Treatment of remittent disseminated sclerosis

FIELD: medicine, neurology, in particular treatment of disseminated sclerosis.

SUBSTANCE: complex therapy includes plasma exchange, interferonotherapy, administration of copaxon, cytostatics, symptomatic and bracing agents, and cyclosporin A. Administration of steroids is excluded. Additionally ceruloplasmine intravenously drop-by-drop in dose of 100 mg and cerebrolysate intramuscularly in dose of 10 ml for 10 days are administered. Claimed method provides stable remission up to 12 months for 89.2 % of patients.

EFFECT: decreased invalidisation due to reconstitution of regulatory relationship between nervous and immune systems.

1 ex, 1 tbl

 

The invention relates to medicine, namely, neurology, and can be used to treat multiple sclerosis (MS).

Tactics modern treatment of MS, regardless of the form of its course, is based on the need of the inhibition autoimmune component of the disease or immune separate immunopathological and neuro manifestations of the disease (Zhuchenko SO, Zavalishin I.A. the Treatment of multiple sclerosis: current opportunities and future prospects // Multiple sclerosis. Selected questions of theory and practice. Edited Iasevoli and Vigilancia. M - 2000. - s-614). It provides steroid pulse therapy (methylprednisolone, solumedrol, metypred), less adrenocorticotropic hormone (ACTH), plasma exchange, interferons alpha and beta, Copaxone - antigen-specific blocker myelin-specific autoimmune reactions, cytotoxic agents (azathioprine, methotrexate), tools symptomatic and restorative therapy.

However, the search for solutions to increase the effectiveness of treatment of MS and reduce the risk of side effects from your medicines remains a challenge for clinical and theoretical neuroscience.

The prototype of the present invention are available in the literature scattered single information about the use in treatment of MS drug cyclosporine A (Sandimmun is) - Demina TL, Boyko A.N., Belyaeva IA and other results of the use of cyclosporine a (Sandimmune) in patients with active multiple sclerosis // J. struct. Dokl Ross. the NAC. fo. "Man and medicine". - M - 1998. - p.59; Perova EL the Treatment of multiple sclerosis, " Vestn. 1st Reg. the wedge. hospitals of the city. 2002. No. 2. - p.32-36.

As for the Cerebrolysin and ceruloplasmin in the available literature guidance on their use in the treatment of MS, we have not met, although in neurological practice in other diseases they were used (Rahimkulov A.S., security R.M., Rizvanov A.S., Borisov I. the results of the treatment of cerebrovascular diseases by the method of endonasal electrophoresis with ceruloplasmin, cerebrolysinum and tankana // Health Bashkortostan. - 2004. No. 5. - s-93; Gromov O.A., Kudrin A.V. Modern concept of neurotrophic actions of Cerebrolysin. The overview. // International. honey-so (Moscow). 2002. No. 2. - s-149; dobrotin N.A., Rotnitzky, A., Gladysheva M.V., Ezhova G.P. Multifunctional ceruloplasmin, the rationale for the use of // the Success of contemp. Biol. - 1999. t. No. 4. - s-379.

The objective of the invention is to design (rationale) method pathogenetically oriented treatment of MS, which allows to increase the effectiveness of treatment of disease.

The technical result - increase of efficiency of treatment limitation applied what I steroid therapy.

The proposed combined method is as follows: carry out a basic treatment of MS, including plasmapheresis, interferons alpha and beta, Copaxone - antigen-specific blocker myelin-specific autoimmune reactions, cytotoxic agents (azathioprine, methotrexate), tools symptomatic and restorative therapy. From regimens eliminate steroids, but complement the purpose of immunosupressant - cyclosporine a (Sandimmune), offset metabolism of ceruloplasmin and Cerebrolysin.

Cyclosporin a is an immunosuppressive drug, which is associated with suppression of cell-mediated immune responses, targets which are T-lymphocytes. Apply cyclosporine a dose of 25 mg 2 times a day inside a month. Receiving cyclosporine And combine with the introduction of ceruloplasmin and Cerebrolysin.

Ceruloplasmin is a copper-containing enzyme α globulin fraction of human serum that improves the stability of cell membranes, is involved in immunological reactions, ion exchange, has antioxide action, inhibits lipid peroxidation and stimulates haematopoiesis, reduces toxicity and immunosuppression. Administered intravenously at 100 mg isotonic HaCl or 5% glucose solution for 10 days daily.

Cerebral the ZAT - released from the protein hydrolysate of the brain of pigs, normalizing metabolism in the brain tissue and the Central nervous system by improving protein synthesis in nerve cells, increasing the sustainability of brain tissue to intoxication, hypoxia, hypoglycemia, as well as stimulation of total production of hormones. The drug activates the integrative processes in the Central nervous system. Injected intramuscularly with 10 ml for 10 days.

The treatment was repeated after 6 months. Under our supervision there were 22 patients with relapsing-remitting course of MS in age from 19 to 42 years. The evaluation of treatment efficacy was performed using Kurtzke scales and disability EDSS, were considered immune status, the duration of remission. Used regimen was most effective in patients with the first and second stages of the disease. In patients with baseline level of disability 2-3 points on the EDSS scale the degree of disability as a result of treatment decreased by 0.5 to 1.0 score regressed pyramidal and cerebellar symptoms, the duration of remission increased to lit. Changing the integral (our observations) immunological blood parameters are presented in the table.

The results of clinical observations and reflected in the table clinical and immunological evidence suggests that this act is about combination therapy of relapse MS provides the translation of his current stage in sustained remission, obviously due to the recovery of regulatory relationships of the nervous and immune systems, this is particularly evidenced by the decrease in the level of HLA-DR+lymphocytes, reflecting reduced demand for the perception of antigenic information coming from brain structures, and increasing migration activity of leukocytes, including lymphocytes, indirectly reflects the decrease in patients proinflammatory cytokine background. In other words, stops (or pauses) the pathogenetic chain of autoimmune disease process.

Example

Patient S., 32 years old (case history No. 22912). In March 2002 suffered a neuritis of the facial nerve, which in outpatient treatment regressed. Since January 2003, the patient appeared numbness in the lower extremities, unsteadiness when walking, double vision (diplopia) in the eyes.

Objectively admission: CHN - horizontal nystagmus melcorazmashisty, lack of convergence on both sides. Nasolabial folds are symmetrical, the tongue in the midline. CXP uniform, hand moderate vividness, with feet high, no pathologic reflexes. In the Romberg unstable, wobbling, coordination of sample runs with light intention on both sides. Loss of sensitivity is not revealed. Meningeal signs.

Patient treatment offered is the manual.

A content analysis of HLA-DR+lymphocytes, size IML and concentration JgM showed that all three indicators in paired blood samples underwent the following dynamics: the number of HLA-DR+lymphocytes decreased from 35%to 27%, IML increased from 0.83 to 1.90, and the content of JgM decreased from 2.3 to 1.5. This observation 2 of the three argumentorum indicators included in the range of physiological norm, and IML exceeded her, indicating mobilization of the protective provisions of the immune system. Clinically this patient has a remitting course of MS.

As a result of such spent combination therapy, with the exception of steroids, the disease has steadily gained a remitting course with persistence to work in their field. Separate administration of the preparations was not accompanied by the formation of stable clinical and immunological remission of RS.

Thus, the proposed method, including means pathogenetically oriented therapy may be recommended for the treatment of PC.

A method for the treatment of relapsing-remitting multiple sclerosis through comprehensive treatment including plasmapheresis, interferon therapy, injection of Copaxone, drugs, symptomatic and fortifying agents, cyclosporine A, characterized in that preclude the introduction of steroi the s and additionally within 10 days administered drugs: ceruloplasmin intravenously at 100 mg and Cerebrolysin intramuscular injection of 10 ml.



 

Same patents:

FIELD: veterinary science.

SUBSTANCE: the present innovation deals with freezing the tissues of animal parenchymatous organs followed by defrosting, homogenization and hydrolysis. Hydrolysis should be conducted at the presence of succinic acid at pH being -4.0 and 45°C. Hydrolyzate should be decanted followed by addition of 3%-caustic soda solution up to pH=7.0; moreover, it is necessary to add novocain powder to hydrolyzate up to 0.4-0.5% concentration and gel of aluminium oxide hydrate at 2-3 mg/ml. The preparation obtained should be packed into 50-ml vials to be sterilized due to autoclaving at the mode of 1.0 atm. for 20 min. The innovation provides less reactogenic final product of prolonged action and increased anti-infectious activity.

EFFECT: higher efficiency.

2 ex, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of aminoquinoline and aminopyridine. Invention describes compounds of the general formula (I): wherein R1 means hydrogen atom or direct or branched (C1-C4)-alkyl group; R2 means hydrogen atom or direct or branched (C1-C4)-alkyl group; R3 means hydrogen atom or direct or branched (C1-C4)-alkyl group or phenyl group, thienyl group or furyl group optionally substituted with one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group or halogen atom; R4 and R5 form in common 1,3-butadienyl group optionally substituted with methylenedioxy-group or one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group, hydroxy-group or halogen atom; R6 means hydrogen atom or cyano-group; R7 means hydrogen atom or direct or branched (C1-C4)-alkyl group, phenyl group, benzyl group, thienyl group, or furyl group optionally substituted with methylenedioxy-group or one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group, hydroxy-group, trifluoromethyl group, cyano-group or halogen atom; X means -NH-group, -NR8-group or sulfur atom, or oxygen atom, or sulfo-group, or sulfoxy-group wherein R8 means direct or branched (C1-C4)-alkyl group or (C3-C6)-cycloalkyl group; n = 0, 1 or 2, and their salts. Also, invention describes a method for preparing compounds of the formula (I). a pharmaceutical composition based on thereof, using compounds of the formula (I) as antagonists of A3 receptors for preparing a pharmaceutical composition used in treatment of different diseases (variants), compounds of the formula (IA), (II), (III) and (IV) given in the invention description. Invention provides preparing new compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

15 cl, 6 tbl, 6 dwg, 172 ex

FIELD: organic chemistry, medicine, allergology.

SUBSTANCE: invention relates to a method for treatment of allergy by administration to patient the therapeutically effective dose of a pharmaceutical composition comprising compound of the formula (I) . Invention provides the enhanced effectiveness of treatment.

EFFECT: improved treatment method.

7 cl, 3 dwg, 49 ex

FIELD: veterinary medicine.

SUBSTANCE: method involves introducing a drug as injection. The drug is based on common viper poison like Vipraxin. Basic dose is equal to 4-6 ml per cattle head. Before introducing the basic dose, animals are sensitized with the same preparation, the sensitizing dose being equal to 0.5-1 ml per cattle head.

EFFECT: improved functional activity of immune system; improved biochemical properties and increased organism stability.

5 tbl

FIELD: veterinary medicine.

SUBSTANCE: method involves introducing a drug as injection. The drug is based on common viper poison like Vipraxin. Basic dose is equal to 4-6 ml per cattle head. Before introducing the basic dose, animals are sensitized with the same preparation, the sensitizing dose being equal to 0.5-1 ml per cattle head.

EFFECT: improved functional activity of immune system; improved biochemical properties and increased organism stability.

5 tbl

FIELD: organic chemistry, polysaccharides.

SUBSTANCE: invention describes polysaccharide of the formula (I):

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EFFECT: improved preparing method.

16 cl, 26 dwg, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: method involves administering Corbiculin at a dose of 2 g three times a day when prediluted with 50 ml of water. The treatment course is 21 days long or longer until alanine aminotransferase and aspartate aminotransferase indices assume normal values.

EFFECT: enhanced effectiveness in normalizing hyperenzymemia and relieving clinic manifestations of cytolytic syndrome.

2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new N-acylated pseudodipeptides comprising acidic group in neutral or charged form by one end of pseudodipeptide and accessory functionalized branching by the opposite end and corresponding to the general formula (I): wherein each R1 and R2 means acyl group of saturated or unsaturated, linear or branched carboxylic acid comprising from 2 to 24 carbon atoms, unsubstituted or comprising a substitute or substitutes chosen from hydroxyl, alkoxy- and acyloxy-groups; coefficient n has values from 0 to 3; coefficients p and q have values from 1 to 3; coefficient m has values from 1 to 3 except for a case when X means carboxyl or one of its derivative, and in this case it means values form 0 to 3; Y means oxygen atom (O) or -NH; X and Z mean accessory functionalized branching or acidic group in neutral or charged form chosen from the following groups: carboxyl, carboxy-(C1-C5)-alkoxy-, carboxy-(C1-C5)-alkylthio-, phosphono-(C1-C5)-alkoxy-, dihydroxyphosphoryloxy-, hydroxysulfonyloxy-, (carboxy-(C1-C5)-alkyl)aminocarbonyl, (dicarboxy-(C1-C5)-alkyl)aminocarbonyl, (ammonio-(C1-C5)-aminocarbonyl, carboxy-(amino-(C1-C5)-alkyl)aminocarbonyl under condition that at least one substitute among X and Z means an accessory functionalized branching, and their enantiomers and diastereoisomers. Proposed compounds show immunomolulating properties as adjuvants and these compounds can be grafted to antigen to modulate the immune response or can be grafted to pharmacophore to improve the therapeutic effect or its directed delivery.

EFFECT: improved preparing methods, improved and valuable medicinal properties of substances and compositions.

48 cl, 3 tbl, 112 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: method involves administering Indinol as alternative means to hormone medication at a dose of 200 mg per day for 2 months following hysteroscopy operation. Then, the dose is reduced to 10 mg per day during the next 2 months. Kipferon is to be concurrently intravaginally administered at a dose of 1 suppository daily during 10 days.

EFFECT: stimulated estradiol production in liver; enhanced effectiveness of local receptor-correcting and immunomodulating action.

2 cl, 5 tbl

Caspase inhibitors // 2274642

FIELD: medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new compounds that represent inhibitors of caspases, in particular, inhibitors of interleukin-1β-converting enzyme and their pharmaceutical compositions. Proposed compounds can be used successfully as agents directed against diseases mediated by interleukin-1, apoptosis and factor inducing interferon-γ or by interferon-γ.

EFFECT: valuable medicinal and biochemical inhibitors.

35 cl

FIELD: organic chemistry, medicine, ophthalmology, pharmacy.

SUBSTANCE: invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the general formula (I): wherein X1, X2, X3, X4 and X5 mean -CH2 or one of them represents -NH and another X1-X5 represent -CH2; k = 0, 1 or 2; when t = 2, then radicals R1 are similar or different; R1 represents direct or branched (C1-C8)-alkyl or (C1-C8)-alkoxy-group; A means phenyl or pyridinyl; R2 means hydrogen atom (H), hydroxyl, halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; n = 0, 1-4; radicals R2 are similar or different, when n > 1; p = 0 or 1-5; Y means -OC(O); Z means -CH, or to their pharmaceutically acceptable salts. Compounds of the formula (I) possess agonistic activity with respect to muscarinic receptors and can be used in medicine as medicinal preparations for treatment of neurodegenerative diseases or diseases associated with increased intraocular pressure.

EFFECT: valuable medicinal properties of derivatives.

6 cl, 1 tbl, 2 dwg, 16 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition stimulating adenosine receptors and comprising one or some compounds of the formula (I) and new compounds of the formula (II) . The composition provides the effective modulation of the adenosine system.

EFFECT: valuable properties of modulators.

12 cl, 541 ex

FIELD: organic chemistry, neurology, medicine.

SUBSTANCE: invention relates to a new medicinal agent used in treatment of feeble-mindedness comprising a derivative of 2-aryl-8-oxodihydropurine, namely, a derivative of 2-aryl-8-oxodihydropurine that comprises acetamide group at position 7 or 9 of purine ring. Invention proposes compounds of formulae (Ia) and (Ib) wherein radicals X1, Y1, R12, R13, R22, R23, R32, R42 and R43 have the corresponding values, or their pharmaceutically acceptable acid-additive salt. Also, invention proposes using compounds of the formulae (Ia) and (Ib) or their pharmaceutically acceptable acid-additive salt for preparing a medicinal agent used in treatment or prophylaxis of feeble-mindedness wherein feeble-mindedness represents deterioration of the teaching process, dysmnesia, dysmnesia-based disorientation, mental dysfunction, Alzheimer's disease, cerebrovascular feeble-mindedness and/or senile feeble-mindedness, and in treatment or prophylaxis of higher cerebral dysfunction. Invention provides the development of a medicinal preparation for prophylaxis or treatment of feeble-mindedness symptoms associated with diseases that can induce feeble-mindedness and higher cerebral dysfunction.

EFFECT: valuable medicinal properties of agents.

12 cl, 3 tbl, 5 ex

FIELD: medicine, neurology, therapy, pharmacy.

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EFFECT: valuable medicinal properties of preparation.

11 cl, 3 tbl, 1 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: claimed method includes blending of active base and auxiliary ingredients to form tablet corn, representing composition of sugar powder, monocrystalline cellulose, vinylpyrrolidone and calcium stearate; humidifying of obtained mixture; drying of obtained granules; dry granulation through granulator with standardized holes; pelletization of standardized granules to produce tablet corn; and coating. Mixture is humidified with 5-7 % starch mucilage in starch mucilage/humidifying mixture mass ratio of 1:25-30, wherein mixture is blending with starch mucilage for homogeneous distribution wet in whole mass.

EFFECT: tablets with increased hardness and enhanced pharmacological activity.

2 cl, 2 ex

FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacy.

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EFFECT: valuable medicinal properties of agent.

1 tbl

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 1 tbl, 20 ex

FIELD: medicine, pediatrics, psycho-neurology.

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EFFECT: higher efficiency of therapy.

3 ex

FIELD: organic chemistry of heterocyclic compounds, biology, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines of the general formula (1): or (2): or their pharmaceutically acceptable salts, N-oxides or hydrate possessing physiologically active properties, in particular, eliciting ability to induce apoptosis in tumor cells causing their death. In the general formula (1) or (2) X represents sulfur or oxygen atom; Y represents sulfur atom, group -SO, group -SO2, group -NH or group -NR6; R1 represents aryl, substituted aryl, heteroaryl; R2 and R5 represent hydrogen atom, alkyl, allyl, substituted benzyl, group -CH2-C(O)R3, group -CH2-C(O)NR3R4 wherein R3, R4 and R6 represent inert substitute. Also, invention relates to new combinatory libraries for search compound-leaders and candidates for medicinal compounds preparing by screening the combinatory libraries.

EFFECT: valuable medicinal properties of compounds.

9 cl, 1 tbl, 9 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of pyridopyrimidines of the formula (I): or (II): wherein Z means nitrogen atom (N) or -CH; W means -NR2; X1 means oxygen atom (O), -NR4 (wherein R4 means hydrogen atom or alkyl), sulfur atom (S) or -CR5R6 (wherein R5 and R6 mean hydrogen atom); X2 means oxygen atom (O); Ar1 means unsubstituted or substituted phenyl; R2 means hydrogen atom, alkyl or acyl; R1 means hydrogen atom, alkyl, halide alkyl and others; R3 means alkyl; cycloalkyl and others; R8 and R9 mean hydrogen atom, alkylsulfonyl and others, and to their pharmaceutically acceptable salts, and to intermediate compounds that are used for preparing compounds of the formula (I) and (II). Indicated compounds show inhibitory activity with respect to activity of p38 kinase and can be used in preparing a medicine agent for treatment of p38-mediated disturbances.

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

38 cl, 3 tbl, 116 ex

FIELD: veterinary science, animal feeding.

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EFFECT: higher efficiency.

72 cl, 2 dwg, 15 ex, 20 tbl

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