RU2609252C1 - Method for treating viral hepatitis or liver cirrhosis with "alloplant" biomaterial - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: injection introduction of dispersed "Alloplant" biomaterial, dissolved in physiological solution in ratio 30-50 mg of biomaterial per 4.0-12 ml of physiological solution, is performed in dose 0.5-1.0 ml of solution per 1 injection. Treatment is carried out in sessions 8-10 in number per a course. The following prescriptions of points are alternated from session to session: the first session - paired points on posterior surface of trunk on the right and on the left of posterior-medial meridian - V18 Ganshu, V19 Danshu, V47Hunmen, V48 Yanggang, V49Yishe, and points on posterior-medial meridian - T8 Jin Suo, T9 Zhiyang; the second session - points on the anterior surface of trunk on the right of anterior-medial meridian - F13 Zhangmen, F14 Qimen, VB24 Riyue, VB25 Jingmen, RP19 Fuai and points on anterior-medial meridian - J5 Shimen, J12 Jungwan, J14 Tanjung, and so on with repetition after each session. Injections are realised with interval between sessions from 1 to 7 days and course duration from 2 to 4 weeks. Treatment is performed at the background of basic therapy.

EFFECT: method makes it possible to increase treatment efficiency, which is achieved due to introduction of Alloplant into biologically active points in claimed sequence.

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Description

The invention relates to medicine, in particular to reflexology, hepatology and can be used to treat acute and chronic viral hepatitis or cirrhosis of the liver.

Viral hepatitis is a serious medical and social problem. According to WHO, 1/3 of the world's population is a carrier of various types of hepatotropic viruses. Currently, about 2 billion people around the globe are infected with viral hepatitis; in 300-400 million people, the infection proceeds in a chronic form. At the same time, 25% of them die every year from cirrhosis of the liver and hepatocellular carcinoma (Shakhgildyan IV, Mikhailov MI, Onishchenko GG “Parenteral viral hepatitis (epidemiology, diagnosis, prevention”, M .: FGOU VUNMTS Roszdrav , 2003. - 384 pp.) Thus, the development of new and effective methods of treating this pathology, along with the prevention of complications, seems to be very relevant.

According to modern concepts, the main factor determining the processes of liver damage and elimination of the virus is the body’s immune response (Druzhinin A.V., Anikushina A.K., Sotnikova N.Yu. “Features of the immune response of patients with HBV infection depending on the course of the disease ", Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2002, T. XII, - No. 1. - Appendix No. 16. - p. 25). Currently, many methods of pathogenetic therapy are proposed, including the use of immunostimulants and immunomodulators (ribomunyl, prodigiosan, pyrogenal, myelopid, splenin, thymalin, T-activin, derinat, half-dan, immunal, various interferons - viferon, anaferon, etc.). Disadvantages - due to the fact that most of the above drugs are high molecular weight substances of animal, microbial, plant origin of varying degrees of purification, there is a great risk of allergic reactions and the development of autoimmune or mediated immune systems disorders. Thus, according to both domestic and foreign researchers, the use of immunostimulants can cause increased lysis of both infected and healthy hepatocytes, that is, a pronounced immune response activates the immune mechanisms of liver damage (Rare GR, Gerlach TJ, Diepoldier N.M. et al ., "Roleofthespecific T-cellresponseforclearanceandcontrolofhepatitis C virus.", J. ViralHepatit, - 1999. Vol. 6. - Suppl 1. - P. 36-40).

Known methods of basic therapy, including the normalization of the gastrointestinal tract, the correction of metabolic disorders and the reduction of hepatocytolysis (diet No. 5 according to Pevzner, regimen, treatment of concomitant diseases of the digestive system and other organs and systems, the use of hepatoprotectors, vitamins, antispasmodics, enzyme preparations, enterosorbents , detoxification and other means (Grigoriev P.Ya., Yakovenko EP “Diagnosis and treatment of chronic hepatitis and cirrhosis of the liver.” Soviet medicine, 1985, N 12, S. 61-67).

However, basic therapy is not effective enough and is often accompanied by a chronic process with an outcome in liver cirrhosis.

There is a method of treating cirrhosis of the liver by means of intraoperative injection into the liver tissue of dispersed Alloplant biomaterial (RF Patent No. 2189257, IPC A61L 27/00, published on 09/20/2002, Alloplant biomaterial for regenerative surgery). The specified biomaterial has extremely low antigenic properties and provides selective tissue growth at the implantation site without rejection and scarring. The known method stimulates the regeneration of liver tissue with the restoration of its structure and volume. The disadvantage of this method is the invasiveness of the intervention, the high cost and inaccessibility, due to the need for operating and trained personnel.

A known method of treating toxic hepatitis and cirrhosis of the liver by endoscopic cannulation of the umbilical vein with dispersed Alloplant biomaterial (RF Patent No. 2205647, IPC A61K 35/32, publ. 06/10/2003). The method allows, thanks to the known properties of the Alloplant biomaterial, to stimulate the regeneration of hepatocytes. But just like the previous one, it is traumatic and difficult to implement.

Closest to the proposed and taken as a prototype is a method of treating various diseases by means of acupuncture administration of Alloplant biomaterial (RF Patent No. 2238076, IPC A61H 39/08, published on 20.10.2004). According to the invention, dispersed Alloplant biomaterial in an amount of 10-100 mg is diluted in 5-15 ml of physiological saline and injected into biologically active points with the aim of their long-term stimulation and prolongation of the effect. The disadvantages of the method are the complexity of acupuncture diagnostics, accessible only to narrow specialists, and the lack of an optimal prescription of points, which makes it impossible to use the known method by doctors who do not know the methods of reflexology.

The objective of the invention is to develop an effective and affordable method for the treatment of viral hepatitis or cirrhosis.

The technical result is to increase the effectiveness of treatment due to the correction of the systemic immune response.

The problem is solved, and the technical result is achieved by the method of treating viral hepatitis or cirrhosis of the liver by injection of dispersed Alloplant biomaterial, diluted in physiological saline in a ratio of 30-50 mg of biomaterial per 4.0-12 ml of saline, to biologically active points, which is carried out by sessions in the amount of 8-10 per course, alternating from session to session of the following point recipes: the first session is paired points on the back of the body to the right and left of the rear midpoints meridian - V18 Gan Shu, V19 Dan Shu, V47 Hun Men, V48 Yang Gang, V49 Yi She and points on the posterior median meridian - T8 Jin So, T9 Zhi Yan, the second session - points on the front surface of the body to the right of the mediocred meridian - F13 Zhang Men, F14 Qi Men, VB24 Zhi Yue, VB25 Jing Men, RP19 Fu Ai and points on the anteromedian meridian - J5 Shi Men, J12 Zhong Wan, J14 Tan Zhong, and so on with repetition through each session, with injections being carried out at intervals between sessions from 1 to 7 days and the duration of the course from 2 to 4 weeks, 0.5-1.0 ml of solution per 1 injection, and treatment e carried out against the background of basic therapy.

The achievement of the technical result is due to the following.

The possibility of restoring all the structural elements of the liver parenchyma with its cirrhotic lesion by local administration of dispersed Alloplant biomaterial is known. This is provided by stimulation of the activity of liver macrophages, which is a key factor in liver regeneration and involution of connective tissue in cirrhosis (L. Musina, “Cirrhosis of the liver and its correction using Alloplant biomaterial.” - Orenburg, 1999 (cand.)). The general immunostimulatory activity of acupuncture is known, as well as the high concentration and special morphometric characteristics of macrophages (CD68), T-helpers (CD4), T-suppressors (CD45R) in the projection of the acupuncture point and outside it (Guryanova EA "Morphofunctional aspects of the influence of acupuncture on the interaction of neurotransmitters in the structures of the organs of immunogenesis and skin ”, Cheboksary 2011, doct.). There are known hepatotropic, aimed at the hepatobiliary system, clinical effects of stimulation of the points of the meridians of the liver, gall bladder, spleen, anteroposterior and posterior median meridian (AM Ovechkin. "Fundamentals of Zhenju Therapy", Saransk, ed. Golos, 1991; I. Z. Samosyuk, VP Lysenyuk. “Acupuncture”, M .: Ast-Press book, 2004).

The authors of the proposed invention revealed the possibility of indirect activation of a monocyte-macrophage link, elimination of damaging agents and regeneration of hepatocytes in the liver parenchyma with acupuncture administration of dispersed Alloplant biomaterial. To do this, experimentally, using immunological control methods, a set of biologically active points for acupuncture was found that are optimal for the treatment of viral hepatitis or cirrhosis. This set of points is a unified recipe for alternating effects on points of the front and rear surfaces of the body. When exposed to the points of the back surface of the trunk, 12 segmental points are used, including 5 symmetrical pairs, on both sides of the posterior median meridian, namely the shu points of the bladder meridian - V18 Gan Shu, V19 Dan Shu, V47 Hun Men, V48 Yan Gang, V49 And She, 2 points on the posterior meridian - T8 Jin So, T9 Zhi Yang. These points are affected in the 1st, 3rd, 5th and further sessions. The impact on the points of the front surface of the body includes 8 points, of which 5 are segmental-local points in the right hypochondrium, namely 2 points of the liver meridian - F13 Zhang Men, F14 Qi Men, 2 points of the gallbladder meridian - VB24 Zhi Yue, VB25 Jing Men, 1 point of the spleen-pancreas meridian - RP19 Fu Ai, as well as 3 immune points on the anteromedian meridian - J5 Shi Men, J12 Zhong Wan, J14 Tan Zhong. The sequential alternation of points proposed by the authors allows achieving the maximum effect from stimulation of acupuncture points without the danger of their depletion.

Thus, the method proposed by the authors revealed a new effect from the acupuncture administration of dispersed Alloplant biomaterial, which consists in normalizing lymphocyte subpopulations and reducing the number of cytokines, in particular, TNF-α and circulating immune complexes in peripheral blood. Also, a new property of the dispersed Alloplant biomaterial was revealed, based on the specificity of the immune response, which consists in increasing titers of anti-HBc Ig G immunoglobulins, which, along with the disappearance or reduction of anti-HBc Ig M titers, is evidence of the formation of a reliable post-infectious immune response.

The method is as follows. All patients are prescribed basic therapy, including half-bed, bed rest, diet No. 5A according to Pevzner, detoxification and symptomatic agents according to indications (Grigoryev P.Ya., Yakovenko EP "Diagnosis and treatment of chronic hepatitis and cirrhosis of the liver.” Soviet medicine, 1985, N 12, pp. 61-67). Dispersed Alloplant biomaterial for acupuncture administration is pre-diluted in physiological saline in the ratio of 30-50 mg of biomaterial per 4-12 ml of solution, depending on the number of points involved in the session. Injections are carried out in the following acupuncture points: in the 1st, 3rd, 5th and further sessions, 12 points are used: 10 shu-points of the bladder meridian and 2 points of the posterior median meridian - V18 Gan Shu, V19 Dan Shu, V47 Hun Men , V48 Yang Gang, V49 Yi She and T8 Jin So, T9 Zhi Yang, introducing from 0.5 to 1.0 ml of solution per point. In the 2nd, 4th and further sessions, 8 points are involved: 5 segmental-local points of the meridians of the liver, gall bladder and spleen in the right hypochondrium and 3 immune points of the anteromedian meridian - F13 Zhang Men, F14 Qi Men, VB24 Zhi Yue, VB25 Jing Men, RP19 Fu Ai and J5 Shi Men, J12 Zhong Wan, J14 Tan Zhong. Thus, there is an alternation of points from session to session, the time interval between which is from 1 to 7 days. An acceptable interval between sessions from 1 to 7 days was determined experimentally, characterized by the achievement of a macrophage-histiocytic phase and correlated with the results of studies on the processes of resorption in tissues of Alloplant biomaterials (R. A. Khasanov “Injection forms of allografts of the Alloplant series. Obtaining and biological activity ”, Perm, 1999, (cand.)). The course of treatment includes 8-10 sessions for 2-4 weeks. The method is well tolerated by patients and has no adverse reactions.

Clinical examples

Example 1

Patient C., 47 years old. 8 months ago he underwent a course of treatment in the infectious diseases department of the hospital with a diagnosis of acute viral hepatitis B, icteric form, moderate severity. From the epidemiological history — he had no contact with infectious patients, but more than a year ago he was engaged in dental treatment. He fell ill acutely, with pain in the right hypochondrium, an increase in the liver and spleen, pigment exchange disorders (skin itching, dark urine, icteric sclera). Received standard (basic) treatment. The period of convalescence proceeded without features, was discharged in a satisfactory condition, however, over the next months he noted periodically occurring nausea, pain in the right hypochondrium, general weakness. When examining 6 months after discharge: objectively: the liver is moderately painful, protrudes from the edge of the costal arch by 1 cm along the midclavicular line, the spleen is not enlarged, moderate sclerotic ictericity. Biochemical analysis of blood: total bilirubin 81.4 μmol / L, direct bilirubin 15.2 μmol / L, indirect bilirubin 24.3 μmol / L, ALT 144.2 u / L, ACT 151.4 u / L. An immunological examination revealed: positive HbsAg, HbeAg, antiHbsIgM, immune status: CD3 ⁺ - 1.29 * 10 ⁹ / l, CD4 ⁺ - 0.68 * 10 ⁹ / l, CD8 ⁺ - 0.43 * 10 ⁹ / l CD19 ⁺ - 0.13 * 10 ⁹ / L; CD25 ⁺ - 0.09 * 10 ⁹ / L. A course of treatment was carried out according to the proposed methodology, which included 10 sessions over twenty two days. He endured the procedure easily, there were no side effects, there were no complications during the treatment period. After the 3rd session, weakness decreased, nausea stopped and appetite improved. By the end of the second week, the size of the liver returned to normal. By the 14th day from the start of therapy: total bilirubin 57.4 μmol / L, direct bilirubin 7.3 μmol / L, indirect bilirubin 18.6 μmol / L, ALT 85.5 u / L, ACT 95.4 u / L. 4 weeks after the start of treatment, normalization of the immune status was observed: the number of CD8 ⁺ , CD19 ⁺ decreased with an increase in the number of CD3 ⁺ , CD4 ⁺ - lymphocytes. Her condition is satisfactory, no complaints. The liver is painless on palpation, the size is within normal limits. It has been observed for three years. There are no signs of a chronic process. Performance fully restored.

Example 2

Patient E., 71 years old. Sick about a year, when she began to notice the appearance of pain in the epigastrium and in the right half of the abdomen, an increase in the abdomen (ascites) and associated shortness of breath, general weakness. Six months ago, she was examined and underwent a course of treatment at the hospital. Viral infections, parasitic invasion, oncopathology, occupational hazards were excluded. Has no bad habits. Diagnosed with cirrhosis, idiopathic (cryptogenic), subcompensated. A course of conservative therapy (albumin, polyglucin, 5% glucose intravenously, diuretics, oral lactulose). Discharged with improvement, but the phenomena of ascites and general weakness persisted. From therapeutic measures - diet number 5. Taken for treatment according to the proposed according to the invention method. Objectively - ascites of 2 degrees (the abdomen is symmetrically enlarged with signs of portal hypertension on the anterior abdominal wall). Liver - the front edge protrudes 1.0 cm below the costal arch, tuberous, painless. Ultrasound: There was an increase in both lobes of the liver with a predominance of the right lobe. Against the background of mid-focal diffuse heterogeneity of the liver parenchyma, multiple isoechoic nodes and hyperechoic strands were determined both along the portal vein branches and along intersegmentary septa. The increase in volumetric blood flow in the portal vein was determined by 68.7%, in the splenic vein by 35.4% compared with the norm due to the expansion of the diameter of their trunks. Biochemical analysis at the beginning of treatment - dysproteinemia (total protein 88.2 g / l, albumin 36.5 g / l), cholesterol 7.86 mM / l, ALT 121.3 u / l, ACT 154 u / l, total bilirubin 87 mg / L, direct bilirubin 8.3 μmol / L, indirect bilirubin 19.6 μmol / L, ESR 35 mm / h. Within 14 days, 8 sessions were carried out according to the scheme proposed according to the invention, and for the session, a dilution of 50 mg of biomaterial per 12 ml of saline was used. Sessions tolerated satisfactorily, there were no complications.

After 1 month after treatment: the patient feels well and working capacity as good. Ultrasound: The size of the liver is close to normal, the heterogeneity of the liver parenchyma is preserved, the number of isoechoic nodes and hyperechoic strands has significantly decreased. According to a biochemical blood test, the indicators approached the norm - total protein 88.2 g / l, albumin 56.4 g / l, cholesterol 6.46 mM / l, ALT 76.3 u / l, ACT 64 units / l, total bilirubin 25 mg / L, direct bilirubin 5.3 μmol / L, indirect bilirubin 15.6 μmol / L, ESR 15 mm / h.

A total of 12 patients with viral hepatitis and 7 patients with cirrhosis were treated. All patients reported positive treatment outcomes.

Thus, the proposed invention improves the treatment of hepatitis or cirrhosis of the liver due to the correction of the systemic immune response. The method has no adverse reactions, is well tolerated by patients and can be recommended for wide clinical use.

Claims (1)

A method for the treatment of viral hepatitis or cirrhosis of the liver by injection of dispersed Alloplant biomaterial, diluted in physiological saline in a ratio of 30-50 mg of biomaterial per 4.0-12 ml of saline, to biologically active points, which are carried out with sessions in the amount of 8-10 for the course alternating from session to session the following point recipes: the first session - paired points on the back of the body to the right and left of the posterior meridian - V18 Gan Shu, V19 Dan Shu, V47 Hun Men, V48 Yang Gang, V49 Yi She and then ki on the posterior median meridian - T8 Jin So, T9 Zhi Yan, the second session - points on the front surface of the body to the right of the mediocrine meridian - F13 Zhang Men, F14 Qi Men, VB24 Zhi Yue, VB25 Jing Men, RP19 Fu Ai and points on the anterior median meridian - J5 Shi Men, J12 Zhong Wan, J14 Tan Zhong, and so on with repetition through each session, moreover, injections are carried out with an interval between sessions of 1 to 7 days and a course duration of 2 to 4 weeks of 0.5 -1.0 ml of solution for 1 injection, and the treatment is carried out against the background of basic therapy.