RU2215546C1 - Method for treating inspecific ulcerous colitis - Google Patents

Abstract

FIELD: medicine, gastroenterology. SUBSTANCE: it is suggested to introduce intraarterially, into area of affected colonic wall, microcrystalline suspension of hydrocortisone. Simultaneously, one should introduce disaggregants and heparin. The present method provides local deposition of preparation along with prolonged curative action. EFFECT: higher efficiency. 1 ex, 3 dwg

Description

 The invention relates to medicine, namely to gastroenterology, and can be used in the treatment of patients with ulcerative colitis (ULC).

 Nonspecific ulcerative colitis: a chronic inflammatory and destructive disease of the mucosa and submucous membranes of the colon with a primary lesion of its distal part (rectum). The incidence occurs in 2-7: 100,000 of the population, mainly in women aged 15 to 30 years (Jarrell B.E., Carabasi R.A., 1996). The etiology of inflammatory changes in the intestinal wall in this disease remains unknown, however, the generally accepted theory is the effect of one or more antigens of intestinal origin leading to a change in the body's immune reactivity and local inflammation (Schacter T., Kirsner J.B., 1980). These reactions are controlled by genetic factors that affect the body's reactivity.

 A known method for the treatment of UC by exposure to drugs on the inflammatory process in the wall of the colon. The main significance is given to two of their groups: sulfasalazine (salofalk), used intravenously or orally, or topically, in the form of suppositories and enemas, and corticosteroids, also administered topically with enemas, or systemically, intravenously (Jarrell BE, Carabasi RA, M . GEOTAR, Medicine, 1997, 102 pp.). However, the known method is not effective enough, due to the low bioavailability of the administered drugs.

 The closest to the achieved positive result is a method of treatment by using corticosteroids (prototype) with pronounced anti-inflammatory and immunosuppressive properties (Beeken WL 1988, in the book "Gastroenterology". M: Medicine, 1988, part 3, p.63-64 ) Of the latter, prednisone and hydrocortisone are used both parenterally (intravenously) and topically, through the mouth and in the form of enemas. However, the known method does not provide a local high concentration in the lesion, which in this disease is the wall of the colon. When introduced through the mouth or into the lumen of the colon with a high activity of the inflammatory process, the absorption of drugs slows down sharply, which requires the appointment of their higher doses. A low activity of drugs in a pathologically altered intestinal wall is also observed with their parenteral administration, since they do not have organ-specificity. The use of higher doses and long courses of corticosteroid therapy is accompanied by undesirable side effects affecting almost all systems of the body.

 A positive result of the claimed invention is to increase the effectiveness of the treatment of ulcerative colitis by targeted administration of corticosteroids, and in particular hydrocortisone, into the vascular region of the affected colon.

 A positive result is achieved by the fact that hydrocortisone is injected intraarterially directly into the region of the affected colon in the form of a microcrystalline suspension after preliminary intraarterial administration of disaggregants in order to reduce local thrombotic effects and improve microcirculation.

 The essence of the invention: local administration of drugs leads to a more pronounced therapeutic effect on the affected intestinal wall, in lower total doses and with less systemic side effects. As one of the ways to increase the local concentration of the drug agent in the intestinal wall, an intra-arterial, in the upper or lower mesenteric artery is proposed.

 The method is as follows.

 Before the course of treatment, patients undergo instrumental confirmation of the nature and localization of the pathological process, including irrigoscopy, sigmoidoscopy or colonoscopy with a biopsy. Given the invasiveness of the method, it is used only with a persistent recurrent course of the disease, and in the absence of effect after a known traditional course of treatment.

 After sedation, in X-ray, aseptic conditions, according to the Seldinger technique, under local anesthesia with novocaine or another drug, the right or left femoral artery is punctured with a puncture needle from the Seldinger kit. Next, a metal angiographic guidewire is first introduced through its lumen and, finally, an X-ray contrast catheter for selective catheterization and angiography of mesenteric vessels with a diameter of 6 French (Fr), the tip of which is specially modeled for selective catheterization of the visceral branches of the abdominal aorta. Under the control of X-ray television, the catheter tip is installed in the lower mesenteric artery, which is determined by the localization of the pathological process (distal or proximal colon) (Fig. 1). According to special indications (with prolonged stubborn course of inflammatory diseases of the colon, resistance to traditional methods of treatment), in case of damage to the right half of the colon, catheterization of the superior mesenteric artery is performed. Then, selective angiography is performed by the introduction of radiopaque water-soluble preparations (urographin, omnipack) with registration of the arterial, capillary and venous phases of the blood flow. On angiograms, the architectonics of the arterial and venous channels of the affected intestinal wall is determined, the location of the catheter is documented, the tip of which remains at the mouth of the artery for further regional infusion. For the prevention of thrombosis, the catheter lumen is filled with heparinized saline, its peripheral end is placed cutaneous and fixed with a skin suture, not far from the puncture site. The catheter insertion site is isolated with an aseptic dressing.

 In the ward, an automatic dispenser is connected to the peripheral end of the catheter, with which a regional drug infusion is performed.

 Given the nature of the pathological changes in the intestinal wall, the composition of the infusion includes two groups of drugs: the first consists of disaggregants (trental 10 ml i / v per day) and anticoagulants (heparin 2500 IU / a, 4 times) aimed at improving microcirculation in inflammatory an altered wall of the intestine, and the second group of drugs includes hydrocortisone and antibiotics that directly affect the inflammatory process in the intestine. In this case, the main drug is hydrocortisone, which belongs to the group of glucocorticoids. It is a suspension of crystals of irregular shape, the size of which lies in the range from 50 to 800 microns (Hydrocortisone-Richter, Budapest-Hungary, 5 ml bottles containing 125 mg hydrocortisone acetate). This drug has anti-inflammatory, desensitizing and anti-allergic effects, reduces capillary permeability. The introduction of the drug in the form of poorly soluble suspension leads to its deposition in the capillary bed due to microembolization of some of them. This contributes to a longer local therapeutic effect.

 Regional intra-arterial infusion is used continuously for 5-7 days, depending on the clinical effect. It leads to a quick relief of the inflammatory process and gives a prolonged therapeutic effect. With local use of hydrocortisone, systemic side effects are not observed.

 The proposed method is used in the treatment of 9 patients with ulcerative colitis. Complications associated with the use of this method of treatment were not observed. Long-term results up to 1 year were traced in 3 patients. In all cases, according to the clinic, control sigmoidoscopy and colonoscopy showed no signs of exacerbation of the disease.

 Clinical example.

 Patient K., 25 years old (case history 3062), was admitted to the gastroenterological department of the regional clinical hospital with complaints of frequent loose stools mixed with blood and mucus, pain in the left iliac region, rumbling and bloating, nausea, vomiting, body temperature up to 38 degrees severe weakness.

 From the anamnesis of the disease: sick since 1997, when a clinic appeared, similar to the above complaints. Then I was constantly hospitalized 2-3 times a year in the gastroenterological department of the regional hospital. Each treatment course included 3 groups of drugs: prednisone, sulfsalazine and metronidazole. Clinical improvement occurred after 3-5 weeks of inpatient treatment, and then the patient was discharged for outpatient treatment, which included the continuous intake of sulfsalazine and prednisolone.

 Objectively: the patient’s condition is moderate, exhausted, asthenic physique, the skin is pale, their turgor is slightly reduced. By organs and systems without features.

 Locally: the tongue is covered with a white coating, the abdomen is pulled in, there are no palpation symptoms of peritoneal irritation, sharp pain and rumbling in the projection of the transverse colon and sigmoid colon are determined.

The results of laboratory studies. General blood test: red blood cells 3.9 million, hemoglobin 124 g / l, platelets 230 thousand, white blood cells 27.7 thousand .; leukocyte formula: eosinophils 1%, stab neutrophils 19%, segmented neutrophils 69%, lymphocytes 9%, monocytes 2%, erythrocyte sedimentation rate 21 mm / h. Total blood protein 68.4 g / l, albumin 46.3%, globulins: α ₁ -10.3%, α ₂ -16.0%, β-12.3%, γ-15.1%. Serum sodium 136 mmol / L, serum potassium 5.1 mmol / L. Coprogram: feces of liquid consistency, unformed, brown, acid reaction, erythrocytes - a large number, white blood cells up to 20 in sight.

 Sigmoidoscopy 464. The mucous membrane is loose, brightly hyperemic, eroded in places. Starting from 15 cm from the anus, it is contact vulnerable and here multiple ulcerative defects of irregular shape are determined.

 Selective catheterization mesentericography 372 The diameter of the inferior mesenteric artery is 4.6 mm, the arteries in the wall of the sigmoid and rectum are convoluted, there is a symptom of amputation in the rectosigmoid angle and uneven contrast in the parenchymal phase in the sigmoid colon (Fig. 2). The inferior mesenteric vein in the phase of back contrasting with a diameter of 8.2 mm.

Within 9 days the patient underwent regional, continuous intra-arterial infusion of two solutions:
Solution 1. Hydrocortisone 0.5 mg, Ringer-Locke solution 100 ml, heparin solution 2500 UNITS.

 Solution 2. Doxycycline 0.1 g, Claforan 1.0 g, Ringer-Locke solution 100 ml, heparin solution 2500 UNITS.

 Each solution was administered alternately, lasting 6 hours.

 After 9 days, a control laboratory and instrumental examination was performed.

 Total an. blood: erythrocytes 3.7 million, hemoglobin 115 g / l, platelets 290 thousand, leukocytes 4.0 thousand, leukocyte formula: eosinophils 1%, stab neutrophils 5%, segmented neutrophils 47%, lymphocytes 40%, monocytes 7% .

 Sigmoidoscopy 513. Mucous in the area up to 12 cm. Pale pink, moderately edematous, vascular pattern preserved. More proximally, the mucosa in places is moderately hyperemic, slightly swollen.

 Repeated mesentericography before removal of the catheter from the NBA. Contrasted throughout the branches of the inferior mesenteric artery. There is a significant decrease in the deposition of a contrast agent in the wall of the sigmoid colon in the parenchymal phase and in the phase of venous return (figure 3).

 Clinically, the patient notes an almost complete relief of pain along the large intestine. Stool once a day, mushy, without impurities of mucus and blood.

 Examined after 6 months, no complaints, general condition satisfactory, no pain along the colon, stool once a day, mushy, without impurity of blood and mucus. Sigmoscopy 1936. Mucous in the area up to 20 cm. Pale pink, moderately swollen, vascular pattern slightly pronounced. In the sigmoid section of the intestine, the mucosa is moderately hyperemic in places, slightly edematous, and the vascular pattern is preserved.

 The inventive method has the advantage of a prototype: they use regional administration of drugs of pathogenetically directed action, which allows to provide the maximum local therapeutic effect on the pathological process in the intestinal wall and to avoid the side systemic effect of glucocorticoids. The introduction of a water-insoluble form of hydrocortisone in the form of a microcrystalline suspension into the intestinal wall is accompanied by its local deposition and a prolonged prolonged therapeutic effect.

Claims (1)

 A method of treating ulcerative colitis, which involves the administration of corticosteroid anti-inflammatory drugs, characterized in that hydrocortisone is administered intraarterially into the region of the affected colon intestinal wall in the form of a microcrystalline suspension with the simultaneous administration of disaggregants and heparin to exclude thrombotic effects and microembolization.

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