RU2290925C1 - Method for treating penetration-complicated gastric and duodenal ulcerous disease - Google Patents

Abstract

FIELD: medicine, gastroenterology.

SUBSTANCE: it is necessary to prescribe for patients 1 wk before traditional medicinal therapy intravenous injection of mildronat per 5 ml once daily for the period of 7 d. The this preparation should be applied for inner intake per 0.25 g as capsules twice daily, in the morning and afternoon for 3 wk. The innovation interrupts pain syndrome and normalizes circulation in ulcerous area and, thus, increases efficiency of traditional therapy at no complications in the form of perforation and hemorrhage.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, mainly to gastroenterology, and can be used to treat patients with penetrating ulcers of the stomach and duodenum.

Penetration of an ulcer is one of the complications of peptic ulcer of the stomach or duodenum. Morphologically penetrating ulcers are characterized by the fact that as a result of the peptic process in the ulcer defect, all layers of the wall of the stomach or duodenum are completely destroyed and the ulcer penetrates into the adjacent organ adjacent to them. Clinically penetrating ulcers are distinguished by features of the pain syndrome. Already in the process of formation of penetration, pains become constant, aching, sometimes acute. With the formed penetrating ulcer, the pain syndrome is characterized by a pronounced intensity and is permanent. Depending on the organ into which the ulcer penetrates, pain radiates to various areas of the human body (P.Ya. Grigoriev Diagnosis and treatment of peptic ulcer of the stomach and duodenum. - M .: Medicine. - 1986. - S.12-15).

Moreover, in young patients, a progressive course of the ulcer process with persistent pain syndrome is often noted. This feature of the disease, in turn, leads to the development of complications of peptic ulcer such as ulcer perforation or peptic ulcer bleeding (V.Kh. Vasilenko et al. Peptic ulcer. - M .: Medicine. - 1987. P.162-167).

In the occurrence of severe pain, the development of an ischemic zone in the ulcer area is of great importance. Under the influence of hydrochloric acid in the ischemic zone, the peptic effect on the wall of the stomach or duodenum is intensified, which deepens the ulcer defect, and also leads to the occurrence of spastic contractions of the smooth muscle fibers of their walls. This, in turn, causes an increase in intraluminal pressure, impaired microcirculation, and thereby aggravates metabolic processes and enhances tissue ischemia in the ulcer zone, which further reduces the resistance of tissues to ulcer progression. The elimination of the arisen pathological condition of the wall in the ulcer zone requires not only a decrease in the acidity of the gastric juice, but primarily a therapeutic effect on the ischemic zone in the gastric wall. Indeed, clinical practice indicates that treating patients with antacid preparations alone does not always stop the pain syndrome, especially with ulcer penetration (V.Kh. Vasilenko et al., Ibid., Pp. 95-97). Therefore, for the medical treatment of such patients, a complex of medicines is used, namely antacids, antispasmodics, myotropic drugs and anticholinergics. Thus, they are trying to achieve a decrease not only in the level of hydrochloric acid, but also in the severity of the ischemic zone by eliminating spasm of smooth muscles, restoring microcirculation and metabolism in the ulcer zone. However, such a set of medications does not always bring success. As you know, pain causes activation of the sympathoadrenal system. Increased excretion of norepinephrine and adrenaline leads to spasm of peripheral vessels, including vessels of the abdominal organs, which further enhances ischemia in the ulcer area. Therefore, in cases of pronounced pain syndrome, narcotic (promedol) or non-narcotic (ketorol) analgesics are added to the above drug therapy, trying to interrupt the pain impulse and, thereby, reduce the neurohumoral effect on the ischemic zone in the ulcer area. Usually, such treatment is carried out for 2-3 days. If this therapy is ineffective, they perform surgery on the stomach in order to prevent the development of life-threatening complications - perforation of an ulcer or ulcer bleeding. Therefore, with the medical treatment of penetrating gastric and duodenal ulcers, the elimination of pain is an important component of pathogenetic therapy, and its inefficiency serves as an indication for surgery.

As you know, modern drug treatment of patients with gastric ulcer and duodenal ulcer involves the use of developed schemes of anthelibacter therapy. Recent studies have shown that the microorganism Helicobacter pylori not only causes ulcer formation, but also has a negative effect on all stages of ulcer healing, translating it into a chronic one (Yu.A. Kucheryavy, M.G. Gadzhieva Bismuth tricalium dicitrate in erosive-ulcer therapy regimens lesions of the mucous membrane of the gastroduodenal zone // Russian Journal of Gastroenterol., Hepatol., Coloproctol. - 2005. - No. 1. - P.71-75). Schemes of traditional anti-Helicobacter pylori treatment include agents that reduce the acidity of gastric juice, namely proton pump inhibitors (the drug soars or omez, or others) and 2 antibiotics.

In the patent literature there is information about several methods of treating gastric ulcer and duodenal ulcer. In particular, the “Method for the treatment of gastric ulcer and duodenal ulcer” is described (RF patent No. 2192867, IPC A 61 K 33/00, publ. Bull. No. 32, 2002), which proposes to combine conventional drug therapy with the intake of mineral-containing Trepelom preparation of the Pervomaisky field in the Alatyr district of the Chuvash republic or the Shadrinsk field of the Kurgan region in the form of an aqueous suspension containing 4-6 g of tripoli in 150-200 ml of water.

In addition, a “Method for the treatment of gastric and duodenal ulcer” was proposed (RF patent No. 2240119, IPC A 61 K 31/4045, publ. Bulletin No. 32, 2004), which envisages supplementing the traditional drug therapy with 50 mg of Imigran drug. -80 mg.

Also known is a "Method for the treatment of gastric ulcer and duodenal ulcer" (RF patent No. 2250767, IPC A 61 K 31/4439, 31/505, 31/513, publ. Bulletin No. 12, 2005), which involves ingestion omeprazole 20 mg 2 times a day and Xymedon 500 mg 2 times a day for 12 days.

A “Method for the treatment of Helicobacter-associated chronic duodenal ulcer” is proposed (RF patent No. 2252777, IPC A 61 K 38/05, 31/29, 31/4184, 31/422, publ. Bulletin No. 15, 2005), providing for the traditional anti-Helicobacter pylori ulcer. supplement the therapy with the drug lycopid, used orally at a dose of 10 mg once a day on an empty stomach for 10 days.

Published "Method for the treatment of diseases of the stomach and duodenum caused by Helicobacter pylori" (RF patent No. 2265437, IPC A 61 K 31/43, 31/7048, publ. Bull. No. 34, 2005), characterized in that they use a suspension 1-2 antibiotics applied to the mucous membrane of the affected organ with the possibility of localizing the drug, and almagel is used as an antacid.

The main disadvantage of the methods described above is the lack of drugs in their composition that eliminate severe pain by eliminating ischemic sites in the ulcer area. These methods are intended for the treatment of patients with unexpressed pain syndrome, i.e. in the absence of penetration of the ulcer.

The prototype of the claimed invention is a method for the treatment of gastric ulcer and duodenal ulcer, described by V.T. Ivashkin, A.A. Sheptulin, E.K. Baranovskaya et al. in the manual for doctors “Recommendations for the diagnosis and treatment of peptic ulcer. - M. - 2004. - P.26-27. The essence of the method, taken as a prototype, is that patients with peptic ulcer of the stomach and duodenum associated with Helicobacter pylori are prescribed anti-Helicobacter therapy of the following composition: proton pump inhibitor, for example, the drug soars 20 mg 2 times a day, and 2 antibiotics - clarithromycin 500 mg 2 times a day and amoxicillin 1000 mg 2 times a day. The course of treatment is 7 days. After that, both antibiotics are canceled, and the dose of the drug is reduced by 2-4 times and is recommended to be used as maintenance therapy for 3-4 weeks.

The disadvantage of this method is the lack of a drug in this therapy that eliminates the ischemic zone in the ulcer area and thereby eliminates the pain syndrome and at the same time creates conditions for successful healing of the ulcer under the influence of anti-Helicobacter therapy.

The aim of the present invention is to develop a method for the treatment of gastric ulcer and duodenal ulcer, complicated by penetration, involving the elimination of tissue ischemia in the ulcer and pain syndrome for subsequent anti-Helicobacter therapy. The goal is achieved by the fact that 7 days before the traditional anti-Helicobacter therapy, the drug is prescribed Mildronate 5 ml once a day intravenously, and then during the anti-Helicobacter therapy and after this drug is taken 0.25 g orally in the form of capsules 2 times a day morning and afternoon. The drug mildronate as a structural analogue of gamma-butyrobetoin (a substance that is part of each cell) has the following therapeutic properties: 1 - reduces peripheral resistance of blood vessels, 2 - reduces platelet aggregation and increases blood flow, 3 - thanks to these two properties improves oxygen delivery and nutrients in the ischemic zone, removes metabolic products from it and reduces acidosis, 4 - regulates energy metabolism in the ischemic zone by activating glycolysis and inhibition of β-oxidation fatty acids, 5 - restores the mechanisms of ATP transport, 6 - regulates calcium homeostasis in cells (I.Ya. Kalvins Mildronat - mechanism of action and prospects for its use. - Riga: PJSC "Grindeks". - 2001. - 4 p .; M .Dambrova, D. Daya, E. Liepinis et al. Biochemical mechanisms of action of mildronate under conditions of ischemic stress // Medical business. - 2004. - No. 2. - P.68-73).

A detailed description of the method and examples of its practical implementation

For severe pain syndrome in patients with gastric and duodenal ulcer complicated by penetration, after endoscopic and (or) X-ray diagnostics of penetration of the ulcer process, and study of contamination of the mucous membrane of the gastroduodenal zone of Helicobacter pylori, 7 days before the administration of anti-Helicobacter therapy, patients are prescribed intravenous therapy 5 ml of the drug Mildronate 1 time per day for 7 days. After this, patients take this drug orally at 0.25 g in the form of capsules 2 times a day, in the morning and at lunch for 3 weeks.

As the pain syndrome subsides on the 8th day of treatment with the drug Mildronate, patients are prescribed traditional anti-Helicobacter therapy, for example, first-line drugs: a proton pump inhibitor (pariet or omeprazole, or another) and 2 antibiotics - clarithromycin 500 mg 2 times a day and amoxicillin 1000 times mg 2 times a day for 7-10 days. After that, both antibiotics are canceled, and the dose of the proton pump inhibitor is reduced by 2-4 times and it is recommended to take 3-4 weeks.

The results of the treatment of patients with peptic ulcer of the stomach and duodenum complicated by penetration by the proposed method are illustrated by the following examples.

Example 1. B-noy M-v, 43 years old, turned to the City Polyclinic No. 1 of the city of Rostov-on-Don with complaints of severe constant pain in the epigastric region and right hypochondrium, which become even more pronounced after eating and saved at night. In this regard, the patient abstains from eating. A history of about 4 years suffers from peptic ulcer of the duodenum. Previously treated on an outpatient basis and in hospitals. The exacerbation of the disease occurred in the spring and autumn time of the year. When fibrogastroduodenoscopy revealed an ulcer of size 0.8 × 1.4 cm, a depth of 0.3-0.4 cm on the posterior upper wall in the postclavicular part of the duodenum, penetrating into the lower surface of the liver. The mucosa of the duodenum is hyperemic, edematous. Cicatricial and ulcerative deformity of the duodenal bulb is noted. In the blood test, the glucose content of 6.2 mmol / l, total lipids of 4.2 g / l, phospholipids of 1.78 g / l, saturated fatty acids in phospholipids of 59.7% - the norm is 57.03 ± 0.32%, increased the content of norepinephrine is 68.2 μg / day, adrenaline 26.8 μg / day, 17-corticosteroids 18.8 μg / day and 17-hydroxycorticosteroids 9.7 μg / day. Due to the presence of a penetrating duodenal ulcer and severe pain, the patient was prescribed the drug Mildronate intravenously 5 ml once a day for 7 days, and then in capsules 0.25 g 2 times a day in the morning and lunch for 23 days. After 3 days of treatment, the pain significantly decreased, and by the 5th day they completely disappeared. The blood glucose level during this period was 4.1 mmol / l, total lipids 3.9 g / l, phospholipids 1.83 g / l, saturated fatty acids in phospholipids 64.9%, the excretion of norepinephrine 36.1 μg / day, adrenaline 17.9 mcg / day, 17-corticosteroids 17.3 mcg / day and 17-hydroxycorticosteroids 6.9 mcg / day. The cessation of pain and a decrease in the level of the studied hormones indicated the restoration of blood circulation in the ischemic zone near the ulcer defect. Against this background, on the 8th day of treatment with the drug Mildronate, the patient was prescribed anti-Helicobacter therapy with first-line drugs: soars 20 mg 2 times a day, clarithromycin 500 mg 2 times a day, amoxicillin 1000 mg 2 times a day for 10 days. After this, the patient took the drug soars 20 mg once a day in the morning on an empty stomach. With endoscopy of the stomach and duodenum 3 weeks after the start of treatment, it was revealed that the ulcer was in the healing phase. Its size was reduced to 0.4 × 0.6 cm. By the end of the monthly course of treatment, the ulcer had completely healed. The patient is recommended to continue taking the inside of the drug 10 mg once a day on an empty stomach for 1 month.

Example 2. Patient Tv, 47 years old, was admitted to the surgical department of BSMP-2 in Rostov-on-Don with suspicion of perforation of a duodenal ulcer. He noted severe constant pain in the epigastric region, which radiated to the back, as well as nausea and vomiting at the height of the pain syndrome. Often self-induced vomiting to reduce pain. Suffers from peptic ulcer 9 years. During this period of time, he was repeatedly treated in hospitals and on an outpatient basis. Fibrogastroduodenoscopy revealed a 0.9 × 1.2 cm ulcerative defect on the posterior wall of the duodenum, as well as edema and hyperemia of the mucous membrane of the stomach and duodenum.

During a fluoroscopy of the stomach, rapid evacuation of barium suspension along the duodenum, as well as a peptic niche measuring 0.6 × 0.9 cm along the back contour of the duodenum penetrating into the head of the pancreas were revealed. In the blood test, glucose is 5.9 mmol / l, the content of total blood lipids is 5.2 g / l, phospholipids 1.62 g / l, saturated acids in phospholipids 61.4%. There was an increased excretion of norepinephrine 62.3 μg / day, adrenaline 23.2 μg / day, 17-corticosteroids 17.1 μg / day and 17-hydroxycorticosteroids 8.6 μg / day. Given the severity of the pain syndrome, the patient was prescribed the drug Mildronate 5 ml intravenously once a day for 7 days, and then 0.25 twice a day, in the morning and at lunch, for 3 weeks. After 4 days, the pain syndrome completely disappeared. During this period, the blood glucose level was 4.3 mmol / L, total lipids 4.9 g / L, phospholipids 1.68 g / L, saturated fatty acids in phospholipids 66.3%. The levels of norepinephrine decreased by 36.1 μg / day, adrenaline by 15.9 μg / day, 17-corticosteroids 16.3 μg / day and 17-hydroxycorticosteroids 6.9 μg / day. These indicators indicated normalization of blood circulation in the ulcer area. In this regard, the patient started anti-Helicobacter therapy with first-line drugs: soars 20 mg 2 times a day, clarithromycin 500 mg 2 times a day, amoxicillin 1000 mg 2 times a day for 7 days. After this, the patient took the drug soars 20 mg once a day in the morning on an empty stomach. With fibrogastroduodenoscopy, 4 weeks after the start of treatment, complete healing of the ulcer was revealed (stage of the red scar).

The proposed method treated 8 patients with penetrating gastric ulcers and 13 patients with penetrating duodenal ulcers. Ulcer healing within 4 weeks of treatment was noted in 17 individuals; 4 observations required treatment for 5 weeks. The relief of pain occurred on the 2nd-5th day of treatment with the drug Mildronate. During treatment, no patients had complications in the form of ulcer perforation or ulcerative bleeding.

Claims (1)

A method of treating gastric ulcer and duodenal ulcer complicated by penetration, involving drug therapy, characterized in that patients are prescribed intravenous administration of 5 ml of the drug mildronate 1 time before the start of traditional drug therapy to eliminate ischemia in the ulcer zone and eliminate pain syndrome per day for 7 days, and then this drug is taken orally at 0.25 g in the form of capsules 2 times a day, in the morning and at lunch, for 3 weeks.