A method of treating diseases characterized by autoimmune aggression

 

(57) Abstract:

The invention relates to medicine, in particular to the treatment of diseases characterized by autoimmune aggression. To do this, depending on the nature and severity of the disease the patient is administered parenterally sodium salt of DNA in a dose of 0.5 to-4.0 mg/kg once in four days, combined with the introduction of the human alpha-fetoprotein in one dose of 500-5000 IU/kg once or twice a day, every day. The treatment is 14-30 days. Alpha-fetoprotein is injected subcutaneously, intramuscularly or intravenously, and DNA injected intramuscularly. While the introduction of drugs can be done combined in the same syringe. The method allows to increase the effectiveness of the treatment of diseases characterized by autoimmune aggression, lengthen the average term remission. 1 C. p. F.-ly.

The invention relates to medicine and can be used to treat diseases characterized by autoimmune aggression.

It is known that the main pathogenetic mechanisms in the development of a number of diseases are autoimmune processes. So, for example, at first glance, different clinical course of the disease, such as diabetes, respecification autoimmune aggression.

It is known that the treatment of diseases associated with immunological disorders by type of autoimmune reactions is the purpose of adjuvant therapy, aimed at the suppression of allergic and autoimmune processes. The essence of therapy is the purpose of numerous drugs aimed at blocking gistaminopodobnykh agents, immunoglobulins, and prescription of pharmacological agents - of immunosuppressants and corticosteroids. As a rule, such regimens to achieve temporary unstable remission, known as immunosuppressants and corticosteroids cause the development of tolerance and do not have selective effects on certain parts of cellular and humoral immunity.

Known, for example, a method of treating diabetes mellitus I-St and II-nd type, characterized by autoimmune aggression, consisting in the use of complex medicines, such as insulin or Zagorodnyaya drugs, kokarboksilaza, lipoic acid, sodium bicarbonate, antihyperlipidemics drugs [1].

Use in complex therapy of diabetes insulinotherapy drugs, antidiabetic substances and likemichael therapy, which in most cases can not effectively protect the patient from developing neurological, urological, vascular and other complications.

There is a method of treatment of adhesive disease of the abdominal cavity, consisting in the use of hyaluronidase (lidz), ronidase, vitreous body, pyrogenal and atsemina [2]. However, the use of these drugs in the treatment of adhesive disease is ineffective, and the resulting effect is temporary, as preparations containing hyaluronidase, can only temporarily reduce the viscosity of hyaluronic acid. In case formed adhesions these medicinal substances are generally not effective.

There is a method of treatment of adhesive disease of the abdominal cavity, which consists in the surgical excision of adhesions [3]. However, any surgery on the abdomen, even when removing adhesions, entails repeated, and even even more intensive development process.

There is a method of treatment of ulcerative colitis [4], including the use of desensitizing means (diphenhydramine, pipolphen and others), vitamins (A, E, C, K, group B), bacteriostatic drugs (salazopiridazin, salofalk and others), cor is agent ulcerative colitis (autoimmune aggression) therapy listed drugs are generally ineffective. The further course of events in the disease ends surgery (colectomy, coloproctectomy) with the imposition of an ileostomy, which leads the patient to profound disability.

There is a method of treatment of liver cirrhosis using liver funds (zelibor, legalon, kateryn, bilignin, Essentiale, and others) [5]. These drugs have a pronounced hepatoprotective effect, but only if the anatomical preservation of hepatocytes. The main link in the development of liver cirrhosis is an autoimmune component to the destruction of hepatitas and replacement of liver tissue with scar tissue. When formed scar degeneration of the liver of these drugs, even in combination with other pathogenetic means not able to affect the reparative regeneration hepatocites, and can only to a greater or lesser extent, to replace the remaining hepatocytes from aggression.

There is a method of treating myasthenia gravis, consisting in the use of drugs cholinesterase blockers (neostigmine, galantamine, kalymin other) [6].

However, the effect of anticholinesterase drugs is limited by their pharmacodynamics. If deep is terazol therapy and, as a consequence, the different nature of complications. Thus, pathogenetic therapy of anticholinesterase drugs has no radicalism and temporary, help, symptomatic character.

There is a method of treatment of myocardial infarction, postinfarction koronarokardioskleroze and thrombocytopenia lesions of the great vessels, consisting in the use of anticoagulants and fibrinolytic drugs [7]. However, when therapy with anticoagulants there is a risk of haemorrhagic complications, and when formed clots anticoagulant therapy is ineffective. When the formation of scar tissue anticoagulants and fibrinolitiki have no therapeutic value.

Thus, known methods of treatment of diseases characterized by autoimmune aggression, have low efficiency and does not provide access to the persistent long-term remission.

The most closest to the claimed method of the prototype is a method of treating diseases characterized by autoimmune aggression, using nucleinate sodium [8]. Nukleinat sodium is a sodium salt of the nucleic acid obtained G3 weeks. Repeat the treatment two or three times a year. The method reduces the time of treatment of immunodeficiency States, but does not provide output to persistent long-term remission.

The disadvantages of the prototype are insufficient effectiveness of the method and short remission (9 months).

An object of the invention is to increase the efficiency of the method and lengthening the time of remission.

This object is achieved by the proposed method lies in the following.

The patient, depending on the nature and severity of the disease, parenterally administered sodium salt of DNA obtained from sturgeon milk, at a dose of 0.5-4 mg/kg weight of the patient once in four days course 14-30 days in combination with the introduction of the human alpha - fetoprotein (AFP) in a dose of 500-5000 IU/kg once or twice per day daily rate 14-30 days. The introduction of drugs carried out comprehensively in the same syringe. While AFP is administered subcutaneously, intramuscularly or intravenously, and DNA injected intramuscularly once in 4 days, because DNA is eliminated from the body on the 4th day. When used together (in same syringe) DNA mixed with AFP and injected intramuscularly once in 4 days.

Mol. m - 300-500 kDa

Protein - 0,7 - 1,5%

The RNA content-0.5 to 2.0%

The content of polysaccharides is not more than 2%

Hyperchromic effect - 37 - 46%

Available in 0.5 -5%-aqueous solution of Na-DNA in 0.1-0.9 per cent NaCl solution, packaged in vials or ampoules of 1, 2 and 5 ml.

AFP is a protein whose properties are well studied. It consists of one polypeptide subunit. Its molecular weight is 74 KD. Get AFP from abortive human material (natural AFP) or from ospowiki in the embryonic cells of the human lung (recombinant AFP) [10].

AFP does not cause allergies and other side effects.

AFP is produced in the form of a lyophilisate (white porous mass), packaged in ampoules or vials with a volume of 1 cm³dissolves easily in water or 0.9% sodium chloride solution. In one vial (vial) contains 75 micrograms AFP.

The proposed method was treated 50 patients with diseases: diabetes, adhesive disease, ulcerative colitis, myasthenia gravis, myocardial infarction, postinfarction koronarokardioskleroze, thrombocytopenia lesions of the great vessels, liver cirrhosis. Positive clinical EF who is 29 months.

Specific contraindications or side effects were noted. In most cases, to obtain a clear clinical effect was only one course of treatment.

theoretical basis of obtaining a clear clinical effect in a complex DNA-AFP is the following.

It is known that entered into the organism's DNA selectively accumulate in areas of damaged cells and tissues of various etiology, acting as endogenous material for regeneration. Its constituent nitrogen compounds (adenine, guanine) are the structural basis for the low-molecular biologically active coenzymes and cofactors, limiting biological processes in all organs and tissues of the body. Regeneration of cells and tissues that are in the extreme metabolic conditions, through the splitting of microsomal enzymes DNA segments and use them to restore the damage.

It is also known that the damaged cells and tissues, entering a phase of reparative regeneration, embryonnaires and ectopiceski begin to distinguish fetal antigens, in particular AFP, to protect their own regenerating CL is specificeski immunity and regulate immunological reactions in the body, thus providing favorable conditions for reparative regeneration of damaged cells and tissues.

The integrated use of DNA in conjunction with the AFP allows you to get a new synergetic effect, due to the immunosuppressive properties of the first and stimulating the regeneration properties of the second drug.

The main significant difference between the proposed method in comparison with the prototype is the integrated use of DNA in conjunction with AFP in experimentally selected, the optimal mode, which allows to improve the clinical effect of treatment and to extend periods of remission. Empirically when using drugs in the clinic, it was found that the use of AFP in a dose of less than 500 IU/kg of body weight of the patient, and DNA in a dose of less than 0.5 mg/kg does not provide significant clinical effect, and the use of drugs in doses exceeding 5000 IU/kg for AFP and 4 mg/kg for DNA leads to an unjustified increase of consumption of drugs without a corresponding strengthening of therapeutic effect.

Know the use of DNA for the treatment of malignant tumors [12], where the antitumor activity of DNA caused by the stimulation of specific immunodeficiency, the cumaceans, and as vectors for targeted delivery of cytotoxic drugs in cancer cells [13,14].

The proposed technical solution, the native DNA is used in combination with AFP new functionality to obtain a new non-obvious clinical effect. Sharing DNA and AFP provides obtaining complementary and mutually reinforcing effect, and allows you to achieve restoration of impaired immunity and repair of damaged cells and tissues.

In connection with what is known in the patent and scientific and technical sources of a similar method of treatment of diseases characterized by autoimmune aggression, not detected, it is possible to draw a conclusion on the conformity of the proposed technical solution the criteria of "novelty and inventive step".

The invention is illustrated by the following specific examples of the treatment of diseases characterized by autoimmune aggression.

Example 1.

Patient I. , 37 years old, diagnosis: diabetes mellitus, diabetic steatosis, was hospitalized with 13.10.95 on 17.11.95, Kurgan oblast clinical hospital.

Upon receipt of a complaint on the floor who urinoma, 4 units of regular insulin 1 time per day.

With 15.10.95, started therapy by the claimed method: the patient was administered together (in same syringe) 0.5 mg/kg Na-DNA and 500 IU/kg AFP intramuscularly 1 time in 4 days course of 6 injections. To 3 injections fasting blood sugar levels and sugar curves is normalized. Started a gradual reduction in dose of oral hypoglycemic drugs and insulin, and by the end of the second week of treatment, these drugs have been cancelled. Later, all the results of surveys on the level of blood sugar within the normal range in urine - sugar is not detected, the phenomenon hepatosis, polydispersity and polyuria disappeared. The duration of remission 32 months.

Example 2.

Patient K. , 37 years old, diagnosis: diabetes mellitus, diabetic steatosis, was hospitalized with 12.10.95 on 12.11.95, Kurgan oblast clinical hospital.

On admission, the blood sugar level - 13,8-21,09 mmol.

Gets Humulin 28% 1 time per day. With 14.10.95, started therapy by the claimed method: the patient was injected Na-DNA in a dose of 2 mg/kg intramuscularly 1 time in 4 days course 7 injections and AFP at a dose of 1000 IU/kg intravenously 1 time per day every day for 28 days. In the first week of the blood sugar level of normalize the exchange latest by the 12th day of treatment. Later, all the results of surveys on the level of blood sugar within the normal range in urine - sugar is not detected, adequate diuresis. The duration of remission 29 months.

Example 3.

The patient Was, 31 years old, diagnosis: male, was hospitalized with 11.09.95 on 13.10.95, Kurgan oblast clinical hospital.

In 1994 after appendectomy - kriz bulbar disorders. The diagnosis of myasthenia gravis was confirmed by biografia, proteinemia samples positive. The patient received 2 courses of inpatient treatment (antilinearity drugs, xenofobia) without effect.

With 13.09.95, started therapy by the claimed method: the patient was administered together (in same syringe) 4 mg/kg Na-DNA and 5000 IU/kg AFP intramuscularly 1 time in 4 days course of 7 injections. In the result of complaints of fatigue no, proteinemia sample is negative, electromyography was normal. Need to use anticholinesterase no funds. Atony of the bowel and bladder no. Remission - 19 months.

Example 4.

Patient S. , aged 65, diagnosed with ulcerative colitis, was hospitalized with 18.10.95 on 22.11.95, Kurgan oblast clinical hospital.

I the course of 3 injections and AFP at a dose of 3000 IU/kg intravenously 2 times a day every day for 12 days. In the course of treatment was subjective and objective improvement. Blood within the physiological norm. Remission - 26 months.

Example 5.

Patient L., aged 45, diagnosed with adhesive disease of the abdominal cavity, enrolled in proctological Department of Kurgan oblast clinical hospital 16.10.95.

With 17.10.95, started therapy by the claimed method: the patient was injected Na-DNA in a dose of 2 mg/kg intramuscularly 1 time in 4 days course of 5 injections and AFP at a dose of 1000 IU/kg intravenously daily for 20 days. By the end of treatment disappeared asymmetry of the abdomen, heaviness and pain in the liver, disappeared nagging pains in mesogastric and right iliac region, the chair was normalized disappeared fetid odor in the urine, the stool, the temperature is normalized. After treatment, the patient resorbed postoperative scars and formed postoperative hernia. 15.11.95, patient surgery: gryzhesechenie postoperative hernia repair with grafting soft tissue. After entering the peritoneal cavity and upon examination of organs and tissues of abdominal adhesions is not detected, the color of the lobes and the size is within normal limits. Made gryzhesechenie with plastics, the layer seams on posleoperatsi place of residence. Remission - 34 months.

Example 6.

Patient N. , 55 years old, diagnosis: extensive myocardial infarction posterior wall (cardiogenic shock), was hospitalized with 04.03.95 on 07.04.95, Kurgan oblast clinical hospital.

The clinic performed emergency resuscitation measures and started therapy by the claimed method: the patient was injected Na-DNA in a dose of 2 mg/kg intramuscularly 1 time in 4 day course 8 injection and AFP at a dose of 4000 IU/kg intravenously daily for 30 days. During the treatment, General condition of the patient improved. Registered the decrease of the area of infarction, until complete resorption with restoration of blood circulation in the infarction zone, restoration of function of the cardiac muscle and metabolism. The patient is in satisfactory condition prescribed by place of residence. Remission - 36 months.

Example 7.

The patient And. 52 years old, diagnosed with cirrhosis of the liver, was hospitalized with 03.01.95 on 05.03.95, From history: in 1994, he suffered a viral hepatitis b, suffered from chronic alcoholism. A serious condition, revealed gross violations protein and carbohydrate metabolism, bilirubinuria, high creatinine and urea in the blood. The liver is flat, hilly, stands of p. the ATA therapy by the claimed method: introduced the Na-DNA in a dose of 1 mg/kg 1 time in 4 days the course of 10 injections and AFP at a dose of 4500 IU/kg intravenously, daily for 30 days. In the course of treatment, there was a positive trend, implying the decrease in liver size, disappearance of ascites in the abdominal cavity, the normalization of protein and carbohydrate metabolism. Remission-14 months.

The use of the present invention will improve the effectiveness of the treatment of diseases characterized by autoimmune aggression and to increase the duration of remission.

Sources of information

1. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. I, sec. 649-663; 4.11, S. 10, 45, 103-111, 113, 137.

2. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. II, sec. 71-72, 172, 181, 202.

3. Surgical diseases/ Ed.: M. I. Kuzin, O. S. Sirob, M. A. Chistov and others ; Ed. by M. I. Cousin.- M.: Medicine, 1986.-704 C.

4. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. I, sec. 276-280, Ch. II S. 310.

5. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. I, sec. 514-515.

6. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. I, Sec. 244-254.

7. Mashkovsky M. D. Medicines. M.: Medicine, 1994.- Ch. II, sec. 79-85, 86-90.

8. Zemskov, A. M., Perederiy Century BC, Zemskov C. M. and other Secondary immunodeficiency States and their correction is x2">

10. RF patent N 2100031, class A 61 K 38/00, publ. 27.12.97, bull. N 36.

11. Polezhaev L. C. Loss and restoration of regenerative capacity of tissues and organs in animals.- M.: Nauka, 1968.-C. 269-274.

12. RF patent N 20074972 class. A 61 K 31/70, publ. 30.12.93, bull. N 47-48.

13. U.S. patent N 4966753, class A 61 K 39/00, publ. 30.10.90.

14. RF patent N 2026687, class A 61 K 38/00, publ. 20.01.95, bull. N 2.

1. A method of treating diseases characterized by autoimmune aggression, by administering drugs, characterized in that the patient parenterally administered sodium salt of DNA obtained from sturgeon milk, at a dose of 0.5-4.0 mg/kg of body weight of the patient once in four days, combined with the introduction of the human alpha-fetoprotein in one dose of 500-5000 IU/kg once or twice daily, the rate of 14-30 days.

2. The method according to p. 1, characterized in that the introduction of DNA and alpha-fetoprotein exercise combined in the same syringe.