RU2105552C1 - Method for treating peptic gastric and duodenal ulcer - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves administering repair-and-regeneration preparation. Vipraxinum is used as preparation of this kind and 2-% lidocain solution (trimecain) is additionally applied. The preparations are administered as subcutaneous and intracutaneous injections once per 24 h with Vipraxinum contents making up 25-50% of total injection dose. Vipraxinum contents in the total single injection dose is increased to 100% when compared to the initial one during the first part of treatment course and it is reduced from 100% to the initial dose during the second part. EFFECT: enhanced effectiveness of treatment. 1 tbl

Description

 The invention relates to medicine in gastroenterology and can be used to treat gastric ulcer and duodenal ulcer.

 Peptic ulcer is a chronic relapsing disease characterized by the formation of ulcers of the stomach and duodenum. Peptic ulcer develops as a result of general and local disorders of the nervous and hormonal regulation of trophic mucosa, disorders of the secretory and motor functions of the gastroduodenal system. A peptic ulcer of the mucous membrane develops as a result of an imbalance between the factors of acid-peptic aggression of the gastric contents and the protective properties of the mucous membrane of the stomach and duodenum. The factors of acid-peptic aggression include: an increase in the production of hydrochloric acid, pepsin and pepsinogen, an upset motor function of the stomach and duodenum. The weakening of the protective properties of the mucous membrane can be the result of a decrease in the production and violation of the qualitative composition of the gastric mucus, a decrease in the regenerative capabilities of the mucous membrane, and a deterioration in blood circulation. In the development of peptic ulcer, a violation of the functions of the endocrine system is of great importance.

 The treatment of peptic ulcer is complex. It is aimed at eliminating the damaging effect of the acid-peptide factor, normalizing motor and evacuation functions of the stomach and duodenum, stimulating the regeneration of epithelial cells of the mucous membrane and gastric mucus formation, normalizing nerve and hormonal disorders, improving blood circulation of the gastric mucosa and duodenum.

 For treatment, antacids (magnesium oxide, calcium carbonate in the form of talkers) are used, enveloping, astringent (bismuth nitrate, the main component of the preparations is vicalin, vicair), as well as quinolytic (atropine sulfate, metacin) and antispasmodic (no-shpa, papaverine hydrochloride) medicines. Tranquilizers and sedatives are used (diazepam, elenium, phenazepam, valerian preparations). Physiotherapy is widely used. Patients should follow a diet and be under medical supervision for a number of years. In case of scarring ulcers, hyperbaric oxygenation is used, the introduction of drugs or preparations with reparative-regenerative properties directly into the zone of the ulcer defect (Handbook of a Practitioner. M. Medicine, 1981, p. 169-170).

 A known method of treating chronic duodenal ulcer (ed. Certificate. USSR N 1412791) by introducing a reparative-regenerative drug using T-activin (calf thymus preparation) using an endoscope and a needle into the submucosal layer of the pyloric stomach of the stomach.

 The method provides the activation of the healing process and the transition of the ulcer process from the stage of acute destructive inflammation to the regeneration phase, reduces the autogenic properties of the ulcer and helps to normalize the body's immune state. However, the method requires special equipment, must be performed by highly qualified specialists and, in addition, is associated with the occurrence of a negative neuropsychic factor in the patient.

 There is also known a method of treating gastric ulcer and duodenal ulcer (author's certificate. USSR N 1197671), adopted as a prototype, including endoscopic administration of a reparative-regenerative preparation into the zone of ulcerous defect, using freshly isolated leukomass.

 The method provides for the creation of an increased concentration of leukocytes in the affected area, which are absorbed by bacteria and pathogenic agents, including cells of dead tissue, cleansing the area of the ulcer defect and contribute to the healing and regeneration of the tissues of the mucous membrane in the affected area. The introduction of leukomass also has a mediated immunomodulating effect on the body, helping to reduce treatment time. The disadvantage of the prototype method is that its implementation requires special equipment for the introduction of the drug and its preparation, the appropriate qualifications of specialists, and, in addition, is also associated with the occurrence of a negative neuropsychological factor in the patient.

 The technical problem underlying the invention is to simplify the method and reduce the treatment time for peptic ulcer of the stomach and duodenum, achieving stable remission.

 The stated technical problem is achieved by the fact that in the method of treating gastric ulcer and duodenal ulcer according to L.V.Dubinina, consisting in the introduction of a reparative-regenerative drug, according to the invention, vipraxin is used as a reparative-regenerative drug and an additional 2% solution is used lidocaine (trimecaine), and the total single dose of drugs is determined at the rate of 0.01-0.02 ml per 1 kg of patient weight, and the initial content of vipraxin is 25-50% of the total single dose, the introduction is carried out in in the form of subcutaneous or intradermal injections 1 time in 24 hours by chipping along the abdominal wall or on the back of the projection of the stomach, with 5-10 injections being carried out, increasing the content of vipraxin in a single dose from the initial to 100% in equal parts and then continuing the injection, reducing the content of vipraxin in a single dose in the reverse order from 100% to the initial.

 The invention consists in the following.

 In the proposed method for the treatment of peptic ulcer of the stomach and duodenum, vipraxin is used as a reparative-regenerative drug.

 Vipraxin (Viproxinum pro inijectionibus, VFS 42-1481-84 "Vipraxin for injection") is an aqueous solution of dry native unfractionated venom of the common viper (Vipera berus berus).

 Vipraxin has anti-inflammatory and analgesic properties, however, when introduced into the body, it causes vascular spasms, heart rhythm disturbance, decreased blood pressure, therefore it is contraindicated in patients with diseases of the cardiovascular system, liver and kidneys, a tendency to angiospasm, and cerebral and venous circulation insufficiency. The mechanism of action of vipraxin on the human body is unknown (Mashkovsky M.D. Medicines. M. Medicine, 1988, v. 2, pp. 165-166).

The composition of the venom of the viper ordinary includes various enzymes, including proteases, phosphodiesterase, 5'-nucleotidase, phospholipase A ₂ , hyaluronidase, kininogenase, as well as other soluble low molecular weight protein fractions, such as neurotoxins (Orlov B.N. Poisonous plants and animals of the USSR. M. Higher School, 1975, p.69).

 Studies conducted by M.Yu.Samel (Samel M.Yu. Abstract for the degree of Candidate of Chemical Sciences, Tallinn, 1987) showed that the protease content in the poison is 72-84% by weight according to Brack and Lowry.

 As noted above, the mechanism of action of vipraxin on the human body has not been studied, especially when it is co-administered with lidocaine. However, monitoring the course of the treatment process according to the claimed method, the response of the body to treatment, as well as the achievement of the therapeutic effect, suggest the following mechanism of their effect on the patient’s body with a sufficient degree of certainty.

 Since vipraxin contains proteins that are foreign to the human body, it is an antigen, its ingestion into tissues causes a response of the body: in the area of vipraxin, the number of leukocytes and macrophages increases sharply, and the body begins to actively produce B and T lymphocytes.

 Thus, the body’s struggle with the antigen substance at the same time mobilizes the body’s protective functions to fight not only the antigen itself, but also the manifestations of the disease: removal of sick and dead cells and bacteria, as well as metabolic products in the area of the ulcer defect.

The proteases that make up vipraxin provide the dissolution of fibrinous deposits on cell membranes in the zone of ulcer defect, contributing to the restoration of K ⁺ and Na ⁺ metabolism in these cells, their nutrition and, as a consequence, the restoration of tissue metabolism and regenerative processes.

 Obviously, vipraxin also has an effect on the pituitary-adrenal gland system, normalizing the activity of the endocrine glands of the gastrointestinal tract (Mashkovsky MD Medicines. M. Medicine, 1988, v. 2, p. 164).

 Thus, vipraxin in the proposed method of treatment performs a reparative-regenerative function on the one hand, and, obviously, an immunomodulatory function on the other hand.

 Since vipraxin is a potent biologically active substance for the body and causes a number of negative manifestations when it is administered, in the proposed method it is used with lidocaine or trimecain to level these manifestations.

 In addition, lidocaine is a conductive anesthetic, therefore, its joint administration with vipraxin provides a more rapid and "targeted" (directed) intake of vipraxin to the diseased organ.

 Lidocaine (Lidocainum Diethylamino-2,5-dimethylacetanilide hydrochloride) is a conductive anesthetic, has a strong local anesthetic effect, provides a long and deep pain relief. It is low toxic, well tolerated by the body, does not cause local irritation. Lidocaine has a pronounced antispasmodic effect, regulates the heart rate.

 The other conductive anesthetic trimecaine (Trimecaimun Diethylamino-2,4,6-trimethylacetolinide hydrochloride) has the same properties (Mashkovsky M.D. Medicines. M. Medicine, 1988, v. 1, p. 344-334).

 In addition to the described effects on the body, vipraxin and lidocaine (trimecain) act as blockers of pain impulse during treatment.

 As a rule, the effect of a pain factor that occurs at a certain stage of the disease is considered only as a symptomatic factor and the influence of pain as a factor aggravating the pathogenesis of the disease is not considered.

 However, it is known that the flow of pain impulses from the injury zone to the central nervous system (CNS) causes an organism to respond from each of its systems.

 Under the influence of pain impulses, both parts of the autonomic nervous system are excited. As a result, peripheral vascular spasm, pilomotor effect, hormonal changes, changes in metabolic processes develop.

 The response of pain impulses to the cardiovascular system leads to vasospasm due to an increase in the tone of the sympathetic-adrenaline system. Centralization of blood circulation develops due to the fact that blood passes from arterioles to venules via metarteriols, bypassing the capillaries. In the tissues, toxic metabolic products accumulate, causing capillary paralysis. Under the influence of pain irritation, a marked inhibition of secretion of the glands of the digestive tract occurs, the secretory function of the pancreas is inhibited (Smolnikov V.P. Agapov Yu.Ya. Anesthesiology Handbook. M. Medicine, 1970, pp. 11-13).

 Thus, stopping a pain impulse from a zone of a peptic ulcer is a priority when conducting a course of treatment.

 Lidocaine, which has a quick anesthetic effect, performs a short-term (3-5 h) interruption of the pain impulse in the central nervous system immediately after administration, and the neurotoxins that make up vipraxin carry out further blockade of the pain impulse. Moreover, as the content of vipraxin in the total single dose of the injection increases during the course of treatment, the role of neurotoxins as blockers of the pain impulse increases.

 Stopping a pain impulse in the central nervous system interrupts the body's responses to this impulse. At the same time, peripheral blood supply and tissue metabolism are improved, metabolic processes, secretory functions of the pancreas are normalized, and normal motor function of the stomach and duodenum is restored.

 Thus, the interruption of the pain impulse eliminates secondary manifestations that exacerbate the course of the disease.

 In the proposed method of treatment, the content of vipraxin in the total single dose of the injection is not constant. Initially, the minimum content of vipraxin is administered against the background of the maximum content of lidocaine in a total single dose. Further, as the body overcomes the immune barrier, the vipraxin content in the total injection dose is increased to 100% with a corresponding decrease in the lidocaine content.

 This is because as the body gets used to the action of vipraxin, the need for lidocaine as a drug that reduces the negative effects of vipraxin decreases, and the neurotoxins that make up vipraxin perform the function of interrupting the pain impulse.

 The maximum therapeutic effect on the body is achieved when the injection contains 100% vipraxin.

 Then, in order to consolidate the therapeutic effect of vipraxin and eliminate the drug withdrawal syndrome, it is consistently uniformly reduced in its content in the total single injection dose in the reverse order from 100% to the initial one, respectively increasing the lidocaine content in the dose. In this case, the introduction of lidocaine at the second stage of the course of treatment is used to eliminate the negative manifestations of the effects of vipraxin accumulated in the body.

 Thus, lidocaine in the treatment process according to the proposed method performs both an independent function (anesthetic) and the function of a concomitant drug that promotes the manifestation of the complex of therapeutic properties of vipraxin and ensures that vipraxin “enters” the body and “leaves” it without negative consequences for the latter.

 The introduction of vipraxin with lidocaine is carried out by injection subcutaneously or intradermally by chipping the projection of the stomach along the abdominal wall or from the back.

 Such an introduction ensures a uniform distribution of drugs along the nerve innervation zone and ensures their quick and targeted entry to the diseased organ and interruption of the pain impulse.

The total single dose of injection is determined from the calculation of 0.01-0.02 ml per 1 kg of patient weight, and the initial content of vipraxin in it is 25-50%
The value of the total single dose of the injection and the initial content of vipraxin in it is determined based on the general condition of the patient and the presence of concomitant diseases.

 The declared values of the total single dose and the content of vipraxin in it are optimal for achieving a therapeutic effect.

 An increase in the total single dose of more than 0.02 ml per 1 kg of the patient’s weight, as well as an increase in the initial content of vipraxin in it over 50%, leads to a strong hyperergic reaction of the body to the drug and, as a consequence, to discontinuation of treatment, which is undesirable as in this case, the resumption of the course of treatment becomes problematic due to the possibility of the drug withdrawal syndrome.

 Reducing the total single injection dose of less than 0.01 ml per 1 kg of patient weight, as well as the initial content of vipraxin in it of less than 25%, does not lead to the achievement of a therapeutic effect.

 The treatment method involves conducting the first half of the course of treatment (5-10 injections) by uniformly increasing the content of vipraxin in the total injection dose from the initial to 100% and the second half by uniformly decreasing in the reverse order the vipraxin content in the total single dose from 100% to the initial.

 The stated rate of increase and decrease in vipraxin content in the total single dose of injection during the course of treatment is optimal, changing it in one direction or another also causes either a hyperergic reaction of the body, or does not ensure the achievement of a therapeutic effect.

 The invention is illustrated by examples of specific performance, in which the results of treatment of patients according to the method of L.V.Dubinina on the basis of the Novosibirsk Research Institute of Immunology and 1 clinical hospital in Novosibirsk are presented.

 Initially, the patient underwent a test for the susceptibility of the body to vipraxin by subcutaneous injection into the shoulder region. Control after 24 hours, assessed the overall reaction of the body. In the case of a positive reaction of the body to the drug (the appearance of a rash, headache, dizziness, fever, fever), treatment is contraindicated. Otherwise, a course of treatment of 10-20 injections was prescribed.

 Example 1. Patient F. 34 years old, weight 78 kg. Appealed in June 1993, complaints of hunger pain in the epigastric region to the left of the midline, subsiding 20-30 minutes after eating, as well as frequent nausea, sometimes vomiting. Exacerbations 3-4 weeks 2 times a year in spring and autumn.

 Diagnosis: gastric ulcer in the acute stage. Sick for 2 years, no special treatment was carried out. On palpation, pain in the epigastric region. According to fibrogastroscopy (FGS), there is a large amount of mucus in the stomach on an empty stomach, the mucous membrane of the antrum is intensely hyperemic, swollen, two ulcers 0.3 and 0.5 cm in diameter are visible along the large curvature of the antrum, the edges are uneven, saped, fibrinoid necrosis areas of the bottom and edges of ulcers.

 Treatment with vipraxin and a 2% solution of trimecaine from 15 injections was prescribed. In this case, the total injection dose of 1.6 ml (at the rate of 0.02 ml per 1 kg of patient weight); initial content of 0.4 ml (25%) of vipraxin.

 Injections were performed subcutaneously according to the projection of the stomach on the anterior abdominal wall according to the scheme (vipraxin, ml of trimecaine, ml): 0.4-1.2; 0.6-1.0; 0.8-0.8; 1.0-0.6; 1.2-0.4; 1.4-0.2; 1.6; 1.4-0.2; 1.2-0.4; 1.0-0.6; 0.8-0.8; 0.6-1.0; 0.4-1.2.

 As a result of treatment, a significant improvement after the first week of treatment. Pain, nausea, and vomiting disappeared. According to the FGS after treatment: peptic ulcers are erosions with a diameter of 0.2 and 0.3 cm, covered with granulations. Conclusion according to the FGS: scarring of ulcers. Persistent remission for 3 years.

 Example 2. Patient T., 55 years old, weight 78 kg, was admitted for treatment in January 1995. Upon receipt of a complaint of nausea, vomiting after eating, after 2 hours, epigastric pain to the right of the midline.

 Diagnosis: peptic ulcer of the duodenum, stage of exacerbation of peptic ulcer, sick for many years with exacerbations 2-3 times a year. She was repeatedly treated in-patient with temporary relief, in 1994 she underwent a course of autohemotherapy.

 According to FGS: the duodenal bulb is deformed, on the back wall there are two isolated ulcerative defects of irregular shape 1x1 cm in size with an infiltration shaft, the edges are undermined, the bottom is covered with fibrin, hyperemia.

 A treatment of 9 injections was prescribed, with a total injection dose of 0.8 ml (based on 0.01 ml per 1 kg of patient weight); initial vipraxin content of 0.4 ml (50%).

 Injections were performed intradermally according to the projection of the stomach on the anterior abdominal wall according to the scheme (vipraxin, ml lidocaine, ml): 0.4-0.4; 0.5-0.3; 0.6-0.2; 0.7-0.1; 0.8 and in the reverse order for 0.4-0.4.

 As a result of treatment, pain in the epigastric region decreased, nausea decreased, and vomiting disappeared.

 According to the CSF: ulcerative defects are erosions with a diameter of about 1 cm, covered with red granulations, there is no infiltration shaft.

 Conclusion: cicatricial ulcer of the duodenal bulb.

 In June 1995, a second course of treatment was carried out according to the same scheme. As a result, according to the FGS: scarring of ulcers. Persistent remission of 1.5 g.

 Example 3. Patient R. 46 years old, weight 82 kg. Received treatment in December 1994. Upon receipt of a complaint of epigastric pain 15-20 minutes after eating, night pain, nausea, vomiting, belching. Bouts of chest pain after passing 100 m and climbing to the 2nd floor.

 Diagnosis: chronic relapsing gastric ulcer with localization of the ulcer; a history of chronic cholecystitis (calculous), coronary heart disease (CHD), unstable angina IIFK.

 Fibrogastroscopy: an ulcer in the pyloric stomach with a diameter of about 0.4 cm, with ragged edges and an ulcer along a large curvature with a diameter of about 0.8 cm with ragged edges, the bottom of the ulcers is lined with fibrin, a large amount of mucus in the stomach, pyloric stenosis, rough folds, swelling of the mucosa shell, hyperemia.

 He has been suffering from peptic ulcer for 12 years, seasonal exacerbations, he received inpatient and outpatient treatment at least 2 times a year with blood transfusion, activin, a bismuth preparation and denol courses. According to gastrofibroscopy, ulcer healing is absent. Lack of remission for more than 2-3 months.

 Prescribed treatment with vipraxin and lidocaine 2% of 17 injections. Moreover, the total injection dose of 1.2 ml (based on 0.015 ml per 1 kg of patient weight); initial vipraxin content of 0.4 ml (33%).

 Injections were performed 1 time per day subcutaneously in the projection of the stomach along the back according to the scheme (vipraxin, ml lidocaine, ml): 0.4-0.8; 0.5-0.7; 0.6-0.6; 0.7-0.5; 0.8-0.4; 0.9-0.3; 1.0-0.2; 1.1-0.1; 1,2; 1.1-0.1; 1.0-0.2; 0.9-0.3; 0.8-0.4; 0.7-0.5; 0.6-0.6; 0.5-0.7; 0.4-0.8.

 After the seventh injection, a decrease in nausea, the absence of vomiting and pain at night was noted. After completion of the course of treatment according to the FGS: complete scarring of the lesser ulcer in the pyloric department, longitudinal folds are moderate, the size of the second ulcer has decreased to a diameter of about 0.4 cm.

 Conclusion: a healed ulcer of the pyloric department, a scarring ulcer of great curvature of the stomach.

 In May 1995, the patient was given a second course of treatment using the same technique. Prior to treatment, exacerbation of peptic ulcer was not observed.

 After a second course of treatment according to FGS: scarring of the ulcer of a large curvature of the stomach.

 During the treatment period, the patient took medications for the treatment of coronary heart disease (nitrates, calcium antagonists), and during the treatment the dose of the drug decreased from 8 to 1 tablet per day. During the treatment period, exacerbation of cholecystitis and angina attacks were not observed.

 As a result of treatment of gastric ulcer by the proposed method, the patient has stable remission for 1.5 years.

 The proposed method for the treatment of peptic ulcer of the stomach and duodenum according to L.V.Dubinina from 1990 to 1996 treated 67 patients. The treatment results are summarized in table.

 It should be noted that in 40% of patients treated by the proposed method, the presence of concomitant diseases (IHD, angina pectoris, lack of movement function, chronic cholecystitis, hypertension, atherosclerosis) was noted. During treatment, exacerbations of concomitant diseases were not observed.

 In 1991, an immunological index (ratio of the number of T-lymphocytes to B-lymphocytes) was determined in 5 patients. After a course of treatment with vipraxin and lidocaine (trimecaine), the immunological index (the ratio of T-lymphocytes to B-lymphocytes) increased about 2 times, which confirms the immunomodulatory effect of vipraxin during treatment.

 Thus, based on the foregoing, the method of treating gastric ulcer and duodenal ulcer according to L.V.Dubinina allows to achieve the following technical result: the method is quite simple, based on the use of affordable drugs, does not require special equipment; patients take outpatient treatment both during an exacerbation of the disease and in the interictal period; allows to provide a high therapeutic effect; does not cause the patient a negative neuropsychic factor, since it is not associated with direct mechanical intervention in the zone of a peptic ulcer; expands the scope of known drugs and reduces the number of contraindications in the appointment of a course of treatment.

 The results of clinical trials of the proposed method allows us to conclude that it additionally provides an increase in the body's immunity.

 The invention can be used in medicine.

Claims (1)

 A method of treating gastric ulcer and duodenal ulcer by administering a reparative-regenerative drug, characterized in that vipraxin is used as a reparative-regenerative drug and an additional 2% solution of lidocaine (trimecaine) is used, and the total single dose of drugs is determined from the calculation of 0, 01 0.02 ml per 1 kg of the patient’s weight, and the initial content of vipraxin 25 50% of the total single dose, the introduction is carried out in the form of subcutaneous or intradermal injections once every 24 hours by piercing through the abdominal wall stomach, while 5 10 injections are carried out, increasing in equal proportions the content of vipraxin in the total single dose from the initial to 100%, then continue the injection, reducing the content of vipraxin in the total single dose in the reverse order from 100% to the initial.