Method and preparation for treating benign thyroid neoplasms

FIELD: medicine, therapy.

SUBSTANCE: as a sclerotherapeutic preparation one should choose ethoxysclerol to carry out 1-2 courses of therapy at intervals between the courses being 14-21 d. Preparation should be introduced under ultrasound control by introducing 0.5-4%-ethoxysclerol solution at the quantity of 0.5-1 ml/ml nodal volume in case of nodal-type neoplasm. In case of cystic neoplasm - at the quantity of 3-5 ml. Introduction should be fulfilled after liquid aspiration only. One day before the onset of every course of sclerotherapy Movalis 7.5 mg should be prescribed once daily after meals for 5-10 d. The innovation enables to avoid surgical therapy, and, also, increase patients' quality of life due to carrying out sclerosing along with interrupting the pronounced pain syndrome and in some cases heal the disease mentioned.

EFFECT: higher efficiency of therapy.

2 cl, 4 ex

 

The invention relates to medicine, namely therapy, particularly to a method of treatment of benign tumors of the thyroid gland.

Known methods of treatment of benign tumors of the thyroid gland by sclerosing benzylpenicillin sodium salt (1) and are involved in the administration of a medicinal product is 96% ethanol (2) - (prototype) with the number of procedures from 6 to 10 with different injection interval.

However, according to domestic and foreign researchers, the treatment of such methods and using only one medication does not provide a sufficient therapeutic effect. So sclerotherapy drug - dental - causes insufficient local sclerosis lesions and, therefore, not possible in the shortest possible time to achieve the desired therapeutic effect (1).

Closest to the present invention is sclerotherapy through the introduction of 96% ethanol, which causes a local inflammatory process and to obtain the desired result requires a large number of injections. In addition, it triggers the expressed painful syndrome. According to literature known methods of sclerotherapy does not give the desired result, full cure benign tumors in 100% of cases, and only 37.8% of (2). These methods and Tr is traditionally used medicines for holding sclerotherapy do not allow for treatment in a shorter time and with a minimum number of injections and, therefore, during treatment additionally injured parenchyma, vessels, which are richly supplied with thyroid tissue, nerve endings in the thyroid gland. Often repeating sessions of sclerotherapy can have a negative impact on the psychological attitude of a patient undergoing treatment.

The new technical problem solved by this invention is to increase efficiency by reducing treatment time, reduce the number of complications and more sustainable therapeutic effect, as well as in the search for medicines, allowing effective treatment.

The set task is solved by a new method of treatment of benign tumors of the thyroid gland by injecting a sclerosing drug under control of the ultrasonic monitoring 1-2 sessions of sclerotherapy for which impose 0.5-4% solution of atoxisklerol in nodular tumors in the amount of 0.5-1 ml per ml of volume of the node in patients with cystic neoplasms, after aspiration of the fluid in the amount of 3-5 ml, courses sclerotherapy repeated after 14-21 days, and the day before the start of each course sclerotherapy prescribed MOVALIS in a dose of 7.5 mg once daily after a meal within 5 to 10 days. As well as a new tool for the treatment of benign tumors of the thyroid gland, which when enaut drug atoxicity.

New in the present invention is that spend 1-2 sessions of sclerotherapy by introducing, under the control of ultrasound 0.5 to 4% solution for injection atoxisklerol in nodular tumors in the amount of 0.5-1 ml per ml of volume of the node in patients with cystic neoplasms after aspiration of the fluid 3-5 ml depending on the size and nature of benign tumors visualized on the monitor of the ultrasonic device (Hypo-, ISO-, hyperechoic, presence of cystic degeneration) we recommended various concentrations of atoxisklerol from 0.5% to 4%. The interval between courses is 14-21 days. And the day before the start of each course sclerotherapy prescribed MOVALIS in a dose of 7.5 mg once daily after a meal within 5 to 10 days.

In the analyzed literature not found in a given set of distinctive features, allowing to achieve the proposed positive effect.

This solution can be used with success in medical practice.

Thus, the proposed solution meets the criteria of the invention: "novelty", "inventive step", "industrially applicable".

The method is as follows.

Drug atoxicity (polidocanol) manufactured by a company "Kreussler & .GmbH. Pharma (Germany) and allowed for clincheck is the first application in Russia (registration number of the drug P # 011397/01-1999 from 25.09.97). The drug is an injectable solution for intravenous administration. Atoxicity is venoskleroziruyuschim drug-based polidocanol. The drug has venocclusive and local anesthetic action. Atoxicity damages the vascular endothelium, causing denaturation of proteins, has at the time of introduction of the anticoagulant effect. The desired effect of sclerosing - fibrotic scar, the development of fibrous tissue. Atoxicity is an anesthetic. It not only reduces the local excitability of sensory receptors, but also interrupts the feedback on the sensitive nerve fibers. This explains the absence of pain during sclerotherapy. Produced atoxicity in various dosage: 0,5%, 1%, 3% and 4% solution for injection in ampoules of 2 ml

The method is as follows.

Patient with diagnosis of nodular goiter with different disease duration prescribe treatment, which consists in the fact that one day before the beginning of each course sclerotherapy patient is prescribed once daily after a meal within 5-10 days MOVALIS" is a drug related to NSAIDs class roloway acid has analgesic, antipyretic effect at a dose of 7.5 mg per day. The mechanism of the above effects is the ability of the "MOVALIS" to inhibit the biosynthesis of prostaglandins, which are mediators of inflammation. Then perform sclerotherapy of 0.5-4% solution for injection atoxisklerol under the control of ultrasound according to the following scheme: injected sclerosant is 0.5 - 4% solution for injection atoxicity in the amount of 0.5-1 ml per ml of volume of the node when the node tumors. The patient with cystic neoplasm for adequate parietal sclerosing and effective obliteration after aspiration of the fluid in the amount of 3-5 ml depending on the size and nature of patterns of benign neoplasms. After 8-10 days after injection of 0.5-4% solution for injection atoxisklerol the patient dynamic ultrasound examination of the thyroid gland to assess the effectiveness of treatment. Break between courses 14-21 day, and at the same time during the second course prescribed MOVALIS in a dose of 7.5 mg per day for 5-10 days.

Thus, in the proposed scheme, the number of sclerotherapy is reduced to 1-2 procedures.

Sclerotherapy carried out as follows.

1. Give the patient corresponding to the puncture position.

2. Handle the place of projection of the examined body and regional area 96% alcohol.

3. Applied to the patient's skin gel for ultrasound sterile "Ultragel-designed for invasive procedures under the control of the ul is Razluka, transesophageal echocardiography and other procedures requiring sterile gel. As is known, the gel serves as an effective contact medium for the ultrasound.

4. Define the scope of the sclerosing.

5. Tear off one consumer packaging with needle, push the paper packaging, no fingers touching the needle, deploy the package to maintain sterility of the needle.

6. Tightly, firmly, put the needle on the cone of the syringe and remove the protective cap and the container.

7. Fill the syringe with medication, depending on the nature and scope of education (0.5 to 4% solution for injection atoxisklerol in the calculated dose).

8. The ultrasonic sensor apparatus equipped with needle adapter and under ultrasound is introduced into the Central part of the tumor, and slowly by pressing the plunger of the syringe injecion sclerosing substance, controlling its distribution on the ultrasound screen.

9. The needle is removed. Remove sterile gel with the skin of the neck of the patient.

10. The wound treated with 96% alcohol.

11. Remove the protective coating with bactericidal plaster 2,5×7.2 cm, the wound impose a gauze pad and stick to the skin.

Specific examples of the implementation of the method

Example 1. Patient Medvedev A.L., 34 years, 12.11.02, turned to the Medical unite is a group of "Health" on the consulting hours after carrying out the necessary examination, was diagnosed with diffuse nodular goiter, solitary node of the right lobe of the thyroid gland. Autres. In outpatient map shows the diagnostic and treatment phases. The total site was 3.0 ml of the Patient's assigned treatment according to the treatment of benign tumors of the thyroid gland by the proposed method.

1. One day before the first course of sclerotherapy (21.10.02,) appoints MOVALIS in a dose of 7.5 mg once daily after a meal for 10 days.

2. 23.11.02, had started the first course of sclerotherapy. Sclerotherapy was performed in specially equipped for this purpose the Cabinet with all the rules of asepsis. For this patient gave corresponding to the puncture position: the patient was in supine with a roll under the shoulders, with a maximum head thrown back. Handled place of projection of the examined body (the front surface of the neck) 96% alcohol, struck a sterile gel used for invasive ultrasound. Identified area of sclerotherapy under ultrasound monitoring. Opened one consumer packaging with a needle. Pushed a piece of paper packaging, no fingers touching the needle, deployed the package to maintain sterility of the needle. Tightly, firmly, and put the needle on the cone of the syringe and took off the protective cap and packaging. In the syringe scored the 3% solution for injection atoxicity in a volume of 0.5 ml and through the puncture adapter under ultrasound slowly by pressing the plunger of the syringe were injected with sclerosant, controlling its distribution on the ultrasound screen.

A necessary condition for the introduction of sclerosants is clear pathological fixation of education or an entire lobe of the thyroid gland. Fixing cysts or node with cystic content is produced using the needle adapter by pressing to the trachea and to the spine. The needle is removed. Remove sterile gel with the skin of the neck of the patient. The wound treated with alcohol. Remove the protective coating with bactericidal plaster 2,5×7.2 cm, the wound impose a gauze pad and stick to the skin.

The patient had received 2 courses of sclerotherapy due to the presence of bulk node with an interval of 14 days by the method described above, and one day before the beginning of the 2nd year was appointed "MOVALIS in a dose of 7.5 mg once daily after a meal for 7 days. Long - term results-when ultrasound after 1, 3, 6 months site is not rendered.

Example 2. The patient Gryaznov V., 41 years, 18.01.03, turned to the Medical Association "Health" diagnosed with a cyst of the right lobe of the thyroid gland, autres. Conducted additional tests verified the diagnosis and performed sclerotherapy cystic formations on the above methodology. One day before the course sclerotherapy was appointed "MOVALIS in a dose of 7.5 mg once a day after por the EMA food for 10 days. Was conducted 1 year sclerotherapy: 1% solution for injection atoxisklerol in an amount of 5 ml was introduced in cystic formation (total cysts of 18.4 ml) after aspiration of the fluid in an amount of 10 ml, then 8 days re-introduced sclerosant in the dose of 1 ml Under sonographic control above sclerotherapy performed after 1, 3, 6 months the cyst could not be visualized.

Example 3. The patient Knyazeva, A., 56 years, 09.03.03, turned on the advice of the Medical Association "Health" with a diagnosis of diffuse nodular goiter. The site of the isthmus. Autres. After further examination and verification of the diagnosis we had produced a hardening of the node isthmus above described method. Was conducted 1 year sclerotherapy. Before the course was assigned MOVALIS in a dose of 7.5 mg once daily after a meal for 8 days. The course of sclerotherapy was performed as follows: introduced a 0.5% solution for injections atoxisklerol in a volume of 1 ml In routine ultrasound examination at the place of benign tumors in three and then six months was visualized connective tissue fibers and fibrous elements. The size of the thyroid gland was normal in related conservative therapy.

The result of the above sclerotherapy significantly positive. One month after the exclusion of the spent treatment control ultrasound studies showed no tumors. After 10 months after the end of treatment the result was the following: in the thyroid gland in the place previously described solitary node in the form of a hypoechoic tissue with anechoic mass with inclusions visualized the presence of Hyper-isoechogenic education, i.e. the substitution of a follicular endocrinocytes fibrous elements. Thus, the treatment efficiency of the proposed method is very high.

Example 4. The patient Zakharko L.D., 25 years, 27.02.03, turned to the Medical Association Health Advisory after receiving the necessary examination methods was diagnosed with a cyst of the left lobe of the thyroid gland. Autres. Total cyst was 6.6 ml. Therapy of benign neoplasms of the thyroid gland using the proposed method of treatment was carried out as follows.

One day before the first course of sclerotherapy appointed "MOVALIS in a dose of 7.5 mg once daily after a meal for 10 days. Spending the first course of sclerotherapy were injected with 1% atoxicity in volume of 3 ml After 21 days again spent the introduction of sclerosant in the amount of 0.5 ml

The patient had received 2 courses of sclerotherapy with an interval of 21 days by the method described above, and one day before the beginning of the 2nd year was appointed "MOVALIS in a dose of 7.5 mg once daily after a meal in ECENA 7 days. Long - term results-when ultrasound after 1, 3, 6 months site is not rendered.

The proposed method can be used for the treatment of benign tumors of the thyroid gland. A necessary condition is a preliminary fine-needle aspiration fine-needle biopsy of the thyroid gland under the control of an ultrasonic apparatus with further study of the cytological material.

Mode sclerotherapy: sequence and volume of injection of sclerosants has been proved experimentally and clinically. Dose less than 0.5% was impractical to obtain a stable therapeutic effect achieved sclerosing, and dose more than 4% inappropriate, because it may cause ekstratireoidne fibrosis, hematoma and thrombosis. Necessary and sufficient dose "MOVALIS" 7.5 mg once daily also chosen experimentally and clinically. Under observation (survey data) were 187 patients, male and female, aged 18 to 65 years with a variety of benign neoplasms of the thyroid gland observed in Health organization "Health" in Tomsk. The average age of 38.5±of 3.27 years). These patients received conventional therapy with L-thyroxine without expressed positive dynamics. After this it was decided to use sclerotherapy data PA is yentob. The results of the treatment were evaluated on the basis of the analysis of clinical and laboratory disease activity. The overall efficiency of this method is 81%.

Sclerotherapy in our opinion has advantages over simple aspiration of cysts, as simple aspiration of cysts of the thyroid gland is very often accompanied by recurrence that requires further use radical methods of treatment and accordingly reduces the amount of healthy thyroid tissue. In the past with the lack of effect was used for introduction into the cavity of the cyst various sclerosants (tetracycline, and others).

Significant new features helped to increase the effectiveness of the treatment to 82.5% compared to 72.5% of the prototype method and to reduce the treatment time by reducing the number of procedures performed, to reduce side effects by reducing trauma and pain for the actual thyroid tissue, and for the sick.

Thus, this invention improves the efficiency by reducing treatment time and reduce the number of complications by reducing the number of injections, reducing the morbidity due to integrated use of drugs and conducting sclerosing on the background of non-steroidal anti-inflammatory therapy, and stopped pronounced pain is Indra.

The application of the proposed method of treatment in clinical practice, as demonstrated in clinical trials to significantly enhance the quality of life for patients suffering from chistoso-nodular goiter, to reduce the period of disability, in some cases, to completely get rid of this disease and to avoid unnecessary surgical treatment, and possible postoperative complications.

Because study shows that the positive effect of the developed technique is observed at 82.5% in patients with various thyroid diseases. You can make an informed conclusion that sclerosing therapy under the control of ultrasonography by introducing atoxisklerol should take place in endocrinology practice, as a relatively simple, safe, effective way to treat nodules and cysts of the thyroid gland. Moreover, it is minimally invasive, cost low-cost and can be used as an outpatient method in the conditions of the clinic without the need for hospitalization.

Contraindication for carrying out the proposed method of treatment are questionable and suspicious for a malignant process nodules.

1. The use of atoxisklerol as a means to treat benign but is of obrazovanii thyroid gland.

2. Treatment of benign tumors of the thyroid gland through the course of sclerotherapy, wherein spend 1-2 sessions of sclerotherapy with breaks between courses 14-21 day, which impose 0.5-4%solution for injection Atoxisklerol under the control of ultrasound at a dose of 0.5-1 ml per ml of volume of the node when the node tumors and in patients with cystic neoplasm in the amount of 3-5 ml after aspiration of the fluid, the day before the start of each course sclerotherapy prescribed MOVALIS in a dose of 7.5 mg once daily after a meal, and take "Movalis in 5-10 days.



 

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9 cl, 4 tbl, 1 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (I) in racemic form, enantiomer form or in any combinations of these forms possessing affinity to somatostatin receptors. In the general formula (I): R1 means phenyl; R2 means hydrogen atom (H) or -(CH2)p-Z3 or one of the following radicals: and Z3 means (C3-C8)-cycloalkyl, possibly substituted carbocyclic or heterocyclic aryl wherein carbocyclic aryl is chosen from phenyl, naphthyl and fluorenyl being it can be substituted, and heterocyclic aryl is chosen from indolyl, thienyl, thiazolyl, carbazolyl, or radicals of the formulae and and it can be substituted with one or some substitutes, or also radical of the formula: R4 means -(CH2)p-Z4 or wherein Z4 means amino-group, (C1-C12)-alkyl, (C3-C8)-cycloalkyl substituted with -CH2-NH-C(O)O-(C1-C6)-alkyl, radical (C1-C6)-alkylamino-, N,N-di-(C1-C12)-alkylamino-, amino-(C3-C6)-cycloalkyl, amino-(C1-C6)-alkyl-(C3-C6)-cycloalkyl-(C1-C6)-alkyl, (C1-C12)-alkoxy-, (C1-C12)-alkenyl, -NH-C(O)O-(C1-C6)-alkyl, possibly substituted carbocyclic or heterocyclic aryl; p = 0 or a whole number from 1 to 6 if it presents; q = a whole number from 1 to 5 if it presents; X means oxygen (O) or sulfur (S) atom n = 0 or 1. Also, invention relates to methods for preparing compounds of the general formula (I), intermediate compounds and a pharmaceutical composition. Proposed compounds can be used in treatment of pathological states or diseases, for example, acromegaly, hypophysis adenomas, Cushing's syndrome and others.

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

11 cl, 2 tbl

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to crystalline polymorphic modifications of strong acting epotilone analog of forma A and forma B represented by the formula (I): Invention proposes a crystalline substance representing a mixture of form A and form B of epotilone analogs. Invention proposes two variants of a method for preparing crystalline polymorphic modification representing form A. Also, invention proposes a pharmaceutical composition inhibiting angiogenesis and comprising an active component that represents crystalline polymorphic modification of epotilone analog of form A, form B or a crystalline polymorphic modification of epotilone analog of the formula (I) wherein this modification has no amorphous component, and a pharmaceutically acceptable carrier. Also, invention proposes a method for treatment of cancer comprising administration in mammal the effective dose of crystalline polymorphic modification of epotilone analog. Invention provides preparing crystalline polymorphic modifications of strong acting epotilone analog of the formula (I) characterizing by improved properties for using in therapy of cancer species.

EFFECT: improved preparing methods, valuable medicinal properties of compounds and composition.

16 cl, 9 dwg, 7 tbl, 5 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to derivatives of dihydronaphthalene represented by the formula (I):

wherein radical values are determined in the description and to its nontoxic salts. The proposed compound is a regulator of receptors activated by a peroxisome proliferator (PPAR) of α- and γ-type. The agent can be useful as a hypoglycemic agent, hypolipidemic agent, agent for prophylaxis and/or treatment of diseases associated with metabolic disturbances, agent increasing the content of HDL-cholesterol and reducing the content of LDL-cholesterol and/or VLDL-cholesterol and agent for weakening diabetes mellitus factor risk, and/or X-syndrome. Also, invention claims derivative of dihydronaphthalene representing 3-{5-{2-[2-(4-methylphenyl)-5-methyloxazol-4-yl]ethoxy}-3,4-dihydronaphthalen-1-yl}propanoic acid.

EFFECT: valuable medicinal properties of compounds and agent.

21 cl, 15 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: the present innovation should be fulfilled due to performing sclerotherapy with 96%-ethanol under ultrasound control at the dosage of 0.5-1 ml/ml of nodal volume in case of nodal neoplasms and 3-5 ml in case of cystic neoplasm after liquid aspiration. Moreover, a day before each course of sclerotherapy one should introduce Movalis for 5-10 d once daily after meals. The course of sclerotherapy should be started with introducing 96%-ethanol, then 8-10 d later it is necessary to introduce benzyl peniccilin sodium salt at the dosage of 0.5-1 ml/ml of nodal volume in case of nodal neoplasm, and 0.5 ml after liquid aspiration - in case of cystic neoplasm. The innovation enables to decrease side manifestations of complex therapy performed due to decreasing the quantity of injections.

EFFECT: higher efficiency of therapy.

1 cl, 4 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide of the formula: and to its pharmaceutically acceptable salts. Also, invention describes a pharmaceutical composition inhibiting activity of protein-tyrosine kinases and comprising the indicated compound, a method for treatment of disorders associated with protein-tyrosine kinases, such as an immune disorder, and oncology disease, and a method for cancer treatment.

EFFECT: valuable biochemical and medicinal properties of compounds and composition.

5 cl, 2 tbl, 581 ex

FIELD: medicine, coloproctology.

SUBSTANCE: the present innovation deals with treating idiopathic dry pruritus ani, moreover, under out-patient conditions. One should apply netting-like picture onto affected part of skin in perianal area, lines should be applied at the distance of 1 cm against each other. Moreover, this picture should be applied either with brilliant green onto the skin of perianal area, or it is possible to apply a netting-like picture applied at transparent roentgen film. Then, one should inject subcutaneously 0.1 ml 70%-alcohol with insulin syringe for the whole length of its needle into every point of lines' intersection. This enables to provide stable interruption of dry pruritus ani, for 3-5 mo due to denervation of sacro-coccygeal nervous plexus and, also, prevent the development of post-surgical cutaneous necrosis due to minimal cutaneous traumatism.

EFFECT: higher efficiency of therapy.

2 cl, 1 ex

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