Method for correcting cytolytic syndrome in chronic hepatitis cases

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


The invention relates to medicine and can be used for functional recovery of the liver in chronic hepatitis infectious and non-infectious origin.

It is known that pathological processes in the liver, with various acute and chronic diseases are accompanied by cytolytic syndrome, i.e. a violation of the structure and function of membrane systems of hepatocytes. Its progression can lead to decompensation of vital functions of the liver. Special attention should be paid to the group of chronic diffuse hepatitis, in which, in contrast to acute processes develop destructive inflammatory changes in the liver parenchyma occurring as an independent disease and therefore require differentiated treatment. They can be both communicable and non-communicable nature.

Syndrome integrity of hepatocytes (cytolysis syndrome) characterized by an increase in plasma activity of indicator enzymes - AST, Alt, LDH and isoenzymes - LDH and LDH specific liver enzymes: fructose-1-hospitalilty, sarbadhikari, as well as the concentration of ferritin, serum iron, vitamin B12 and bilirubin mainly due to increase direct fraction. In assessing the severity of the pathological process, the main value in the highlighted activity of Alt and AST. The higher their level in blood serum is less than 5 times compared with the upper limit of normal is considered as a moderate, 5 to 10 times as the average degree and over 10 times as high severity of the inflammatory process in the liver. Morphological basis of this syndrome are hydropic and acidophilic degeneration and necrosis of hepatocytes from damage and increased permeability of cell membranes.

Despite the diversity of etiologic factors in chronic liver diseases on the cellular level revealed similar mechanisms of degradation, among which a special role is played by the free-radical oxidation processes involving reactive oxygen species. In recent work it was shown that the intensification of the processes of free radical oxidation of lipids, on the one hand, and reduced activity of the antioxidant system, on the other hand, are essential for the formation of cytolysis [2, 4]. Therefore, one of the most important problems of modern medicine is the use of drugs that have system-wide effect and has membrane stabilizing and antioxidant properties. Such drugs membranostabiliziruyuschee and antioxidant action, as glucocorticosteroids, ascorbic acid, cytochrome C, quercetin, found only limited applications to the interview. While they give a lot of side effects and recommended antioxidants (ascorbic acid, cytochrome C, quercetin, represent only askarruttavista (water-soluble) link antiradical protection system cells.

Hepatoprotective effect has Heptral, Phosphogliv [3, 6]. However, their appointment requires the observance of the regimen of administration of the drug in the form of intravenous infusions, and then oral intake, which creates inconvenience for outpatient treatment [7, 8].

Drugs Kars, legal, hepatophilic containing the extract of the fruit of the plant, milk Thistle, and essential phospholipids possess hepatoprotective and antioxidant effects. However, the effectiveness of these drugs in controlled clinical studies using control liver biopsies done in early Scandinavian, and then in European hospitals, did not confirm the expected positive result (Thaler N., 1983, is quoted in Argetnina, 1994). These drugs can lead to increased activity of transaminases and to the emergence or strengthening of cholestasis [1, 5].

Thus, for practical health remains the task of finding new, more effective means, is able to accelerate functional in the formation of the liver or to protect the hepatocytes from the damaging effects of hepatotropic viruses and other pathogens.

The objective of the invention is to develop an effective method for correcting cytolytic syndrome. The problem is solved by assigning Corbicula 2 g orally 3 times a day after meals, pre-dissolved in water.

Corbicula - preventive food product (RF patent No. 2219805, IPC A 23 L 1/30)with hepatoprotective and antioxidant effect.

As shown by analysis of the available scientific and patent information, information relating to the use of Corbicula, for the correction of cytolytic syndrome with chronic hepatitis infectious and non-infectious origin not found.

The study included 35 patients aged from 18 to 62 years. In the study group included 20 patients in the control and 15. Patients in both groups are comparable in sex, age, nosological forms and severity of the disease and received a standard basic therapy in the form of diet regime, complex detoxification activities (drinking plenty of fluids, intravenous 5% glucose solution 500 ml or ingestion of interdata, rehydron within 7-10 days). In the group included the patients with chronic hepatitis of different etiology: 20 - with viral hepatitis b and C (57%), 8 with alcoholic liver disease (23%), 4 with non-alcoholic steatohepatitis (11%), 3 - with compensated liver cirrhosis (alcoholic and viral e is eologie) (9%). For the correction of cytolytic syndrome patients from the main group assigned Corbicula 2 g three times a day after meals, pre-dissolved in 50 ml of water prior to normalization of liver enzymes (Alt and AST). Patients of the control group as hepatoprotective therapy received Carsil 2 tablets 3 times a day. Criteria of effectiveness of the drug are: the dynamics of subjective complaints (severity major klinichnih syndromes) and assessment of the General condition of the patient in points, the degree of recovery of liver function according to laboratory (functional liver function tests) and instrumental (ultrasound of the abdominal cavity) studies. Evaluation of the clinical and laboratory data is carried out before and after a course correction cytolytic syndrome. The effectiveness of the study drug is evaluated on the basis of the above criteria according to the following scale: poor - absence of clinical improvement, deterioration, conservation signs of activity of the process; satisfactory clinical improvement, reduction of activity, the preservation of the signs of activity of the process; good - noticeable clinical improvement, disappearance of signs of activity and significant improvement in biochemical parameters.

Data from clinical and laboratory research process is Statisticheskii generally accepted in medicine methods of variation statistics. In all patients before surgery hepatoprotective drugs noted complaints about the feeling of heaviness and re-dull pain in the right hypochondrium in 69% of cases (24 people), often without any irradiation in 14% of cases (4 persons)arising after errors in diet, at least - after negative emotions in 6% of cases (2 people), a feeling of bitterness in the mouth in 71% of cases (25 people), podtashnivaet in 57% of cases (20 people). Objective examination revealed Palmar erythema in 23% of patients (8 persons), subikterichnost sclera in 43% of patients (15 people), mild tenderness in the right hypochondrium, 71% of patients (25 people). Dyspeptic syndrome combined with vegetativnymi disorders: weakness, fatigue, unstable sleep, irritability in 63% of cases (22 people). Hepatomegaly was detected in 25% of cases, splenomegaly is 15%.

Dynamics of the main clinical syndromes in the groups are presented in table 1. As can be seen from the table, after 3 weeks in the study group was significantly compared with the control group also noted the disappearance of weakness, heaviness in the upper abdomen, the disappearance of nausea, appetite improved in 90% of patients (18). 25% of patients (5 people) there was a decrease in the size and density of the liver.

40% (6 persons)
Table 1
Dynamic is and clinical symptoms in patients with hepatitis on the background correction cytolytic syndrome in different ways
Clinical syndromeThe main group (n=20)Control group (n=15)
Before adjusting CorbiculaAfter the correction CorbiculaBefore adjusting the KarsAfter correction of the Kars
Pain in the right hypochondrium:
- dull, aching, long70% (14 persons)5% (1 person)*80% (12 persons)40% (6 persons)
without irradiation10% (2 persons)020% (3 persons)20% (3 persons)
- short-term10% (2 persons)5% (1 person)20% (3 persons)10% (2 persons)
Nausea, belching65% (13 persons)10% (2 people)*70% (11 people),the50% (8 persons)
The feeling of bitterness in the mouth75% (15 persons)15% (3 respondents)*70% (11 persons)40% (6 persons)
Weakness, fatigue90% (18 persons)10% (2 people)*90%(14 persons)40% (6 persons)
Loss of appetite80% (16 persons)10% (2 people)*80% (12 persons)
Hepatomegaly45% (9 persons)25% (5 persons)*40% (6 persons)40% (6 persons)
* - P<0,05 compared with the control group differences authentic

In the study of biochemical parameters in most patients with HG source revealed increased activity of Alat and thymol turbidity tests, symptoms of intrahepatic cholestasis (hyperbilirubinemia, increased activity of betalipoprotein and the activity of Alp (alkaline phosphatase)). As can be seen from table 2, the patients of the main group receiving Corbicula, after 3 weeks, normalization of bilirubin, thymol turbidity tests, GGT, cholesterol. These indicators in the control group tended to decrease, but the rate did not fit. The level of Alt was decreased in both groups, but in the main group, where used Corbicula, after 3 weeks there was normalization of the studied parameters compared with the control group, where the normalization did not occur. Analysis of all these changes gave the basis to assess the results of the correction of cytolytic syndrome as good in 25 patients (71%) and satisfactory in 10 patients (29%).

Table 2
Dynamics of biochemical indices in patients with hepatitis in the background to correct them in different ways
Indicators biochemistry of bloodGroup to correctionGroup after correction
Bilirubin (mol/l)33,3±3,932,6±3,618,5±1,8*25,8±2,2
Alt (ľkat/l)1,4±0,61,5±0,40,9±0,2*1,3±0,2
Thymol turbidity test (ed)5,9±1,05,3±0,93,7±0,5*4,8±1,1
GGT (me/l)71,2±35,568,8±29,555,2±19,5*6,8±20,1
Alkaline phosphatase (me/l)86,2±26,388,9±20,375,7±24,5*85,0±21,5
Cholesterol (mol/l)5,1±0,125,5±0,34,8±0,3*5,3±0,4
The main group (n=20) - correction Corbicula
Control group (n=15) - correction of the Kars
* the degree of reliability of the data differences compared with the control group (P<0,05)

Drug Corbicula was well tolerated by the patients, side effects, its use is not marked.

Example 1. Patient A., 37 years. Hurts hepatitis b and C since 1999, Asked for a consultation with complaints of weakness, weakness, paleness of skin and yellowing of the sclera, and recurrent pain in the right hypochondrium. Blood bilirubin total - 57.5 mmol/l, direct - to 27.0 mmol/l, indirect - to 30.5 mmol/l, the activity of ASAT - of 693, 3 u/l, Alat - 1319 IU/L. Appointed Corbicula order correction syndrome cytolysis within 21 days (2 g, 3 times a day after meals, pre-dissolved in water). When you re-inspection within a week after receiving Corbicula - continued complaints only on rare pressing pain in the right hypochondrium. Paleness of skin and mucous membranes, weakness, yellowing of the sclera disappeared. Blood bilirubin total - 22,0 mmol/l associated - 13 mmol/l, the level of Alat - 35 u/l, AST - 40 IU/l Is within 9 months of follow-up. The condition is not getting worse.

Example 2. Patient B., 46 years old. Sick With hepatitis C about 2 years. Previously used drugs, was taking a course in narcological dispensary. When the treatment complained of nausea, bitter taste in the morning in the mouth, weakness, heaviness in the right poreber is e, epigastric discomfort. On ultrasound hepatomegaly with diffuse changes of a liver and signs of cirrhosis. During examination:

IndicatorsResults studies
The total bilirubin (mol/l) -59,018,0of 17.0
Bilirubin is associated (mol/l)39,025,0to 12.0
Thymol turbidity test (units)854
Alt (units/l)175,093,036
AST (units/l)136,9100,540,2
Alkaline phosphatase (units/l)240,7112,754,0
GGT (units/l)176,990,566,9

The patient was appointed the inventive correction of cytolytic syndrome (reception Corbicula 2 g 3 times a day after meals, pre-dissolved in water). The course of therapy was 56 days. Tolerability was good, without complications. Biochemical parameters and General condition of the patient improved (disappeared nausea, bitter taste in the mouth, periodic Bo is in the right hypochondrium). The patient is on a dynamic outpatient observation. In the autumn of conducted maintenance therapy Corbicula (2 g, 3 times a day for 14 days).

Example 3. Patient A., aged 40. Obese II century, non-alcoholic steatohepatitis. Complained of heaviness in the right hypochondrium, weakness, nausea and a bitter taste in the mouth. When examining activity detected Alat-4N, ASAT-2N, bilirubin increased due to the direct fraction to 43.9 mmol/L. When ultrasound signs of fatty hepatosis. Markers of viral hepatitis negative. After taking Corbicula orally 2 g 3 times a day after meals, pre-dissolved water, within 21 days marks a significant improvement in well-being: disappeared weakness, nausea, bitter taste in the mouth. Biochemical parameters during the control study were within normal limits.

Thus, when the appointment for the correction of cytolytic syndrome drug Corbicula installed its high clinical efficacy in patients with chronic hepatitis of different etiology. Corbicula has good portability, none of the 20 patients treated with the drug at a dose of 2 g 3 times a day after meals, pre-dissolved in water, not noted any side effects and allergic reactions. The proposed correction method allows to effectively work on pathological symptoms Zab the diseases, to neutralize HyperTerminal. He successfully can be used for conservative and outpatient correction cytolytic syndrome broad range of patients with chronic diffuse liver diseases.

Sources of information

1. Aprosyn SG // Klin. the honey. - 1984. No. 9. - P.27-32.

2. Nikitin E.V. Clinical and pathogenetic status of lipid peroxidation and enzymatic antioxidant system in patients with viral hepatitis b: Thesis ... Dr. med. Sciences. - Odessa, 1990. - 278 S.

3. Podymova S.D., Naginsky M. evaluation of the efficacy of Heptral in patients with chronic diffuse liver disease with cholestasis // Clinical medicine. - 1998. No. 10. - P.45-48.

4. The roller N, Smania CENTURIES, Ohrimovich L.M. Clinical pharmacology hepatoprotectors. - Ternopil, 1995. - 272 S.

5. Sorenson S.N. Viral hepatitis. - L., 1987.

6. Stroganov of GI, I.E. science, Nikitin I.G. and other Theoretical and practical aspects of the use of glycyrrhizin // prospects of Clinical gastroenterology, Hepatology. - 2003. No. 1. - P.35-39.

7. Van Rossum THUS, A.G. Vulto, Hop W.Q, Schalm S.W. Glycyrrhizzinn-Induced reduction of ALT in European patient With chronic hepatitis // Am.J.Gastroenterol. - 2001. - Vol.96. No. 8. - P.2432-2437.

8. Yamamura Y. et al. The phamacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbontetrachloride intoxicated rats // Biopharm drag Dispos. - 1997. - Vol.18. - P.717-772.

The method for correcting cytolitic the ski syndrome in chronic hepatitis, including hepatoprotective drug, characterized in that designate Corbicula 2 g 3 times a day after meals, pre-dissolved in 50 ml of water course of 21 days or more prior to normalization of Alt and AST.


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3 dwg, 2 ex, 3 tbl

FIELD: medicine and biopharmacology.

SUBSTANCE: claimed biotransplant contains culture of genetically non-modified mesenchyme stem cells (MSC), including fibroblasts of hair follicule dermal papillae, epithelial cells including ones obtained from hair follicle stem niche. Biotransplant is used in intradermal administration. Method for alopecia treatment includes intradermal administration of biotransplant containing from 10 to 100 millions cells to patient, in procedure room by micropapulic method. Biotransplant is administered in physiological solution with concentration from 1 to 10 millions per 1 ml. Total transplant amount is 1-10 millions depending on lesion area and type of alopecia.

EFFECT: method for alopecia treatment with high reproducibility.

12 cl