Method of treating liver cancer

FIELD: medicine.

SUBSTANCE: inventions relate to medicine, namely to oncology, and deals with treatment of liver cancer. For this purpose 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt in dose from 10 to 30 mg per day is introduced. Treatment is carried out in accordance with therapeutic regimen, in accordance to which continuous daily introduction for from 1 to 4 weeks is performed. After that period of medication withdrawal for from 1 to 3 weeks follows.

EFFECT: inventions ensure essential reduction of side effects, such as deep vein thrombosis, and in addition considerably improve therapeutic effect of TAC-101 in treatment of liver cancer.

4 ex

 

The scope of the invention

This invention relates to a method of treatment of liver cancer, which use 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid low dose.

Background of invention

Liver cancer is vysokokachestvenny, and one million patients die from this disease each year, and this number of patients is on the fifth place in the number of deaths [E1-Serag, H. B., and Mason, A. C., Rising incidence of hepatocellular carcinoma in the United States., N. Engl. J. Med., 340, pp.745-750, 1999; Taylor-Robinson, S. D., Foster, G. R., Arora, S., Hargreaves, S., and Thomas, H. C., Increase in primary liver cancer in the UK, 1979-94 Lancet, 350, pp.1142-1143, 1997].

Believe that the liver cancer involves the formation of a variety of cancer cells in different places entirely or almost simultaneously in the effect on the liver of hepatovirus or alcohol [Slaughter DP, Southwick HW, Smejkal W., "Field cancerisation" in oral stratified squamous epithelium; Clinical implications of multicentric origin., Cancer, 6, pp.963-968, 1953]. In our country the main cause of liver cancer, as it is infected with hepatitis C. the Possibility of cancer recurrence is very high as the hepatitis C cannot be completely eliminated, even if the cancer cells are removed temporarily or destroy. The degree of recurrence, as reported, is from 16 to 29% from 1990 to 1997 [Hepatic Cancer, "I. Change of Number of Patients", "3. Method for Calculation of Number of Patients, the Tendency of Cancer Patients and Actual Condition According to Therapeutic Method", Medical Research Co., Ltd., pp.2030, 2001.]

Accessible ways of treatment of liver cancer is surgical resection of visible lesions liver, radiowave thermocoagulation therapy, treatment with injections of ethanol, treated by mortality caused by microwave coagulation, and the like. However, this treatment is sometimes insufficient, and therefore, desirable to develop chemotherapy as a systemic treatment.

As chemotherapy in patients with advanced cancer, which does not apply the above mentioned methods of treatment or transcatheter arterial embolization, and in patients with recurrence after these treatment methods have recently been applied as chemotherapy therapy intra-arterial injection of CDDP, ADM or 5-FU. However, as regards the treatment of intra-arterial injection using a combination of lipiodol in the form of oil contrast medium and the above-mentioned drugs, indicated that the efficiency amounted to 13.0% of the full response and 30,0% efficiency, and in relation to chemotherapy, except combinations rescattering arterial embolization and lipiodol reported that the efficiency was of such a level as 2.5% of full answer and 3.1% efficiency, and these clinical results are unsatisfactory. In addition, the above-mentioned combination therapy has this problem, as the phenomenon of complications, such as ulcer [Hisakazu Tanigawa, "Topical Injection Therapy and Intraarterial Injection Therapy", Clinical Therapy of Cancer, 40, pp.1490-1497, 1994].

As explained above, there is still no standard method of therapeutic treatment of liver cancer, which always guarantees a certain level of clinical results. In particular, intra-arterial injection is problematic from the point of view of technique and complications for the patient, and therefore desirable to develop chemotherapy for replacement of this therapy. In addition, because liver cancer has a high resistance to chemotherapy, even stabilization of cancer, i.e. therapy to prevent proliferation of the tumor to prolong life difficult. It is therefore very desirable to develop chemotherapy, which makes it possible conservative treatment of tumors.

4-[3,5-Bis(trimethylsilyl)benzamido]benzoic acid (hereinafter in the description of this connection may be referred to as "TAS-101") is a synthetic retinoid, we present the following chemical formula (1), and this compound, known to be suitable as a means for cancer treatment, causing the differentiation of cancer cells means inhibitor of cancer metastasis, therapeutic agent for the treatment of vascular diseases or for the treatment of hypertrophy of the heart (Display Japanese patent application (KOKAI) No. 2-247185, the brochure of International Publication WO 96/32101, WO 03/089005 and t the th similar).

[Formula 1]

TAS-101 exerts antitumor activity via selective binding to nuclear receptors in retinoic acid-α (RAR-α; RSC-α) activation thereby transcription through these receptors. Currently, this pairing has the clinical study as available oral anti-cancer drugs.

In pharmacological experiments using models of liver cancer in animals have shown antitumor activity of TAS-101 [Murakami K, Matsuura T, Sano M, et al., 4-[3,5-Bis(trimethylsilyl)bensamido]benzoic acid (TAC-101) inhibits the intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of tumor-bearing animals., Clin. Exp.Metastasis. 16, pp.633-643, 1998; Muracami K, Wierzba K, Sano M, et al. TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span., Clin. Exp.Metastasis., 16, pp.323-331, 1998]. However, the clinical effect of TAS-101 in patients with liver cancer still was not known.

In the United States of America have conducted clinical trials phase I clinical trials phase I/II, in which TAC-101 was administered at a high dose in the range from 60 to 80 mg/day patients with lung cancer, and these trials showed that the drug exhibits decreasing tumor effect (CR and PR). However, it was also found that the introduction of this drug often causes deep vein thrombosis (DVT), and because we get the side effects, which is DLT (dose limiting toxicity, the dose is sufficient to achieve clinical goals of therapeutic treatment of cancer [Naiyer A. et al. Initial Clinical Trial of Oral TAC-101, a Novel Retinoic Acid Receptor - Alpha Selective Retinoid, in Patients With Advanced Cancer, Journal of Clinical Oncology, 20. pp.3522-3532, 2002].

Description of the invention

A goal that should be achieved according to this invention

The purpose of this invention to provide a new and effective chemotherapeutic treatment for cancer of the liver.

A means to a goal

In order to achieve the above objectives, conducted various studies on the dose regimens for patients with liver cancer when using TAC-101. In the result, unexpectedly found that when a low dose of from 10 to 30 mg per day is achieved satisfactory therapeutic effect in cancer of the liver with an almost complete prevention of progression to liver cancer, and this dose gave almost no occurrence of deep vein thrombosis, which allows extremely safe chemotherapeutic treatment of liver cancer. This invention is made on the basis of these data.

The invention thus provides a method of therapeutic treatment of liver cancer, which involves the step of introducing 10-30 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salts patients who NTU with liver cancer.

In accordance with preferred embodiments of the above invention are represented: the above method, wherein therapeutic treatment of liver cancer is stopping therapy of liver cancer; the aforementioned method, wherein therapeutic treatment of liver cancer is conservative therapy of liver cancer; and the above-mentioned method, in which essentially disposable occurrence of deep vein thrombosis therapeutic treatment of liver cancer.

In accordance with preferred embodiments of the present invention presents: the above method which includes a step of introduction from 15 to 25 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt; the aforementioned method, which involves the step of introducing a 20 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt; the aforementioned method, wherein the treatment is carried out with therapeutic regime, consisting of a long daily injection within 1 to 4 weeks with the subsequent abolition of medicine from 1 to 3 weeks; the aforementioned method, wherein the treatment is carried out with therapeutic regime, consisting of a long daily injection within 2 weeks with the subsequent abolition of the medication for 1 week; Vicenza the economic way when any of the above therapeutic regimes repeated at least twice; the aforementioned method, and liver cancer is a progressive hepatocellular carcinoma; the aforementioned method, and liver cancer is a primary cancer of the liver; and the above-mentioned method, and the treatment is carried out together with a therapy selected from the group consisting of surgical liver resection, radiofrequency thermoplegia therapy, therapy by infusion of ethanol and therapy caused by microwave coagulation mortality.

According to another aspect of the present invention presents a drug for therapeutic treatment of liver cancer, which contains from 10 to 30 mg of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt in one introduction. Preferably represented by the above medicinal product, which contains from 15 to 25 mg of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt in an injection; and more preferably represented by the above medicinal product, which contains 20 mg of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt in an injection.

According to an additional aspect of the present invention presents the use of 4-[3,5-bis(t is Immission)benzamido]benzoic acid or its physiologically acceptable salts for the manufacture of drugs for therapeutic treatment of liver cancer, moreover, the specified medicinal product used for the introduction of from 10 to 30 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt. In accordance with preferred embodiments of the above-mentioned application, and the drug is used for the introduction of from 15 to 25 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salts, and above use, and drug use to injection of 20 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt. In accordance with the above preferably using a specified drug used for oral administration.

The best way of carrying out the invention

The active ingredient TAS-101 used in therapeutic method of this invention may be manufactured by a method described in the display Japanese patent application (KOKAI) No. (Hei)2-247185.

therapeutic method of the present invention differs in that the TAS-101 as the active ingredient used is from 10 to 30 mg per day. According to therapeutic method of the present invention, for example, receive a standard dose of a medicinal product in the appropriate form, which contains TAS-101 is as active ingredient, and the above dosage may be used by injecting the patient with one standard dosage forms or more. Preferably, receive and enter drug containing from 10 to 30 mg TAS-101 in one standard dosage form. The route of administration is not specifically limited, and the drug is administered orally or parenterally. Oral administration is preferred from the standpoint of ease of use.

Examples of forms of the drugs suitable for oral administration include solid preparations such as tablets, coated tablets, pills, powders, granules and capsules, and non-solid preparations, such as solutions, suspensions and emulsions. These drugs examples single dose include one tablet for tablets, one capsule to capsule, one package of the set, divided by soldering by heating for powders or fine granules, or one container or one bottle for non-solid preparations, and these forms well known to any person skilled in the art. These drugs can be packaged so that a daily dose of from 10 to 30 mg may be entered at one time or divided into 2 to 4 doses per day. The packaging method is not limited, because this method is known as a commonly used method of packaging in this area. For example,tablets can be packaged in a packaging material for protection against moisture and oxygen.

For the production of these drugs, you can use one or more of the pharmaceutical additives, such as pharmaceutically acceptable carrier. The above-mentioned preparations can be produced in accordance with commonly used methods of manufacture of dosage forms, usually well-known experts in this field.

As carriers for formulation in the form of tablets, you can use devices such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose and silicic acid; binders, such as water, ethanol, propanol, potato starch, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, hydroxypropylcellulose, hypromellose, potassium phosphate and polyvinylpyrrolidone; disintegrators such as dry starch, sodium alginate, agar powder, laminaria powder, sodium bicarbonate, calcium carbonate, esters of fatty acids and polyoxyethylenesorbitan, sodium lauryl sulfate, monoglyceride of stearic acid, starch and lactose; such overwhelming disintegration funds as sucrose, stearic acid, cocoa butter and gidrirovannoe oil; such amplifiers intake, as salt of the Quaternary ammonium and valium n is sodium; such increase wetting substances, such as glycerin and starch; binders, such as starch, lactose, kaolin, bentonite and colloidal silicic acid; and such improves the slip substance, as purified talc, salt of stearic acid, boric acid powder and polyethylene glycol. Tablets can be made in the form of tablets with conventional coating, such as a covered sugar pills, protected by a gelatin tablets, tablets with intersolubility coating, film-coated tablets, double-layered tablets, multilayered tablets, and the like.

As carriers for the manufacture of a medicinal product in the form of pills, you can use devices such as glucose, lactose, starch, cacao butter, utverjdenie vegetable oil, kaolin and talc; binders, as powder Arabian gum, powder tragakant, gelatin and ethanol; dezintegriruetsja substances, such as laminaran and agar and the like.

Capsules can be produced in the usual way by mixing the above ingredients with the above as examples of the various auxiliary substances, and then fill with a mixture of hard gelatin capsules, soft capsules, etc.

When the desired oral liquid medicines oral solutions, syrups, elixirs and p can be made in the usual way by using improving the taste of funds, stabilizers for improving the smell of funds, etc. In the above preparations of examples of corrective taste of funds include sucrose, orange peel, citric acid, tartaric acid and the like, examples of the buffer means include sodium citrate and the like, and examples of stabilizers include tragakant, Arabian gum, gelatin, etc.

In the above-mentioned preparations can optionally add dyes, preservatives, perfumes, flavoring means, sweeteners, etc. or other medicinal substances.

In accordance with therapeutic method of the present invention TAS-101 you can enter once a day or fractionally from 2 to 4 times a day so as to achieve a dosage of from 10 to 30 mg per day. The dose may be appropriately selected depending on the method of administration, indicators of the patient, such as age, gender, etc., the severity of the disease, etc. are More preferred daily dose can range from 15 to 25 mg per day, and the most preferred dose is 20 mg per day. Based on the selection of the above-mentioned doses occurrence of deep vein thrombosis can be essentially completely prevented, while a high therapeutic effect against cancer of the liver can be saved. In addition, based on the selection of vyshenazvany the second dose can be essentially prevented the progression of liver cancer, and thereby can be achieved with conservative therapy of liver cancer, while it is possible to avoid adverse reactions.

As modes of therapy preferred therapeutic mode, when making long-term daily administration within 1 to 4 weeks, and then provided the cancellation period medicines for 1 to 3 weeks. Preferred therapeutic mode in which carry out long-term daily administration for 2 weeks, and then provided the cancellation period medicines for 1 week. More preferably, at least two-fold repetition of one of the above therapeutic regimes, and most preferably at least fourfold repetition.

Cancers of the liver as a target for therapeutic method of the present invention is not specifically limited. For example, this therapy is applicable when any hepatocellular carcinoma, cholangiocarcinoma carcinoma, hepatocytes blastoma, hepatocytes and cholangiocytes mixed cancer, anaplastic carcinoma, cystadenocarcinoma biliary tract carcinoid tumors and the like. The preferred option aims hepatocellular carcinoma. Liver cancer mainly classified on primary liver cancer and metastatic liver cancer. therapeutic method of this from the retene is applicable when any of these types of cancer. The preferred option aims of primary liver cancer. In particular, the method of the present invention can be used as an excellent therapeutic method against progressive hepatocellular carcinoma.

Examples

The invention will be more specifically explained by examples. However, the scope of the present invention is not limited to these examples.

Example 1: Tablets

TAS-101 20 mg

Starch 100 mg

Magnesium stearate 15 mg

Lactose 45 mg

Only 180 mg

Based on the above ratios of ingredients produced tablets 180 mg in the usual way.

Example 2: Granules

TAS-101 15 mg

Lactose 340 mg

Corn starch 450 mg

The hypromellose 10 mg

Just 820 mg

Based on the above ratios of the ingredients was obtained granules in the usual way.

Example 3: Capsules

TAS-101 10 mg

L-Hydroxypropylcellulose 20 mg

The hypromellose 5 mg

Magnesium stearate 3 mg

A total of 48 mg

Based on the above ratios of ingredients received capsules in the usual way.

Example 4: a Clinical study

<Method>

In patients with advanced hepatocellular carcinoma was applied two treatment TAS-101, and each of this course included the long-term daily oral administration in t is the treatment for 14 days with the subsequent abolition of the medicines for 7 days. The average age of patients was 65 years (range from 30 to 85). 22 patients had received previous therapy, the details of which were as follows: 18 patients (55%) with chemotherapy; 10 patients (30%) with surgery; 4 patients (12%) with radiotherapy; 1 patient (3%) with immunotherapy; and 2 patients (6%) with other types of therapy. Introduction continued in patients without DLT (dose limiting toxicity (OTD; DLT) and without deterioration in cancer. In accordance with the "optimal" development Simon [Simon, R., "Optimal two-stage designs for phase 2 clinical trials", Control Clin. Trials, 10, pp.1-10, 1989], the recommended dose determined in phase I, and then promptly started part of phase II. Patients who received the recommended dose as part of phase I, conducted the data analysis, when they were taken in as patients on the part of phase II.

Part of the research phase I was started at a dose of 40 mg/day TAS-101. OTD was observed in two patients of the five and, accordingly, the dose was reduced to 20 mg/day for use in seven patients.

When part of phase II was additionally treated 21 patients at a dose of 20 mg/day. All patients who received TAC-101, produced a safety assessment, and patients who received the drug for at least 28 days (i.e. 2 courses), conducted an assessment of effectiveness. Conclusion about the effectiveness was done in accordance with the who criteria every 6 weeks [P shall be chaired by the who reports the results of cancer treatment. Geneva (Switzerland): World Health Organization Offset Publication No. 48; 1979]. In particular, after determining evaluate pathological changes in each patient, the response was classified as complete response (CR), partial response (CHO; PR), minimal response (MO; MR), stabilization of the disease (Sz; SD) or progressive disease (PZ; PD) in relation to effectiveness evaluation. When the above-mentioned test "" means the disappearance of all the pathological changes observed in the four weeks or more: "CHO" means 50% or more reduction in greatest diameter education and perpendicular to the smallest diameter of all of the observed lesions in relation to the original level, and this state was maintained for 4 weeks or more; "municipality" means a 25-50% reduction in maximum diameter education and perpendicular to the smallest diameter of all of the observed lesions in relation to the original level or reduction of high values of α-fetoprotein (AFP) without proliferation of the tumor; "SC" means the tumor that is not so significant as the decrease in MO, and proliferation of the tumor is not as high as when PZ; and "PZ" 25% or more increase in the minimum size of the tumor at the beginning of therapy or the appearance of new lesions.

<Results>

Of the 5 patients treated with 40 mg/day in phase I, in 2 patients abradale development OTD. One patient developed arthralgia, myalgia, exfoliative dermatitis and the occurrence of venous thrombosis, and another patient developed fatigue, dermatitis and thrombosis of Vena cava. Of the 7 patients who were treated with 20 mg/day, only one patient had observed the development OTD (pancreatitis and fatigue), and respectively 20 mg/day was identified as the maximum tolerated dose (MTD; MTD). In 28 patients who were treated with 20 mg/day, treatment, including 2 courses or more may be used in 21 patients, and these patients assessed the effectiveness. The average treatment for the period of injection was 2 of treatment (range 1 to 14). Although CHO or was not observed, it was possible to use four or more courses of treatment in 9 patients, which was significantly stopped the progression of the disease.

For all of the 21 patients who received 20 mg/day, the term insolvency treatment (SNL; TTF) was 6.6 weeks (range from 1.3 to 48). Among them SNL was 12 weeks or more for 9 patients in whom the development of liver cancer was significantly stopped for a long period of time, and there was no deterioration (9/21, 42%). When the above-mentioned treatment, although treatment was discontinued in one patient due to manifestations of grade 4 pulmonary embolism (PE), one patient with the manifestation of 3 degrees of venous thromboembolism (VTE) and one PAC is enta with a 3 degree increase of aspartate aminotransferase (AST), most of the patients suffered from only mild side effects, about 2 degrees, which, in detail, are: fatigue (9 patients/32%), myalgia and elevated triglycerides (each 8 patient/28,6%), dermatitis (6 patients/21,4%), increased AST, alanine aminotransferase (ALT), nausea (each 4 patient/14.3%) and anorexia (3 patients/10,7%).

The above results revealed that therapeutic method comprising applying TAS-101 at the dose of 20 mg/day, in particular, the introduction within 2 weeks at the interval of every 3 weeks, highly acceptable to patients with advanced liver cancer. In addition, the long introduction was successfully apply some patients, and these patients were observed with visible stabilization of the tumor for a long period of time.

Industrial applicability

In accordance with therapeutic method of this invention sufficient therapeutic effect can be achieved with liver cancer, and cancer of the liver can be completely stopped. therapeutic method of the present invention there are almost no occurrence of deep vein thrombosis is thus achieved extremely safe chemotherapy of liver cancer.

1. The method of therapeutic treatment of liver cancer, which includes stage rst is placed from 10 to 30 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt to a patient with liver cancer, in which the treatment is carried out according to a therapeutic regimen, which provide continuous daily administration within 1 to 4 weeks, followed by a withdrawal period of the medicinal product from 1 to 3 weeks.

2. The method according to claim 1, wherein therapeutic treatment of liver cancer is a therapy that reduces liver cancer.

3. The method according to claim 1, in which the occurrence of deep vein thrombosis is suppressed far below the level of deep vein thrombosis that occurs when traditional therapy of liver cancer.

4. The method according to claim 2, in which the occurrence of deep vein thrombosis is suppressed far below the level of deep vein thrombosis that occurs when traditional therapy of liver cancer.

5. The method according to any one of claims 1 to 4, which includes a step of introduction from 15 to 25 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt.

6. The method according to one of claims 1 to 4, which includes a step of introducing a 20 mg per day of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salt.

7. The method according to claim 5, in which the treatment is carried out with therapeutic regime, which provide continuous daily administration for 2 weeks, followed by a withdrawal period medicines for 1 week.

8. The method according to claim 6, in which the treatment is done according to terapeuticas the th mode, at which carry out continuous daily administration for 2 weeks, followed by a withdrawal period medicines for 1 week.

9. The method according to any of claims 7 and 8, in which any of the above therapeutic regimes, repeat at least twice.

10. The method according to any one of claims 1 to 4 or 7 and 8, where liver cancer is a progressive hepatocellular carcinoma.

11. The method according to claim 5, in which liver cancer is a progressive hepatocellular carcinoma.

12. The method according to claim 6, in which liver cancer is a progressive hepatocellular carcinoma.

13. The method according to claim 9, in which liver cancer is a progressive hepatocellular carcinoma.

14. The method according to any one of claims 1 to 4 or 7 and 8, where liver cancer is a primary cancer of the liver.

15. The method according to claim 5, in which liver cancer is a primary cancer of the liver.

16. The method according to claim 6, in which liver cancer is a primary cancer of the liver.

17. The method according to claim 9, in which liver cancer is a primary cancer of the liver.

18. Application of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid or its physiologically acceptable salts for the manufacture of drugs for therapeutic treatment of liver cancer, and specified medicinal product used for the introduction of from 10 to 30 mg of 4-[3,5-bis(trimethylsilyl)benzamido]benzo who Inoi acid or its physiologically acceptable salt per day, at which carry out continuous daily administration within 1 to 4 weeks, followed by a withdrawal period of the medicinal product from 1 to 3 weeks.



 

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18 cl, 4 tbl

FIELD: chemistry.

SUBSTANCE: water-soluble organosilicon derivatives of polyols are proposed, composition of which has formula (CH3)4-nSi(O-R-OH)n·x HO-R-OH in excess polyol, where R=-CH2-CH(OH)-CH2-, -CH2CH(CH3)-, (-CH2-CH2-O-)mCH2-CH2-, 0.5≤x≤2.9, n=2-4, m=7.7 or 12.0, with dynamic viscosity of 0.8-29.0 Pa·s (20±0.5°C), obtained by reacting (methyl)ethoxysilanes with polyols in molar ratio 1:(2.2-6.9) while heating the reaction mass to 120-130°C, maintaining this temperature for not less than 4 hours while stirring intensely with subsequent removal of the formed alcohol. Synthesis can take place in the presence of a catalyst, for example tetrabutoxy titanium - in amount of 0.04-0.06 mol per mole of (methyl)ethoxysilane. Also proposed a hydrogels based on said organosilicon derivatives of polyols, containing water and a gel-forming additive, with the following ratio of components in wt %: organosilicon derivatives of polyols in excess polyol 44.95 - 98.01; gel-forming additive 0.01-0.50; water - the rest. Proposed water-soluble organosilicon derivatives of polyols and hydrogels based on the said derivatives are physiologically active compounds, exhibit transcutaneous and vulnerary activity, have considerable effect on morphofunctional state of the skin and can be recommended as independent agents and as ointment bases of various pharmaceutical compositions with vulnerary activity.

EFFECT: obtaining novel water-soluble biologically active organosilicon derivatives of polyols which can be used as independent agents with transcutaneous and vulnerary activity and as bases of pharmaceutical compositions for local application.

3 cl, 2 dwg, 2 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: present invention concerns therapeutic compositions for treating skin diseases, such as wounds, abrasions, ulcers, burns, infections, irritations, microbial, mud and water exposures, psoriasis, acne, scars, age spots, sclerosis and other physical or chemical damages, which contain cationic organosilane quaternary ammonium compounds and hydrogen peroxide in the aqueous medium.

EFFECT: invention also concerns the methods of therapeutic purification and skin treatment with said compositions.

35 cl, 5 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention concerns cosmetology and dermatology, namely to creation of an agent for foot care at chronic venous insufficiency (CVI) of the lower limbs. The agent for foot care at chronic venous insufficiency of the lower limbs, characterised by that it represents a gel and contains a complex perfume thickener, a micellar solution of dihydroquercetin, liposomal concentrate, microemulsion concentrate including silicon-fluoroorganic liquids, a bile solution. Gel is intended for reduction of weariness of feet, normalisation and restoration of a microcirculatory bed of a skin and subcutaneous fat, reduction of puffiness and morbidity for long time.

EFFECT: maintenance of neogenesis of cells of a skin and an endothelium of vessels.

3 cl, 3 ex, 15 tbl, 5 dwg

FIELD: medicine.

SUBSTANCE: 24 hours prior to the examination, children aged 3 to 8 year old takes in 100 ml lactulose (Duphalac) with water of room temperature in amount 1-1.5 liters within 4-6 hours. The second dose lactulose (Duphalac) 100 ml follows with water of room temperature in amount 1-1.5 liters. To prevent overaerogenesis and to reduce discomfort, Espumisan (Simethicone) is prescribed in dosage 15 ml 3 times a day. For children aged 8 to 18 years old, there is prescribed 200 ml lactulose (Duphalac) with water of room temperature in amount 1.5-2.0 litres within 4-6 hours followed with the second dose of lactulose (Duphalac) 200 ml with water of room temperature in amount 1-1.5 litres. Additionally Espumisan (Simethicone) is introduced in dosage 15 ml 3 times a day or 3-6 capsules 3 times a day.

EFFECT: effective cleansing of gastrointestinal tract in children of different age, thus ensuring good visualisation of large intestine mucosa and decreasing drug load on organism of younger children, preserving normal microflora of large intestine and preventing overaerogenesis.

2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly obstetrics and hestosis treatment for the pregnant. Method involves endovascular laser irradiation of blood for six days. Further, polyphepan is administered internally for eight days in the dosage of 0.5 g per kg of pregnant body weight for 3-4 times per day.

EFFECT: therapeutic effect with reduced treatment duration and medication load on organism of the pregnant due to the selected regimen.

1 ex

FIELD: medicine.

SUBSTANCE: antibacterial and rehydration therapies are combined with prescribed sorbents, symptomatic therapy. From first day of disease prescribed is infusion herb collection consisting of silverweed rhizome, salvia leaves, milfoil herb, St. John's wort herb, inula rhizomes with roots, tickseed herbs, mint leaves, fennel fruits and buckthorn bark at ratio of components 2:2:2:2:2:2:2:2:1. Infusion is taken up dosed 1\3 glass 3 times a day, 30 min before meal within 10 days. Then within three weeks after basic therapy appoint infusion from silverweed rhizome, salvia leaves, milfoil herb.

EFFECT: provides accelerated normalisation of clinical-laboratory indicators, and prevention of infectious complications without by-effects.

2 cl, 1 tbl, 1 ex

FIELD: medicine; pharmacology.

SUBSTANCE: agent contains organic-silica sorbate as methyl silica acid hydrogel, non-organic sorbates aerosol or clay minerals. The agent contains one or several species of alive or killed eubacteria as a microbal mass, from the following groups: Bifidobacteria, lactobacilli and streptococci, which amount is calculated from mass of sorbate aqueous suspension, in addition, the agent contains the plant extraction. An acceptable ointment base can be added to the agent. The agent can be made as an ointment, the emulsion ointment (cream), or as a paste. The method includes preparation of 5-95% aqueous suspension, which consists of sorbate composition, and following insertion of alive or killed microbial mass to specified limits, then the plant extractions is added and the mixture is stirred until complete homogenisation.

EFFECT: agent shows the significant antiviral and antimicrobial effects.

5 cl, 4 tbl, 4 ex, 6 dwg

FIELD: medicine.

SUBSTANCE: method involves treating injured skin regions with low intensity electromagnetic radiation in bandwidth of 30-300 GHz acting with modulated signal of 0.03 Hz of 0.1 MkW/cm2. Organosilicon glycerohydrogel Si(C3H7O3)4xC3H8O3yH2O , where 3≤x≤10, 20≤y≤40, is applied to ulcer boundary at the end of every irradiation session at a dose of 0.1 g per 1 cm2 of injured surface.

EFFECT: deep drug penetration into tissues; stimulated reparative processes.

FIELD: medicine, surgery.

SUBSTANCE: invention describes an agent used in topical treatment of suppurative sluggish vast surface wounds that comprises boric acid, pepsin and sorbent based on highly-dispersed silica in the following ratio of components, g: boric acid, 5; pepsin, 10, and sorbent based on highly-dispersed silica, 20. Using the proposed agent provides reducing cleansing and epithelization of wound and treatment period of a patient in hospital.

EFFECT: improved and valuable medicinal properties of agent.

2 ex

FIELD: veterinary science.

SUBSTANCE: on should apply 1-(ethoxy)sylatrane as a stimulating agent for reproductive capacity in female furred animals and viability of their offspring. The innovation enables to improve reproductive function in females and viability of whelps.

EFFECT: higher efficiency.

3 ex, 3 tbl

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