substance. Used as antianginal means (3).

Known drug cardiovascular actions "Isomac-retard" in the form of capsules containing 20 and 40 mg of active ingredient isosorbide dinitrate. Use "Isomac-retard" as an antianginal means (4).

Known drug "Isaac" in the form of a spray containing a single dose of 1.25 mg of active ingredient isosorbide dinitrate (200 doses in the vial). Use "Isaac" as antianginal means (5).

Known drug cardiovascular actions "Socket" in the form of tablets containing 20, 40 and 60 mg of isosorbide dinitrate; in the form of aerosol (300 doses in the vial with a capacity of 15 ml of 1.25 mg of active ingredient per dose); in the form of solution for infusion (0.1% of active substance in the ampoule 10 ml); in the form of a cream (50 g vial containing 1 g ointment 100 mg of active substance). Use "Socket" as antianginal means (6).

You know the "Digoxin" for the treatment of diseases of the cardiovascular system in the form of tablets 0.00025 g 0.0001 g and in the form of 0.025% injectable solution in ampoules of 1 ml of the Medium used in the treatment of heart failure, it shows high card is Botanichesky activity. Significant nedostatki "Digoxin" is quite a wide range of contraindications, in particular, the presence of cumulative effects with long-term use, which leads to impaired activity of the cardiovascular system (7).

Known drug cardiovascular actions Digitoxin in the form of tablets to 0.0001 g and in the form of candles to 0.00015, the Tool is used in the treatment of heart failure that requires long term treatment, especially when the tendency to tachycardia. "Digitoxin" shows high biological activity. Dose means and duration of treatment should be strictly individual, as well as in connection with cumulative properties of the medicinal product in patients manifest side effects typical of glycosides in case of overdosing and long-term use of the drug, which leads to severe disorders of the cardiovascular system (8).

The most similar to the claimed means is the drug "Coroperate" in the form of a patch containing as an active substance of the isosorbide dinitrate treatment. Applied as slow release forms of isosorbide dinitrate to prevent strokes and heart failure (9).

The disadvantages of the prototype include the following:

- duration is ostopenia optimal level of specific activity (TTS 2-3 hours after admission; in the inventive tool in the form of a gel mild angina occurs within 2-5 min, reduction of blood pressure after 15-20 min);

- the need for the patch significantly more active substances than in the gel, due to physico-chemical characteristics of the adhesive basics - dry solid masses on glue, diffusion of the active substance from which, compared with gel-based, hindered, resulting in a reduced level of bioavailability of the active substance;

- the presence of local irritation caused by the presence of an adhesive based on a number of chemical substances that provide adhesion of the patch to the skin;

- the impossibility of providing a variety of ways of introducing medicines into the body (e.g., nasal way for the proposed drug in gel form, in which the optimal level of activity of active substances occurs within 2-5 min).

The basis of the invention is the task of creating funds on the basis of foregone and isosorbide dinitrate in the form of a gel, the qualitative and quantitative composition which would allow to achieve a high level of bioavailability of the active substances, to avoid negative side effects such as local irritation, to provide a variety of ways of introducing Lekarstvo the th tool in the human body.

The problem is solved in that the means for the treatment and prevention of cardiovascular diseases, containing the active substance of the isosorbide dinitrate treatment and a pharmaceutically acceptable carrier, in accordance with the invention, further comprises paridon, and as the pharmaceutically acceptable carrier contains a gel-based, in the following ratio, wt.%:

of the isosorbide dinitrate treatment (FS W-175-958-98)3,00-6,00
tridon (FS W-4/37-1307-01)3,00-6,00
gel-basedrest

The problem is solved also by the fact that, in accordance with the invention, gel-based contains a thickener, non-aqueous hydrophilic solvent, a hydrophobic solvent, a preservative, neutralizing agent, emulsifier and water clean.

The problem is solved also by the fact that, in accordance with the invention as a thickener use carbomer, or zacapa, or acid.

The problem is solved also by the fact that, in accordance with the invention, as the non-aqueous hydrophilic solvent use glycerin, or polyethylene oxide-200, or polyethyleneoxide-400, or polyethyleneoxide-600, or propylene glycol, or dimethyl sulfoxide, or ethyl alcohol, or Speer is propyl, or mixtures thereof.

The problem is solved also by the fact that, in accordance with the invention, as hydrophobic solvents used vaseline oil, or sunflower oil, or peach oil, or sesame oil, or castor oil, or Dimethicone.

The problem is solved also by the fact that, in accordance with the invention, as preservative use formaldehyde solution, or nipagin, or nipazol, or triclosan, or mixtures thereof.

The problem is solved also by the fact that, in accordance with the invention, as a neutralizing agent use 15-25% solution of ammonia or sodium hydroxide, or potassium hydroxide, or triethanolamine, or ethanolamine, or diisopropanolamine, aminomethylpropanol, or Tris(hydroxypropylammonium), or ethoxylated gemoliticheskie amines, or sodium tetraborate, or trometamol.

The problem is solved also by the fact that, in accordance with the invention, used as an emulsifier tween-80 or tween-60, or tween-40, or pemulen.

The problem is solved also by the fact that, in accordance with the invention, carbomer represents a polyacrylic acid or its resin.

The technical result, which is obtained by carrying out the invention, is to achieve a high level of bioavailability of the active washes is in, and to avoid negative side effects such as local irritation, to provide a variety of ways of introducing medicines into the body.

Example 1. Charged to the reactor water clean, add with stirring carbomer (Carbopol-934) and leave for 10-12 hours, after which the resulting mixture was again mixed and added to it with stirring 25% ammonia solution to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 load vaseline oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in vaseline oil. In the mixer No. 2 sequentially load glycerin, propylene glycol, ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, formaldehyde solution, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

faridon3,00
of the isosorbide dinitrate treatment/td> 4,50
carbomer (Carbopol-934)0,50
glycerin5,00
propylene glycol9,00
ammonia solution 25%0,20
ethyl alcohol 96%6,50
formaldehyde solution0,05
vaseline oil8,00
tween-805,00
purified waterrest

Example 2. The inventive tool get analogously to example 1 in the following ratio, wt.%:

faridon3,50
of the isosorbide dinitrate treatment5,00
carbomer (Carbopol 974 PNF)0,70
glycerinof 5.40
propylene glycol4,00
ammonia solution 25%0,30
ethyl alcohol 96%9,50
formaldehyde solution0,06
vaseline oil9,10
tween-805,50
purified waterrest

Example 3. The inventive tool get analogously to example 1 in the following ratio comp is required, wt.%:

faridon4,50
of the isosorbide dinitrate treatment5,50
carbomer (Carbopol-941)2,50
glycerin5,00
propylene glycol4,00
the ammonia solution 15%2,00
ethyl alcohol 96%10,50
formaldehyde solution0,05
vaseline oil8,00
tween-805,00
purified waterrest

Example 4. The inventive tool get analogously to example 1 in the following ratio, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,00
carbomer (Carbopol-934)1,00
glycerin6,00
propylene glycol7,50
the ammonia solution 20%0,60
ethyl alcohol 96%8,00
formaldehyde solution0,10
vaseline oil10,00
tween-807,00
purified water rest

Example 5. The inventive tool get analogously to example 1 in the following ratio, wt.%:

faridon5,50
of the isosorbide dinitrate treatment3,00
carbomer (Carbopol-940)0,50
glycerin12,00
propylene glycol9,00
the ammonia solution 20%0,20
ethyl alcohol 96%6,50
formaldehyde solution0,20
vaseline oil12,00
tween-8010,00
purified waterrest

Butt 6. The inventive tool get analogously to example 1 in the following ratio, wt.%:

0,20
faridon6,00
of the isosorbide dinitrate treatment4,00
carbomer (Carbopol 974 PNF)2,50
glycerin12,00
propylene glycol5,00
the ammonia solution 15%2,00
ethyl alcohol 96%10,50
formaldehyde solution
vaseline oil12,00
tween-8010,00
purified waterrest

Example 7. Charged to the reactor water clean, add with stirring carbomer (Carbopol-940) and leave for 10-12 hours, after which the resulting mixture was again mixed and added thereto under stirring triethanolamine to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 load vaseline oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in vaseline oil. In the mixer No. 2 sequentially load glycerin, propylene glycol, ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, formaldehyde solution, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

carbomer (carbopol-940)
faridon5,00
of the isosorbide dinitrate treatment4,50
1,00
glycerin6,00
propylene glycol7,50
triethanolamine1,00
ethyl alcohol 96%8,00
formaldehyde solution0,10
vaseline oil10,00
tween-807,00
purified waterrest

Example 8. Charged to the reactor water clean, add, with stirring, carbomer (Carbopol-934) and leave for 10-12 hours, after which the resulting mixture was again mixed and added to it with stirring sodium hydroxide to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 load vaseline oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in vaseline oil. In the mixer No. 2 sequentially load glycerin, propylene glycol, ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, formaldehyde solution, suspension foregone and suspension isosorbide dinitrate, mix on the homogeneity, receiving target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,00
carbomer (Carbopol-934)1,00
glycerin6,00
propylene glycol7,50
sodium hydroxide0,32
ethyl alcohol 96%8,00
formaldehyde solution0,10
vaseline oil10,00
tween-807,00
purified waterrest

Example 9. Charged to the reactor water clean, add while stirring the zacapa and leave for 10-12 hours, after which the resulting mixture was again mixed and added thereto under stirring 15% ammonia solution to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 load vaseline oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in vaseline oil. In the mixer No. 2 sequentially load propylene glycol and ethyl alcohol and stirring until ablaut of the isosorbide dinitrate treatment, getting the suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, formaldehyde solution, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes.

The inventive solution has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,00
the zacapa1,60
propylene glycol5,80
the ammonia solution 15%1,00
ethyl alcohol7,10
formaldehyde solution0,10
vaseline oil10,50
tween-807,70
purified waterrest

Example 10. Charged to the reactor water clean, add with stirring acid and leave for 10-12 hours, after which the resulting mixture was again mixed and added to it with stirring potassium hydroxide to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 load vaseline oil, heated to a temperature of 55-65°add in premesis the Institute chopped paridon and dispersed it, getting the suspension foregone in vaseline oil. In the mixer No. 2 sequentially load the glycerol and ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, formaldehyde solution, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,20
acmid0,80
glycerin12,00
potassium hydroxide0,30
ethyl alcohol7,10
formaldehyde solution0,10
vaseline oil10,50
tween-807,70
purified waterrest

Example 11. Charged to the reactor water clean, add with stirring carbomer (Carbopol 974 PNF) and leave for 10-12 hours, after which the resulting mixture was again mixed and added thereto under stirring amino is ethylpropane to pH 5.0-7.0, receiving a uniform transparent gel mass. In the mixer No. 1 load castor oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in castor oil. In the mixer No. 2 sequentially load the polyethylene oxide-400, propylene glycol, ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add tween-80, nipagin, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment4,80
carbomer (Carbopol 974 PNF)1,00
the polyethylene oxide-4006,90
propylene glycol7,30
aminomethylpropanol0,80
ethyl alcohol8,00
nipagin0,10
castor oil8,50
tween-809,70
purified waterrest

Example 12. Charged to the reactor water clean, add with stirring carbomer (Carbopol-940) and leave for 10-12 hours, after which the resulting mixture was again mixed and added to it with stirring potassium hydroxide to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 download Dimethicone, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in Dimethicone. In the mixer No. 2 sequentially load glycerin, propylene glycol, dimethyl sulfoxide and added with stirring to the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate in the mixture of solvents. In the reactor with gel mass with stirring consistently add pemulen, nipagin, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,00
carbomer (Carbopol-940)1,00
glycerin7,00
propylene glycol 7,30
potassium hydroxide0,30
the sulfoxide10,00
nipagin0,10
Dimethicone10,00
pemulen5,00
purified waterrest

Example 13. Charged to the reactor water clean, add with stirring carbomer (Carbopol-940) and leave for 10-12 hours, after which the resulting mixture was again mixed and added thereto under stirring ethanolamine to pH 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 download sunflower oil, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in sunflower oil. In the mixer No. 2 load isopropyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate. In the reactor with gel mass with stirring consistently add tween-80, a mixture of nipagin and nipazola, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes. The inventive solution has the following ratio of components, wt.%:

Fori is it 5,00
of the isosorbide dinitrate treatment6,00
carbomer (Carbopol-940)1,25
ethanolamine0,60
isopropyl alcohol15,00
nipagin/nipazol0,12 mg/0.03 mg
sunflower oil8,50
tween-809,70
purified waterrest

Example 14. Charged to the reactor water clean, add with stirring carbomer (Carbopol-934) and leave for 10-12 hours, after which the resulting mixture was again mixed and added to it with stirring potassium hydroxide to a pH of 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer No. 1 download Dimethicone, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in Dimethicone. In the mixer No. 2 load ethyl alcohol and stirring of the isosorbide dinitrate treatment, receiving a suspension of isosorbide dinitrate. In the reactor with gel mass with stirring consistently add pemulen, triclosan, suspension foregone and suspension isosorbide dinitrate, mix until smooth, obtaining the target product - Forint-gel, which is Packed in tubes.

Declare the medium is in has the following ratio of components, wt.%:

faridon5,00
of the isosorbide dinitrate treatment5,00
carbomer (Carbopol-934)1,50
potassium hydroxide0,30
ethyl alcohol10,00
triclosan0,20
Dimethicone10,00
pemulen5,00
purified waterrest

The inventive tool is a medicine cardiovascular actions for local application in the form of a homogeneous gel consistency, white or slightly yellowish color, with low specific smell.

Cardiovascular disease (ischemic heart disease, arterial hypertension and others) are one of the main causes of disability and mortality. This is not only a quantitative increase in these diseases, but also defeat these kinds of pathology is increasingly young populations. Treatment of such patients should be comprehensive and include both struggle with risk factors for coronary heart disease and clinical manifestations of angina. In the pathogenesis of coronary heart disease along with atherosclerotic coronary stenosis and the clear is recognized, the role of dynamic coronary stenosis, symptoms which reduce or eliminate the drugs based on calcium antagonists, one of the representatives is paridon - active substance of the proposed drug. You must take into account the high efficiency of calcium antagonists in their use as antihypertensive drugs.

Tridon (2,6-dimethyl-3,5-diethoxycarbonyl-4-(2-deformational)-1,4-dihydropyridines) antagonist of calcium ions exhibiting hypotensive, antispasmodic and koronarorasshiryayuschee activity. Apply faridon with hypertension I-II degree, strokes voltage at a dose of from 20 to 30 mg 3 times a day, the daily dose to 150 mg of the Term half-life of the drug from the body is 2-4 hours. Side effects of foregone may be headache, dizziness, fatigue, facial flushing, skin rash. In rare cases, nausea, vomiting, constipation, sleep disorders, nervous condition, edema of the lower extremities. When using the main active substance - foregone, in quantities less than the declared values are not achieving the desired therapeutic effect, and when used in a quantity greater than the declared value is not observed dose-dependent increase of the level of the specific activity of the probable presence of side effects.

Of the isosorbide dinitrate treatment (nitro is orbit or 1,4,3,6-dianhydro-D-sorbitol, the dinitrate treatment) - one of the main organic nitrate antianginal actions. When administered in tablet form onset of action observed after 30-50 min, maximum effect - 1.5-2.0 hours, the duration of action is 4-6 hours. Take a dose of 5-30 mg 3-4 times per day. When prolonged use can develop tolerance, and therefore increasing the appropriate level of specific activity and possible negative side effects.

In preclinical and clinical studies of the proposed drug as the main Comparators used faridon in the form of tablets and the isosorbide dinitrate treatment in the form of tablets. Among the various ways of introducing drugs into the body using a tablet form provides a relatively low bioavailability of active substances. Therefore, considerable interest is a way of introducing them through the skin, which is a long and continuous flow of active substances in the bloodstream, which contributes to the prolongation of therapeutic effect.

The authors conducted an experimental study on the introduction into the organism of the active substance of foregone in the form of a patch and the proposed drug in gel form. Thus we obtained the following results:

- patch with foredoom (Sistema cm) contains 500 mg of active substance, the recommended dose is 1-3 system (500-1500 mg) depending on the pathology of the disease. The optimal level of specific activity occurs within 3.5 to 4.0 hours, the level of bioavailability - release of active substances is 6-10%;

- daily dose (2 doses) composition foredone with isosorbide dinitrate treatment is 60-240 mg; mild angina occurs within 2-5 min, blood pressure lowering in 15-20 minutes; if natalina method of administration is through 2-5 minutes

The level of bioavailability - release of active substances is 80% or more.

Hitherto unknown application foregone and isosorbide dinitrate in gel form.

Qualitative and quantitative composition the proposed drug for the treatment of cardiovascular diseases pharmacologically defined and substantiated in experiments on animals by comparative studies of different composition samples of the gels. The necessary and sufficient ingredients and selected conditions of carrying out the process, providing multiple pharmacological effect of the proposed drug, chemical-physical and mechanical-technological properties of the dosage form.

Dolinskii research specific activity of the proposed drug on animals (as Comparators used tablet foregone and isosorbide dinitrate) showed that the claimed means exerts antianginal, antiarrhythmic and hypotensive action level or more Comparators, but with a significant prolonging effect. The duration of antianginal action increases about 2 times and the duration is 10-12 hours (the duration of action of the drug comparison foregone is 4-8 hours. The duration of antiarrhythmic actions proposed drug is increased to 8-10 hours.

With long-term use (within 3 months) of the inventive tool has not shown allergenic, irritant action and adverse effects on vital organs of animals. The results of animal studies of acute toxicity, indicate that the claimed product is practically non-toxic drugs.

New drug combinations form foregone and isosorbide dinitrate can reduce or eliminate the consequences of such negative manifestations characteristic of drugs based on calcium antagonists, as a sharp rise and fall of the concentration of the active substance in the blood plasma and reflex reactions that accompany this phenomenon, and the development of tolerance to drugs on the basis of isosorbide dinitrate.

Clinical studies of the inventive medium spans the VA was conducted on 30 patients of the main group and 30 patients in the control group, patients with coronary heart disease with stable angina pectoris without myocardial infarction in combination with hypertension 1-P stage. The average age of the patients was 52,2±5.8 years. The objective of the research was to study the tolerability and safety of use "Forinit-gel"; the establishment of its maximum safe dose and dosage regimen; evaluation of its antianginalnoe and hypotensive effect. As comparative drugs were used tableted forms of Isosorbide dinitrate" (10 mg) and Foregone" (10 mg).

Patients of the main group 2 days after discontinuation of antianginal and hypotensive drugs, conducting dosed physical load (DFN) and daily monitoring of arterial pressure (AP) was appointed the inventive tool within 4 days of Queuing at a dose of 60 mg (2 cm), 120 mg (4 cm), 180 mg (6 cm) and 240 mg (8 cm). Every 2 hours was assessed systolic and diastolic blood pressure (SBP, Add), heart rate (HR), tolerability and side effects of the proposed drug.

After analysis of the dynamics of blood pressure and heart rate, depending on the dose Forinit-gel" and the period of time from the start of application tools the following data were obtained (table 1).

80,0±4
Tables is 1

Duration, changes in blood pressure and heart rate, depending on the dose Forinit-gel"
Forinit - gelIndicatorsBaselineThe time from the beginning of application tools
2 hours4 hours6 hours8 hours10 hours
60 mgDt160,0±5156,0±5160,0±6154,0±5154,0±5154,0±5
Add96,0±495,0±496,0±492,0±594,0±596,0±5
HR78,0±578,0±578,0±580,0±576,0±574,0±5
120 mgDt155,0±4150,0±5142,0±5138,0±6147,0±5150,0±6
Add94,0±394,0±488,0±384,0±580,0±477,0±5
HR64,0±477,0±478,0±582,0±577,0±5
180 mgDt164,0±5158,0±5140,0±6138,0±5of 149.0±5157,0±6
Add95,0±390,0±484,0±580,0±583,0±580,0±5
HR66,0±480,0±384,0±486,0±485,0±480,0±5
240 mgDt162,0±6154,0±6132,0±7130,0±6142,0±6155,0±6
Add97,0±692,0±480,0±476,0±581,0±688,0±5
HR64,0±480,0±488,0±594,0±590,0±484,0±5
Of the isosorbide dinitrate treatment, FaridonDt158,0±6140,0±5146,0±6155,0±6160,0±5140,0±5
Add95,0±484,0±382,0ଔ 90,0±493,0±580,0±4
HR75,0±582,0±582,0±478,0±376,0±480,0±4
Note: SBP - systolic blood pressure Add - on diastolic blood pressure heart rate - heart rate

The research results presented in Table 1 show that the inventive tool at a dose of 60 mg per day has no significant effect on changes in indicators of blood pressure and heart rate in a controlled periods of time. In doses of 120-180 mg showed a significant reduction of blood pressure and increased heart rate; at the dose of 240 mg these changes occurred even more. The analysis of the results obtained in the control group of patients who took oral forms of Isosorbide dinitrate" (10 mg) and Foregone" (10 mg) suggest that the decline in the blood pressure and increase heart rate also occurred, but the maximum change in these parameters was evident after 2-3 hours from the moment of reception of preparations, and after 6 hours of their hypotensive action was stopped. The main group of patients the maximum effect was observed after 4-6 hours after application Forinit-gel on the skin, lasted 8 hours and returned kushtrim values after 10 hours.

The portability of the proposed drug was assessed in points on a five-point scale, the estimation results are presented in Table 2.

Table 2

The portability of the proposed drug
Forinit-gel dosePortability (number of patients, %)
1 point (very good)2 points (good)3 points (satisfactory)4 points (unsatisfactory)5 points (very unsatisfactory)
60 mg30 (100%)----
Mg26 (86.6 per cent)4 (13,3%)---
Mg20 (66,7%)5 (16,7%)5 (16,7%)--
Mg15 (50%)6 (20%)6 (20%)3 (10%)-
Of the isosorbide dinitrate treatment,

10 mg

Paridon, 10 mg
25 (83,3%)3 (10%)2 (6,7%)--

The data in table 2 indicate that the dose of 60 mg of the inventive means "very good" carry 100% of patients of the main group; a dose of 120 mg "very good"was 86.7%, "well" - 13,4%; 180 mg "very good" - 66,7%, "good" is 16.7%, "satisfactory" by 16.7%; 240 mg "very good" - 50%, "good"-20%, "very good" - 20%, "poor" - 10%. With increasing doses up to 180-240 mg in 36.6% of the patients showed tachycardia, headache, redness of the skin. Thus, new drug combinations form foregone and isosorbide dinitrate provides an opportunity to significantly increase the dose of the drug, increasing the level of its specific activity without negative side effects.

The results of the study impact of the proposed drug tolerance permissible physical activity of patients suggest that the use of individually tailored dose of the drug for weeks significantly increased the tolerance to this indicator, as well as increased coronary reserve.

To analyze the effectiveness of the proposed drug is important indicator of the needs of patients in the use of nitroglycerin in the week.

The results show that the use of "Forinit-gel patients with ischemic heart disease by 39% had reduced their weekly need for nitroglycerine, reduced the number of anginal pain by 10% without taking nitroglycerin.

Hypotensive effect of the proposed drug was studied using the daily monitoring of blood is Alenia.

Table 3

Hypotensive effect of the proposed drug after one week course (use 1 time per day)
The drug, blood pressure (BP)The interval of time per day (hour)
9-1212-1515-1818-2121-0000-33-66-9
Forinit-gelDt164±9154±6144±4144±6152±7155±6160±7163±9
Add95±592±590±687±589±693±595±494±6
Of the isosorbide dinitrate treatment, 10 mg

Paridon, 10 mg
Dt166±8140±6152±5157±5158±6159±7159±8168±8
Add99±490±589±693±595±494±696±48± 6
Note: SBP - systolic blood pressure Add - on blood pressure diastolic

In the daily monitoring of arterial pressure, which was held one week after treatment the claimed means of observed hourly fluctuations in blood pressure with the maximum hypotensive effect until the sixth hour after the application of the proposed drug, because of its prolonged action. Patients of the control group statistically significant decrease in blood pressure was observed from the second to the fourth hour from initiation of the comparison drug.

The results of the study antianginal and hypotensive effects of the proposed drug and Comparators indicate that when the weekly treatment claimed by means of ischemic heart disease in combination with hypertension "good" and "satisfactory" antianginal effect was observed in 86.8% of patients, and drugs comparison - 83,3%; "good" and "satisfactory" hypotensive effect in the treatment of the claimed means - in 93.3% of patients, and drug comparisons - 90.0% of patients.

The inventive tool with long-term use virtually harmless: does not show negative effects on the functional state vital the organs and systems, no irritants on the skin.

Thus, the claimed combination for the treatment of cardiovascular disease through the rational selection of the dosage form and combination of ingredients helps to achieve a high level of specific activity and its prolongation, to reduce or Eliminate the negative side effects.

Sources of information

1. Mashkovsky PPM Medicines. Kharkov: Torsing, 1997, Vol. 1, p.390.

2. Mashkovsky PPM Medicines. Kharkov: Torsing, 1997, T.1, s.

3. On The Main Page. Drugs in Russia: a Handbook. M: Attraversare, 2001, B-245.

4. On The Main Page. Drugs in Russia: a Handbook. M: Attraversare, 2001, B-220.

5. On The Main Page. Drugs in Russia: a Handbook. M: Attraversare, 2001, B-245.

6. On The Main Page. Drugs in Russia: a Handbook. M: Attraversare, 2001, B-245.

7. Mashkovsky PPM Medicines. Kharkov: Torsing, 1997, Vol. 1, s.

8. Mashkovsky PPM Medicines. Kharkov: Torsing, 1997, Vol. 1, c.359.

9. Mashkovsky PPM Medicines. M: LLC "New Wave", 2001, vol. 1, s (prototype).

1. For the treatment and prevention of cardiovascular diseases, containing the active substance of the isosorbide dinitrate treatment and pharmaceutical is viable media characterized in that it further comprises paridon, and as the pharmaceutically acceptable carrier contains a gel based on the following ratio, wt.%:

Of the isosorbide dinitrate treatment3,00-6,00
Faridon3,00-6,00
Gel-basedRest

2. The tool according to claim 1, characterized in that the gel-based contains a thickener, non-aqueous hydrophilic solvent, a hydrophobic solvent, a preservative, neutralizing agent, emulsifier and water clean.

3. The tool according to claim 2, characterized in that the thickener used carbomer, or zacapa, or acid.

4. The tool according to claim 2, characterized in that as a non-aqueous hydrophilic solvent use glycerin, or polyethylene oxide-200, or polyethyleneoxide-400, or polyethyleneoxide-600, or propylene glycol, or dimethyl sulfoxide, or ethyl alcohol, or propyl alcohol, or mixtures thereof.

5. The tool according to claim 2, characterized in that as the hydrophobic solvent used vaseline oil, or sunflower oil, or peach oil, or sesame oil, or castor oil, or Dimethicone.

6. The tool according to claim 2, characterized in that the preservative used solution of formaldehyde, is whether nipagin, or nipazol, or triclosan, or mixtures thereof.

7. The tool according to claim 2,characterized in that as a neutralizing agent use 15-25%solution of ammonia or sodium hydroxide, or potassium hydroxide, or triethanolamine, or ethanolamine, or diisopropanolamine, aminomethylpropanol, or Tris(hydroxypropylammonium), or ethoxylated gemoliticheskie amines, or sodium tetraborate, or trometamol.

8. The tool according to claim 2,characterized in that the emulsifier used tween-80 or tween-60, or tween-40, or pemulen.

9. The tool according to claim 3, wherein the carbomer is a polyacrylic acid or its resin.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds including all its enantiomeric and diastereomeric forms, and to their pharmaceutically acceptable salts wherein indicated compound corresponds to the formula: wherein A represents a conformationally limited ring system chosen from the group comprising the following formulae: (a) (d) and (e) wherein carbon atoms labeled by asterisks can be in any stereochemical configuration or their mixtures wherein Y has a formula: -(CH2)b-R15 wherein index b = 1-4, and R15 represents -OH, -NH2, guanidine-group, and Z has a formula: wherein R represents hydrogen atom; R9 represents naphthylmethyl; R10 represents -C(X)N(R16)2 wherein each R16 represents independently hydrogen atom or (C1-C10)-alkyl; X represents oxygen atom; or Z represents naphthylmethyl wherein W has a formula: wherein R represents phenyl substituted optionally with halogen atom of OH-group wherein fragment L is chosen from the group comprising: -NH- or -NHC(O)-; B represents hydrogen atom of fragment of the formula: wherein fragments R2, R3 and R4 are chosen independently among the group comprising hydrogen atom, -NHC(O)CH3, benzyl substituted optionally with hydroxy-group or halogen atom, imidazolylmethyl; or fragments R2, R3 and R represent in common naphthalinyl or isoquinolinyl; or one radical among R2, R3 and R4 represents hydrogen atom and two radical among R, R3 or R4 chosen in common form piperidine ring or tetrahydroisoquinoline ring substituted optionally with the group -C(O)CH3. Also, invention relates to a pharmaceutical composition possessing the agonistic activity with respect to MC-3/MC-4 receptors based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of disorders mediated by function of MC-3/MC-4 receptors.

EFFECT: valuable medicinal properties of compounds and compositions.

17 cl, 14 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: method involves administering required dose of renin-angiotensin inhibitor Ramipryl or its salt combined with a hypotensive drug, means for reducing cholesterol content, diuretic or aspirin to patients showing no signs of left ventricle dysfunction or cardiac insufficiency.

EFFECT: prevented cardiovascular attacks, angina pectoris, diabetes manifestations.

18 cl, 5 tbl

FIELD: medicine.

SUBSTANCE: method involves administering required dose of renin-angiotensin inhibitor Ramipryl or its salt combined with a hypotensive drug, means for reducing cholesterol content, diuretic or aspirin to patients showing no signs of left ventricle dysfunction or cardiac insufficiency.

EFFECT: prevented cardiovascular attacks, angina pectoris, diabetes manifestations.

18 cl, 5 tbl

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to using the natural triterpenoid of the lupan order, namely betulin, as a capillary-restorative agent. It was found capillary-restorative properties of 1% alcoholic solution of betulin being without its toxic effect on organism. Betulin as 1% alcoholic solution decreases penetrability of mouse skin vessels by 2 times more effective as compared with the known capillary-restorative agent dihydroquercetin. The new agent can be used in treatment of many diseases.

EFFECT: valuable medicinal properties of agent.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves administering Eucanol at a daily dose of 3-4 g and Ispradin at a daily dose of 1.2-1.3 mg twice a day. Eucanol is taken during a meal and Ispradin is taken 30-40 min before meals.

EFFECT: enhanced effectiveness of treatment; reduced drug consumption.

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutically acceptable salts of 2,4,6-trimethyl-2-hydroxypyridine with lower dicarboxylic acids of the general formulae (1-a-d): possessing an antioxidant activity wherein X means a simple bond (compound 1a), oxalate, C8H11NO x C2H2O4; X means -CH2 (compound 1b), malonate, C8H11NO x C3H4O4; X means -CH2-CH2 (compound 1c), succinate, C8H11NO x C4H6O4); X means the group -CH2CH(OH) (compound 1d), malate, C8H11NO x C4H6O5. Also, invention relates to a pharmaceutical composition of salt of the formula (1c) possessing geroprotecting and anti-ischemic activities, and to a method for preparing these salts.

EFFECT: improved preparing method, valuable medicinal properties of substances and pharmaceutical composition.

3 cl, 5 tbl, 6 ex

FIELD: pharmacy, chemical technology.

SUBSTANCE: invention relates to methods for preparing simvastatin of high purity degree from lovastatin by the following stages: (a) opening lactone ring in addition of lovastatin in reaction with amine for formation of amide; (b) protection of 1,3-diol moiety by a protecting group; (c) removal of 2-methylbutyryl group joined by ester bond through oxygen atom at position 8 in hexahydronaphthalene ring; (d) joining of 2,2-dimethylbutyrate group by formation of ester bond to hydroxyl at position 8; (e) removal of protecting group; (f) conversion of amide to acid salt, and lactone ring closure resulting to formation of simvastatin. Semi-synthetic statin is prepared from statin by carrying out the following steps: (a) opening lactone ring by reaction of statin with amine resulting to formation of amide; (b) protection of 1,3-diol moiety by using the protecting group; (c) removal of group R1 joined by ester bond through oxygen atom at position 8 in hexahydronaphthalene ring; (d) joining group R2 by formation of ester bond to hydroxyl at position 8; (e) removal of protecting group; (f) conversion of amide to acid salt, and (g) lactone ring closure with formation of semi-synthetic statin. Invention provides enhancing purity degree of the product.

EFFECT: improved preparing methods of statins.

17 cl, 19 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to arylated amides of furan and thiophene carboxylic acids of the formulae (Ia) and (Ib) wherein W means oxygen or sulfur atom; R(1) means -C(O)OR(9) or -COR(11) wherein R(9) and R(11) mean independently of one another CxH2x-R(14) wherein x means 0, 1, 2 or 3; R(14) means phenyl, and to their pharmaceutically acceptable salts also. Also, invention describes a pharmaceutical composition and using proposed compounds a medicinal agents. Compounds can be used as anti-arrhythmic biologically active substances and especially in treatment and prophylaxis of atrium arrhythmia.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 29 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention describes valsartan salts chosen from the group involving monosodium, monopotassium, disodium, dipotassium, magnesium, calcium, bis-diethyl (or dipropyl, or dibutyl)-ammonium salts or their hydrates, and mixtures of these salts also. Also, invention relates to a method for their preparing and a pharmaceutical composition comprising thereof. Proposed salts can be in crystalline, partially crystalline, amorphous or polymorphous form. Prepared salts show high quality of crystalline lattices that is a base for chemical and physical stability of new compounds.

EFFECT: improved preparing method, improved and valuable properties of salts.

11 cl, 11 tbl, 16 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active ortho-substituted nitrogen-containing bis-aryl compounds. Invention describes compounds of the formula (I): wherein A1, A2, A3, A4, A5, A6, A7 and A8 mean independently of one another nitrogen atom or -CH and wherein at least one or two (not above) these groups mean nitrogen atom; R(1) means -C(O)OR(9) or -COR(11) wherein R(9) and R(11) mean independently of one another CxH2x-R(14) wherein x has a value 0, 1, 2, 3 or 4 and R(14) means alkyl c 1, 3, 4, 5 or 6 carbon atoms, phenyl or isoxazolyl wherein phenyl and isoxazolyl are not substituted or substituted with 1, 2 or 3 substitutes chosen from the group consisting of F, Cl, Br, J, CF3, OCF3, alkyl with 1, 2, 3 or 4 carbon atoms and alkoxy-group with 1, 2, 3 or 4 carbon atoms; R(2) means hydrogen atom; R(3) means CyH2y-R(16) wherein y has a value 0, 1, 2, 3 or 4but y can't mean 0 if R(16) means -OR(17), and R(16) means alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3 carbon atoms, -OR(17), phenyl or pyridyl wherein phenyl and pyridyl are not substituted or substituted with 1, 2 or 3 substitutes chosen from the group consisting of F, Cl, Br, J and alkoxy-group with 1, 2, 3 or 4 carbon atoms; R(17) means hydrogen atom; or R(3) means -CHR(18)R(19) wherein R(18) means alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms and R(19) means -CONH2; R(4) means hydrogen atom; R(30) and R(31) mean hydrogen atom, and their pharmaceutically acceptable salts also. Also, invention describes a pharmaceutical composition showing effect that inhibits K+-channel and comprising the effective amount of at least compound of the formula (I) and using compounds of the formula (I). Invention provides preparing new compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 8 tbl, 35 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to an anti-inflammatory ointment with hypolipidemic effect. Proposed ointment comprises ephthylline-base for ointment, a statin wherein lescol (fluvastatin) is used as statin, and ephthylline comprises 40% of ephthiderm. Invention provides enhancing the curative effect and hypolipidemic effect and effects on enzymatic systems of biological membranes that results to prolongation of curative effect of ointment.

EFFECT: valuable medicinal properties of ointment.

3 cl, 2 tbl

FIELD: cosmetology, esthetic surgery, applied biopharmacology.

SUBSTANCE: invention relates to medicative and cosmetic agents, and uses of biologically active substances based on natural biological complexes. Claimed method includes application of Mirralgin balm having analgesic, anti-inflammation and resolving action, Reventon balm, having vessel restorative action, for edema reducing and microcirculation improving. In process of blepharoplastic eye boundary bandage microemulsion having recovery and animative action on eaves skin is applied, and in process of facelifting cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied. Mirralgin balm and Reventon balm treatment is carried out sequentially or alternatively. In another embodiment after skin cleaning and treatment of damaged zone with anti-septic agent Bacteriophage gel, which disinfects skin surface, prevents biofilm forming, accelerates cicatrizing process is applied, then posttraumatic zone is treated with cleaning milk, toned up with tonic lotion and cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied.

EFFECT: method for skin structure recovering without skin trauma.

4 cl, 7 ex, 1 tbl

FIELD: veterinary science, medicine, pharmacy.

SUBSTANCE: invention relates to agents used in treatment of dermatomycosis in animals and humans. Ointment for treatment of dermatomycosis in animals and humans comprises acetylsalicylic acid, 5% iodine alcoholic solution and glycerol taken in the definite ratio of components. Invention enhances effectiveness of treatment, decreases time in treatment of dermatomycosis and prevents appearance of new foci of diseases and relapses.

EFFECT: enhanced effectiveness of treatment.

6 ex

FIELD: medicine, contraception.

SUBSTANCE: invention proposes antibacterial and contraceptive compositions that comprise the following components: (1) matrix-forming substance; (2) bioadhesive substance; (3) buffer substance; (4) moistening substance, optionally; (5) preserving agent, optionally, and (6) water. Proposed compositions are suitable for their placement into vagina wherein compositions form semisolid matrix in contact with testicular fluid, cause thickening cervical mucus, form a bioadhesive layer on vagina surfaces, maintain the natural acid pH value in vagina about less 5 in the presence of testicular fluid ejected by a male and don't disturb essentially the natural microbiological balance in vagina. Compositions and methods decrease and/or prevent transfer of diseases transferring by sexual way and act as vaginal contraceptives with less adverse effect as compared with conventional vaginal contraceptives and can be used therefore for a long time. Compositions and methods are simple for using and don't require a physical device for their retention into vagina during using.

EFFECT: improved and valuable properties of compositions and methods.

36 cl, 17 tbl, 11 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to an agent for topical using used in treatment of joint diseases. The proposed agent comprises glucosamine salt, chondroitin sulfate and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness due to using low-molecular saccharides that results to elevating diffusion delivery rate of the substance to the joint zone and providing the achievement of synergistic effect in treatment of joint diseases.

EFFECT: enhanced effectiveness and valuable medicinal properties of agent.

2 cl, 3 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to preparations for external using in treatment of joint diseases. The proposed agent comprises a saccharide - glucosamine salt and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness of agent due to using low-molecular saccharides that results to the elevating diffusion delivery rate of active substance to the join zone.

EFFECT: improved and valuable properties of agent.

2 cl, 5 ex

FIELD: medicine, dermatology, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical gel composition for applying on skin. The composition comprises at least one vitamin D or analog of vitamin D, at least one corticosteroid, at least one solvent and an excipient enhancing viscosity. Viscosity value of the composition is in the range from 5 mPa x s to 500 mPa x s. The composition is designated for treatment of psoriasis and associated states in humans. The composition is suitable for applying on skin, shows the improved absorption and stable at 40°C in storage for 3 months.

EFFECT: improved and valuable properties of composition.

22 cl, 2 tbl, 1 ex

FIELD: medicine, endocrinology, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to nateglynide-containing preparation used in treatment of diabetes mellitus that comprises nateglynide as an active component and a carrier wherein nateglynide in amorphous form and indicated carrier represents hydrophilic material. Amorphous property of crystalline nateglynide is provided by the following methods: 1) by dissolving nateglynide crystals in pharmacologically acceptable solvent in common with hydrophilic materials taken among the group consisting of water-soluble polymers, water-swelling polymers, sugar alcohols and salts followed by granulation in fluidized layer, granulation by stirring at high rate, drying by spraying and process for coat applying for granulation of amorphous nateglynide; 2) by mixing nateglynide crystals with hydrophilic materials taken among the group of water-soluble polymers, water-swelling polymers, sugar alcohols and salts and the following application of the high shift force to the prepared mixture; 3) by mixing nateglynide crystals with hydrophilic materials taken among the group of water-soluble polymers, water-swelling polymers, sugar alcohols and salts and the following plasticizing the prepared mixture in melt by heating and milling at cooling; 4) by dissolving nateglynide crystals in pharmacologically acceptable liquid additives wherein liquid additives represent water-soluble polymers that are liquid at 37°C. Using amorphous nateglynide allows preparing the nateglynide preparation with immediate release wherein the dissolving rate of medicinal agents is high and without crystalline transition during preparing or preserving preparations.

EFFECT: valuable pharmaceutical properties of preparation.

6 cl, 3 tbl, 9 dwg

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes using xenogenous oligo-and/or polyribonucleotides, namely total RNA and tRNA, as an active component of external anhydrous medicinal agent for a single treatment of skin tumor relapse (for example, basalioma) or infections caused by herpes virus and the corresponding method for treatment. The claimed external anhydrous medicinal agents decline effectively relapses of indicated diseases after a single intake.

EFFECT: enhanced effectiveness and valuable medicinal properties of agents.

5 cl, 2 ex

FIELD: veterinary science.

SUBSTANCE: the suggested preparation contains dense propolis, vegetable oil, extract out of dead bees based upon glycerol, lanolin, honeycombs' cutting off, moreover, all the components should be taken at certain quantitative ratio, weight%: honeycombs' cutting off 15-20, dense propolis 20-25, extract out of dead bees upon glycerol 7.5 -10, lanolin 20-25, vegetable oil - the rest, moreover, honeycombs' cutting off includes honey residues. The preparation in question is of high biological activity, provides shortened terms for recovery in animals and excludes allergic reactions.

EFFECT: higher efficiency for therapy.

1 cl, 8 ex

FIELD: medicine.

SUBSTANCE: method involves administering Eucanol at a daily dose of 3-4 g and Ispradin at a daily dose of 1.2-1.3 mg twice a day. Eucanol is taken during a meal and Ispradin is taken 30-40 min before meals.

EFFECT: enhanced effectiveness of treatment; reduced drug consumption.

Up!