Agent "foridone-gel" for treatment and prophylaxis of cardiovascular diseases

FIELD: medicine, cardiology, chemical-pharmaceutical industry.

SUBSTANCE: invention relates to an agent used in treatment and prophylaxis of cardiovascular diseases. The claimed agent comprises the following components, wt.-%: foridone as an active substance (3.00-6.00) and pharmaceutically acceptable carrier - gel base (the balance) consisting of a thickening agent, non-aqueous hydrophilic solvents, hydrophobic solvents, preserving agent, neutralizing agent, emulsifier and purified water. Invention provides achievement of high level of prolongation of specific activity of agent, reducing or excluding negative adverse effects.

EFFECT: improved and valuable medicinal properties of agent.

8 cl, 5 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.

It is known for the treatment of cardiovascular diseases - ointment "Nitro", which contains 2% nitroglycerin ointment and the basis, including paraffin, cetanol, oxypropylation 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 (1).

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 (2).

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 environments is tion (3).

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 biological activity. A significant disadvantage "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 (4).

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 negative 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 (5).

The most similar to the claimed means is the drug "Tridon" in the form of tablets containing the e 0.01 g active substance foregone (2,6-dimethyl-3,5-diethoxycarbonyl-4-(2-deformational)-1,4-dihydropyridines) and a pharmaceutically acceptable carrier. Faridon refers to antagonists of calcium, it is used as an antihypertensive, antispasmodic, koronarorasshiryayuschee remedy for the treatment of diseases of the cardiovascular system. The treatment time by foredoom depend on the severity of the disease and can take several months. The initial therapeutic effect occurs at the end of the first week, lasting through 2-3 weeks. The term half-life of the drug from the body is 2-4 hours. Taken orally 3 times per day, the daily dose to 150 mg Possible side effects of redness of the face, headache, tachycardia, which takes place after dose reduction or withdrawal of the drug (6).

The disadvantages of the prototype should include a small period (the period of the half-life of the drug from the body is 2-4 hours), side effects such as reddening of the face, headache, tachycardia, which takes place after dose reduction or withdrawal of the drug. Such phenomena to a large extent can be attributed to the negative properties of the dosage form of foregone - tablets, which in this case is kratkodeystvuyuschim form and which cannot be attributed to the acceptable forms for drugs on the basis of calcium antagonists in connection with the sharp rise and fall in concentration of the active substance in the blood plasma and reflex reactions, is the quiet accompany this phenomenon (see recommendations Cardiological scientific center of the Russian Academy of medical Sciences: a New medical journal. - 1996. - №3-4. - P.12-16). Thus, for reasons that hinder the prototype to achieve the technical result obtained in the present invention include the fact that its qualitative and quantitative composition is not possible to achieve a high level of prolongation of the specific activity, reduce or eliminate the negative side effects.

The basis of the invention is the task of creating funds on the basis of foregone in the form of a gel, the qualitative and quantitative composition which would allow to achieve a high level of prolongation of the specific activity, reduce or eliminate the negative side effects.

The problem is solved in that the means for the treatment and prevention of cardiovascular diseases, containing the active substance paridon and a pharmaceutically acceptable carrier, in accordance with the invention as a pharmaceutically acceptable carrier use a gel base containing thickener, non-aqueous hydrophilic solvent, a hydrophobic solvent, a preservative, neutralizing agent, emulsifier and the water purified in the following ratio of components, wt.%:

tridon (FS W-4/37-1307-01)3,00-6,00
gel-basedrest

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

The problem is solved in accordance with the invention 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.

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

The problem is solved 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, or aminomethylpropanol, or Tris(hydroxypropylammonium), or the ethoxylated innolipa the ical amines, or sodium tetraborate, or trometamol.

The problem is solved in accordance with the invention as emulsifier using tween-80 or tween-60, or tween-40, or pemulen.

The problem is solved in accordance with the invention, the carbomer is a polyacrylic acid or its resin.

The technical result, which is obtained by carrying out the invention, is to achieve a high level of prolongation of the specific activity, the reduction or exclusion of negative side effects.

Cited specific examples of carrying out the invention.

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 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 reactor with gel mass with stirring consistently load glycerin, propylene glycol, ethyl alcohol, tween-80, formaldehyde solution and the suspension foregone, mix until smooth, getting relevo the product gel foregone, which is Packed in tubes.

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

faridon3,00
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 of components, wt.%:

rest
faridon3,50
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 water

Example 3. The inventive tool get analogously to example 1 in the following ratio of components, wt.%:

faridon4,50
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 of components, wt.%:

faridon5,00
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
rest

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

faridon5,50
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

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

faridon6,00
carbomer (carbopol 974 PNF)2,50
glycerin12,00
propylene glycol5,00
the ammonia solution 15%2,00
ethyl alcohol 96%10,50
formaldehyde solution0,20
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 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 reactor with gel mass with stirring consistently load glycerin, propylene glycol, ethyl alcohol, tween-80, formaldehyde solution and the suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
carbomer (carbopol 940)1,00
glycerin6,00
propylene glycol7,50
triethanolamine1,00
ethyl alcohol 96%8,00
formaldehyde solution0,10
vaseline oil 10,00
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 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 reactor with gel mass with stirring consistently load glycerin, propylene glycol, ethyl alcohol, tween-80, formaldehyde solution and the suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

td align="right"> 0,10
faridon5,00
carbomer (carbopol 934)1,00
glycerin6,00
propylene glycol7,50
sodium hydroxide0,32
ethyl alcohol 96%8,00
formaldehyde solution
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 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 reactor with gel mass with stirring consistently load propylene glycol, ethyl alcohol, tween-80, formaldehyde solution and the suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
the zacapa1,60
propylene glycol5,80
the ammonia solution 15%1,00
ethyl alcohol 96%7,10
formaldehyde solution0,10
10,50
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 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 reactor with gel mass with stirring consistently load glycerin, ethyl alcohol, tween-80, formaldehyde solution and the suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
acmid0,80
glycerin12,00
potassium hydroxide0,30
ethyl alcohol 96%7,10
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 to it with stirring, aminomethylpropanol to pH 5.0-7.0, getting a homogeneous transparent gel mass. In the mixer 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 reactor with gel mass with stirring consistently load the polyethylene oxide-400, propylene glycol, ethyl alcohol, tween-80, nipagin and suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
carbomer (carbopol 974 PNF)1,00
the polyethylene oxide-4006,90
propylene glycol7,30
aminomethylpropanol0,80
ethyl alcohol 96%8,00
nipagin010
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 load Dimethicone, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in Dimethicone. In the reactor with gel mass with stirring consistently load glycerin, propylene glycol, dimethylsulfoxide, pemulen, nipagin and suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
carbomer (carbopol 940)1,00
glycerin7,00
propylene glycol7,30
potassium hydroxide0,30
the sulfoxide10,00
nip is gin 0,10
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 load 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 reactor with gel mass with stirring consistently load isopropyl alcohol, tween-80, a mixture of nipagin and nipazola and suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
carbomer (carbopol 940)1,25
ethanolamine0,60
isopropyl alcohol30,00
nipagin/nipazol0,12 mg/0.03 mg
sunflower oil 8,50
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 load Dimethicone, heated to a temperature of 55-65°add with stirring chopped paridon and dispersed it, getting the suspension foregone in Dimethicone. In the reactor with gel mass with stirring consistently load ethyl alcohol, pemulen, triclosan and suspension foregone, mix until smooth, obtaining the target product - gel foregone, which is Packed in tubes.

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

faridon5,00
carbomer (carbopol 934)1,10
potassium hydroxide0,30
ethyl alcohol 96%30,00
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 stenosis of the coronary arteries is a well-recognized 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 ions is Alicia, 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 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.

In preclinical and clinical studies of the proposed drug as the main comparator drug used faridon 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 long and uninterrupted settlement is upline active substances in the bloodstream, what contributes to the prolongation of therapeutic effect.

The transdermal route of administration of foregone in the body in the inventive qualitative and quantitative composition of components has many advantages in comparison with oral method of administration, namely: the possibility of reducing the dose of the drug; the reduction or elimination of manifestations of toxicity or other side effects if necessary, increase the dose, with the exception of factor biotransformation of foregone in the liver, resulting in its bioavailability is only 20-50%; a more accurate choice. Hitherto unknown application foregone in the form of a gel.

Qualitative and quantitative composition the proposed drug for the treatment of cardiovascular diseases pharmacologically validated 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 study the specific activity of the proposed drug on animals (as p is apart comparisons used tablet foregone) showed that the claimed means exerts antianginal, antiarrhythmic and hypotensive action at the level of the comparison drug, but with prolonging effect. The duration of antianginal action increases about 2 times and the duration is 10-12 hours (duration of the comparison drug 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 acute toxicity indicate that the claimed product is practically non-toxic drugs.

New dosage form foregone 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.

Thus, the claimed tool provides a slower maximum concentration foregone in plasma, the systemic effect of the drug, as well as a longer presence on setoudeh substances in the body.

Clinical studies of the proposed drug was carried out on 45 patients with ischemic heart disease with stable angina 1-P functional classes, as well as patients with essential hypertension stage I and II: group 1 (main - 30 patients)in the treatment which was applied the proposed facility, group 2 (control 15 patients), which received basic therapy with the exception of the proposed drug and other calcium channel blockers. The average age of the patients was 52,2 year. Was appointed as the first daily 2 times daily 500 mg gel (25 mg foregone). Daily dose of foregone - 50 mg Gel was applied and gently rubbed or on the skin of the abdomen, or upper part of the front surface of the chest, or on the skin of the forearm. When reaching the initial therapeutic effect within 2-3 weeks the dose can be reduced to 250 mg (12.5 mg foregone). Daily dose of 25 mg foregone. Used for the treatment of patients with ischemic heart disease, patients with unstable angina, hypertensive heart disease stage I and II, in complex therapy of patients with acute myocardial infarction, arterial hypertension, to improve tolerance to physical activity.

According to the study of the dynamics of indicators of clinical blood of patients 1 and 2, groups can make the substance of the conclusion, that the proposed facility will have no adverse impact on these indicators.

The results of studies of the impact of the proposed drug and drug comparisons on the condition of patients with coronary heart disease Serce (stable angina) are shown in table 1.

Table 1

The dynamics of the frequency of angina attacks in patients of groups 1 and 2
The group of patientsThe average frequency of angina attacks per day
Before the treatmentAfter the treatment
12,74±0,320,75±0,18*
22,63±0,290,81±0,21*
*p>0,05 in comparison between groups; p<0,05 in comparison with the original data.

Based on the analysis of the dynamics of the frequency of angina attacks in patients of groups 1 and 2 we can conclude that in patients with ischemic heart disease (stable angina) claimed a tool in combination with the means of basic therapy shows significant impact on the incidence of angina attacks, helps to reduce them.

Table 2

Dynamics of change of e is astrocartography patients of groups 1 and 2
The group of patientsThe number of observationsPositive dynamics of ECG (decrease signs of ischemia)
The absolute number%
1232086,9
211981,8
p>0,05 compared between groups.

The study of the dynamics of changes in the electrocardiograms of 1 and 2 groups of patients (table 2) allowed us to establish that 86.9% of cases in group 1 and in 81.8% of cases in group 2 improved electrocardiogram.

Table 3

Dynamics of changes in blood pressure in patients with hypertension groups 1 and 2
Group

sick
The level of arterial pressure, mm Hg
Before the treatmentAfter the treatment
GARDENDadGARDENDad
1covers 175.6±2,54108,13±2,18153,7±2,4989,92±1,78
2176,2±2,28105,74±2,23159,2±3,41 91,5±3,27
p>0,05 compared between groups

The data of table 3 indicate that in patients with hypertension in both groups there is a decrease in diastolic blood pressure (DBP), but this reduction is more than 1 group. In group 1 patients prevails reduction in systolic blood pressure (SBP).

The results are a proof of the presence in the claimed anti-ischemic agent, antianginal and hypotensive properties.

Table 4 shows the results of clinical studies of antianginal effect of the proposed drug and the comparator drug.

Table 4

The antianginal effect of the proposed drug (group 1) and the comparison drug (group 2)
The performance of the clinical examinationThe number of patients (%)
group 1 (n=30)group 2 (n=15)
Decrease pain66%60%
Disappearance of pain syndrome30%27%
Reducing the frequency of angina attacks (for the week)77%60%
Reducing the signs of hypoxia the AI attack on the EKG 63%53%
The reduction processes of depolarization in the myocardium according to ECG57%47%

The data of table 4 show that the inventive tool shows more significant antianginal effect than the comparison drug.

Table 5 shows the results of a clinical study of the dynamics of blood pressure when applying the proposed drug and the comparator drug.

Table 5

Dynamics of blood pressure in patients when the use of the proposed drug (group 1) and the comparison drug (group 2)
Blood pressure (BP)group 1group 2
Before the treatmentAfter the treatmentBefore the treatmentAfter the treatment
HELL systolic187,4±6,8143,4±4,5*189,5±9,6144,5±5,6*
HELL diastolic100,6±3,887,6±3,5*101,7±9,188,3±5,7*
p <0.05 with respect to the source data

R* - >0,05 in compared groups

p> Studies have shown that the proposed facility complies with the optimal tolerability of the drug does not cause pathological changes in laboratory parameters during the clinical examination of patients.

To determine prolongirovannomu steps of the proposed drug studies have been conducted his clinical pharmacokinetics (6 patients with an average weight of 68.3 kg). The proposed tool was applied on the forearm at a dose of 1 g, which corresponds to 50 mg of foregone. This dose was chosen based on effective doses and was below the range toxic level foregone. The obtained values of pharmacokinetic parameters indicate the gradual admission of foregone in the blood system and prove the optimality of established dosage form, which eliminates the effect of the rapid rise in the concentration of active substance in the blood, characteristic of calcium antagonists. Analysis of the pharmacokinetic curve of the proposed drug showed that the period of time during which the concentration of foregone is in the blood plasma at therapeutic level is 12 hours, which is significantly higher than when using tablets foregone, the period which is 3-4 hours.

Thus, the claimed means exceeds p is eparat comparison of the level of antianginal and hypotensive action and clinical tolerability, does not cause pathological changes in laboratory parameters during the clinical examination of patients; provides long-term systemic effect, in which therapeutic concentration of foregone in plasma is maintained for 12 hours.

The proposed tool allows you to provide more effective protection for patients with strokes, seizures which are often observed in the night and pre-dawn hours, due to the constant maintenance of blood required concentration of foregone, which results in prolongation of effect, ensures longer hypotensive effect in comparison with the pill decreases the frequency and amount of the claimed means a day (for example, tablets foregone - 3-4 times a day, and for Foregone-gel 2 times a day).

In the process of conducting clinical studies have revealed the possibility intranasal use of the proposed drug, in which therapeutic effect of foregone is already apparent after 10 minutes and lasts for 8-10 hours.

Thus, the rational choice of a new dosage form and combination of its ingredients in the inventive tool performs supplied invention the problem of prolongation of therapeutic action, reducing the dose of the active substance and the number of methods per day, reduce or exclude negativnyh side effects.

LITERATURE

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

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

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

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

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

6. Mashkovsky PPM Medicines. Kharkov: Torsing, 1997, Vol. 1, s (prototype).

1. For the treatment and prevention of cardiovascular diseases, containing the active substance paridon and a pharmaceutically acceptable carrier, characterized in that as the pharmaceutically acceptable carrier used gel base containing thickener, non-aqueous hydrophilic solvent, a hydrophobic solvent, a preservative, neutralizing agent, emulsifier and the water purified in the following ratio, wt.%:

Faridon3,00-6,00
Gel-basedRest

2. The tool according to claim 1, characterized in that the thickener used carbomer, or zacapa, or acid.

3. The tool according to claim 1, characterized in that as a nonaqueous g is profiling solvents used glycerin, or polyethyleneoxide-200, or polyethyleneoxide-400, or polyethyleneoxide-600, or propylene glycol, or dimethyl sulfoxide, or ethyl alcohol, or propyl alcohol, or mixtures thereof.

4. The tool according to claim 1, characterized in that as the hydrophobic solvent used vaseline oil, or sunflower oil, or peach oil, or sesame oil, or castor oil, or Dimethicone.

5. The tool according to claim 1, characterized in that the preservative used solution of formaldehyde, or nipagin, or nipazol, or triclosan, or mixtures thereof.

6. The tool according to claim 1, 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(hydroxypropyl-Ethylenediamine), or ethoxylated gemoliticheskie amines, or sodium tetraborate, or trometamol.

7. The tool according to claim 1, characterized in that the emulsifier used tween-80 or tween-60, or tween-40, or pemulen.

8. The tool according to claim 2, wherein the carbomer is a 34 polyacrylic acid or its resin.



 

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1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: about 10 min before occlusion of carotid arteries into total carotid artery at the side of reconstruction it is necessary to introduce nicotinamide solution at 2.0 mg/kg body weight. The innovation provides cerebral protection against ischemic lesion in case of reconstructive operations upon carotid arteries under local anesthesia, at keeping patient's consciousness, in particular, in case of contraindications for total anesthesia and at necessity for verbal contact between a doctor and a patient under operation.

EFFECT: higher efficiency.

4 dwg, 1 ex, 1 tbl

FIELD: medicine, pharmacology, phytotherapy.

SUBSTANCE: invention relates to the development of preparations of vegetable origin that show effect on the blood rheology indices. Invention represents the hemorheological agent from vegetable raw as red clover alcoholic extract. Agent can be prepared as liquid of dry extract. Also, invention relates to methods for preparing this agent. Method for preparing the hemorheological agent involves extraction of red clover herb with ethyl alcohol aqueous solution being extraction is carried out twice followed by combining the extracts. Prepared red clover extract can be used in treatment of patients with cardiovascular and other diseases for reducing the enhanced blood viscosity, the spontaneous aggregation of blood formed elements and enhancing the reduced capacity of erythrocytes for deformability. Proposed agent can be used in treatment of diseases accompanying with the enhanced blood viscosity syndrome (ischemic heart disease, brain vascular diseases and so on).

EFFECT: improved preparing method, valuable medicinal properties of agent.

4 cl, 2 ex

FIELD: medicine, cardiology, phytotherapy, pharmaceutical industry.

SUBSTANCE: invention relates to composition used in treatment of cardiovascular diseases. The composition for treatment of cardiovascular diseases comprises a mixture of the following medicinal plants: haw-thorn fruits or flowers, motherwort herb, Japanese pagoda-tree (Sophora) fruits, valerian roots, Eleutherococcus senticosus roots, Bunge's ziziphora or wild basil herb taken in the definite ratio of components. Also, the composition for treatment of cardiovascular diseases comprises a mixture of 30-40% alcoholic tinctures of the following medicinal plants: haw-thorn fruits or flowers, motherwort herb, Japanese pagoda-tree (Sophora) fruits, valerian roots, Eleutherococcus senticosus roots, Bunge's ziziphora or wild basil herb taken in the definite ratio. Proposed compositions promote to effective treatment of cardiovascular diseases.

EFFECT: valuable medicinal properties of composition.

4 cl, 11 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new bis-aryl compounds of the formula (I): wherein one among A1-A4 means nitrogen atom and others mean -CH or -CR5; A5-A8 mean -CH or -CR5; R5 means halogen atom or (C1-C)-alkyl; R(1) means -C(O)OR(9), -COR(11); R(9) and R(11) mean CxH2x-R(14); x means 0, 1,2, 3 or 4 and x can't mean 0 if R(14) means -OR(15); R(14) means (C1-C6)-alkyl or phenyl; R(15) means (C1-C5)-alkyl; R(2) means hydrogen atom; R(3) means CyH2y-R(16) wherein y means 0, 1, 2, 3 or 4 and y can't mean 0 if R(16) means -OR(17); R(16) means (C1-C6)-alkyl, phenyl or pyridyl; R(17) means hydrogen atom, (C1-C5)-alkyl, phenyl or pyridyl, or R(3) means -CHR(18)R(19); R(18) means hydrogen atom or CzH2z-R(16) wherein R(16) means abovementioned values; z means 0, 1, 2 or 3; R(19) means -CONH2; R(4) means hydrogen atom; R(30) and R(31) mean hydrogen atom, and to their pharmaceutically acceptable salts also. Compounds of the formula (I) possess anti-arrhythmic activity and can be used in medicine.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

11 cl, 30 ex

FIELD: medicine, intensive therapy.

SUBSTANCE: it is necessary to apply 2 ml fentanyl, 2 ml tramadol, 1-2 ml droperidol into one syringe to be dissolved with physiological solution up to 10 ml. Solution should be injected at the rate of 1 ml per 6-10 sec intravenously. The innovation enables to completely interrupt pain syndrome, avoid its relapsing and, thus, decrease the frequency of therapeutic side effects that leads to favourable hemodynamic situation in this category of patients.

EFFECT: higher efficiency of therapy.

FIELD: medicine, cardiology.

SUBSTANCE: the present innovation deals with treating patients with ischemic cardiac disease at the background of type II diabetes. For this purpose, in case of stenocardia of functional class II and type II diabetes of average severity degree one should introduce enalapril at the dosage of 20 mg/d in combination with trental at the dosage of 400 mg/d, and at stenocardia of functional class III and type II diabetes of severe flow one should introduce enalapril at the dosage of 30 mg/d in combination with trental at the dosage of 400 mg/d. The innovation suggested normalizes monocytic-macrophageal link of immune system.

EFFECT: higher efficiency of correction.

2 ex, 4 tbl

FIELD: pharmaceutical industry.

SUBSTANCE: therapeutical composition contains sea-buckthorn extract, biologically active component isolated from medicinal leech or its parts, aqueous-alcoholic extract of horse-chestnut fruitage, methyluracyl, anestesin, Carbomer, triethanolamine, methylparben, Bronopol, butyloxyanisol, and water. Utilization of the composition promotes activation of metabolic processes in rectum mucosa, anesthetizes and accelerates microcirculation of blood, produces antithrombic and thrombolytic effects, which results in rapid achievement of stable therapeutical effect in suppressing hemorrhoids and inflammatory process in rectum.

EFFECT: enhanced therapeutical efficiency.

2 tbl

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a composition comprising one or more corticosteroids and/or hormonal steroids in the range from 0.025 to 5 wt.-% of the total composition mass and hyaluronidase in the amount from 25 to 4000 UTR per 1 g of the composition in the suitable carrier medium. The composition can comprise nonhormonal anti-inflammatory agents. The composition can be prepared in different medicinal formulations, such as gel, ointment, cream, aerosol with additives known from a person skilled in the art of the corresponding field. Betamethasone is the preferable corticosteroid. Ointment is the preferable medicinal formulation. Treatment by using corticosteroids in combination with hyaluronidase provides the improvement of state in 90% of patients, and after their treatment their prepuce can be drawn off easily.

EFFECT: improved medicinal properties of composition, enhanced effectiveness of treatment.

11 cl, 6 ex

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to creating drugs for treatment and prevention of inflammatory lesions of support-motor apparatus (myosites, arthrites, tendovaginites, etc.). Therapeutical composition according to invention contains, wt %: essential oil of silver fir 1.0-2.0, camphor 4.0-5.0, oil extract of red capsicum 0.06-0.08, biologically active component isolated from medicinal leech or its parts 0.01-6.5, Ibuprofen 60.0-65.0, ethoxydiglycol 3.0-5.0, Emulgin B2 0.4-0.6, Carbomer 0.5-0.8, triethanolamine 0.6-0.8, methylparben 0.2-0.3, propylparben 0.02-0.03, butyloxyanisol 0.08-0.1, Bronopol 0.04-0.05, and water the rest. Composition activates metabolic processes in skin and subcutaneous fat layer, normalizes blood supply, eliminates stagnant phenomena, accelerates getting active therapeutical substances into membranes of biological cells, which results in rapid achievement of stable therapeutical effect in what concerns elimination of inflammatory process in joints and muscles.

EFFECT: increased therapeutical efficiency.

2 tbl

FIELD: pharmaceutical industry and cosmetics.

SUBSTANCE: composition contains, wt %: biologically active component isolated from medicinal leech or its parts 0.01-6.0, menthol 0.15-0.25, aqueous-alcoholic extract of horse-chestnut fruitage 8-10, camphor 0.15-0.30, ethoxydiglycol 3-5, polyethyleneglycol 1500, 0.8-1.2, emulgin B2, 0.8-1,2, Carbomer 0.6-0.8, triethanolamine 0.6-0.8, methylparben 0.25-0.35, Bronopol 0.04-0.06, butyloxyanisol 0.06-0.08, and water to 100%. Composition is made in the form of gel and provides antithrombic and analeptic effects on skin and hypodermic tissues, enhances antiinflammatory action, favors deep penetration of active components through skin, strengthens venous vessel walls, improves microcirculation of blood, and accelerated restoration of vascular wall tone.

EFFECT: expanded therapeutical possibilities.

2 cl, 2 tbl

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

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: 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

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