CN112704727B

CN112704727B - Application of terlipressin in preparation of medicament for dynamic intestinal obstruction

Info

Publication number: CN112704727B
Application number: CN202110037892.2A
Authority: CN
Inventors: 周智; 雷宇; 钟珊
Original assignee: Second Affiliated Hospital of Chongqing Medical University
Current assignee: Second Affiliated Hospital of Chongqing Medical University
Priority date: 2021-01-12
Filing date: 2021-01-12
Publication date: 2023-05-16
Anticipated expiration: 2041-01-12
Also published as: CN112704727A

Abstract

The invention relates to an application of terlipressin in preparation of a medicament for treating dynamic intestinal obstruction. The dynamic ileus is the dynamic ileus complicated with the middle and late liver diseases, and the dynamic ileus can also be the dynamic ileus complicated with the primary peritonitis caused by liver cirrhosis. The technical scheme of the invention can support and supplement the existing treatment scheme to a certain extent, and has important clinical significance for treating complicated patients with liver cirrhosis complicated with dynamic intestinal obstruction.

Description

Application of terlipressin in preparation of medicament for dynamic intestinal obstruction

Technical Field

The invention relates to the technical field of new application of medicines, in particular to application of terlipressin in preparation of medicines for treating dynamic intestinal obstruction.

Background

Incomplete ileus refers to a disease in which part of intestinal contents cannot pass through the intestinal tract normally and smoothly due to various reasons, and pathological and physiological changes occur in intestinal tracts and organisms. According to the cause, mechanical ileus, dynamic ileus, and blood-borne ileus can be classified. Among them, the pathogenesis of dynamic intestinal obstruction is complex and various, and dynamic intestinal obstruction can be classified into paralytic intestinal obstruction and spasmodic intestinal obstruction. Currently, the mainstream view is that it is caused by dysfunction of intestinal wall muscle due to nerve reflex or toxin stimulation, and causes loss of intestinal peristalsis or intestinal canal cramps (pathogenesis and diagnosis analysis of dynamic ileus, wang Xueyuan et al, 2010). In recent years, the disease has a remarkable rising trend, particularly high incidence in autumn and winter, and the disease can occur in all age groups and all sexes. The treatment mode of the disease is conventional treatment and operation treatment. The conventional treatment method comprises the following steps: the methods have poor clinical treatment effects, are difficult for some patients to tolerate, and some patients can develop new complications, such as aggravated infection, hepatorenal syndrome, digestive tract hemorrhage and the like. The clinical management of dynamic ileus in patients with advanced liver disease is very tricky and difficult, and more effective treatments need to be sought. No specific medicine for treating dynamic ileus exists at present, and once the dynamic ileus is diagnosed, patients are required to fasted, depressurized or enemad in gastrointestinal tract to relieve symptoms such as abdominal distension, abdominal pain and the like. However, these symptomatic methods have no effect on most patients, and some patients are uncontrollable due to ileus, and new complications occur and the treatment is abandoned.

Furthermore, in a large number of clinical works, the team of the present invention found that many patients were not single-onset dynamic ileus, but often co-located with other complex diseases, such as cirrhosis of the liver with concurrent dynamic ileus due to multiple causes, resulting in greater treatment difficulty. Hepatitis b, among viral hepatitis, is statistically a major cause of cirrhosis. If the treatment is not timely, the liver cirrhosis decompensation period can be entered. Liver cirrhosis decompensation refers to the development of liver cirrhosis to a certain extent beyond liver function decompensation, and common complications are as follows: primary peritonitis, gastrointestinal hemorrhage, hepatorenal syndrome, etc. The treatment difficulty of the liver cirrhosis in the period is extremely high, the prognosis is poor, and the death rate of the liver cirrhosis in 3 years is more than 70 percent (the entecavir and manna disinfection pill are applied to the treatment of the hepatitis B liver cirrhosis in the compensatory period, ma Xueru, 2016). Because of more complications in the decompensation stage of liver cirrhosis and great treatment difficulty, a medicine suitable for treating liver cirrhosis complicated with dynamic intestinal obstruction caused by various reasons is needed.

Disclosure of Invention

In view of the above, the invention aims to provide a medicament for treating dynamic intestinal obstruction, which has the following specific technical scheme.

Use of terlipressin in the manufacture of a medicament for the treatment of dynamic ileus, which is a dynamic ileus that is the complication of liver disease.

Further, the dynamic ileus is a secondary dynamic ileus complicated by middle and late liver disease.

Further, the dynamic ileus may also be cirrhosis with primary peritonitis and dynamic ileus.

Further, the medicament also contains pharmaceutically acceptable carriers and/or auxiliary agents.

Further, the medicament contains terlipressin and optionally one or more pharmaceutically acceptable carriers, diluents or excipients and is added using a suitable preparation method or procedure. The term "pharmaceutically acceptable" as used herein refers to compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of patients without undue toxicity, irritation, allergic response, or other problem and complication, and are commensurate with their intended use.

The dosage forms of the medicine comprise tablets, water aqua, injection or suspending agent. Such formulations may be prepared by any method known in the pharmaceutical arts, for example, by mixing the active ingredient with carriers or excipients.

Modes of administration of the above drugs include oral administration and/or injection administration. Preferably by injection.

Further, the doses of the above drugs in the injection administration mode are as follows: 1 mg/dose, once every 8-12 hours (2-3 times per day depending on the condition of the patient), and the administration period is 3-5 days. When terlipressin is used for treating other bleeding symptoms, the recommended dosage of terlipressin obtained in batches is: intravenous injection, 2-4mg once for adult, followed by 1mg every 4-6 hours for 2-3 days, until bleeding control. The dosage of terlipressin used for treating complicated dynamic intestinal obstruction is obviously different from the dosage of the obtained batch indication.

A pharmaceutical combination composition for the treatment of dynamic ileus comprising terlipressin and an anti-infective agent. The pharmaceutical combination composition is suitable for the situation that infection occurs.

Further, the dynamic ileus is a dynamic ileus that is concurrent with liver disease.

Further, the anti-infective drug comprises imipenem and/or biapenem.

In one embodiment of the invention, imipenem and/or Abipenem are/is used in combination with terlipressin, so that the treatment effect on patients with incomplete ileus complicated with cirrhosis is better. The pharmaceutical combination compositions provided by the present invention may actually include other anti-infective drug species. Including antibacterial antibiotics, antiviral, antifungal, etc.

Advantageous effects

The invention provides an application of terlipressin in preparation of a medicament for treating dynamic intestinal obstruction. Terlipressin itself is a drug approved for topical use in the treatment of bleeding in the gastrointestinal tract and genitourinary system and post-operative bleeding as well as gynecological surgery. In the actual clinical work, the team of the invention discovers that in the treatment of the patients with liver cirrhosis complicated with dynamic ileus and liver cirrhosis complicated with primary peritonitis complicated with dynamic ileus, the application of terlipressin can lead the condition of the patients with the original ileus to be relieved in time, and compared with the traditional conventional treatment means, the application of terlipressin obviously shows better curative effect. Therefore, the technical scheme of the invention can support and supplement the existing treatment scheme to a certain extent, and has important clinical significance for treating complicated patients with liver cirrhosis complicated with dynamic intestinal obstruction.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. Other figures may be derived from these figures without inventive effort for a person of ordinary skill in the art.

FIG. 1 is a graph of changes in intestinal impact of a patient with ileus and after treatment (a: significant intestinal gas accumulation with ileus, level, b: substantial disappearance of intestinal gas accumulation after treatment with terlipressin);

FIG. 2 is a graph of the change in intestinal effect of a patient with and after ileus (a: the level of fluid displayed by the abdominal plat when ileus occurs, b: the increase in ileus before it is treated by conventional treatment, c: the relief of ileus after use of terlipressin);

FIG. 3 is a graph of changes in intestinal impact of a patient with ileus and after treatment (a: showing fluid levels with ileus and b: significantly reduced fluid levels after treatment with terlipressin).

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.

As used in this specification, the term "about" is typically expressed as +/-5% of the value, more typically +/-4% of the value, more typically +/-3% of the value, more typically +/-2% of the value, even more typically +/-1% of the value, and even more typically +/-0.5% of the value.

Example 1

Preparation of a medicine for treating complicated dynamic intestinal obstruction

The medicament contains terlipressin and optionally one or more pharmaceutically acceptable carriers, diluents or excipients and is added using a suitable preparation method or procedure. The term "pharmaceutically acceptable" refers to compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of patients without excessive toxicity, irritation, allergic response, or other problem and complication, and are effective for their intended use.

For example, for administration in the form of an injection, the active pharmaceutical ingredient (terlipressin) may be admixed with a pharmaceutically acceptable non-toxic inert carrier (e.g., glycerol, mannitol, sorbitol, water, etc.). Is prepared by pulverizing the active ingredient compound into a suitable fine size and then mixing with a pharmaceutically acceptable carrier.

The pharmaceutical formulations may be in unit dosage form, each unit dosage containing a predetermined amount of the active ingredient. The administration method may be used as long-term or short-term therapy. The amount of active ingredient admixed with the carrier material to prepare a single dosage form will vary depending upon the disease to be treated, the severity of the disease, the time of administration, the route of administration, the rate of excretion of the compound employed, the time of treatment and the age, sex, weight and condition of the patient. Preferred unit dosage forms are those containing a daily dose or divided dose of the above-described active ingredient or an appropriate fraction thereof. In general, the most desirable levels of concentration at which the compound is administered are those that generally provide effective results in the treatment of a particular disease (treatment of dynamic ileus) without causing any deleterious or toxic side effects.

Terlipressin (chemical name is N-alpha-triglycinyl-8-lysine-vasopressin, molecular formula is C ₅₂ H ₇₄ N ₁₆ O ₁₅ S ₂ . Terlipressin is an artificially synthesized long-acting vasopressin preparation which is metabolized into an active product through enzyme cleavage after entering a human body to play a pharmacological role. It has the main functions of shrinking blood vessel and resisting bleeding. Currently, the indications for which terlipressin has been approved are only topical applications for the treatment of bleeding in the gastrointestinal tract and the genitourinary system, and post-operative bleeding, gynaecological surgery, and the like. In the existing clinical study, terlipressin is mainly used for treating hepatorenal syndrome, esophageal varices hemorrhage, refractory shock, intra-operative hypotension and the like (terlipressin clinical study progress, qi Hu and the like, 2012). There is no published literature showing that it can be used to treat concurrent dynamic ileus.

In actual clinical work, the team of the invention finds that when terlipressin is used for treating patients with liver cirrhosis of gastrointestinal hemorrhage and hepatorenal syndrome, the conditions of enhanced intestinal peristalsis, increased stool frequency and the like can occur after a few patients are treated, and the mechanism is presumed to be as follows: terlipressin constricts visceral vascular smooth muscle and reduces visceral blood flow, thus potentially alleviating intestinal wall edema due to peritonitis; in addition, terlipressin can also act on intestinal smooth muscle to promote intestinal peristalsis and increase defecation and evacuation of intestinal tract. This discovery provides the inventive team with insight into the application of terlipressin to the treatment of cirrhosis patients with concurrent dynamic ileus.

Example two

Clinical data for terlipressin treatment of concurrent dynamic ileus

We collected case data from 12 patients. The details are as follows.

1) Permit xx, male age 49. Admission diagnosis: 1. chronic acute liver failure; secondly, alcoholic cirrhosis decompensation, ascites and splenomegaly; 3. gastrointestinal hemorrhage: esophageal gastric fundus varices rupture and bleed; 4. spontaneous peritonitis; fifth, pulmonary infection; sixthly, hypoalbuminemia. The treatment is as follows: symptomatic support treatment such as protecting liver, removing jaundice, supplementing albumin, promoting urination, inhibiting acid, protecting stomach, stopping bleeding and the like, and is subjected to imipenem anti-infection treatment. On the 4 th day of hospital admission, the abdominal pain of the patient is relieved as compared with the prior abdominal pain, the abdominal distension and the abdominal pain are still complained, the stool is yellow in color, the hidden blood is negative, the abdomen bulge is shown by the examination, the abdominal muscle is tensed, and the right abdomen tenderness is obvious. Perfecting abdomen vertical and horizontal position X-ray: 1. the small intestine qi accumulation and effusion in the abdominal cavity is slightly expanded, and the possible intestinal obstruction is considered, so that the clinical follow-up treatment is combined. 2. Peritoneal effusion. The infusion method is characterized in that the infusion method is used for fasted and prohibited drinking, clysis and 1mg of terlipressin is pumped into q12h (once administered every 12 hours) for treatment, and abdominal distension of a patient is obviously relieved after the infusion method is used for 3 days, so that the patient can self-relieve the bowels, and no abdominal distension appears after the diet is opened.

2) Bear x, male 47 years old. Admission diagnosis: 1. chronic acute liver failure; secondly, liver cirrhosis decompensation period after hepatitis B; 3. chronic viral hepatitis b; fourth, primary peritonitis; fifth, spleen size; sixthly, pneumoconiosis. The treatment is as follows: the anti-infective piperacillin and sulbactam are used for symptomatic support treatment such as liver protection, enzyme reduction, jaundice elimination, antiviral, albumin supplementation and the like after admission. After 3 days of admission, the abdominal tenderness of the patient was aggravated before, and imipenem anti-infective therapy was used instead. After 1 week of admission, the complaint of abdominal distension is evident. Checking: abdomen bulge, abdomen scattered light tenderness, high muscle tension and abdomen upright and lying position X-ray film prompt: the middle abdomen, small intestine, is marked by the symptoms of qi and liquid, taking into account ileus. The special vasopressin is pumped into the body for q12 hours by 1mg micro pump after the medicine is fasted and forbidden, the abdominal pain and abdominal distention of the patient are obviously improved before the medicine is treated for 2 days, the anus is used for exhausting and defecating, and the intestinal obstruction is considered to be relieved before the medicine is used for relieving.

3) Wuxx, male 71 years old. Admission diagnosis: 1. primary liver cancer is accompanied by intrahepatic metastasis; second, chronic viral hepatitis B; third, erosive gastritis. The treatment is as follows: the method is used for treating liver protection, antivirus, anti-tumor and the like, and is used for treating selective hepatic angiography and tumor nourishing arterial super-selectivity TACE operation in parallel, the following postoperative day is that the patients have poor spirit and appetite, obvious abdominal distension and can not be solved, the abdomen bulge is shown by the examination, the abdomen is slightly tender, the percentage of neutrophils is 91.9% >, and the C-reactive protein is more than 200 mg/L. Procalcitonin 2.5400 ng/ml ≡. Abdomen upright and lying position X-ray film prompt: low intestinal insufficiency ileus. Considering primary peritonitis and intestinal insufficiency, fasted and prohibited drinking, clysis and piperacillin sodium sulbactam sodium anti-infection treatment are carried out, and on the third day after operation, abdominal distension of a patient is not improved, abdominal tenderness is not improved, biapenem anti-infection treatment is converted, meanwhile, 1mg of terlipressin is micro-pumped into q12 hours for treatment, and on the fourth day after operation, abdominal distension of the patient is obviously improved and stool is discharged by oneself.

4) King xx, male 50 years old. Admission diagnosis: active hepatitis B liver cirrhosis decompensation. The treatment is as follows: after admission, the medicine is used for supporting and treating the symptoms such as liver protection, enzyme reduction, jaundice elimination, virus resistance and the like. Patients complain of abdominal distension, nausea, slightly distended abdomen, high tension, taking spontaneous peritonitis into consideration, the piperacillin sulbactam anti-infection treatment, after treatment, the jaundice further rises, liver failure appears, biapenem anti-infection treatment is replaced, artificial liver treatment is carried out, and the symptoms of the patients are better. When the patient is admitted for 2 weeks, the patient has abdominal distension again, the stool is not dissolved, the anus is occasionally exhausted, the abdomen is distended, the upper abdomen is pressed and painful, the borygmus is weakened, and the abdomen stands in the lying position and is flattened with X pieces: the small intestine in the upper abdominal region is slightly distended and accumulated with multiple small levels, and intestinal obstruction may occur. The method is characterized in that symptomatic treatments such as fasted, forbidden, vinegar enema and the like are carried out, 1mg of terlipressin is micro-pumped into the anus for q12 hours, after 3 days of treatment, the anus has defecation, abdominal distention is obviously improved before, and hunger sensation is obvious. Review abdomen upright and lying position plain film shows: the small intestine has slight accumulated qi and accumulated liquid, and compared with the former tablet, the small intestine has reduced accumulated qi and accumulated liquid. The graph of the intestinal tract influence of the patient before and after treatment can be seen in FIG. 1.

5) Field x, 42 years old men. Admission diagnosis: 1. chronic acute liver failure; second, chronic viral hepatitis B; third, spontaneous peritonitis; fourth, hypoalbuminemia. The treatment is as follows: the medicine is used for symptomatic treatment of liver protection, imipenem anti-infection, acid inhibition, stomach protection, blood coagulation correction and the like after admission. After two days of admission, the abdominal distension of the patient is obvious, the abdominal tension is slightly high, abdominal tenderness and rebound pain exist, and the abdomen vertical and horizontal X-ray film shows that: lower intestinal insufficiency ileus may occur. Fasted, liquid paraffin is orally taken to relieve constipation, 1mg of terlipressin is micro-pumped into q12h, and after 2 days of treatment, the patient can automatically relieve the stool for 4 times, and the abdominal distention is obviously relieved.

6) Qin x, 50 years old men. Admission diagnosis: 1. alcoholic combined liver cirrhosis decompensation stage, splenomegaly and ascites; second, chronic viral hepatitis B; third, spontaneous peritonitis; fourth, hypoalbuminemia; fifthly, peptic ulcer; type ii diabetes. The treatment is as follows: liver protection, enzyme reduction, jaundice elimination and albumin supplementation are treated symptomatically after admission; and the abdominal distension of the patient is improved after the artificial liver treatment and the anti-infection treatment of the paracillin and the sulbactam are carried out for one week, and the abdominal distension of the patient is changed into the imipenem anti-infection treatment for 1 week and the abdominal cavity is punctured in parallel to pump the ascites. Two weeks after admission, the patient still feels obvious abdominal distension aggravated, and the abdominal percussion is a drummer, and the abdomen upright and lying position X-ray film is checked: 1. the middle abdomen, small intestine and qi accumulation and fluid accumulation are slightly expanded, and the possibility of intestinal obstruction is considered, and the clinical follow-up is combined. 2. The lower right lung had little chronic inflammation. The patient is prescribed to be fasted and prohibited to drink, enema is carried out, and terlipressin is pumped into q12h for treatment by 1mg in a micro-quantity way, after 2 days, the abdominal distension of the patient is obviously relieved before, after 4 days of treatment, the abdominal distention of the patient is completely relieved, and the abdomen is soft without tenderness and rebound pain.

7) Liu Shix, male 63 years old. Admission diagnosis: 1. the decompensation period of hepatitis B cirrhosis, ascites and hypoproteinemia; second, primary peritonitis; type ii diabetes; fourth, renal insufficiency. The treatment is as follows: is used for treating the symptoms such as diuresis, liver protection, blood sugar control, moxifloxacin anti-infection and the like. On the 3 rd day of admission, the patient complains about obvious abdominal distension, unreliated stool, abdominal percussion bulging, mobility voiced sound positive, abdominal distension and abdominal upright and lying position flat tablet prompt: 1. the abdominal small intestine is dispersed in the accumulated air and part of the intestinal cavity expands the accumulated liquid, and the close follow-up of the possibility of the external incomplete intestinal obstruction is suggested. 2. The abdomen density was increased, and the abdominal fat line and the lumbar muscle line on both sides were not clearly developed, suggesting abdominal dropsy. Taking intestinal obstruction into consideration, ordering patients to forbid fasted food, and taking liquid paraffin for moistening intestines and glycerin enema for 3 days, wherein the abdominal distention of the patients is not obviously improved, and the abdominal upright and lying position tablet is reviewed: 1. the abdominal small intestine powder is characterized by qi accumulation, partial intestinal cavity expansion hydrops and gas-liquid level display, and is more aggravated before, so that the possibility of intestinal obstruction caused by low-level insufficiency of the small intestine is prompted, and close follow-up is suggested. 2. The abdomen density was increased, and the abdominal fat line and the lumbar muscle line on both sides were not clearly developed, suggesting abdominal dropsy. The treatment of protecting liver, promoting urination, controlling blood sugar, and relaxing bowels by enema is continued, and 1mg micro pump of terlipressin is added for q12h treatment, after 1 week, abdominal distention symptoms are relieved before, and the abdomen upright and lying position X plain film is reviewed: 1. the abdominal cavity is slightly accumulated with qi in the small intestine and slightly distended in the intestinal cavity, and the scope and the degree are reduced before the patient is asked to combine with clinic and follow-up. 2. The abdomen density is increased, the developing undersqing degree of the double-side abdominal fat line and the lumbar muscle line is slightly lower than that of the front side, and the clinical combination is requested. 3. The remaining signs are essentially the same as before. The graph of the changes in intestinal tract influence of the patient before and after treatment can be seen in FIG. 2.

8) Liu xx, male 66 years old. Admission diagnosis: 1. chronic acute liver failure; second, decompensation of hepatitis B liver cirrhosis; third, spontaneous peritonitis; fourth, chronic hepatitis B; fifth, hypoalbuminemia; sixth, paroxysmal atrial fibrillation. The treatment is as follows: the anti-infective piperacillin sulbactam is used for treating the infection, and is used for treating the artificial liver, so that the abdominal distending pain of patients is relieved slightly before and the appetite is improved. After 1 week, the patient again shows obvious abdominal distension, distended abdomen, light tenderness of whole abdomen, no rebound pain, slight tension of abdominal muscles, and the substitution of imipenem anti-infection treatment still shows abdominal distension, and the improvement of abdomen vertical and horizontal position X plain tablets is suggested: 1. low-lying obstruction of the small intestine. 2. The transmittance of the abdomen changes, accounting for the potential for abdominal dropsy. 3. Left lower abdominal high density nodules. 4. Bilateral pleural effusion in the projection range. When the terlipressin is added and 1mg of terlipressin is micro-pumped into the patient for q12 hours for treatment, the abdominal distention of the patient is obviously relieved before the patient is treated in 3 days, and the number and the amount of the stool are obviously increased.

9) Plum xx, male 59 years old. Admission diagnosis: 1. a decompensation period of chronic viral hepatitis b; 2. a decompensation period of alcoholic cirrhosis; 3. esophageal varices rupture and bleed; 4. portal hypertension gastric disease; 5. hypersplenism; 6. silicosis; 7. hypoalbuminemia; 8. a large amount of ascites; 9. hypokalemia; 10. spontaneous peritonitis. The diagnosis and treatment process comprises the following steps: the method is characterized by actively infusing human serum albumin, orally supplementing potassium, simultaneously carrying out symptomatic support treatment such as antiviral, liver protecting, imipenem anti-infection and the like, and carrying out abdominal cavity puncture liquid suction examination treatment. The abdominal distension and the abdominal upright and lying position of the emergency treatment patient after 1 day of hospital admission are shown in a flat sheet: lower intestinal insufficiency ileus may occur. Taking into account that the secondary paralytic ileus of spontaneous peritonitis may be large, fasted and prohibited; the terlipressin is added and 1mg of the micro-pump is used for q12 hours, and after 3 days of treatment, the patient can relieve dark green stool for 3 times, and the abdominal pain and the abdominal distention are obviously relieved.

10 Gold xx, male 57 years old. Admission diagnosis: 1. primary liver cancer is accompanied by lung, peritoneum, portal vein and gallbladder metastasis; 2. in decompensation stage of hepatitis B liver cirrhosis, varicose vein of stomach fundus and esophagus, ascites, splenomegaly and portal hypertension; 3. chronic viral hepatitis b; 4. spontaneous peritonitis; 5. hypertension; 6. pleural effusion; 7. gall bladder calculus. The treatment is as follows: symptomatic support treatment such as fluid infusion, liver protection, piperacillin sulbactam anti-infection and the like is carried out after admission. The abdominal distension of the patient is obvious, the abdominal distension and the abdominal muscle tension are obvious, the abdominal tenderness is obvious, and the abdomen vertical and horizontal X-ray prompt is completed: 1. the abdominal cavity small intestine qi accumulation accompanied with qi-liquid balance should be closely reviewed in consideration of the possible intestinal obstruction. 2. Peritoneal effusion. Taking the liquid paraffin for forbidden and fast feeding, accompanying the disease, glycerol enema and oral liquid paraffin for relaxing the bowel, placing a stomach tube for gastrointestinal decompression and other symptomatic treatments, the abdominal distension of the patient is not obviously improved after 3 days of treatment, the imipenem anti-infective treatment is converted, 1mg of terlipressin is micro-pumped into q12h, and the abdominal pain and the abdominal distension of the patient are obviously relieved before 3 days of treatment according to the new scheme.

11 Ancient xx, 53 years old. Admission diagnosis: 1. decompensation of hepatitis B liver cirrhosis, splenomegaly and abdominal dropsy; 2. chronic acute liver failure; 3. spontaneous peritonitis; 4. hypoalbuminemia; 5. hypokalemia; 6. ileus (intestinal obstruction); 7. cerebral hemorrhage sequelae. The treatment is as follows: after admission, the food is temporarily fed 1. Forbidden to drink, glycerin enema is carried out; 2. piperacillin sulbactam anti-infective therapy; 3. liver protection, antivirus, albumin supplementing, and diuretic. After 2 days of treatment, the patient can relieve a small amount of dry stool, the abdominal distention is not obviously improved, and the patient can discharge the stool after 2 days of treatment by adding 1mg of terlipressin and pumping the terlipressin for q12 hours, and the abdominal distention is obviously improved, and the abdomen is soft, free of tenderness, rebound pain and muscle tension.

12 Chua xx, male 55 years old. Admission diagnosis: 1. a decompensation period of hepatitis B liver cirrhosis; 2. after the varicose vein ligation operation of the esophagus and the stomach bottom; 3. primary peritonitis; 4. incomplete ileus; 5. ascites; 6. hypoalbuminemia; 7. after splenectomy; 8. portal hypertension gastric disease; 9. hiatus hernia. The treatment is as follows: 1. fasting and forbidding; 2. imipenem (tenability) cilastatin sodium powder injection anti-infection treatment; 3. terlipressin 1mg was micropump into q12h;4. liver protection, enzyme reduction, antivirus, albumin supplementing, and diuresis. After 2 days of treatment, the patient relieves the stool, the abdominal distention is obviously improved, and the abdomen is soft, and has no tenderness, rebound pain and muscle tension. Review abdomen upright and lying position X-ray: 1. lower intestinal insufficiency is relieved slightly before the patient is asked to follow. 2. Peritoneal effusion may occur. After the treatment is continued for 7 days, the general condition of the patient can be relieved, and the abdominal distention is obviously relieved before. The graph of the changes in intestinal tract influence of the patient before and after treatment can be seen in FIG. 3.

Table 1 summary of clinical case data for patients

Age range of patient	42 years old-71 years old
		Sex of patient	Man's body&Female
Indication of disease	Incomplete ileus, dynamic ileus
		Complications of the invention	Cirrhosis, incomplete ileus, peritonitis in patients with chronic acute liver failure caused by various reasons.
Administration mode	Administration by injection
		Dosage for administration	1mg, administered once every 12 hours
Treatment time	3-5 days, individual patients had improved treatment for 1 week
		Auxiliary medicine	Imipenem, biapenem
The common manifestation of the drugs after administration	After the administration, the patient can relieve the stool or increase the stool frequency, and the abdominal pain and the abdominal distention are obviously relieved.

Summarizing: from the clinical data, when incomplete ileus appears in patients with cirrhosis complicated with primary peritonitis, on the basis of conventional treatment, terlipressin is added for micro-pumping treatment, and the ileus symptoms (detailed cases) of the patients can be relieved or relieved quickly after 3-5 days of treatment course, so that the clinical prognosis is obviously improved. After terlipressin is added, all treated patients have the phenomenon of knowing the stool or increasing the stool frequency and obviously relieving abdominal pain and abdominal distention, so that terlipressin can be considered to be effective in treating incomplete ileus.

Example III

Patient with terlipressin administration and conventional treatment patient observations contrast

Table 2 comparison of terlipressin treated patients and observations of conventional treated patients

* Remarks: conventional therapies herein refer to therapies relative to the administration of terlipressin, including contraceptive support therapies such as fasting, feeding withdrawal, enema, anti-infection, anti-viral, albumin supplementation, and diuretic.

Summarizing: the conventional treatment methods cannot achieve better treatment effects or are effective after a plurality of days. The patients' illness can be relieved by adopting terlipressin for treatment, generally 2-3 days.

The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above-described embodiments, which are merely illustrative and not restrictive, and many forms may be made by those having ordinary skill in the art without departing from the spirit of the present invention and the scope of the claims, which are to be protected by the present invention.

Claims

1. Use of terlipressin in the manufacture of a medicament for the treatment of dynamic ileus, wherein the dynamic ileus is a dynamic ileus complicated with liver disease.

2. The use of claim 1, wherein the dynamic ileus is a secondary or advanced liver disease.

3. The use of claim 2, wherein the dynamic ileus is also cirrhosis with primary peritonitis and dynamic ileus.

4. The use according to claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier and/or adjuvant.

5. The use according to any one of claims 1 to 4, wherein the dosage form of the medicament comprises a tablet or an aqueous formulation.

6. The use according to claim 5, wherein the aqueous formulation is an injection or suspension.

7. The use according to any one of claims 1 to 4, wherein the mode of administration of the medicament comprises oral administration and/or injection administration.

8. The use according to claim 7, wherein the medicament is administered by injection in a dose of: 1 mg/time, and once every 8-12 hours, the administration period is 3-5 days.