RU2520599C1 - Method for endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is performed is an endoscopic approach; further, biopsy forceps with a rolled complex bioplastic material cut in size of an ulcerous defect are introduced into a working path of a fibrogastroduodenoscope, laid on the ulcerous defect with the use of the biopsy forceps, and controlled with the use of an endoscopic examination 5-7 days later. The bioplastic material contains hyaluronic acid, a phosphate buffer system, omeprazole and clarithromycin taken in a certain equivalence ratio.

EFFECT: non-invasive treatment of ulcer and reduced length of mucosal tissue regeneration.

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Description

The invention relates to medicine, namely to abdominal surgery, gastroenterology, and may find application in the treatment of gastroduodenal ulcers.

Currently, current trends in the treatment of gastric ulcer are aimed at developing methods that replace surgical treatment, such as the creation of new drugs and new technologies for minimally invasive endoscopic techniques. Drug treatment of gastric ulcer includes two main pharmaceutical groups - antacids and blockers of gastric secretion.

Antacids neutralize hydrochloric acid, which is part of the gastric juice. These drugs contain magnesium, aluminum, calcium, as well as combinations thereof. Secretoblockers act in a depressing manner on the mechanisms of hydrochloric acid secretion. Among the antiulcer drugs, blockers of H ₂ histamine receptors, prostaglandins, and proton pump inhibitors are distinguished.

More recently, antibiotics began to be used against peptic ulcer to get rid of its main cause - Helicobacter pylori bacteria. The Second Maastricht Agreement puts in the first place among the indications for anti-helicobacter therapy gastric ulcer and duodenal ulcer, regardless of the phase of the disease (exacerbation or remission), including their complicated forms (Malfertheiner P., Megraud F., C. O 'Morain et al. Current concepts in the management of Helicobacter pylori infection the Maastricht 22000 Consensus Report. // Aliment. Pharmacol. Ther. 2002. V.16. P.167180). It is especially noted that eradication therapy for peptic ulcer disease is a necessary therapeutic measure, and the validity of its use in this disease is based on obvious scientific facts.

Drug treatment of peptic ulcer has a limitation associated with the systemic effect of drugs on the body, which is accompanied by the appearance of side effects, so the priority is the use of methods and means that act locally on the ulcerative process of the gastric mucosa. In this direction, the most appropriate and promising is the use of endoscopic methods in combination with local drug exposure, i.e. drug delivery to the focus of the disease in the stomach (duodenum).

A known method of endoscopic chipping of the gastric mucosa with a drug (Patent for the invention of the Russian Federation No. 2179858, A61K 38/02, A61P 1/04). Transendoscopic ulceration of the ulcer with splenopid is performed. The drug in a dose of 115-230 mg is diluted in 10 ml of a 0.25% solution of novocaine or saline and injected in 2-3 ml at three points along the edges of the ulcer in the submucosal layer. Treatment is also carried out against the background of traditional antiulcer therapy, including H ₂ histamine blockers and anti-Helicobacter pylori. Chipping procedures are carried out with an interval of 2-3 days, the number of procedures is 4-6. The method reduces the scarring of ulcers.

The disadvantage of this method is the inability to preserve the drug for a long time in the focus of the disease, which requires frequent procedures (4-6 per treatment course). Invasive manipulation, possibly a complication in the form of bleeding from the injection site. It should be borne in mind that this is an unpleasant and painful procedure.

The technical result of the proposed method for endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material is minimally invasive (non-surgical) treatment of ulcers and a reduction in the time of regeneration of tissues of the mucous membrane of the organ.

The problem is solved by the fact that in the method of endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material, including endoscopic access, biopsy forceps with integrated bioplastic material folded into a tube cut out by the size of the ulcerous defect are inserted into the working channel with a ulcerative defect, and the ulcerative defect is inserted into the working channel of the fibrogastroduodenoscopic ulcers control is carried out by endoscopic examination after 5-7 days, while the bioplastic material contains hyaluronic acid, phosphate buffer system, omeprozole and clarithromycin in the following ratio of components, wt.%:

hyaluronic acid 90 phosphate buffer system 5 omeprozole 2 clarithromycin 3

The phosphate buffer system neutralizes the excess hydrochloric acid and protects the underlying gastric mucosa from the aggressive effects of gastric juice.

Bioplastic material contains omeprazole in its structure, which inhibits the H ⁺ - K ⁺ -ATPase enzyme ("proton pump") in the parietal cells of the stomach and thereby blocks the final stage of hydrochloric acid synthesis. This leads to a decrease in the level of basal and stimulated secretion, regardless of the nature of the stimulus.

In addition, clarithromycin is included in the bioplastic material, which has a bactericidal effect against Helicobacter pylori, recognized by many researchers as a cause of peptic ulcer. Clarithromycin, unlike most macrolide antibiotics, is not hydrolyzed and is resistant to hydrochloric acid [Lapina TL, Ivashkin VT Modern approaches to the treatment of peptic ulcer of the stomach and duodenum // Russian Medical Journal. - T.3, No. 1, 2001. - 10-15; Lapina T.L. Modern approaches to the treatment of acid-dependent and N. pylori-associated diseases // Clinical prospects of gastroenterology, hepatology. 1, 2001. - 21-27].

Thus, for the new method of endoscopic bioplasty of gastroduodenal ulcers, a complex bioplastic material is used having the composition shown in the table.

Component Quantitative measure,% Component function Hyaluronic acid 90 The matrix carrier for the farm. drugs, effective regenerant. Provides adhesion (adhesion) to the gastric mucosa and prolonged biodegradation (14 days) Phosphate buffer system 5 Neutralization and protection against the irritating effect of excess hydrochloric acid in the area of a peptic ulcer Omeprazole 2 Neutralization and protection against the irritating effect of excess hydrochloric acid in the area of a peptic ulcer Clarithromycin 3 Bactericidal against Helicobacter pylori

Due to the branched network of hyaluronic acid macromolecules, the polymer is able to retain the above components in its inert chemical state in its structure. Using analytical chemistry methods, it was proved that no chemical reactions occur in the polymer matrix of hyaluronic acid, and omeprozole and clarithromycin remain chemically stable.

To date, the medical literature has not described methods for the endoscopic use of bioplastic materials for gastroduodenal ulcers, since complex biomaterials have not been developed with acid resistance, adhesion to the gastric mucosa and the ability to persist for a long time in the area of the ulcer defect until it is completely healed with the depot effect of the drug for omeprozole and clarithromycin.

The fundamental scientific novelty of the solutions in the proposed method of endoscopic bioplasty is the use of complex bioplastic material in endoscopic technology for the treatment of gastroduodenal ulcers. The properties of acid resistance and adhesion of the biomaterial to the mucous membrane allow the biomaterial to remain in the area of the ulcer defect for a long time with the effect of its accelerated regeneration.

In fact, an innovative solution is proposed to use complex bioplastic materials that have a local therapeutic effect due to the presence of omeprozole and clarithromycin. This provides a prolonged effect of the drugs and accelerate the healing of the gatroduodenal ulcers, which ultimately prevents surgical treatment and significantly (by 60%) reduces the patient’s hospital stay.

The method is as follows.

First, for the method of endoscopic bioplasty of gastroduodenal ulcers, a complex bioplastic material is prepared as follows.

1. The prescription amount of crystalline hyaluronic acid powder is diluted in 100 ml of distilled water, a viscous hydrocolloid is obtained, which is subjected to standard lyophilization for 3 hours to obtain an elastic film with an area of 100 square meters. see (10 × 10 cm).

2. A prescription amount of omeprazole and clarithromycin is added to 10 ml of phosphate buffered system, mixed thoroughly.

3. The resulting mixture is poured into a flat glass dish, there is placed an elastic film of a polymer of hyaluronic acid, incubated for 1 hour.

4. After an hour, the film completely absorbs 10 ml of a mixture of omeprazole, clarithromycin, phosphate buffer system. Integrated bioplastic material is ready for use.

Then, biopsy forceps are inserted into the working channel of the fibrogastroduodenoscopy with the extraction of the lips of the forceps through the distal opening of the channel. A fragment of a complex bioplastic material folded into a tube, cut out by the size of a ulcer defect (1-2 cm in diameter), is fixed with biopsy forceps. An endoscopic examination is performed, during which a complex bioplastic material is placed on the ulcer defect using biopsy forceps. The procedure is carried out once with a control endoscopic examination after 5-7 days. The method provides a reduction in the time of scarring of ulcers, as well as scarring of long-term non-healing ulcers that are not treatable by other means.

Examples of specific performance.

Example 1

Patient Sh., 39 years old, was admitted to the emergency department on September 11, 2012 with complaints of weakness and vomiting of "coffee grounds". Ulcerative history denied. At admission: a state of moderate severity. The skin is pale in color. The pulse of 108 beats per minute, blood pressure 10/60 mm Hg The abdomen on palpation is soft, painful in the epigastrium. With a digital examination of the rectum on the glove, black feces are determined. Fibrogastroduodenoscopy was performed: on the posterior wall of the duodenal bulb, a peptic ulcer up to 1.5 cm in diameter up to 0.5 cm deep with spots of hematin hydrochloride was detected. Conclusion: chronic duodenal ulcer complicated by bleeding. Low risk of relapse (Forrest IIC). Hospitalized in the surgical department.

The department conducted conservative hemostatic therapy, antiulcer therapy (proton pump inhibitors iv). Against the background of conservative treatment, the condition improved. In the control FGDS after 24 hours, the bottom of the ulcer is covered with fibrin. An endoscopic application of bioplastic material was performed on a ulcer defect. Subsequently, the patient received conservative antiulcer therapy in a lower dosage, including oral proton pump inhibitors and anti-Helicobacter pylori. FGDS control 5 days after application - ulcer healing.

Example 2

Patient D., 48 years old. Suffers from peptic ulcer for 6 years. Twice a year exacerbation of an ulcer. He was treated on an outpatient and inpatient basis with temporary success. Last exacerbation from 10/15/2012. He was treated on an outpatient basis, received oral proton pump inhibitors and anti-Helicobacter pylori. Due to the lack of effect, on October 30, 2012, he was hospitalized in the therapeutic department, where he received a complex of antiulcer drugs (proton pump blockers, antibiotics, antacids, vitamins). Against the background of the treatment, the pain syndrome decreased, but there was no endoscopically positive dynamics. FGDS control from 10.10.2012, an ulcer on the lesser curvature of the stomach 2 cm in diameter. An endoscopic application of bioplastic material for a ulcer defect was performed. Subsequently, the patient received conservative antiulcer therapy, including oral proton pump inhibitors and anti-Helicobacter pylori. FGDS control 5 days after application: the defect decreased to 1 cm, the bottom is filled with granulation tissue. FGDS control 10 days after application: the defect healed.

Thus, in comparison with the prototype, the method of endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material provides:

- increasing the effectiveness of endoscopic treatment of gastroduodenal ulcers;

- prevention of surgical operations;

- a significant reduction in the terms of regeneration of tissues of the mucous membrane of the organ, and therefore, the patient’s hospital stay.

Claims (1)

The method of endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material, including endoscopic access, characterized in that biopsy forceps are inserted into the working channel of the fibrogastroduodenoscopy with a complex bioplastic material folded into the tube, cut to the size of the ulcer defect, and the ulcers are checked with the help of biopsy endoscopic examination after 5-7 days, while the bioplastic material contains hyaluronic acid, phosphate buffer system, omeprozole and clarithromycin in the following ratio of components, wt%:
hyaluronic acid 90 phosphate buffer system 5 omeprozole 2 clarithromycin 3