CN102205115A - Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen - Google Patents
Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen Download PDFInfo
- Publication number
- CN102205115A CN102205115A CN 201110128992 CN201110128992A CN102205115A CN 102205115 A CN102205115 A CN 102205115A CN 201110128992 CN201110128992 CN 201110128992 CN 201110128992 A CN201110128992 A CN 201110128992A CN 102205115 A CN102205115 A CN 102205115A
- Authority
- CN
- China
- Prior art keywords
- ulinastatin
- shock
- medicament
- toxic shock
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention relates to a rescue medicament in the field of medical treatment, in particular to a rescue medicament, namely ulinastatin or a urinary trypsin inhibitor (UTI) for toxic shock caused by acute abdomen (particularly mesenteric angiemphraxis and the like). The medicament is a preferred medicament for the toxic shock. In the pharmacodynamic study of the ulinastatin for resisting shock, the ulinastatin also can improve the average arterial blood pressure and the average arterial blood flow of superior mesenteric artery occlusion shock of rats, and has an extremely better effect on shock rescue.
Description
Technical field
The present invention is the rescue medication of medical field, is especially rescuing toxic shock, particularly because of person due to the mesentery angiemphraxis etc., with the application of ulinastatin as first-selected medication.
Background technology
Ulinastatin (U1inastain or human urine trypsin inhibitor, Urinary TrypsinInhibitor UTI) is a kind of urinary trypsin inhibitor of separation and purification gained from male's urine, it is glycoprotein, contain 143 aminoacid, its bioavailability of intravenously administrable is 100%, half-life is more than 40 minute, after the administration, at kidney, run-up in the liver, the 5min peaking, 2h distributes the highest in seminal vesicle, and drug main will pass through renal excretion, and 12h is respectively 73% and 2.3% at urine and defecate after the administration.Mainly being that the original shape medicine is drained from urine in the 30min in discharge process, almost all is catabolite in the urine behind the 4h.This catabolite can suppress the active hyperfunction of multiple hydrolytic enzyme simultaneously, therefore is used for the treatment of acute pancreatitis etc.
Shock is to cause histanoxia owing to the peripheral circulation obstacle reduces effective blood flow of main organs, can not keep the state of normal metabolic function.Since histanoxia, and then discharge the factor that increases the weight of to suffer a shock, form vicious cycle.Therefore, the catecholamine and the development that the adrenocortical hormone that Antishock function is arranged can suppress to suffer a shock of boosting arranged, keep the stable of organism internal recycle.
Acute abdomen is common one of the reason of shock that causes, and the mesentery angiemphraxis is one of key factor that causes acute abdomen.The mesentery angiemphraxis can be formed by multiple reason, as volvulus, intussusception, intestinal obstruction, intestinal adhesion compressing, celiocele incarceration strangulation, or Mesenteric artery thromboembolism that is caused by the heart, angiopathy and abdominal part, colon cancer operation etc. or venous thrombosis etc. all can form, development rapidly, the state of an illness is heavily endangered, as untimely processing, mortality rate is high.
Aspect the treatment when toxic shock, the most important thing is to remove the causative factor that causes it, but this class disease difficult diagnosis or seek medical advice evening often, before such as methods such as the operation removal cause of disease, if there is not positive auxiliary emergency measures, often lose the effective time of treatment.But when rescuing this type of shock, generally be that blood volume is kept in transfusion at present, correct acid-base balance and electrolyte disturbance, and other symptomatic treatment, as vasoactive agent, hormone etc.Still lack effective measures more,, strive for the treatment that improves with the time that alleviates or delay to suffer a shock and take place.
Report is arranged, and (aprotinin Apr) has Antishock function in the protease inhibitor that extracts from pulmonis Bovis seu Bubali---aprotinin.At present, do not see ulinastatin and the relevant report of mesentery folder closing property shock as yet, do not look for through patent retrieval both at home and abroad and see relevant ulinastatin and the relevant entry of mesentery folder closing property shock.
Summary of the invention
The purposes that the purpose of this invention is to provide the salvage drug of the toxic shock that ulinastatin causes as acute abdomen.
Purpose of the present invention realizes in the following manner:
Toxic shock due to the use of the salvage drug of the toxic shock that ulinastatin causes as acute abdomen, particularly mesentery are blocked.Dosage is 2-4 time/day, and quiet of each 10-20 ten thousand units use 2-3 days.
Ulinastatin of the present invention generally uses with the form of pharmaceutical composition, this compositions contains the ulinastatin and the pharmaceutically acceptable auxiliaries as active component for the treatment of effective dose, the pharmaceutical composition that contains ulinastatin is usually with the intravenous route administration, and main dosage form comprises ulinastatin lyophilized injection and injection liquor.
Sterilization composition through intravenous administration, one to loose be solid sterilization composition form, these compositionss can also contain additive, particularly mannitol, lactose, gelatin hydrolysate, sodium chloride, glucose etc. can be dissolved in aquesterilisa or various other injection sterile medium in use.
Sterilization combination through intravenous administration also can be an aqueous solution, and these compositionss can also contain additive, particularly mannitol, sodium chloride, glucose etc.
Ulinastatin method for preparing freeze-dried powder: get ulinastatin aqueous solution 5,000 ten thousand units of the bacterium of going out, add 10 gram mannitol dissolvings, regulate pH to neutral, add injection water to 1000 milliliter, add sodium chloride and regulate aseptic filtration, in the packing cillin bottle, lyophilization under the aseptic condition.
The ulinastatin injection preparation: get ulinastatin aqueous solution 5,000 ten thousand units that sterilized, add 10 gram mannitol dissolvings, regulate pH to neutral, add injection water to 1000 milliliter, add sodium chloride and regulate, the filter of no mistake in treatment bacterium is in the packing cillin bottle.
The specific embodiment
For making the purpose, technical solutions and advantages of the present invention clearer, below in conjunction with specific embodiment, the present invention is described in more detail.
Experimental results show that giving Wu Sitading (being UTI) before bulldog clamp closes on the implementation rat mesentery can make the mean arterial blood pressure of laboratory animal and average blood flow volume significantly improve.Mean arterial blood pressure (UTI group 10.3 ± 0.9Apr group 8.4 ± 0.8P＜0.01) and average blood flow volume (UTI group 66 ± 5Apr group 40 ± 9P＜0.01).To taking place, shock plays the excellent prevention effect during to rescue.
Why ulinastatin has the good preventing effect in prevention or shock process, be to have an effect by following mechanism according to modern study;
Because shock is to cause histanoxia owing to the peripheral circulation obstacle reduces effective blood flow of main organs, therefore, the catecholamine and the development that the adrenocortical hormone that Antishock function is arranged can suppress to suffer a shock of boosting are arranged, keep the stable of organism internal recycle.
The ulinastatin countershock is not to remove the cause of disease that causes this shock, but suppress by thermal burn, endotoxin, hemorrhage, a series of disorders such as the circulation that takes place when allergy etc. cause shock, metabolism, endocrine, ulinastatin can comprehensive playing be adjusted and resistant function when shock takes place, thereby plays the effect that delays and alleviate the shock generation.
Experimental example 1 scald property shock
Press the Hechter method, the following position of mice axil line is immersed in 65 ℃ of hot water, continue 10S, observe 4 hours survival rate then.1min and immersion back 15min, 1 hour tail vein injection UTI before immersing hot water, totally 3 times; Volumetric injection is 10ml/kg, the then corresponding injection isometric(al) of matched group normal saline.The results are shown in following table
Protective effect (the X ± SD) of property shock is scalded in ulinastatin (being UTI) intravenous injection to mice
The result shows, ulinastatin (UTI) is scalded the protective effect (r=0.9603, P＜0.01) that the property shock is dose dependent to mice, compares with APR with dosage, and its protective effect is similar.
Embodiment 2 endotoxin shocks
The escherichia coli endotoxin normal saline solution of mice IP2 times LD50 (LD50 that mice IP records is 5.0121ml/kg) is observed 24 hours mice survival numbers, behind the IP endotoxin 5 minutes, 3 hours and 12 hours, according to the form below dosage tail vein injection UTI, the result is as follows.
Ulinastatin (being UTI) intravenous injection is to the protective effect of mice escherichia coli endotoxin shock
Compare with matched group,
*P＜0.05,
*P＜0.01
The result shows, ulinastatin 40000U/kg after the 80000U/kg intravenous injection, can improve the survival rate of mice escherichia coli endotoxin shock, shows significant protective effect, and relevant with dosage.
Embodiment 3 hemorrhagic shocks
During hemorrhagic shock, left heart contractility descends, the left ventricle output reduces, ABF reduces, and these indexs are improved behind the intravenous injection ulinastatin.Give the changes in heart rate not influence of ulinastatin to causing because of losing blood.Even hemorrhagic shock gives ulinastatin and also can improve urine amount and the renal blood flow that has reduced.Do not suffering from the animal of shock, ulinastatin is except that showing slight diuresis, to almost not effect of blood circulation.
Therefore, ulinastatin improves the circulatory disturbance that is caused by shock single-mindedly, and ulinastatin can suppress the development of shock, and the vicious cycle that blocking-up is suffered a shock has important effect.
Experiment Preparation rat hemorrhagic shock model, the rat overnight fasting, with pentobarbital sodium 45mg/kg IP anesthesia, tracheal intubation, autonomous respiration, 0.4% heparin-saline is pressed the 400u/kg intravenous injection, the whole body anticoagulant, a side femoral artery is inserted plastic tube and is used for blood-letting; The opposite side femoral artery is inserted plastic tube and is fed back blood usefulness fully; One side common carotid artery intubate links to each other with rat hydrargyrum inspection pressing, the preceding blood pressure of record blood-letting, then from the quick blood-letting of femoral artery, to blood pressure be 40mmHg (5.33Kpa).Blood pressure often has rise, needs repeatedly blood-letting, and when having only an amount of blood of feedback just can keep 40mmHg, this is the compensatory beginning of mistake up to the blood pressure blood pressure drops.From blood-letting first to the time of losing compensatory beginning is the compensatory time; Total blood volume of being emitted in compensatory process is maximum blood loss.After the appearance mistake is compensatory, the blood of being emitted is failed back from femoral vein immediately, continued to observe 2 hours.Write down the compensatory time, 2 hours blood pressure behind maximum blood loss and the feedback blood.UTI by 5ml/kg preceding 10 minutes of blood-letting be mixed in the blood of feedback intravenous injection, secondary altogether; Matched group is then given and isometric(al) normal saline, result such as following table
Ulinastatin (being UTI) intravenous injection is to the treatment effect of rat hemorrhagic shock (n=10, X ± SD)
Compare with matched group
*P＜0.05,
*P＜0.01
The result shows that ulinastatin group (UTI group) and matched group compare, and the blood pressure behind the compensatory time of rat hemorrhagic shock, maximum blood loss and the feedback blood is all had to be increased or the rising effect, and is dose-dependence.
Embodiment 4
Treatment effect to closing property of bulldog clamp shock on the rat mesentery: closing property of bulldog clamp shock (SMAO) model on the preparation rat mesentery.Rat is with 10% urethane solution 1g/kg, intraperitoneal injection of anesthesia.Fix and sterilization skin, do median abdominal incision, separate superior mesenteric artery (SMA) and one section ventral aorta; Ventral aorta is connected with blood flow transducer (FC-020T) probe, so that survey blood flow (MABF); The left common carotid artery intubate is led physiograph (manufacturing of Japanese photoelectricity company) through MPU-0.5 type pressure transducer and eight and is connected, with record mean arterial blood pressure (MABP) and heart rate (HR); Separate left external jugular vein and be equipped with administration.Art finishes, and animal was stablized 10 minutes, after the record These parameters, closes the SMA initial part with noinvasive bulldog clamp folder, presss from both sides back 30 minutes from left external jugular vein injection UTI or isometric(al) normal saline, is 5ml/kg.Folder closes to 60 minutes degrees of tightness, and folder closes the abdominal cavity.Before the pine folder, the pine folder reaches back 2 hours of pine at once, the record These parameters.
Ulinastatin (being UTI) intravenous injection is to tremulous pulse on the rat mesentery
The hemodynamic influence of folder closing property shock (n=7, X ± SD)
Compare with the normal saline group,
*P＜0.05,
*P＜0.01
The result shows, the MABP of pseudo-operation treated animal, and MABP and HR are stable at whole experimental session.UTI group and APR group were pressed from both sides back 2 hours in pine, and MABP descends and all is less than the NS group; UTI group and APR group compare, and the decline of the former MABP is less than the latter.Prompting UTI and APR group have preventive and therapeutic effect to the MABP decline of SMAO rat, and UTI is stronger than the APR effect.The MABF of UTI group pressed from both sides back 2 hours in pine, and the reduction degree obviously is less than APR group and NS group.The APR group is organized relatively with UTI group and NS, presss from both sides back 2 hours with pine at once the folder pine, and MABF all obviously reduces, and prompting APR fails to prevent and treat the MABF minimizing of SMAO rat.
Experimental result proves that UTI of the present invention all has tangible prevention and therapeutical effect to the shock due to the multiple reasons such as scald property, toxic, losing blood property and superior mesenteric artery folder close.This research provides experimental basis for the shock that the homemade UTI of clinical practice prevents and treats multiple reason.
With preferred embodiment openly as above they are not to be used for limiting the present invention though the present invention is own, and the content that protection scope of the present invention should be defined with the application's claim protection domain is as the criterion.Anyly have the knack of present technique field person, without departing from the spirit and scope of the present invention, various variations of being done or be equal to replacement all should belong to protection scope of the present invention.
Claims (5)
1. the purposes of ulinastatin in the salvage drug of the toxic shock that acute abdomen causes.
2. purposes according to claim 1, wherein said shock are the toxic shock due to the mesentery angiemphraxis.
3. purposes according to claim 1 and 2, wherein said medicine are lyophilized injectable powder or injection.
4. purposes according to claim 3, wherein said lyophilized injectable powder or injection are equipped with one or more medicine acceptable carrier or additives.
5. purposes according to claim 4, wherein said lyophilized injectable powder can be accepted carrier or additive and be selected from a kind of or its any mixture in mannitol, lactose, gelatin hydrolysate, sodium chloride or the glucose; Described injection loadable body or additive are selected from a kind of or its any mixture in water for injection, mannitol, sodium chloride or the glucose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101289922A CN102205115B (en) | 2011-05-18 | 2011-05-18 | Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101289922A CN102205115B (en) | 2011-05-18 | 2011-05-18 | Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102205115A true CN102205115A (en) | 2011-10-05 |
| CN102205115B CN102205115B (en) | 2012-08-08 |
Family
ID=44694357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101289922A Expired - Fee Related CN102205115B (en) | 2011-05-18 | 2011-05-18 | Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102205115B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044554A (en) * | 2012-05-14 | 2013-04-17 | 旭华（上海）生物研发中心有限公司 | Human urinary trypsin inhibitor (hUTI) of reorganization-dimerization and preparation method and application thereof |
| CN105797143A (en) * | 2016-05-30 | 2016-07-27 | 广东天普生化医药股份有限公司 | Application of ulinastatin containing composition to preparation of medicines for treating bladder cancers |
-
2011
- 2011-05-18 CN CN2011101289922A patent/CN102205115B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 《中国医药导报》 20080430 覃建明 《乌司他丁的药理作用及临床应用进展》 19 1-4 第5卷, 第11期 * |
| 《实用全科医学》 20070731 张秀敏等 乌司他丁治疗重症胰腺炎的作用分析 649 1-5 第5卷, 第7期 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044554A (en) * | 2012-05-14 | 2013-04-17 | 旭华（上海）生物研发中心有限公司 | Human urinary trypsin inhibitor (hUTI) of reorganization-dimerization and preparation method and application thereof |
| CN103044554B (en) * | 2012-05-14 | 2014-08-27 | 旭华（上海）生物研发中心有限公司 | Human urinary trypsin inhibitor (hUTI) of reorganization-dimerization and preparation method and application thereof |
| CN105797143A (en) * | 2016-05-30 | 2016-07-27 | 广东天普生化医药股份有限公司 | Application of ulinastatin containing composition to preparation of medicines for treating bladder cancers |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102205115B (en) | 2012-08-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Loeb | Effect of sodium chloride in treatment of a patient with Addison's disease | |
| Graziani et al. | Dopamine and frusemide in oliguric acute renal failure | |
| JP4463687B2 (en) | Peritoneal dialysis | |
| RU2163487C2 (en) | Use of magnesium-base foodstuff for treatment or prophylaxis of patients tumor and autoimmune diseases | |
| JP2020172520A (en) | Treatment of ascites | |
| Hunyor et al. | Clonidine overdose. | |
| CN102205115B (en) | Application of ulinastatin serving as rescue auxiliary medicament for toxic shock caused by acute abdomen | |
| US8507451B1 (en) | Method for the treatment of type II diabetes | |
| Stanley et al. | Streptozotocin treatment of malignant islet cell tumour. | |
| Amerman et al. | Ferrous sulfate poisoning: Report of a case successfully treated by exchange transfusion | |
| JP2021535171A (en) | Glycolysis-dependent conditions, especially lactate-protected hypoglycemia to treat cancer | |
| Tsimaratos et al. | Chronic renal failure and portal hypertension–is portosystemic shunt indicated? | |
| Itoh et al. | An autopsied case of acute myocarditis with myocardial calcification | |
| KR100198176B1 (en) | Therapeutic Drug for Endotoxin Blood Symptom and Multi-Organ Failure Induced Thereby | |
| Spiegelman | Treatment of diabetes insipidus with synthetic vasopressin | |
| Payne et al. | A fatal reaction following injection of urographic medium: a case report | |
| Colp et al. | Subtotal gastrectomy for duodenal ulcer | |
| CN114796246B (en) | Medicine for treating heart failure and application thereof | |
| Niarchos et al. | Treatment of severe hypertension and hypertensive emergencies with intravenous clonidine hydrochloride | |
| US3632765A (en) | Treatment of shock | |
| Ellis et al. | Metabolic alterations with profound hypothermia | |
| Latorre et al. | Recovery from renal ischemia in rats and dogs | |
| in't Veld et al. | Stimulated sweating in chronic renal failure. | |
| Ffrench | Polyarteritis nodosa presenting as acute diabetes mellitus | |
| Rau et al. | Massive venlafaxine overdose successfully managed with high-dose insulin euglycemic therapy and extracorporeal membrane oxygenation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120808 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |