Drug for treating osteoarthrosis (versions)

FIELD: medicine.

SUBSTANCE: invention represents a drug for treating osteoarthrosis presented as a soft dosage form, containing glucosamine and methyl salicylate as active substances, and additive agents.

EFFECT: enhanced anaesthetic action and lower toxicity of methyl salicylate.

10 cl, 1 tbl, 4 ex

 

The invention relates to the pharmaceutical industry, namely the production of pharmaceuticals for the treatment of osteoarthritis. The invention is a medicinal product consisting of a combination of two or three active substances, one of which is a salt of glucosamine, mainly glucosamine hydrochloride and excipients. The drug is made in the form of a cream-gel, a cream, but is not limited to this.

Osteoarthritis - degenerative-dystrophic diseases of joints, caused by a lesion of the cartilage of the articular surfaces [1].

The main clinical symptoms of osteoarthritis are pain and deformity of the joints, leading to functional failure [2].

Osteoarthritis is the most common form of joint damage and one of the main causes of disability, which causes deterioration in the quality of life and considerable financial costs, especially in the elderly.

Meets osteoarthritis everywhere. In the U.S., it hurts 21 million people (about 7% of the population). Large-scale study in 7 cities of the former USSR have revealed manifest (accompanied by clinical symptoms) osteoarthritis have to 6.43% (41348 people aged over 15 years) [3].

The incidence of osteoarthritis increases sharply with age, reaching third on the population in elderly and senile age.

According to the modern classification of drugs used in the treatment of osteoarthritis, they are divided into the following groups:

1. Symptomatic means of rapid action (non-steroidal anti-inflammatory drugs, acetaminophen, opioid analgesics, corticosteroids and others), which have an impact on clinical symptoms (pain, inflammation, and others).

2. Modifying means of a delayed action (glucosamine, chondroitin, hyaluronic acid), the effect of which is more slowly in comparison with symptomatic drugs and lasts long after application. Data pharmacological agents have chondromodulin action, preventing the degradation of articular cartilage [4].

Glucosamine has chondroprotective properties, reduces the deficit glycosaminoglycans in the body, is a specific substrate and a stimulator of the synthesis of hyaluronic acid and proteoglycans. Improves joint mobility, reduces the need for non-steroidal anti-inflammatory drugs (NSAIDs) [5].

The closest analogue to the present invention is a medicinal product "Thermaskin TGC with active ingredient glucosamine sulphate potassium chloride 4 g in the form of a cream for external use.

The disadvantage of the drug is a weak analgesic the anti-inflammatory effect.

The aim of the present invention is the development of effective drugs for the treatment of osteoarthritis, which has enhanced action on the source of inflammation and pain through the effective permeability of the active substances through the skin and combines at the same time chondroprotective, anti-inflammatory and analgesic effect.

The technical result of the invention is:

1. Enhancing pain killers and anti-inflammatory properties of medicines, which have a chondroprotective effect.

The technical result is achieved due to the introduction of the methyl salicylate medicines with dosage is 0.1 to 5.0 wt. -%, mainly 2,50% wt., and/or lidocaine salt dosage is 0.1 to 5.0 wt. -%, mostly lidocaine hydrochloride with a dosage of 1.0% of the mass.

Methyl salicylate anti - inflammatory analgesic agent. Selectivity inhibits cyclooxygenase, reducing the synthesis of prostaglandins. Normalizes the increased permeability of the capillaries, improves microcirculation, reduces swelling and infiltration of the inflamed tissues. Methyl salicylate in the local application penetrates the tissues unchanged through the skin, with analgesic concentration in the systemic blood flow is not achieved.

Lidocaine is a local anesthetic; analgesia is achieved through the inhibition is the formation and conduction of nerve impulses along the afferent nerve fibers by depolarization of sodium channels.

2. The expansion of the means for the production of medicinal products containing as active substance salt of glucosamine.

The technical result is achieved due to the use as excipients pharmaceutically acceptable preservative (preservatives) with a dosage of 0.0001 to 2.0 wt. -%, mainly: Phenoxyethanol with a dosage of 0.50 wt%, methylparaben with a dosage of 0.15-0.20% wt., primiparae with a dosage of 0.05 wt. -%, benzalkonium chloride in a dose of 0.01 wt. -%, benzyl alcohol with dosage of 0.5 wt. -%, but not limited to.

The drug contains an antioxidant with a dosage of 0.05 to 2.0 wt. -%, mainly: butylhydroxyanisole with dosage 0,20% wt., is equivalent to a dosage of 0.10 wt. -%, metabisulphite sodium dosage of 0.10 wt. -%, but not limited to.

In the composition of the medicinal product contains solvents with a dosage of 5.0-60.0% of mass, as a solvent mainly containing: N-organic with dosage 15,00% wt., propylene glycol with dosage 10,00% wt., the polyethylene oxide 400 dosage 10,00-20,00% wt., hexyleneglycol with dosage 8,00-15,00% wt., 2-pyrrolidone with dosage 20,00% wt., onomatology ether of diethylene glycol with dosage 7,00% wt., butyleneglycol with dosage 12,00% wt., but not limited to.

The drug includes Emul gatory with dosage of 0.5 to 15.0 wt. -%, as emulsifiers mainly contains: macrogol 20 cetosteatil ether with dosage 1,40-2,00% of the mass. and cetosteatil alcohol dosage 3,50-6,80% wt., glycerylmonostearate with dosage 2,30% wt., cetyl alcohol with dosage 3,00-5,00% wt., stearyl alcohol with dosage 0,80-2,50% wt., of the macrogol hydroxystearate with the dosage to 1.60 wt. -%, sorbitan monolaurate with a dose of 1.50 wt. -%, Polysorbate 20 dosage 5,00% wt., but not limited to.

In the drug enters the thickener (thickeners) with a dosage of 0.1 to 7.0 wt. -%, mainly hydroxypropylmethyl phosphate with a dose of 2.50-6.00% per mass., the hypromellose with a dosage of 1.5 wt. -%, gidroxiatilkrahmal with dosage of 5.00 wt. -%, hydroxypropylcellulose with a dosage of 5.00 wt. -%, the methylcellulose with a dosage of 0.10 wt. -%, but not limited to.

In the composition of the medicinal product includes emolliency with a dosage of 3.0-80.0% of mass., mainly: isopropylmyristate with dosage 3,50-5,00% wt., Dimethicone DM 100 dosage 1,00-3,00% wt., hexidecimal with dosage 6,30% wt., white wax with dosage 3,40% wt., white soft paraffin (vaseline white) with dosage 25,00-65,00% wt., isopropyl with a dosage of 5.00 wt. -%, cyclomethicone with dosage of 1.00 wt. -%, vaseline oil dosage 7,00% wt., emulsion wax with a dosage of about 3.00 wt. -%, lanolin b is svodnyy with dosage 15,00% wt., octyldodecanol with dosage 1,50-5,50% wt., but not limited to.

Isopropylmyristate and Dimethicone DM 100 have a softening effect on the skin.

The drug contains an agent that regulates pH, dosage of 0.1-2.0 wt. -%, mainly citric acid monohydrate with dosage 0,20-0,80% of the mass, sodium citrate with a dosage of 0.35 wt. -%, acid of phosphorus with a dose of 0.20 wt. -%, sodium hydroxide with a dosage of 0.1 wt. -%, but not limited to.

As a solvent, and a core component of the framework medicinal product contains purified water to 100% of the mass.

The invention is a medicinal product consisting of a combination of two or three active substances, one of which is a salt of glucosamine, mainly glucosamine hydrochloride and excipients. The drug is made in the form of a cream-gel, a cream, but is not limited to this.

Developed the drug with active ingredients glucosamine salt, mainly glucosamine hydrochloride, and methylsalicylate. The preferred composition of the medicinal product, % mass.:

- glucosamine hydrochloride, 0.5 to 10.0

- methyl salicylate - 0,1-5,0

- preservative (preservatives) is 0.0001 to 2.0

- antioxidant (antioxidants) - 0,05-2,0

- non-aqueous solvent (solvents) - 5,0-60,0

- emulsifier (emulsifier) is 0.5 to 15.0

p> - thickener, and 0.1 - 7,0

- amalendu - 3,0-80,0

agent (agents), regulating the pH of 0.1-2.0

- purified water - the rest is up to 100%.

The drug may be in the form of a cream-gel, a cream, but is not limited to this.

Example 1. The drug is in the form of a cream of the following composition, % wt.:

- glucosamine hydrochloride - 5,0

- methyl salicylate - 2,5

- Phenoxyethanol - 0,50

- butylhydroxyanisole - 0,20

- N organic - 15,00

- propylene glycol - 10,00

the macrogol 20 cetosteatil ether - 2,00

- sitosterolemia alcohol - 6,80

- hydroxypropylmethyl phosphate - 2,50

- isopropylmyristate - 5,0

- Dimethicone DM 100 - 3,0

- octyldodecanol - 5,50

- hexidecimal - 6,30

- citric acid monohydrate - 0,50

- purified water - the rest is up to 100%.

A method of obtaining a medicinal product of example 1 includes the preparation of an aqueous solution of glucosamine hydrochloride, preparation of nonaqueous solution of an antioxidant and methyl salicylate, cooking basics, introduction to the basis of the preservative, the displacement of the substrate with the first two solutions, mixing until obtaining a finished product, packing in tubes or jars.

Under the basis of the present invention should be understood a mixture of non-aqueous diluent (s), thickener agent, regulating pH, emulsifiers and emollients the century

Conducted 3 clinical trial of a medicinal product with active ingredients - glucosamine hydrochloride and methyl salicylate (working title - "Glucosamine plus") in the form of a cream-gel, samples were produced at JSC ğtatkhimpharmpreparatyğ:

1. Preclinical study andprotecting properties of the drug, "Glucosamine plus" (cream), held in the National pharmaceutical University of the Ministry of health of Ukraine, Kharkov, 2011

2. Preclinical Toxicological studies (acute and sub-chronic toxicity, irritant effects) of the drug Glucosamine plus" (cream), held in SE "gntsls", , Kharkov, 05.08.2011,

3. Preclinical study of specific pharmacological activity of the drug Glucosamine plus" (cream), held in SE "gntsls" , Kharkov, 05.08.2011,

In the course of the research it was proved that studied the drug Glucosamine Plus" (cream-gel) shows pronounced chondroprotective activity.

This phenomenon is explained by the peculiarities of the composition of the investigated tools. Medication Glucosamine Plus is the original pharmaceutical composition for external use, which contains cartilage glucosamine hydrochloride and NSAIDs, meticillin have the s-inflammatory, analgesic, distracting action and contribute to the potentiation of the positive impact of hondroprotektor on the course of inflammatory and destructive process in the joints of the patient [6, S. 72].

Thus, the analysis of the results suggests that the drug "Glucosamine Plus" (cream-gel) is a promising tool for the treatment and prevention of degenerative-dystrophic diseases of joints, especially on the background of acute articular syndrome. The drug can be used as monotherapy or as part of complex treatment of osteoarthritis of the damaged joints in high concentrations [6, S. 73].

Acute toxicity study drug was studied on rats with cutaneous applications dose of 3.0 g/kg the Results of studies of acute toxicity showed that the application of cream to rats did not cause the death of animals that do not have a toxic effect on the General condition, behavior, body weight of animals, consumption of food and water, do not affect the absolute and relative weight of internal organs of rats do not cause visible changes in their internal organs.

Sub-chronic toxicity was investigated in experiments on rats with a daily skin applications in doses of 0.3 g/kg and 0.6 g/kg per month. The results of the study showed that the drug Glucosamine Plus cream-gel no effect is and the General condition and behavior, consumption of food and water, the dynamics of body weight of the animals on the functional state of the Central nervous system and the electrophysiological activity of the myocardium, on biochemical indicators of the functional state of the liver and kidneys of animals, the indicators of peripheral blood.

Pathomorphological studies in sub-chronic experiment established that the drug Glucosamine Plus cream-gel in the studied doses does not affect the relative weight of internal organs of rats. After prolonged exposure of the drug no macroscopic and morphological features cardiotoxic and hepatotoxic effect on the organism of experimental animals. The drug does not cause visible changes in the morpho-functional state of the Central (thymus) and peripheral (spleen) link immunogenesis. Glucosamine Plus cream-gel does not cause change in different areas of the cortex of the adrenal glands and related changes mineralocorticoid synthesis.

According to macro - and microscopic examination of the skin found that the drug Glucosamine Plus cream-gel has no irritant effect [7, S. 28].

The aim of preclinical pharmacological studies of the drug Glucosamine Plus cream-gel (JSC "tatchempharmpreparaty) was studied by the group of specific drugs (analgesic, anti-inflammatory activity of the drug.

Analgesic and anti-inflammatory activity of the drug was studied in rats in a model of acute and subacute inflammatory diseases - when carragenine and traumatic inflammation of the foot - in accordance with the basic principles outlined in the "guidelines for the study of new non-steroidal anti-inflammatory drugs.

The research was conducted in comparison with the base cream-gel Glucosamine Plus.

It is established that two-cutaneous application of a cream-gel Glucosamine Plus in a total dose of 200 mg/foot rats with carrageenin swelling of the foot has analgesic and anti-inflammatory effect, resulting in a significant increase in pain threshold and reduced growth inflamed foot rats compared with the untreated control and the group of rats treated with a base of cream-gel. Analgesic effect of the drug amounted to 101.8%, anti-inflammatory effect of 23.9%.

The basis of the cream-gel with two applications in the same total dose (200 mg/foot) had no significant effect on the pain threshold and increase the inflamed foot compared to control.

When 8-day application of rats with traumatic inflammation of the foot in the same daily dose (200 mg/foot) cream-gel Glucosamine Plus who showed analgesic effect, significantly increasing with 3 days of treatment the pain threshold of the injured foot as compared to untreated control and with a group that inflicted basis. Analgesic effect of cream-gel for 3 days was 80%, 5 day - 74,4%, 7 day - 71,6%. The total analgesic effect of the cream-gel was 412,4, which is 2.7 times more than the group receiving the base of the cream-gel - 153,0. In the group of rats receiving the base of a cream-gel, significant differences from the untreated control was not observed.

At the same rats with traumatic edema study drug daily applications anti-inflammatory effect, significantly reducing the growth of swelling of the foot already on the 2nd day of treatment. Anti-inflammatory effect of the drug was: 1 day - 10,2%, 2 day - 25,2%, 3 day - 48,2%, 4 day - 49,5%, 5 day - of 50.9%, 6 day - of 62.8%, 7 day - 71,6%, 8 day - 85,4%. Total anti-inflammatory effect of the cream-gel Glucosamine Plus was 361,1, which is 4.8 times larger than the base - 74,5. Application basics cream-gel had no significant reduction of growth edema.

In General, the results of the study of specific drugs (analgesic, anti-inflammatory) activity of the drug Glucosamine Plus cream-gel (JSC ğtatkhimpharmpreparatyğ) during acute and chronic (exchange) the use of rats in a model of acute and subacute inflammatory Pat the biology testify, that developed the drug has a pronounced analgesic and anti-inflammatory effect caused by the activity of active components, as evidenced by the significantly higher intensity of the pharmacological effects of the drug compared with a basis that does not contain active substances [8, S. 27-28].

Example 2. The drug, made in the form of a cream comprising as active substances glucosamine salt and methyl salicylate containing the following components, wt. -%:

- glucosamine hydrochloride - 5,00

- methyl salicylate - 2,50

- methylparaben - 0,20

- equivalent - 0,10

- polyethylene oxide 400 - 20,00

- hexyleneglycol - 8,00

- glycerylmonostearate - 2,30

- cetyl alcohol - 3,00

- stearyl alcohol - 2,50

- hypromellose - 1,5

- isopropyl - 6,00

- cyclomethicone - 1,00

- petroleum jelly - 7,00

- sodium citrate - 0,35

- citric acid monohydrate - 0,20

- purified water - the rest is up to 100%.

Developed the drug with active ingredients glucosamine salt, mainly glucosamine hydrochloride, methylsalicylate and salt of lidocaine, mainly lidocaine hydrochloride. The preferred composition of the medicinal product, % mass.:

- glucosamine hydrochloride, 0.5 to 10.0

- methyl salicylate - 0,1-5,0

- lidocaine g is drochloride - 0,1-5,0

- preservative (preservatives) is 0.0001 to 2.0

- antioxidant (antioxidants) - 0,05-2,0

- solvent (solvents) - 5,0-60,0

- emulsifier (emulsifier) is 0.5 to 15.0

- thickener, and 0.1 - 7,0

- amalendu - 3,0-80,0

agent (agents), regulating the pH of 0.1-2.0

- purified water - the rest is up to 100%.

The drug may be in the form of a cream-gel, a cream, but is not limited to this.

Example 3. The drug is in the form of a cream-gel of the following composition, % wt.:

- glucosamine hydrochloride - 5,00

- methyl salicylate - 2,50

- lidocaine hydrochloride - 1,00

- Phenoxyethanol - 0,50

- butylhydroxyanisole - 0,20

- N organic - 15,00

- propylene glycol - 10,00

the macrogol 20 cetosteatil ether - 1,40

- cetosteatil alcohol - 6,60

- hydroxypropylmethyl phosphate - 4,00

- isopropylmyristate - 4,00

- Dimethicone DM 100 - 1,00

- citric acid monohydrate - 0,40

- purified water - the rest is up to 100%

A method of obtaining a medicinal product according to the example 3 includes the preparation of an aqueous solution of glucosamine hydrochloride and lidocaine hydrochloride, preparation of nonaqueous solution of an antioxidant and methyl salicylate, cooking basics, introduction to the basis of the preservative, mix the substrate with the first two solutions, mixing until obtaining a finished product, packing in tubes Il the banks.

Example 4. The drug is in the form of a cream-gel, containing as active substances glucosamine salt, methyl salicylate, lidocaine salt, of the following composition, % wt.:

- glucosamine hydrochloride - 5,00

- methyl salicylate - 2,50

- lidocaine hydrochloride - 1,00

- benzalkonium chloride - 0,01

- equivalent - 0,10

- 2-pyrrolidone - 20,00

- onomatology ether of diethylene glycol - 7,00

of the macrogol hydroxystearate - 1,60

- cetyl alcohol - 5,00

- gidroxiatilkrahmal - 5,00

- isopropyl - 5,00

- cyclomethicone - 1,00

- phosphoric acid - 0,20

- purified water - the rest is up to 100%.

Experimental studies of the visual analogue scale (hereinafter YOURS), proving that the pharmaceutical composition containing as active substance salt of glucosamine, methyl salicylate, and pharmaceutical composition containing as active substance salt of glucosamine, methyl salicylate and lidocaine salt, made in soft form of drug, possess superior analgesic properties compared to a pharmaceutical composition comprising as active substance only salt of glucosamine, also made in soft dosage form.

Visual analogue scale is a line length of 100 mm, 0 mm corresponds to the HEA is csemo the patient's condition (no pain), a maximum value of 100 mm corresponds to the worst condition (maximum pain).

Investigated changes in the intensity of pain in volunteers and patients, onset osteoarthritis of the knee, when walking on a flat surface, and the initial value of the intensity of pain (before treatment) in all volunteers was more than 40 mm on YOURS.

The volunteers were divided into 5 groups:

- the first group were treated with the medicinal product "Thermaskin TGC in the form of a cream, with the active substance glucosamine sulfate potassium chloride;

- the second group were treated using the pharmaceutical composition is in the form of a cream containing as active substances glucosamine hydrochloride and methyl salicylate (example 1);

- the third group were treated using the pharmaceutical composition is in the form of a cream containing as active substances glucosamine hydrochloride and methyl salicylate (example 2);

- the fourth group were treated using the pharmaceutical composition is in the form of a cream-gel, containing as active substances glucosamine hydrochloride, methyl salicylate and lidocaine hydrochloride (example 3);

- the fifth group were treated using the pharmaceutical composition is in the form of a cream-gel containing the active substances glucosamine hydrochloride, methyl salicylate and lidocaine hydrochloride (example 4).

In each group there were 20 people, the average age of volunteers in each group were in the range of 60-70 years, the average pain intensity within each group is more than 40 mm on YOUR body mass index all volunteers within each group were within normal limits (of 18.5-25 kg/m2), the number of men and women within each group are equal to each other and amounted to 10 persons.

In the study of pain intensity method YOUR following results (table 1).

Table 1
the results of the research intensity of pain YOUR method
Name of the medicinal productThe average value of the intensity of pain in the knee joint when walking on a flat surface within the group before the treatment, mmThe average value of the intensity of pain in the knee joint when walking on a flat surface within the group after the treatment (4 weeks after using the drug), mmChange in pain intensity after treatment, mm
In addition to the state drug "Thermaskin TGC in the form of a cream 623824
Example 1522828
Example 2562630
Example 3511833
Example 4593227

Table 1 shows that among the five treatment options lowest value changes of pain intensity is observed when the drug "Thermaskin TGC with one active substance - glucosamine sulfate potassium chloride (24 mm).

Therefore, the pharmaceutical compositions containing as active substances glucosamine salt and methyl salicylate (in examples 3 and 4 also contain lidocaine salt), have a stronger analgesic properties.

The strengthening of the anesthetic properties of the pharmaceutical composition is explained by the presence in the composition of NSAIDs - methyl salicylate (in the pharmaceutical compositions according to examples 3-4 contains also with the ü lidocaine).

When developing a pharmaceutical composition caused concern that the use as active substances methyl salicylate will increase its toxicity, because methyl salicylate, as a derivative of salicylic acid in its pure form is quite toxic substance.

From the report of preclinical Toxicological studies (acute and sub-chronic toxicity, irritant effects) of the drug Glucosamine plus" (cream), held in SE "gntsls", , Kharkov, 05.08.2011, we can conclude that the toxicity of the pharmaceutical compositions containing as active substances salt of glucosamine and methyl salicylate, is within normal limits.

The achievement of the technical result of the invention in the form of strengthening the anesthetic properties is not to the detriment of the toxicity of pharmaceutical compositions.

The list of references

1. Pokrovsky Century. And. Small medical encyclopedia - Soviet encyclopedia, 1996. - So 4. - 577 C.

2. ICD-10: international statistical classification of diseases and problems related to health. 3 so (4 books). - 10th ed. - Kazan: Medicine, 2003. - 2438 S.

3. Benevolensky L. I., Brzozowski M. M. Epidemiology of rheumatic diseases. - M.: Medicine, 1988. - 237 S.

4. Osteoarthritis: current treatment guidelines [Electronic what electronic resource]. - Centuries povorozniuk, D. M. H., Professor, Institute of gerontology AMS Ukraine, Kyiv, 2003. - Mode of access: http://health-ua.com/articles/469.html

5. Instructions for use of the medicinal product "Thermaskin TGC.

6. Preclinical study andprotecting properties of the drug, "Glucosamine plus" (cream), held in the National pharmaceutical University of the Ministry of health of Ukraine, Kharkov, 2011

7. Preclinical Toxicological studies (acute and sub-chronic toxicity, irritant effects) of the drug Glucosamine plus" (cream), held in SE "gntsls", , Kharkov, 05.08.2011,

8. Preclinical study of specific pharmacological activity of the drug Glucosamine plus" (cream), held in SE "gntsls" , Kharkov, 05.08.2011,

1. Drug for the treatment of osteoarthritis, soft dosage form comprising as active substance salt of glucosamine, characterized in that it contains the following components:
- the active substance is:
glucosamine salt
methyl salicylate
auxiliaries.

2. Drug under item 1, characterized in that it contains components in the following dosages, wt.%:
- the active substance is:
glucosamine salt is 0.5 to 10.0
methyl salicylate - 0,1-5,0
supporting the substance - the rest is up to 100%.

3. Drug under item 1, characterized in that salts of glucosamine mainly contains glucosamine hydrochloride in the amount of 5.00% wt. and contains methyl salicylate mainly in the amount of 2.50% wt.

4. Lekarstvenno tool under item 1, characterized in that it contains components in the following dosages, wt.%:
- glucosamine hydrochloride, 0.5 to 10.0
- methyl salicylate - 0,1-5,0
- preservative (preservatives) is 0.0001 to 2.0
- antioxidant (antioxidants) - 0,05-2,0
- non-aqueous solvent (solvents) - 5.0 to 60.0 sec
- emulsifier (emulsifier) is 0.5 to 15.0
- thickener, and 0.1 - 7,0
- amalendu - 3,0-80,0
agent (agents), regulating the pH of 0.1-2.0
- purified water - the rest is up to 100%.

5. Drug under item 1, characterized in that the active substance further comprises a lidocaine salt.

6. Drug under item 5, characterized in that it contains components in the following dosages, wt.%:
- the active substance is:
glucosamine salt is 0.5 to 10.0
methyl salicylate - 0,1-5,0
lidocaine salt is 0.1 to 5.0
- excipients - the rest is up to 100%.

7. Drug under item 5, characterized in that salts of glucosamine mainly contains glucosamine hydrochloride in the amount of 5.00% wt., as the salt of lidocaine mainly contains lidocaine hydrochloride in a dose of 100 wt.%.

8. Drug under item 5, characterized in that it contains components in the following dosages, wt.%:
- glucosamine hydrochloride, 0.5 to 10.0
- methyl salicylate - 0,1-5,0
- lidocaine hydrochloride 0.1 to 5.0
- preservative (preservatives) is 0.0001 to 2.0
- antioxidant (antioxidants) - 0,05-2,0
- solvent (solvents) - 5.0 to 60.0 sec
- emulsifier (emulsifier) is 0.5 to 15.0
- thickener, and 0.1 - 7,0
- amalendu - 3,0-80,0
agent (agents), regulating the pH of 0.1-2.0
- purified water - the rest is up to 100%.

9. The drug according to any one of paragraphs.1-8, characterized in that may be in the form of a cream-gel, a cream, but is not limited to this.



 

Same patents:

FIELD: medicine.

SUBSTANCE: composite application of therapeutic preparations is combined with a laser therapy. A basic anti-inflammatory preparation is presented by methotrexate administered subcutaneously in a dose of 15mg once a week, and folic acid administered orally in a dose of 5mg a week. Movalis is additionally prescribed in the form of intramuscular injections in a dose of 15mg once a day. The laser therapy is differentiated depending on a degree of the disease, a degree of endothelial dysfunction manifestation, namely a von Willebrand factor (vWF), haemostasis system activity indices, namely activated partial thromboplastin time (APTT), prothrombin time (PTT), thrombin clotting time (TCT), antithrombin III (AT III), protein C. If observing the degree I of the disease, APTT 30.6±1.5 sec or more, PTT 19.2±0.9 sec or more, TCT 15.1±0.7 sec or more, AT III 92.8±7.6% or more, protein C 0.92±0.02 or more, vWF 108.9±9.6% or less, 6-8 daily procedures of the intravenous laser blood irradiation, on the first day for 15 minutes at wavelength 0.365mcm, on the following day for 5 minutes at wavelength 0.405mcm, radiant power at a light guide end 1.5-2.0mV in a continuous mode; the procedures are alternated every second day. The degrees II and III of the disease, APTT 22.2±5.5 sec or less, PTT 12.8±1.7 sec or less, TCT 11.2±0.9 sec or less, AT III 85.4±1.1% or less, protein C 0.84±0.02 and less, vWF 133.5±2.2% or more, require performing 10 daily procedures of the intravenous laser blood irradiation, on the first day for 15 minutes at wavelength 0.365mcm, on the following day for 5 minutes at wavelength 0.405mcm, radiant power at the light guide end 1.5-2.0mV in a continuous mode; the procedures are alternated every second day.

EFFECT: method enables reducing the clinical manifestations of the disease, provides higher effectiveness of the drug therapy by involving the pathological processes in the haemostasis system.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula IV, VIII-A and X, and to their pharmaceutical acceptable salts possessing the inhibitory activity on PI3-kinase (phosphoinositide-3-kinase). In compounds of formula IV and IX and Wd is specified in a group consisting of, , , and each of which can be substituted. In formula VIII-A, the group Wd represents the group or , wherein Ra is hydrogen, R11 is amino; in compound IV, Wa2 represents CR5; Wa3 represents CR6; Wa4 represents N or CR7; in compound IX, Wa1 and Wa2 independently represent CR5, N or NR4, and Wa4 independently represents CR7 or S, wherein no more than two neighbouring atoms in a ring represent atom or sulphur; Wb5 represents N; B represents a grouping of formula II, as well as in case of compound IV, B means C1-C10alkyl, C3-C10cycloalkyl, C3-C10heterocycloalkyl having one to six ring heteroatoms specified in N, O and S; in case of compound IX, B also means C1-C10alkyl, C3-C10cycloalkyl or 6-merous heterocycloalkyl having nitrogen atom; Wc represents C6-C10aryl or 5-18-merous heteroaryl having one or more ring heteroatoms specified in N, O and S, or phenyl or 6-merous heteroaryl respectively is equal to an integer of 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, respectively; z is equal to 1; Y is absent. The other radical values are specified in the patent claim.

EFFECT: compounds can be used for treating such diseases, as cancer, bone disorders, an inflammatory or immune disease, diseases of the nervous system, metabolic disorders, respiratory diseases, thrombosis or cardiac diseases mediated by PI3-kinase.

68 cl, 11 dwg, 7 tbl, 55 ex

FIELD: medicine.

SUBSTANCE: composition 16-21ml consisting of a mixture of therapeutic preparations: Dona glucosamine sulphate 3.0 ml; ChondroGuard, or Mucosatum, or Chondrolon chondroitin sulphate - 2.0 ml; Alflutop 2.0 ml; Actovegin 4.0-5.0 ml; glucocorticosteroids Depo-Medrol 1.0-2.0 ml in the concentration of 40 mg/ml, or Diprospane 1.0-2.0 ml in the concentration of 7 mg/ml, or Metipred 1.0-2.0 ml in the concentration of 62.5 mg/ml; vitamins B1, B6, B12 Combilipen 2.0 ml, or Milgamma 2.0 ml, or Neurobion 3.0 ml; 95% or 70% ethanol 2.0-4.0 ml, is administered into a pathologically changed region. That is immediately followed by exposing the pathologically changed region and adjoining segments to a session of A shock-wave therapy in the following mode: pressure 1.2 - 4.0 bar, frequency 7-12 Hz, beat quantity 8000-14000 for 20-40 minutes. The complex procedures are performed within the course of 1-6 times every 7-10 days.

EFFECT: method enables the direct exposure on the pathologically changed region to achieve the optimum concentration of drug preparations therein with avoiding systemic prescription and preventing a risk of side effects.

3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of general formula [1] or their pharmaceutically acceptable salts, which possess properties of an inhibitor of the JAK2 thyrokinase activity. In general formula radicals are selected from group (I) or (II). In group (I) X represents CH or N; R1 represents a halogen atom and R2 represents H, a halogen atom, CN, or is selected from the groups of formulas

,

or a group -ORP or 5-6-membered heteroaryl, containing 1-4 nitrogen atoms and optionally additionally containing an oxygen or sulphur atom or containing an oxygen atom as a heteroatom, optionally substituted; or (II) X represents -CRA; and RA represents a group of formula , RB represents (a) amino, optionally substituted with one or two groups, selected from the group, consisting of C1-6alkyl, C3-6cycloalkyl, (C3-6cycloalkyl)C1-6alkyl and C1-3alcoxyC1-3alkyl, (b) C1-3alcoxy, (c) hydroxy or (d) a 5-6-membered saturated cyclic amino group, which additionally can contain a heteroatom, selected from an oxygen atom; R1 represents a halogen atom and R2 represents H; R3 -R5 have values given above. Other values of the radicals are given in the invention formula.

EFFECT: compounds can be applied for the prevention or treatment of cancer, for instance hematologic cancer disease or a solid form of cancer, inflammatory disorder, for instance, rheumatoid arthritis, inflammatory intestinal disease, osteoporosis or multiple sclerosis and angiopathy, for instance, pulmonary hypertension, arteriosclerosis, aneurism or varicose veins.

14 cl, 19 tbl, 234 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises intravenous injection of 3-5.5% aqueous solution of lithium chloride based on 2.5-3.5 mmol/kg of animal body weight, and additionally subcutaneously 10-30% aqueous solution of polyethylene glycol-4000 based on 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: increased efficiency and simplification of the method.

4 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises administering the medicinal product, and the medicinal product is used as 10-30% aqueous solution of polyethylene glycol-4000, which is administered subcutaneously in an amount of 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: improvement of efficiency of the method.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), possessing an activity with respect to cytokines, versions of based on them pharmaceutical compositions and their application. Formula (I) compounds can be applied for treatment or prevention asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis or gouty arthritis. In general formula (I) L is selected from the group, consisting of -C(O)-, -CH2-, Ar1 represents a mono-, di- or trisubstituted phenyl ring, where substituents are independently selected from the group, consisting of a halogen and -C1-4alkyl; Ar2 represents an optionally substituted thiadiazolyl ring, where the substituent represents -C1-4alkyl, -C3-5cycloalkyl, -methylcyclopropyl, phenyl or a 5- or 6-membered monocyclic heteroaromatic ring or a bicyclic heteroaromatic ring with 9 or 10 atoms, with the said heteroaromatic ring containing 1, 2 or 3 heteroatoms, selected from the group, consisting of S, O and N, where the said phenyl or heteroaromatic ring is optionally mono- or disubstituted with substituents, independently selected from the group, consisting of a halogen, -C1-6alkyl, optionally substituted with 1-4 fluorine atoms, -O-C1-6alkyl, -CF3 and oxo.

EFFECT: increased efficiency of the application of the compounds.

16 cl, 1 tbl, 46 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to traumatology and orthopaedics, and can be used for treating patients with epicondylitis. That is ensured by applying a complex of measures, in particular a restraint of motions in the involved segment, physiotherapy and drug treatment. A pain syndrome is pre-evaluated by a visual analogue scale (VAS). A proximal forearm is immobilised with an epicondylic bandage in the daytime for 7-10 days in sportsmen, and for 2-3 weeks in common patients. Therapeutic exercises (TE) are prescribed from the first day of treatment. The first part of TE consisting of isometric and static exercises aiming at strengthening arm muscles is done before noon. The second part of TE comprising relaxing exercises is performed in the late afternoon or after any physical loads. The patient continues with the therapeutic exercises after the bandage is removed and to be used for professional or sports loads only. Electric stimulation is conducted daily for 7-10 days with using TENS apparatus or its analogues generating electrical signals covering the enthesis and the involved forearm muscles. Arthrofoon is administered with underlying electric stimulation. If the pain syndrome value according to the VAS is less than 4 points, the preparation is administered as a monotherapy in a dose of 4 weeks a day for three months. If the pain syndrome according to the VAS is more than 4 points, Arthrofoon is administered in a dose of 8 tablets a day in a combination with a selective non-steroid anti-inflammatory preparation in a therapeutic dose for no more than 10 days. The therapeutic regimen also contains Sirdalud 2-4 mg one hour before bedtime for 2 weeks. There are also administered vasodilators improving microcirculation of the involved segment, intramuscularly for 10 days. The therapeutic complex is also added with Milgamma B 2 ml, 5 injections, and another 5 injections triduan. Wobenzyme is administered for 3-4 weeks. Calcemine or Calcemine-advance, the preparations of calcium are administered for six months. The therapeutic course according to the presented regimen is repeated half a year later. The physical exercising for the arm muscles strengthening are to be further done two or three times a week on the average for min. 30 minutes for the life term if suffering high loads or doing any top-class sports for the purpose of maintaining the forearm tonus. The segment of interest is fixed with an orthesis when suffering a load. The therapy with the TENS or similar apparatus of the forearm muscles of interest and the enthesis follow a pronounced load 2-3 hours before bedtime and shall be accompanied with a session of relaxing exercises.

EFFECT: method provides the evident and stable clinical effect characterised by the complete recurrence-free recovery by the physical restoration of the tissue structure within the inflammation with the high quality of life and a surgical intervention avoided.

1 dwg, 2 ex

FIELD: biotechnologies.

SUBSTANCE: invention proposes a molecule that is specifically combined with CD37 and that contains the following from N-end to C-end: (a) CD37-specific scFV containing the following from N-end to C-end: (i) humanized variable region of a heavy chain, which contains CDR1 GYNMN, CDR2 NIDPYYGGTTYNRKFKG and CDR3 SVGPFDS, (ii) linker having 5 to 30 aminoacids inclusive, and (iii) humanized variable region of an easy chain containing CDR1 RASENVYSYLA, CDR2 FAKTLAE and CDR3 QHHSDNPWT; (b) a link region; and (c) immunoglobulin regions CH2 and CH3. The following is described: The following is described: nucleic acid coding the above binding molecule; an expression vector containing the above nucleic acid; and a host cell for production of a binding molecule, which contains the above vector. The invention proposes use of the above binding molecule to obtain a medicinal agent to reduce the number of B-cells, treatment of a disease or an illness, which is related to abnormal activity of B-cells. Besides, the invention describes compositions containing effective number of the above binding molecule to reduce the number of B-cells, treatment of a disease or an illness related to abnormal activity of B-cells.

EFFECT: invention allows obtaining scFV molecule binding CD37, having orientation of variable regions VHVL, with high yield and efficiency in comparison to scFV molecule against CD37, which has orientation of variable regions VLVH.

31 cl, 17 dwg, 13 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to biotechnology and represents a pharmaceutical composition applicable for treating a rheumatic disease and containing the humanised anti-CD4 antibody able to activate CD4+CD25+ regulatory T-cells, and methotrexat. The present invention also discloses a kit and a method of treating the rheumatic disease with using the above pharmaceutical combination and the above kit.

EFFECT: invention enables implementing more effective methods of treating the rheumatic diseases, including rheumatoid arthritis.

57 cl, 8 dwg, 2 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a composition for treating anal fissures in the form of a hydrous gel, containing an active compound in the form of isosorbide dinitrate, a gelation agent, a neutralising agent and a solvent differing by the fact that the composition contains triethanolamine as the neutralising agent taken in equal proportions with the gelation agent which is presented by a lightly crosslinked polymer; the solvent is presented with a mixture of polyethyleneoxide and ethanol in ratio 5-6:1:3-4 with the ingredients of the composition taken in certain proportions, wt %.

EFFECT: invention provides higher clinical effectiveness and reduced length of treatment.

3 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: claimed is application of fat emulsion for parenteral feeding as solvent for compounds which are poorly soluble in water. Fat emulsion contains in 1 l of solution: 30 g of refined soybean oil, 30 g of triglycerides with the average chain length, 25 g of olive refined oil, 15 g of purified fish oil.

EFFECT: obtaining solvent for compounds, poorly soluble in water, which makes it possible to determine parameters and spectrum of biological activity of novel compounds of chemical nature at the stages of pre-clinical and clinical tests, which does not change basic biological constants and possesses biological inertness.

2 tbl, 2 ex

FIELD: biotechnologies.

SUBSTANCE: invention represents a producing method of cream containing fusidic acid, which involves a stage of application of sodium fusidate as an initial active ingredient and conversion of the above sodium fusidate in situ to fusidic acid in an oxygen-free medium by immediate addition of the acid to a cream base containing a preservative, an acid, a cosolvent, an emulsifier, a wax-like product and water.

EFFECT: obtaining cream having high stability at storage and smaller particles of an active ingredient.

9 cl, 11 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and represents dermatological cream, intended for local treatment of bacterial skin infections and for healing wounds associated with them, which contains framycetin sulfate and biopolymer, included into cream base, which contains at least one substance from each of the following groups: preservative, primary and secondary emulsifier, selected from the group which contains ketostearyl alcohol, ketomacrogol 1000, polysorbate-80 and Span-80; paraffin as wax-like product, cosolvent, selected from the group, including propylene glycol, hexylene glycol and polyethylene glycol-400; nitric acid or lactic acid and water, with said biopolymer preferably being chitosan.

EFFECT: invention provides higher therapeutic effect.

8 cl, 10 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention discloses a method of preventing agglomeration of particles of an aripiprazole or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butox]-1H-quinolin-2-one active ingredient in a suspension containing silicone oil and/or a silicone oil derivative in a dispersion medium, wherein the particle size of the active ingredient is 0.1-200 mcm. The method comprises mixing an active ingredient with silicone oil and/or silicone oil derivative in a dispersion medium such that the silicone oil and/or silicone oil derivative is contained in an amount of 0.001-0.2 pts.wt per 100 pts.wt of the active ingredient contained in the suspension. The invention also relates to a hardened composition for preparing a suspension administered by injection or orally.

EFFECT: preventing agglomeration of active ingredients in a suspension without special treatment.

9 cl, 4 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: perftoran is administered intravenously at 5-20 ml per 1 kg of body weight.

EFFECT: reducing side effects in treating methemoglobinemia by the property of perftoran to transform methemoglobin into oxyhemoglobin.

6 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: method for preparing involves forming a dispersion of water-soluble sodium alginate and particles with gelling calcium ions; water-soluble sodium alginate is introduced into calcium carbonate directly in the concentration of 0.08-0.12 wt %, and adding organic acid specified in 2,4-hexanediene, para-toluic, 4-propyloxybenzoic in an amount of 0.12-0.36 wt % with the ratio of calcium salt and the above acids of 2:3, 1:2, 1:3 respectively. The prepared alginate system is settled to form a gel matrix at room temperature that is followed by γ-sterilisation.

EFFECT: hydrogel matrixes hold the shape stability after the γ-sterilisation procedure, possess the excellent tactile properties being soft and elastic, provide the targeted prolonged drug delivery.

6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to pharmaceutics and represents a pharmaceutical composition for parenteral administration containing sub-micron particles of dosocahexaenoic acid ester dispersed in a water phase with the use of mixture of at least two surfactants specified in a) at least one fatty acid polyoxyethylene ester and b) at least one phospholipide derivative, as well as a method for preparing the above pharmaceutical composition.

EFFECT: invention provides higher pharmacological activity.

14 cl, 3 dwg, 3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical and cosmetic industry, in particular to nanoemulsions of a water-in-oil type for transdermal application with biologically active compounds.A nanoemulsion of the water-in-oil type contains 35-80% of a hydrophobic phase, 1-15% of a hydrophilic phase, and a surface-active substance.

EFFECT: nanoemulsion of the water-in-oil type for transdermal application with biologically active compounds possesses good storage stability.

8 cl, 1 dwg, 1 tbl

FIELD: chemistry.

SUBSTANCE: group of inventions relates to a composite organic substance powder for use in medicine, a suspension for use in medicine in which the composite powder is dispersed in water and a method producing the composite powder. In the composite powder, the surface of particles of a poorly water-soluble crystalline organic substance are partially or completely coated with a carboxyvinyl polymer and the average diameter of particles coated with the carboxyvinyl polymer, obtained by calculating the BET specific surface is in the range of 50-400 nm. The method of producing the composite powder includes mixing a poorly water-soluble crystalline organic substance powder, a physiologically acceptable salt, a physiologically acceptable polyol and a carboxyvinyl polymer, pulverising the organic substance powder and removing the salt and the polyol after the pulverisation.

EFFECT: invention enables to obtain a medicinal preparation with a low degree of contamination with a pulverisation medium and with improved bioavailability.

6 cl, 8 dwg, 2 tbl, 38 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly represents a pharmaceutical composition for treating viral diseases and represents a soft dosage form. The maximum positive effect of the invention is ensured by an exact combination of the dosage form ingredients, a sequence of introducing them with taking into account of the stage of the disease when selecting additives.

EFFECT: soft dosage form (0,5% Hiporhamine liniment) based on polymeric hydrophilic additives - polymethacrylic acid (Carbopol) in a combination of glycerol, Tween and castor oil possesses the high biological availability and storage stability.

4 cl, 1 tbl, 2 ex

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