Cdp-choline being the preparation for treating alcoholic abstinence syndrome and therapeutic method due to its application

FIELD: medicine.

SUBSTANCE: the suggested preparation is being cytidine diphosphate choline (CDP-choline) known previously as the preparation to restore cerebral phospholipid structure and for treating mammalians, people among them, subjected to the action of stimulants. Moreover, it is necessary to note that CDP-choline decreases the duration of abstinence symptoms (tremor, convulsions, weakness, emotional instability, nervousness, social reserve) and causes either the decrease or stoppage of alcohol intake.

EFFECT: higher efficiency of therapy.

5 cl, 5 ex

 

The technical field to which the invention relates.

This invention relates to medicinal chemistry and relates to the use of CDP-choline for the treatment of alcohol abstinence syndrome.

Toxic effects of alcohol on the Central nervous system that primarily affect the membrane and synapses of neurons (see Leonard V.E., Alcohol Alcohol., t 4 str-338, (1986)). Histological changes in the structure of neurons are reduced branching of the nerve cells of the hippocampus and Purkinje cells. Comparison of the brain of healthy subjects with brain alcoholism revealed less branching of basal dendrites of pyramidal neurons in the upper part of the cerebral cortex and the motor cortex of the brain (see Ledig, M. and P. Mandel, M S-Medicine Sciences, volume 4, issue 6, str-357, (1988)).

It was also shown that chronic alcohol abuse reduces the sensitivity of the dopamine receptors. This effect is probably associated with changes in rezidentnosti membranes of neurons and the number and functionality of the receptors, as well as with the decrease of the reverse takeover of acetylcholine and deficiency of dopamine (see Carlen P.L et al., Ann.Neurol., v.9, issue 1, p.84-86, (1981)).

CDP-choline (citizen-diphosphocholine, Citicoline) is a key intermediate product in the synthesis of structural phospholipids, located on the IU is bran neurons (see article E.P. Kennedy and S.B. Weiss, J.Biol. Chem., t, str-214, (1956)), and plays an important role in their formation and recovery in case of damage to the phospholipid structure of endogenous or exogenous factors, including a decrease in absorption (absorption) cytidine and choline.

Introduction CDP-choline increases the level of synthesis and release of dopamine (see Martinet M. et al., Biochem. Pharmacol., t, Vol.5, str-541, (1981)), and the levels of choline and acetylcholine in the brain. Introduction repeated doses of CDP-choline leads to increased levels of phospholipids in the brain, which is secondary to increased levels of cytidine and choline in plasma (see Agut J. et al., Ann. New York Acad. Sci., t, str-320, (1993)).

Applicants unexpectedly discovered that the introduction of CDP-choline in patients with alcoholism reduces the duration and intensity of withdrawal symptoms and causes an improvement in a significant proportion of patients.

The object of this invention is the use of CDP-choline or its pharmaceutically acceptable salts as a drug for the treatment of alcohol abstinence syndrome.

Another object of this invention is a method of treatment of alcohol abstinence syndrome, including the introduction of an effective amount of CDP-choline or its pharmaceutically acceptable salt to a patient with alcoholism.

Predpochtitel is about, CDP-choline is administered to a person in the form of the free compounds or pharmaceutically acceptable salts in anhydrous or hydrated form, properly mixed with conventional pharmaceutical carriers and/or excipients in daily doses of from 0.5 to 2 g in terms of free CDP-choline, preferably containing from 0.5 to 1 g as oral and parenteral. Pharmaceutically acceptable salts of CDP-choline include its salts of alkaline or alkaline earth metals, such as salts of sodium, potassium, calcium and magnesium, or its salt accession obtained by adding inorganic or organic acids, such as hydrochloric acid, Hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, triperoxonane acid, citric acid, lactic acid, malonic acid, tartaric acid, acrylic acid, methacrylic acid, malic acid, maleic acid, fumaric acid, benzoic acid, salicylic acid, cinnamic acid, methanesulfonate acid, benzolsulfonat acid, p-toluensulfonate acid and nicotinic acid.

CDP-choline or its salts in the form of both anhydrous and hydrated substances, in accordance with the invention can be administered orally in the form of tablets, capsules, powder, granules, wafers, cakes, solution, WM is enzie, emulsion, syrup, gel, etc., or parenterally in the form of a solution, suspension, emulsion, etc. for intravenous or intramuscular injection.

Information confirming the possibility of carrying out the invention.

EXAMPLES

The invention is illustrated below by examples. Competent professionals in this field will be able to produce any change in the absence of modifications of the specific variant embodiment of the invention and therefore the invention is not limited to the specific details of these examples.

EXAMPLE 1. Tablets 500 mg

CDP-choline, sodium salt 522,5 mg

Talc 30.0 mg

Magnesium stearate 3.0 mg

Silicon dioxide 2.5 mg

Croscarmellose sodium salt 20.0 mg

Corn starch 20.0 mg

Microcrystalline cellulose, s.q.*

*s.q. - sufficient, or as required 780,0 mg

EXAMPLE 2. 25%solution for oral administration.

CDP-choline, sodium salt 26,12 g

70% sorbitol 20,00 g

Methyl ester of p-hydroxybenzoic acid, 0.16 g

Propyl ester of p-hydroxybenzoic acid 0.04 g

Citrate disodium 0,60 g

Saccharin sodium salt 0.02 g

Strawberry essence 0.04 g

Dye Red Punzo 4R 0.50 mg

Anhydrous citric acid 0.05 g

Purified water, s.q.*

*s.q. - sufficient, or as required 100,00 m is

EXAMPLE 3. The solution for injection.

CDP-choline, sodium salt 522,50 mg

Hydrochloric acid, pH 6,0-6,5, s.q.*

Water for injection s.q.*

*s.q. - sufficient, or as required 4,00 ml

EXAMPLE 4. Open clinical study on the effects of RAF-choline syndrome alcohol withdrawal.

The development of the syndrome of alcohol abstinence was evaluated in an open study conducted on 197 patients. CDP-choline is administered in doses of 500 mg/day intramuscularly or 600 mg/day orally for 60 days. At 30 and 60 days during treatment see significantly different (p<0,001) in the definitions. 60 day 55,83% of patients stop drinking alcohol and 31,97% of patients drink significantly less. A significant improvement is observed in terms of anxiety, tremor, violation orientation, insomnia, dysarthria (articulation disorders), tendency to suicide and pain trigeminus nature.

EXAMPLE 5. An open randomized comparative study of the actions of the RAF-choline syndrome alcohol abstinence compared with clomethiazole and vitamin C.

An open randomized comparative study with the traditional treatment of alcohol abstinence syndrome conducted on 40 patients. Patients randomly assigned to two groups of 20 people. One of the groups of IP is result as control and she gets clomethiazole and vitamin b 1B6and In12. Treatment under this scheme is carried out in 8 days, and then patients receive the diazepam until the end of treatment (60 days). Another group of patients receiving treatment in the same way with the addition of CDP-choline in a dose of 500 mg intramuscularly every 12 hours. Within the first 30 days and the addition of CDP-choline in the dose of 200 mg orally every 8 hours in the last 30 days. Patients who receive CDP-choline in addition to the traditional treatment demonstrated significant differences compared to controls at 30 days of treatment in the incidence of tremor (p<0,05), convulsions (p<0,05), weakness (p<0,05), emotional instability (p<0.01), and anxiety (p<0.05) and social isolation (p<0,05).

1. The use of cytidinediphosphocholine or its pharmaceutically acceptable salts as a drug for the treatment of alcohol abstinence syndrome.

2. A method of treatment of alcohol abstinence syndrome, characterized in that the patient alcoholism is administered an effective amount of cytidinediphosphocholine or its pharmaceutically acceptable salt.

3. The method according to claim 2, characterized in that the pharmaceutically acceptable salt of cytidinediphosphocholine chosen from the group comprising its salts of alkaline or alkaline earth metals, or salts thereof formed with inorganic or organic the acids, such as hydrochloric acid, Hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, triperoxonane acid, citric acid, lactic acid, malonic acid, tartaric acid, acrylic acid, methacrylic acid, malic acid, maleic acid, fumaric acid, benzoic acid, salicylic acid, cinnamic acid, methanesulfonate acid, benzolsulfonat acid, p-toluensulfonate acid and nicotinic acid, in anhydrous or hydrated form.

4. The method according to claim 2 or 3, characterized in that cytidinediphosphocholine or its pharmaceutically acceptable salt is administered in a daily dose equivalent to the free cytidinediphosphocholine quantities lying in the range 0.5 to 2,

5. The method according to claim 4, characterized in that the doses are in the range of 0.5-1 g



 

Same patents:

FIELD: medicine.

SUBSTANCE: means comprises amber acid and/or its salts, fructose, dry extraction of Saint John's wort, magnesium ion sources, potassium ion sources as active bases and auxiliary substances, carriers and/or fillers when needed.

EFFECT: enhanced effectiveness of treatment.

4 cl, 4 tbl

The invention relates to the field of creation of biologically active additives and can be used as a General tonic antihypoxic contribute to a reduction of toxic effects of alcohol

The invention relates to pharmaceutical

The invention relates to the field of addiction and AIDS, providing a sobering effect

The invention relates to the field of addiction and AIDS, providing a sobering effect

The invention relates to the field of medicine and relates to new N-pinakamaraming tryptophanase of dipeptides of the formula

C6H5-(CH2)n-CO-NH-(CH2)m-CO-X-Trp-R,

where n=1-5;

m=1-3;

X=L or D-configuration;

R=OH, OCH3OC2H5, NH2, NHCH3,

as well as pharmaceutical compositions containing them

The invention relates to new derivatives of benzothiadiazole, benzoxazoles and benzodiazines formula I in free base form or in the form of a pharmaceutically acceptable acid salt additive that can be used as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic - pituitary), or various diseases that are caused by CRF1or the manifestation of which contributes CRF1such as arthritis, asthma, allergies, anxiety, depression, etc

The invention relates to means on the basis of natural ingredients with antitoxic action of alcohol poisoning, and can be used both in the medical and food industry

The invention relates to the field of medicine and relates to pharmaceutical compositions for the treatment of complex and coronary heart disease, myocardial infarction, myocardiodystrophy, rhythm disturbances associated with the use of cardiac glycosides

The invention relates to new chemical compound, namely the amide glycyrrhizic acid with 5-aminouracil formula I exhibiting anti-HIV activity in cell culture MT-4, with high efficiency by inhibiting the accumulation of virousspecificakih protein P24 (ID50= 55 ág/ml or 52,8 μm), the total viral antigen (ID50= 75 μg/ml or 72,0 μm), which reduces the activity of the reverse transcriptase (reverts) (RT) (ID50= 55 ág/ml or 52,8 μm)

The invention relates to a derivative of gemcitabine formula (I), where R1, R2, R3independently selected from hydrogen and C18and C20saturated and monounsaturated acyl groups, provided that R1, R2, R3can't all be hydrogen

The invention relates to methods for treating diseases caused by hepatitis B virus (also known as HBV and Epstein-Barr (also known as EBV, which include the introduction of an effective amount of one or more of the active compounds disclosed here, or farmatsevticheskii acceptable derivatives or prodrugs of one of these compounds

The invention relates to certain nucleoside derivative, which was found to possess valuable properties for the treatment of tumors

FIELD: medicine.

SUBSTANCE: the suggested preparation is being cytidine diphosphate choline (CDP-choline) known previously as the preparation to restore cerebral phospholipid structure and for treating mammalians, people among them, subjected to the action of stimulants. Moreover, it is necessary to note that CDP-choline decreases the duration of abstinence symptoms (tremor, convulsions, weakness, emotional instability, nervousness, social reserve) and causes either the decrease or stoppage of alcohol intake.

EFFECT: higher efficiency of therapy.

5 cl, 5 ex

FIELD: medicine, biochemistry.

SUBSTANCE: invention proposes applying CDP-choline (cytidinediphosphocholine) or its salt as a prophylactic agent for treatment of cerebral ischemia and a method for such prophylactic treatment. Invention found new and unknown early mechanism of action of CDP-choline or its salt: inhibition of activation of caspase cascade being the effectiveness of this effect is high in prophylactic intake of drug.

EFFECT: valuable medicinal properties of agent.

6 cl, 5 dwg, 4 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new stable crystalline forms of derivative of pyrimidine nucleoside of the formula (I) eliciting the excellent anti-tumor activity. Also, invention relates to pharmaceutical composition eliciting an anti-tumor effect, applying crystalline form for preparing medicinal agent and to a method for prophylaxis or treatment of tumor diseases.

EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of derivative.

10 cl, 2 tbl, 4 dwg, 9 ex

FIELD: organic chemistry, biochemistry, medicine, virology.

SUBSTANCE: invention relates to derivatives of 2'=amino-2'-deoxynucleosides of the formula:

wherein R means hydrogen atom (H), alkyl, aminoalkyl; R1 means -(R2NR3) wherein R2 and/or R3 means H, -OH, -NH2, alkyl, benzyl under condition that R doesn't represent H or methyl when R2 and R3 mean H. Compounds elicit an antiviral activity with respect to measles and Marburg viruses exceeding that of ribavirin.

EFFECT: valuable properties of compounds.

4 tbl, 2 dwg, 18 ex

FIELD: medicine.

SUBSTANCE: method involves carrying out radical operation in combination with intra-operative radiation therapy at a dose of 15 Gray per removed tumor bed and regional metastasis path. The operation combined with intra-operative radiation therapy is done in 3 weeks after finishing polychemotherapy composed of at least 2 courses to reach positive result of tumor reduction more than 75%. Pause between the courses is 3 weeks long. Following scheme is administered: Hemcytabin 1250 mg/m2 in intravenous drop-by-drop introduction during half-an-hour long infusion at the second and the ninth day, Cisplatin 50 mg/m2 is introduced at the first and the eighth day.

EFFECT: stopped progressive tumor development; prevented metastases formation.

Up!