CN103751187A - Application of penehyclidine hydrochloride in treating mesenteric arterial embolism caused by septic shock - Google Patents
Application of penehyclidine hydrochloride in treating mesenteric arterial embolism caused by septic shock Download PDFInfo
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Abstract
The invention discloses application of penehyclidine hydrochloride in treating mesenteric arterial embolism caused by septic shock. The penehyclidine hydrochloride can be used for effectively improving microcirculation and increasing tissue perfusion, and particularly is remarkable in effect in penehyclidine hydrochloride in treating mesenteric arterial embolism caused by septic shock.
Description
Technical field
The invention belongs to medicine field, be specifically related to amyl ethyl quin ether hydrochloride and cause the application in Mesenteric artery thromboembolism at treatment septic shock.
Background technology
Amyl ethyl quin ether hydrochloride, English name Penehyclidine Hydrochloride, chemical name 3-(2-cyclopenta-2-hydroxyl-2-phenyl ethoxy) quinuclidine hydrochloride, molecular formula C
20h
29nO
2hCl, molecular weight 351.92.
Amyl ethyl quin ether hydrochloride is a kind of novel anticholinergic agent, has selectivity M
1, M
3and N
1, N
2receptor antagonism, all has very strong cholinolytic effect to maincenter and periphery, and to M
2receptor is without obvious effect, can effectively avoid for want of tachycardia and blocking-up presynaptic membrane M due to m receptor subtype-selective of atropine
2regulation function, and drug effect is long and side effect is less, is mainly used at present premedication and organophosphate poisoning and rescues.
Shock is a kind of extremely critical and dangerous clinical disease, and onset is anxious, and PD is rapid, as rescued not in time and treating, can jeopardize patient's life at any time.
The essence of shock is that body is subject to the various factors of seriously curing the disease (infection, wound, Hypovolemia, allergy, poisoning, heart or neuromuscular illness etc.), the acute effective blood volume causing reduces, cardiac output declines, vasomotor dysfunction, directly or indirectly causes the minimizing of histoorgan hemoperfusion, anaerobic metabolism to increase and handicapped clinical syndrome.
The common classification of suffering a shock has:
(1) hypovolemic shock: refer to that blood effective ingredient loses, comprise hemorrhagic shock, the slurry property of losing blood shock and indecorous fluidity shock.
(2) traumatic shock: except with lose blood, lose outside the Pass Efficient Cycle amount that liquid etc. causes reduces and have, after tissue injury, the detoxifying function of catabolite and strong pain stimulation are also important factors.
(3) septic shock: the pathogen of infection focus and toxin by blood absorption after due to shock.
(4) neurogenic shock: the neural reflex vasodilation that intense stimulus causes, the shock due to effective blood volume declines.
(5) cardiogenic shock: heart stroke decline blood pressure drops and microcirculation disturbance that cardiac dysfunction causes.
(6) anaphylactic shock: the shock that body causes allergy such as some drugs, food, serum.
After shock occurs, microcirculation disturbance can cause microcirculation arterial blood hypoperfusion, in the microcirculation blood coagulation phase, owing to organizing severe depletion of oxygen, acidosis, capillary wall is undermined to raise with permeability, and blood capillary inner blood is concentrated, stasis of blood stream, blood clotting solidity raises, and produces disseminated inravascular coagulation, forms microthrombus.Because the size of Thromboembolic source, embolus is different with the position of thromboembolism, it is not identical on the impact of body yet.When the tremulous pulse of thromboembolism lacks effective side, prop up circulation time, can cause the infarction of local organization.After Results, the clinical indices of shock can be restored, but arterial thrombosis might not improve.
The symptoms such as normal burst of Mesenteric artery thromboembolism initial stage stomachache, vomiting, stage occurs that abdominal distention, rapid pulse are unable, lip dark purple, finger tip are livid purple, the wet peripheral circulatory failure sign such as cool of skin, and it is downright bad that complication is mainly segmental intestinal ischemia, and incidence rate is over 10%.Mesenteric artery thromboembolism is the disease due to superior mesenteric artery gets clogged, being absorbed for the antibacterial in product and enteric cavity, toxin after intestinal tube hypoxic-ischemic.Can detect by indexs such as blood capillary caliber, micro-blood flow velocity, fluidised forms.
200910058144.1, name is called the patent of invention of " application of amyl ethyl quin ether hydrochloride in preparation treatment endotoxic shock medicine ", disclose the application of amyl ethyl quin ether hydrochloride in preparation treatment endotoxic shock medicine, and by amyl ethyl quin ether hydrochloride aqueous solution, the impact of experiment endotoxemia shock death has been proved.
Document " protective effect of amyl ethyl quin ether hydrochloride synthesis in endotoxic shock rabbits organ " (Chinese Journal of Emergency Medicine the 16th the 2nd phase of volume of February in 2007) discloses the application of amyl ethyl quin ether hydrochloride in endotoxic shock medicine; and by rabbit endotoxin shock model, research amyl ethyl quin ether hydrochloride synthesis in endotoxic shock rabbits blood pressure and the morphologic impact of vitals.
Above two pieces of patents and document, the application of amyl ethyl quin ether hydrochloride in treatment endotoxic shock medicine all disclosed, but the Mesenteric artery thromboembolism septic shock not being caused is for further study, not strong with the associativity of clinical disease, clinical practice specific aim is not high, thereby affects the judgement of application person to the scope of application.
Summary of the invention
The invention provides amyl ethyl quin ether hydrochloride and cause the application in Mesenteric artery thromboembolism at treatment septic shock, can effectively improve microcirculation, increase perfused tissue, the Mesenteric artery thromboembolism particularly septic shock being caused, effect is remarkable.
Amyl ethyl quin ether hydrochloride causes the application in Mesenteric artery thromboembolism at treatment septic shock.
Mesenteric artery thromboembolism of the present invention refers to: the disease due to superior mesenteric artery blocks, being absorbed for the antibacterial in product and enteric cavity, toxin after intestinal tube hypoxic-ischemic.Can detect by indexs such as blood capillary caliber, micro-blood flow velocity, fluidised forms.
Septic shock of the present invention refers to the shock being caused by germ attack.
Preferably, described septic shock refers to the shock being caused by Neisseria meningitidis.
The administering mode of amyl ethyl quin ether hydrochloride of the present invention is intramuscular injection or intravenously administrable.
The specific embodiment
Below in conjunction with the specific embodiment, essentiality content of the present invention is described in further detail.
1.1 experiment material
1.1.1 Experimental agents
Penehyclidine hydrochloride injection (long holder is peaceful): anticholinergic agent, shock treatment.Specification: 1ml:1mg.By Chengdu Lisite Pharmaceutical Co., Ltd., provided, lot number is 111201.Clinical vein injection, first dose of 6mg, optionally every 12h gives 2mg and maintains later, and accumulated dose is 10mg/d.
Adult's quantity of reference in this experiment is 0.1667 mg/kgd(10 mg/60kgd), by man and animal dosage reduction formula A=kW
2/3/ 10000 calculate, and the dosage of rabbit is 0.3632 mg/kgd, and medicine is prepared with normal saline dilution, and concentration is 0.018162 mg/ ml, and administration volume is 10ml/kg.
Pentobarbital sodium (Pentobarbital sodium salt), specification 5g, is produced lot number: 6900183 by Solarbio company.
Compound sodium chloride injection (Compound Sodium Chloride Injection), interior sodium chloride-containing 0.85% ﹑ potassium chloride 0.03% ﹑ calcium chloride 0.033%.By Cologne, Sichuan, pharmaceutcal corporation, Ltd produces, authentication code: the accurate word H20043818 of traditional Chinese medicines, lot number is M13070725.
Dopamine hydrochloride inj (Dopamine Hydrochloride Injection), specification 2ml:20mg, by Jiangsu, pharmaceutcal corporation, Ltd of Ya Bang Johnson & Johnson produces, authentication code: the accurate word H32023366 of traditional Chinese medicines, lot number is 120411.
Benzylpenicillin sodium for injection (Benzylpenicillin Sodium for Injection), specification 2.4g (400Wan unit), is produced by HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory, authentication code: the accurate word H23020930 of traditional Chinese medicines, lot number is A130101017.
1.1.2 laboratory animal and place
70 of Japan large ear rabbits, body weight 2.4-2.8kg, is divided into 7 groups (n=10) at random, and male and female half and half are provided animal production licence number by Sichuan Province plant of laboratory animal special commission: SCXK(river) 2008-14.Rabbit full-valence pellet feed, is provided by Sichuan Province plant of laboratory animal special commission.Freely drink urban life drinking-water.Feeding environment is conventional system, 16～26 ℃ of temperature, relative humidity 40～70%, gravity-flow ventilation, ventilation, natural lighting.
Experimental site: Chengdu qi xanthate thing non-clinical study company limited, animal occupancy permit number: SYXK(river) 2010-096.
1.1.3 experiment reagent and equipment
A type Neisseria meningitidis (NM, Lot:NM-A 1987), is provided by Southwest University for Nationalities Preventive Veterinary Medicine laboratory.Strain culturing, in 100ml meat soup, is cultivated 18h for 36 ℃, is then inoculated in Sanguis caprae seu ovis agar-agar dull and stereotyped, and 36 ℃, at 5%CO
2lower cultivation 18h, collects thalline, with normal saline, washes 2 times.Turbidimetry records thalline quantity (bacterium liquid ultimate density 1x10
11cFU/ml), bacterium liquid is stored in-20 ℃.
BP221S type electronic balance (SARTORIUS), JY601 type electronic balance (the above flat instrument and meter of current chart company limited), syringe is some, venous incubation device, the micro-infusion pump in ep2709-2 (German fresenius-kabi company), the colored plug-in type monitor (medical apparatus corporation, Ltd of U.S. Hewlett-Packard) of HEWLETT M1166A64S, the colored micro-circulation scanning tunnelling microscope (Xuzhou medical apparatus and instruments factory product) of WX-84 type constant temperature, Inspira ASVP animal respirator (Harvard Apparatus), BI-2000 medical image analysis system (Sichuan Tai Meng electronics corporation product), TonocapTM monitor (modelTC-200, Tonom etrics, Datex-Ohm eda Division).
1.2 experimental technique
After family's rabbit ear vein injection pentobarbital sodium anesthesia (30mg/kg), lie on the back fixing (as there is the situation of reviving, appending former dosage 20～40%).Row abdomen median line otch 1～2cm, gets one section of mesostenium and is placed on the lucite convex observation platform that is full of the lucite constant temperature water bath of 38 ℃ of Tyrode liquid and is laid in bath central authorities, presses fixing head.Utilize on the colored micro-circulation scanning tunnelling microscope of WX-84 type constant temperature video image under SONY camera collection microscope, by video frequency collection card, input microcomputer, utilize BI-2000 medical image analysis system to carry out real-time analysis to video image under gathered mirror.Fix a visual field, observe arteriole caliber, arteriole flow velocity, the point of intersect of the capillary network counting index of selection area.
Expose rabbit right flank butt crack, free right common femoral artery, ligation far-end, near-end inserts polyethylene catheter, connects tremulous pulse pressure tester, continues to monitor mean arterial pressure.Free right lateral thigh vein, inserts polyethylene catheter.
Animal is divided into 7 groups at random, and group is: A group, B group, C group, D group, E group, F group, G group.Stablize after 30min, B, C, D, E, F, G treated animal are through intravenous injection bacterium liquid (2.5 x10
11cFU/kg), A treated animal is through intravenous injection equal-volume normal saline (2.5ml/kg), to verify the impact on result of anaesthetic and experimental implementation.After thalline is attacked, mean arterial pressure decline 30% is considered as reaching shock standard.
In the numerical value of healthy group (A group) and the measured index of correlation of experimental group (B, C, D, E, F, G group), the significant difference (P<0.05) that occurs the remarkable meaning of tool shows with respect to healthy group, and experimental group has reached Mesenteric artery thromboembolism standard.
C, D group row endotracheal intubation, tracheal intubation is connected with animal respirator, adjust animal respirator, making its tidal volume is 30ml, respiratory frequency is 30 beats/min, inhaling air oxygen concentration is 100%, and the speed of pressing 25ml/kg/h is through right lateral thigh venous duct input compound NaCl+dopamine hydrochloride (hydrochloric dopamine 1.2mg/kg), continues infusion 2h.E, F group is pressed the speed of 25ml/kg/h through right lateral thigh venous duct input penicillin sodium+compound NaCl+dopamine hydrochloride (containing penicillin sodium 20mg/kg, dopamine hydrochloride 1.2mg/kg), continues infusion 2h.A, B, G group are pressed the speed of 25ml/kg/h through right lateral thigh venous duct input normal saline, continue infusion 2h.Infusion starts after 30min, and D, F, G group give amyl ethyl quin ether through ear vein, and A, B, C, E group give equal-volume normal saline, and administration volume is 10ml/kg.Respectively at through before ear vein administration, after administration after 30min, administration after 60min, administration after 90min, administration 120min observe above microcirculation index and change.
This experiment also can be passed through intramuscular administration.
Statistical method: arteriole caliber, arteriole flow velocity and point of intersect of the capillary network are counted as measurement data, the one factor analysis of variance method that application SPSS 11.0 softwares provide.
Statistical procedures: application SPSS 10.0 for windows softwares carry out statistical procedures, all data with " mean ± standard deviation (
) " represent.The relatively employing one factor analysis of variance of many group sample averages: first each group data are carried out to normal state check, while meeting normal distribution, adopt one factor analysis of variance (ONE-WAY ANOVA), while not meeting, adopt non parametric tests (Nonparametric Tests).The concrete steps of every observation index and derivation parameter being carried out to statistical procedures are, measured value with different observing times carries out administration front and back self relatively (within group variance analysis or non parametric tests), its percentage rate (after=administration, certain time point refers to target value/normal value or basic value, lower same) carries out between group variable analysis or non parametric tests relatively judges its significance.
p<0.05 is that difference has significant statistical significance,
p<0.01 is the statistical significance that difference has highly significant.
1.3 experimental results and conclusion
Table 1 respectively organize rabbit arteriole caliber change (
, n=10)
Note: B, C, D, E, F, G group compare with A group, *
p<0.05, * *
p<0.01; D group compares with C group,
△ p<0.05,
△ △ p<0.01; F group compares with E group,
▲ p<0.05,
▲ ▲ p<0.01; G group compares with B group,
# p<0.05,
## p<0.01.
Table 2 respectively organize rabbit arteriole change in flow (
, n=10)
Note: B, C, D, E, F, G group compare with A group, *
p<0.05, * *
p<0.01; D group compares with C group,
△ p<0.05,
△ △ p<0.01; F group compares with E group,
▲ p<0.05,
▲ ▲ p<0.01; G group compares with B group,
# p<0.05,
## p<0.01.
Table 3 respectively organize rabbit point of intersect of the capillary network change in count (
, n=10)
Note: B, C, D, E, F, G group compare with A group, *
p<0.05, * *
p<0.01; D group compares with C group,
△ p<0.05,
△ △ p<0.01; F group compares with E group,
▲ p<0.05,
▲ ▲ p<0.01; G group compares with B group,
# p<0.05,
## p<0.01.
Result shows: D group, the G group, the F group that give amyl ethyl quin ether hydrochloride are compared with the B group, E group, the C group that do not give amyl ethyl quin ether hydrochloride respectively, rabbit arteriole caliber, arteriole flow velocity and point of intersect of the capillary network counting all occur obviously improving (
p<0.05), the Mesenteric artery thromboembolism that septic shock is caused is described, give amyl ethyl quin ether hydrochloride and can obviously expand blood capillary, reduce blood viscosity, significantly improve Mesentery microcirculation obstacle.
Claims (3)
1. amyl ethyl quin ether hydrochloride causes the application in Mesenteric artery thromboembolism at treatment septic shock.
2. amyl ethyl quin ether hydrochloride causes the application in Mesenteric artery thromboembolism at treatment septic shock according to claim 1, it is characterized in that: described septic shock refers to by Neisseria meningitidis and infects the shock causing.
3. amyl ethyl quin ether hydrochloride causes the application in Mesenteric artery thromboembolism at treatment septic shock according to claim 1, it is characterized in that: the administering mode of described amyl ethyl quin ether hydrochloride is intramuscular injection or intravenously administrable.
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Effective date of registration: 20210510 Address after: 121013 No. 55 Songshan Street, Taihe District, Jinzhou City, Liaoning Province Patentee after: Jinzhou Aohong Pharmaceutical Co.,Ltd. Address before: 610063 Jinjiang Industrial Development Zone, Sichuan, Chengdu Patentee before: CHENGDU LIST PHARMACEUTICAL Co.,Ltd. |
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