The method of treatment of viral hepatitis

 

(57) Abstract:

The invention relates to medicine, in particular to infectious immunology, and is aimed at improving the treatment of viral hepatitis. This goal is achieved by the fact that etiotropic therapy cytokine and antiviral drugs is the infusion of synthetic polypeptide - bis-glutathione related to a new class of drugs - tipatina. The latter is introduced into a specific mode in relation to etiotropic therapy. The method allows to reduce the duration of treatment, to reduce the frequency and severity of side effects. 2 C.p. f-crystals, 2 ill., table 1.

The invention relates to medicine and can be used for the treatment of hepatitis caused by viruses.

Known drugs for the treatment of viral hepatitis, such as interferon, derivatives of nucleosides and nucleotide analogues of pyrophosphate.

The closest analogue of the claimed method of treatment of viral hepatitis is therapy with cytokines, such as interferon and nucleoside analogues, in particular lamivudine, according to the scheme: an 8 - week monotherapy with lamivudine 100 mg / day, then 16 weeks - combination preparato the tients with chronic Hepatitis infection In - J. Hepatology 1998, 28 (Suppl. 1):43.).

However, the introduction of drugs in accordance with the scheme throughout the course of treatment is accompanied by adverse effects. For example, 86.5% of the patients had General malaise and fatigue, 93.4% as headache, almost half (44.5 percent) suffer from pain in the muscles, 42% about nausea and vomiting. Effective this therapy only for 24% of patients. Thus, 4.5 months of treatment are accompanied by a variety of unpleasant sensations, and the only cure is achieved in 24% of treated.

The aim of the invention is to increase the effectiveness of treatment, reduction of duration of therapy, reduce the frequency and severity of side effects.

This goal is achieved by the fact that patients injected bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt or products that contain this compound, at a dose of 10-30 mg intramuscularly for 5-7 days before, during, and 5-7 days after etiotropic therapy within 30-90 days.

As the antiviral drug use reverse transcriptase inhibitors, protease inhibitors or analogs of pyrophosphate.

In particular, use-interferon at a dose of 1 - 3 million ME a day within 30 - 90 days, and in the quality of the cleats 30 - 60 days or roscamat at a dose of 0.4 - 5 mg per day for 5-15 days.

Bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt (patent of the Russian Federation 2089179 dated 14.12.1995, has a differentiated effect on liver cells and the immune system: initiates apoptosis of cells containing the virus, while also stimulating the proliferation and differentiation of unmodified cells of the immune system and the liver.

According to the invention bis-(gamma-L-glutamyl)-L-cysteinyl - bis-glycine disodium salt begin to enter for 5 to 7 days prior to the application of cytokines and antiviral drugs and stopped after 5 to 7 days after in doses of 10-30 mg / day intramuscularly within 30-90 days. As a cytokine used dosage form of interferon as an antiviral drug use reverse transcriptase inhibitors, such as lamivudine at a dose of 300 and 900 mg per day, lasting 30-60 days; protease inhibitors, such as Crixivan, at a dose of 0.5-2 mg per day rate 30-60 days; or analogues of pyrophosphate.

In particular, use-interferon at a dose of 1 - 3 million ME in the day for 30-90 days, and as antiviral drugs lamivudine at a dose of 300 - 900 mg per day for 30 - 60 days, clxiv the Leno content of alanine aminotransferase (Alt) blood of the patient before and after treatment; in Fig. 2 - change in antibody titer to hepatitis C during treatment.

The invention is illustrated in the following examples:

Example 1.

Patient N., 39 years later, in April 1999 with a diagnosis of hepatitis C, chronic, stage of virus replication" asked for help with complaints about General weakness, decreased performance, a feeling of heaviness in the liver after errors in diet.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pale, no rash. In the right iliac region - scar after appendectomy. Abdomen palpation soft, painless. The liver is enlarged, stands out from the edge of a costal arch on 1 see the edge of the liver palpation soft, smooth, rounded. There was a slight swelling of legs. In the cardio-pulmonary system revealed no pathology. The laboratory examination of the blood showed increased level of alanine aminotransferase (Alat) to 44.9 u/l, asparaginases (AST) up to 36.7 u/l

The patient complaints, liver enlargement in size, swelling, increasing levels of Alat indicate liver damage. Detection of blood RNA virus hepatitis "C" indicates circulation in organics-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt intramuscularly, 20 mg - 100 days.

-interferon is administered intravenously at a dose of 3 million ME in the days to 90 days.

lamivudine is an oral, 300 mg/day to 90 days, from 6 th to 95th.

Selective tissue specialization allows us to consider Alat marker enzyme for liver, therefore, to control the functional activity of the body and the adequacy of therapy has detected a change in quantity (Fig.1). By the end of 9 weeks treatment level B becomes normal, demonstrating the restoration of the functional activity of the liver, stopping the destructive effect of the virus on the cells.

During the treatment, the patient noted increased efficiency, increased duration of sleep, improving complexion. Stopped worrying pain in the liver. Any unpleasant sensations are not notes.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pink, no rash. Abdomen palpation soft, painless. The liver does not protrude from the edge of the costal arch. The edge of the liver is not palpated. No edema. In the cardio-pulmonary system without pathology. In the blood - normalization of a level of Alat, the disappearance of the RNA virus hepatitis "C", which indicates the vessel is in the blood: Alat 23,9; AST 25,1, RNA virus hepatitis "C" was not found. Thus, as a result of the treatment is stable remission.

Example 2.

The patient Was 17 years with a diagnosis of hepatitis C, chronic, stage of virus replication", asked for a consultation with complaints of General weakness, insomnia, fatigue, irritability.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pale, no rash. Abdomen palpation soft, painful in the right pogrebennoi area. The liver stands out from the edge of the rib arc 1.5 see no Edema.

In a laboratory study of biochemical parameters of blood within normal values, detected virus RNA of hepatitis "C". The titer of antibody to hepatitis C is 2,054, exceeding the rate of 6.8 times.

The patient revealed astheno-neurotic and astheno-vegetative syndrome, which, combined with tenderness and enlargement of the liver, are manifestations of its dysfunction.

Detection of RNA virus hepatitis "C" refers to the circulation in the body of the virus as the cause of liver damage. The titer of antibodies to hepatitis C confirmed viral etiology since the Complex of bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt with inosine - intramuscular injection of 30 mg to 90 days.

-interferon is administered intravenously at a dose of ME 1 million per day - 90 days

Crixivan - oral, 2 mg/day to 80 days, from the 6th to the 85th.

During treatment, the patient noted increased efficiency, increased duration of sleep, stopped worrying pain in the liver. According to others, improved complexion. Any unpleasant reactions during the administration of drugs notes.

By the end of treatment (Fig. 2) there is a decrease in antibody titer.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pink, no rash. Abdomen palpation soft, painless. The liver does not protrude from the edge of the costal arch. The edge of the liver is not palpated. No edema. In the cardio-pulmonary system without pathology. In the blood - normal amount of Alat, the disappearance of the RNA virus hepatitis "C" which refers to the clinical and laboratory recovery.

At follow-up one month after completion of treatment in the blood - normal levels of enzymes, RNA virus hepatitis "C" was not found.

Example 3.

Patient S. , 32 years old, came for consultation in June 1999 with the previously stalnosti, pain in the liver.

Examination: the right physique, icteric sclera, skin and visible mucous membranes pale, no rash. Abdomen palpation soft, painless. The liver is enlarged, appears from under the edge of the costal arch 1 cm, painful on palpation. The edge of the liver is soft, painful, rounded. No edema. In the cardio-pulmonary system revealed no pathology. The laboratory examination of the blood showed increased level Alt to 50.4 u/l, ASAT to 33.7 u/L. the Level of HBs antigen increased 12.4 times.

The patient complaints, liver enlargement in size, raising the level of Alat indicate liver damage. In the blood DNA of a virus of hepatitis b, which indicates circulation in the body of the virus, which is the etiological factor of liver damage.

Assigned treatment:

bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt intramuscular injection, 20 mg - 90 days.

-interferon is administered intravenously at a dose of 3 million ME in day - 90 days

lamivudine is an oral, 600 mg/day for 70 days.

During the treatment, the patient noted improvement with health normalizing the color of eyes, complexion improvement, ceased to disturb pains in the liver. Kalogria, the sclera is a common color, skin and visible mucous membranes pink, no rash. Abdomen palpation soft, painless. The liver does not protrude from the edge of the costal arch. The edge of the liver is not palpated. No edema. In the cardio-pulmonary system without pathology. In the blood - normalization of a level of Alat, the disappearance of the DNA of the virus of hepatitis b, the decrease in antibody titer in 4.4 times that speaks of clinical and laboratory recovery.

At follow-up one month after the course ends in blood: Alat 21,2; AST 20,1, DNA virus of hepatitis b is not detected, which is evidence of stable remission.

Example 4.

Patient L., aged 27, in March 1999 with a diagnosis of hepatitis C, chronic, stage of virus replication" asked for help with complaints about General weakness, decreased performance, a feeling of heaviness in the liver after errors in diet.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pale, no rash. Abdomen palpation soft, painless. The liver is enlarged, stands out from the edge of a costal arch on 2 see the edge of the liver palpation soft, smooth, rounded. In the cardio-pulmonary system is s (Alat) to 84,9 u/l, asparaginases (AST) to 66.7 IU/L.

The patient complaints, liver enlargement in size, raising the level of Alt and AST indicates liver damage. Detection of blood RNA virus hepatitis "C" refers to the circulation in the body of the virus, which is the etiological factor of liver damage.

Assigned treatment:

bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt intramuscular injection, 10 mg - 100 days, once a day.

-interferon is administered intravenously at a dose of 3 million ME in day - 90 days

lamivudine is an oral, 300 mg/day to 90 days, from 6 th to 95th.

By the end of 7 weeks of treatment the level of Alt and AST was normal, as demonstrated by the restoration of the functional activity of the liver, stopping the destructive effect of the virus on the cells.

During the treatment, the patient noted increased efficiency, increased sleep, improve complexion. Stopped worrying pain in the liver. Any unpleasant sensations are not notes.

On examination, the right body, sclera, normal color of the skin and visible mucous membranes pink, no rash. Abdomen palpation soft, painless. The liver does not protrude from the edge of the rib d and AST, the disappearance of the RNA virus hepatitis "C" which refers to the clinical and laboratory recovery.

At follow-up one month after the course ends in blood: Alat 24,8; AST 23,0, RNA virus hepatitis "C" is not found. Thus, as a result of the treatment is stable remission.

Treatment of viral hepatitis claimed method is not obvious for a wide range of specialists. Traditionally for the treatment of viral hepatitis decision to appoint cytokines, such as interferon as monotherapy or in combination with antiviral agents such as lamivudine. It is believed that interferon blocks replication of RNA virus by binding to specific receptors on the cell surface, lamivudine also inhibits the synthesis of RNA virus, once inside the infected cell.

In the present method the connection is used, which implements a different mechanism of action on hepatitis, and it initiates the destruction of virus-containing cells, and ensures the availability of virus action of specific drugs.

This effect in the treatment of viral hepatitis never previously has not been used. Obvious is also acetonitriles the term "method".

The total reduction course doses of cytokines (interferon and antiviral drugs with high toxicity, in combination with the hepatoprotective effect of bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt leads to decrease the frequency and severity of side effects (see table. ).

This was revealed during long-term clinical and experimental observations, and allows the use specified in the proposed scheme is optimal and sufficient doses of all drugs to be effective against viruses. You can be fully confident that the inventive method will be widely used in practical medicine in the near future, because it is based on the use of manufactured drugs and can be carried out directly by the description of the present invention. The inventive method is highly efficient and available for application to a wide range of Hepatology and medical clinicians experienced in the treatment of viral hepatitis.

The claimed invention has important socio-economic importance, as largely solves the problem of growth of liver disease of viral etiology and reduce serarately, characterized in that the patients receive bis-(gamma-L-glutamyl)-L-cysteinyl-bis-glycine disodium salt, or products that contain this compound, at a dose of 10 to 30 mg intramuscularly for 5 to 7 days before, during and 5 to 7 days after etiotropic therapy within 30 - 90 days.

2. The method according to p. 1, characterized in that as the use of cytokine dosage form of interferon as an antiviral drug use reverse transcriptase inhibitors, protease inhibitors, or analogs of pyrophosphate.

3. The method according to PP.1 and 2, characterized in that use-interferon at a dose of 1 - 3 million IU per day for 30 - 90 days, and as antiviral drugs lamivudine at a dose of 300 - 900 mg per day for 30 - 60 days, Crixivan dose of 0.5 - 2 mg per day 30 to 60 days or roscamat at a dose of 0.4 - 5 mg per day for 5 to 15 days.

 

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