CN103751187B - Amyl ethyl quin ether hydrochloride causes the application in Mesenteric arterial embolism at treatment septic shock - Google Patents
Amyl ethyl quin ether hydrochloride causes the application in Mesenteric arterial embolism at treatment septic shock Download PDFInfo
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Abstract
The invention discloses amyl ethyl quin ether hydrochloride and cause application in Mesenteric arterial embolism at treatment septic shock, effectively can improve microcirculation, increase perfused tissue, particularly to the Mesenteric arterial embolism that septic shock causes, Be very effective.
Description
Technical field
The invention belongs to medicine field, be specifically related to amyl ethyl quin ether hydrochloride and cause application in Mesenteric arterial embolism 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, without obvious effect, effectively can be avoided the tachycardia of atropine for want of caused by m receptor subtype-selective and block presynaptic membrane M
2regulation function, and drug effect is long and side effect is less, is mainly used in premedication at present and organophosphate poisoning is rescued.
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 vitals at any time.
The essence of shock is that body is subject to various factor of seriously curing the disease (infection, wound, Hypovolemia, allergy, poisoning, heart or neuromuscular illness etc.), the acute effective blood volume caused reduces, cardiac output declines, vasomotor dysfunction, directly or indirectly causes the minimizing of histoorgan hemoperfusion, anaerobic metabolism increase and handicapped clinical syndrome.
Common classification of suffering a shock has:
(1) hypovolemic shock: refer to that blood effective ingredient is lost, comprise hemorrhagic shock, slurry property of losing blood is suffered a shock and indecorous fluidity is suffered a 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 are absorbed by the blood rear caused shock.
(4) neurogenic shock: the neural reflex vasodilation that intense stimulus causes, the shock caused by effective blood volume declines.
(5) cardiogenic shock: the heart stroke decline blood pressure drops that cardiac dysfunction causes and microcirculation disturbance.
(6) anaphylactic shock: body is to the irritated shock caused 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 be raised with permeability, and blood capillary inner blood concentrates, 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 Doppler flow mapping, the infarction of local organization can be caused.After Results, the clinical indices of shock can be restored, but arterial thrombosis might not improve.
The Mesenteric arterial embolism initial stage often happens suddenly the symptoms such as stomachache, vomiting, and the stage peripheral circulatory failure signs such as to occur that abdominal distention, rapid pulse are unable, lip dark purple, finger tip are livid purple, skin wets cool, it is downright bad that complication is mainly segmental intestinal ischemia, and incidence rate is more than 10%.Mesenteric arterial embolism is that superior mesenteric artery gets clogged caused disease, being absorbed for the antibacterial in product and enteric cavity, toxin after intestinal tube hypoxic-ischemic.Detect by indexs such as blood capillary caliber, micro-blood flow velocity, fluidised forms.
200910058144.1, the patent of invention that name is called " 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 is proved.
Document " protective effect of amyl ethyl quin ether hydrochloride synthesis in endotoxic shock rabbits organ " (Chinese Journal of Emergency Medicine volume the 2nd phase February the 16th 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 sections of patents and document, all disclose the application of amyl ethyl quin ether hydrochloride in treatment endotoxic shock medicine, but the Mesenteric arterial embolism not do not caused septic shock is for further study, not strong with the associativity of clinical disease, clinical practice specific aim is not high, thus 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 application in Mesenteric arterial embolism at treatment septic shock, effectively can improve microcirculation, increase perfused tissue, particularly to the Mesenteric arterial embolism that septic shock causes, Be very effective.
Amyl ethyl quin ether hydrochloride causes the application in Mesenteric arterial embolism at treatment septic shock.
Mesenteric arterial embolism of the present invention refers to: the disease caused by superior mesenteric artery blocks, being absorbed for the antibacterial in product and enteric cavity, toxin after intestinal tube hypoxic-ischemic.Detect by indexs such as blood capillary caliber, micro-blood flow velocity, fluidised forms.
Septic shock of the present invention refers to the shock caused by germ attack.
Preferably, described septic shock refers to the shock caused by Neisseria meningitidis.
The administering mode of amyl ethyl quin ether hydrochloride of the present invention is intramuscular injection or intravenously administrable.
Detailed description of the invention
Below in conjunction with detailed description of the invention, 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 is treated.Specification: 1ml:1mg.Thered is provided by Chengdu Lisite Pharmaceutical Co., Ltd., lot number is 111201.Clinical vein is injected, first dose of 6mg, and optionally every 12h gives 2mg maintenance 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 normal saline dilution is prepared, and concentration is 0.018162 mg/ ml, and administration volume is 10ml/kg.
Pentobarbital sodium (Pentobarbital sodium salt), specification 5g, is produced by Solarbio company, lot number: 6900183.
Compound sodium chloride injection (Compound Sodium Chloride Injection), interior sodium chloride-containing 0.85% ﹑ potassium chloride 0.03% ﹑ calcium chloride 0.033%.Produced by Cologne, Sichuan pharmaceutcal corporation, Ltd, authentication code: the accurate word H20043818 of traditional Chinese medicines, lot number is M13070725.
Dopamine hydrochloride inj (Dopamine Hydrochloride Injection), specification 2ml:20mg, is produced by Changzhou Yabang Pharmaceutical & Chemical Co., Ltd., 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 (4,000,000 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
Japan large ear rabbit 70, body weight 2.4-2.8kg, is divided into 7 groups (n=10), male and female half and half at random, is provided, animal productiong credit number: SCXK(river by plant of laboratory animal special commission of Sichuan Province) 2008-14.Rabbit full-valence pellet feed, is provided by plant of laboratory animal special commission of Sichuan Province.Freely drink urban life drinking-water.Feeding environment is conventional system, temperature 16 ~ 26 DEG C, 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 DEG C, is then inoculated in Sanguis caprae seu ovis agar-agar dull and stereotyped, 36 DEG C, at 5%CO
2lower cultivation 18h, collects thalline, washes 2 times with normal saline.Turbidimetry records thalline quantity (bacterium liquid ultimate density 1x10
11cFU/ml), bacterium liquid is stored in-20 DEG C.
BP221S type electronic balance (SARTORIUS), JY601 type electronic balance (upper current chart level instruments and meters 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 Hewlett-Packard of the U.S.) 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, then adding former dosage 20 ~ 40%).Row abdomen median line otch 1 ~ 2cm, gets one section of mesostenium and is placed in the lucite constant temperature water bath that is full of 38 DEG C of Tyrode liquid and is laid on the lucite convex observation platform of bath central authorities, press fixing head.To utilize on the colored micro-circulation scanning tunnelling microscope of WX-84 type constant temperature video image under SONY camera collection microscope, input microcomputer by video frequency collection card, 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.After stablizing 30min, B, C, D, E, F, G treated animal is through intravenous injection bacterium liquid (2.5 x10
11cFU/kg), A treated animal through intravenous injection equal-volume normal saline (2.5ml/kg), to verify that anaesthetic and experimental implementation are on the impact of result.After phage attack, Mean Arterial drops 30% is considered as reaching shock standard.
Healthy group (A group) is with the numerical value of the measured index of correlation of experimental group (B, C, D, E, F, G group), occur that the significant difference (P<0.05) of the remarkable meaning of tool shows that, relative to healthy group, experimental group has reached Mesenteric arterial embolism standard.
C, D group row endotracheal intubation, tracheal intubation is connected with animal respirator, adjustment animal respirator, its tidal volume is made to be 30ml, respiratory frequency is 30 beats/min, inhaling air oxygen concentration is 100%, and the speed of pressing 25ml/kg/h inputs compound NaCl+dopamine hydrochloride (hydrochloric dopamine 1.2mg/kg) through right lateral thigh venous duct, continuous infusion 2h.E, F group presses 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), continuous infusion 2h.A, B, G group presses the speed of 25ml/kg/h through right lateral thigh venous duct input normal saline, continuous infusion 2h.After infusion starts 30min, D, F, G group gives amyl ethyl quin ether through ear vein, and A, B, C, E group gives equal-volume normal saline, and administration volume is 10ml/kg.The change of above microcirculation index is observed respectively at 120min after 90min, administration after 60min, administration after 30min, administration before ear vein administration, after administration.
This experiment is also by 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 software provides.
Statistical procedures: application SPSS 10.0 for windows software carries out statistical procedures, all data with " mean ± standard deviation (
) " represent.The comparison of many groups sample average adopts one factor analysis of variance: first carry out Normal distribution test to each group of data, adopt one factor analysis of variance (ONE-WAY ANOVA) when meeting normal distribution, when 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, carry out self comparing before and after administration (intra-class variance analysis or non parametric tests) with the measured value of different observing time, 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 its significance of non parametric tests multilevel iudge.
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 group rabbit arteriole caliber change (
, n=10)
Note: B, C, D, E, F, G group compares 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 each group rabbit arteriole change in flow (
, n=10)
Note: B, C, D, E, F, G group compares 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 each group rabbit point of intersect of the capillary network change in count (
, n=10)
Note: B, C, D, E, F, G group compares 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: by give the D group of amyl ethyl quin ether hydrochloride, G group, F group respectively with do not give the B group of amyl ethyl quin ether hydrochloride, E group, C group compare, obviously improving all appears in rabbit arteriole caliber, arteriole flow velocity and point of intersect of the capillary network counting (
p<0.05), the Mesenteric arterial embolism caused septic shock is described, giving amyl ethyl quin ether hydrochloride obviously can expand blood capillary, reduces blood viscosity, significantly improves Mesentery microcirculation obstacle.
Claims (2)
1. amyl ethyl quin ether hydrochloride causes the application in Mesenteric arterial embolism medicine at preparation treatment septic shock, it is characterized in that: described septic shock refers to and infects by Neisseria meningitidis the shock caused.
2. amyl ethyl quin ether hydrochloride causes the application in Mesenteric arterial embolism medicine at preparation 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. |