CN103638023B - Still there is the application of the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content in treatment infection toxic shock in amyl ethyl quin ether hydrochloride - Google Patents
Still there is the application of the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content in treatment infection toxic shock in amyl ethyl quin ether hydrochloride Download PDFInfo
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Abstract
The invention discloses amyl ethyl quin ether hydrochloride still exists the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content application at treatment infectious shock. Indication of the present invention infects toxic shock and refers to the shock being caused by germ attack, and effect of the present invention is by the amyl ethyl quin ether hydrochloride aqueous solution, rabbit to be infected to the impact of microcirculation disorder due to toxic shock to prove.
Description
Technical field
The invention belongs to medicine field, be specifically related to the novel medical use of amyl ethyl quin ether hydrochloride, still there is the application of the situation of microcirculation disorder in amyl ethyl quin ether hydrochloride particularly through comprehensive treatment measures such as replenishment of blood content in treatment infection toxic shock, described infection toxic shock refers to the shock being caused by germ attack.
Background technology
Amyl ethyl quin ether hydrochloride, English name PenehyclidineHydrochloride, chemical name 3-(2-cyclopenta-2-hydroxyl-2-phenyl ethoxy) quinuclidine hydrochloride, molecular formula C20H29NO2HCl, molecular weight 351.92.
Amyl ethyl quin ether hydrochloride is a kind of novel anticholinergic agent, has selective M1、M3And N1、N2Receptor antagonism, all has very strong cholinolytic effect to maincenter and periphery, and to M2Acceptor is without obvious effect, can effectively avoid for want of tachycardia and blocking-up presynaptic membrane M due to m receptor subtype-selective of atropine2Regulation function, and drug effect is long and side effect is less, is mainly used at present preanesthetic medication and organic phosphorus pesticide 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 at any time patient's life.
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 active ingredient loses, comprise haemorrhagic shock, the slurry property shock of losing blood 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) infect toxic shock: the pathogen of infection focus and toxin by blood absorption after due to shock.
(4) neurogenic shock: the neural reflex blood vessel dilatation that intense stimulus causes, the shock due to effective blood volume declines.
(5) cardiogenic shock: heart stroke decline blood pressure drops and microcirculation disorder that cardiac dysfunction causes.
(6) anaphylactic shock: the shock that body causes allergy such as some drugs, food, serum.
The basic pathological change of shock is tissue perfusion deficiency, and its key is again microcirculation disorder.
Microcirculation disorder is an important step in shock morbidity link, and cellular damage can not be utilized oxygen and nutriment, and causing energy decline is the essence of shock.
If the clinical medicine for antishock drug main symptomatic treatment, has bad reaction more or less now, mainly as follows:
1, supplement effective blood volume
Crystalloid fluid: Ringer lactate solution, compound NaCl, 5%-10% glucose saline etc. are containing the solution of sodium. The supplementary organismic internal environment that can recover of crystalloid fluid is stablized, and appropriate input can also improve and safeguard the filtration rate of renal tubular function and glomerulus containing sodium solution.
Colloidal solution: D-40, albumin, blood plasma, whole blood. Wherein, after HES drip-feed, the long period stays in blood, improve plasma osmolarity, tissue fluid is refluxed and increase, blood volume increases sharply, dilute blood, and increase cell membrane negative electrical charge, and make the cell depolymerization assembled, reduce whole body blood viscosity, improve microcirculation, be mainly used in the treatment of hypovolemic shock, its main bad reaction is: occasionally infusion reaction can occur, nettle rash, itch appear in small number of patients. Dextran can reduce viscosity of blood, prevent thrombosis, reduce disseminated intravascular coagulation generation and improve microcirculation, also have an osmotic diuresis effect, prevent renal failure, its bad reaction is: in medication process, allergic reaction may occur, as there is allergic reaction drug withdrawal in time, use the excessive clotting mechanism that disturbs, increase the weight of heart of patient burden, forbid in hemorrhagic disease or thrombopenia. Whole blood and blood plasma can maintain effective blood volume, improve anaemia and histanoxia, avoid and improve organ dysfunction, but blood transfusion process should be prudent.
2, correct acid poisoning: acid poisoning can increase the weight of microcirculation dysfunction, is unfavorable for the recovery of blood volume, must note correcting acid poisoning, often mends 5% sodium acid carbonate.
3, vasoactive agent: patients with septic shock is the absolute indication that uses vasoactive drug, expands blood vessel pressor agent, contributes to improve microcirculation, protection organ function.
Conventional vasoactive agent has:
(1) vasoconstrictor: norepinephrine, vasopressing
(2) vasodilator
Dopamine hydrochloride: be α, beta receptor activator, make visceral vessel expansion, renal blood flow increase, myocardial contraction strengthens, and bad reaction is: when heavy dose of use, can occur breathing acceleration, arrhythmia cordis.
Phentolamine: pharmacological action blocking-up alpha-receptor, improve microcirculation and reduce the drag loading of heart, bad reaction is: can have orthostatic hypotension, nasal obstruction, feel sick, vomiting, serious artery sclerosis, heart organic lesion etc., renal hypofunction person avoids use.
(3) nitrate esters expands blood vessel medicine: monobel and sodium nitroprussiate, sodium nitroprussiate is to work by discharging NO in body, resistance vessel and capacity vessel are had to equal relexation, it can reduce peripheral resistance, and lightening heart load increases effectively perfusion of tissue, thereby improve microcirculation, bad reaction is: instil too fast, be prone to acute blood pressure drops, be prone to nauseating, vomiting, spirit uneasiness, muscle cramp etc. in medication process. This medicine needs now with the current, and keep in Dark Place, and should avoid and other drug 5 use, pregnant woman's forbidding, renal insufficiency and hypothyroidism person are cautious use of.
At present clinically for the treatment guide that infects toxic shock, comprise the use of liquid resuscitation, vasoactive agent, anti-infective, oxygen therapy (comprising mechanical ventilation), strictly control the comprehensive treatment measures such as hyperglycaemia, blood transfusion, blood purification. In following experiment, selected conventional clinically treatment scheme and first-line drug, wherein, comprehensive treatment measure 1 is oxygen uptake+compound NaCl+Dopamine hydrochloride, and comprehensive treatment measure 2 is Benzylpenicillin sodium salt+compound NaCl+Dopamine hydrochloride.
Summary of the invention
The object of the present invention is to provide amyl ethyl quin ether hydrochloride still to have the application of the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content in treatment infection toxic shock.
Infection toxic shock of the present invention refers to the shock being caused by germ attack.
Described effect of the present invention is by amyl ethyl quin ether hydrochloride, rabbit to be infected to the impact of microcirculation disorder due to toxic shock to prove.
Detailed description of the invention
Still there is the application test of the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content in treatment infection toxic shock in amyl ethyl quin ether hydrochloride.
Experiment material
1.1.1 Experimental agents
Penehyclidine hydrochloride injection (long holder is peaceful): anticholinergic agent, anti-shock treatment. Specification: 1ml:1mg. Provided by Chengdu Lisite Pharmaceutical Co., Ltd., 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 0.1667mg/kgd(10mg/60kgd), by man and animal dosage reduction formula A=kW2/3/ 10000 calculate, and the dosage of rabbit is 0.3632mg/kgd, and medicine is prepared with normal saline dilution, and concentration is 0.018162mg/ml, and administration volume is 10ml/kg.
Yellow Jackets (Pentobarbitalsodiumsalt), specification 5g, is produced lot number: 6900183 by Solarbio company.
Compound sodium chloride injection (CompoundSodiumChlorideInjection), 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 (DopamineHydrochlorideInjection), 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 (BenzylpenicillinSodiumforInjection), specification 2.4g (4,000,000 unit), is produced authentication code: the accurate word H23020930 of traditional Chinese medicines, lot number is A130101017 by HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory.
Animal used as test and place
50 of Japan large ear rabbits, body weight 2.4-2.8kg, is divided into 5 groups (n=10) at random, male and female half and half are provided animal production licence number: SCXK(river by plant of animal used as test special commission of Sichuan Province) 2008-14. Rabbit full-valence pellet feed, is provided by plant of animal used as test special commission of Sichuan Province. Freely drink urban life drinking-water. Feeding environment is conventional system, 16～26 DEG C of temperature, relative humidity 40～70%, gravity-flow ventilation, ventilation, natural lighting.
Experimental site: Chengdu qi xanthate thing non-clinical study Co., Ltd, animal occupancy permit number: SYXK(river) 2010-096.
Experiment reagent and equipment
A type Neisseria meningitidis (NM, Lot:NM-A1987), 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 sheep blood agar-agar flat board, and 36 DEG C, at 5%CO2Lower cultivation 18h, collects thalline, washes 2 times with physiological saline. Turbidimetry records thalline quantity (bacterium liquid ultimate density 1x1011CFU/ml), bacterium liquid is stored in-20 DEG C.
BP221S type electronic balance (SARTORIUS), JY601 type electronic balance (the above flat instrument and meter of current chart Co., Ltd), syringe is some, venous incubation device, the micro-infusion pump in ep2709-2 (German fresenius-kabi company), the colored plug-in type monitor of HEWLETTM1166A64S (medical apparatus corporation, Ltd of Hewlett-Packard of the U.S.), the colored micro-circulation scanning tunnelling microscope of WX-84 type constant temperature (Xuzhou medical apparatus and instruments factory product), InspiraASVP animal respirator (HarvardApparatus), BI-2000 medical image analysis system (Sichuan Tai Meng electronics corporation product), TonocapTM patient monitor (modelTC-200, Tonometrics, Datex-OhmedaDivision).
Experimental technique
After family's rabbit ear vein injection yellow Jackets 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 DEG C of Tyrode liquid and is laid in bath central authorities, presses fixed head. 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 the index such as arteriole caliber, arteriole flow velocity, point of intersect of the capillary network counting of selection area. Insert carbon dioxide monitoring conduit (Tonometrics in stomach undercutTM, Datex-OhmedaDivision, InstrumentariumCorp), close subsequently abdominal cavity, record CO2Tension force.
Expose rabbit right flank butt crack, free right common femoral artery, ligation far-end, near-end inserts polyethylene catheter, connects artery pressure tester, continues to monitor mean arterial pressure. Free right lateral thigh vein, inserts polyethylene catheter.
Animal is divided into 5 groups at random, and group is: A group (blank), B group (comprehensive treatment measure 1), C group (comprehensive treatment measure 1+ amyl ethyl quin ether), D group (comprehensive treatment measure 2), E group (comprehensive treatment measure 2+ amyl ethyl quin ether). Stablize after 30min, B, C, D, E treated animal are through intravenous injection bacterium liquid (2.5x1011CFU/kg), A treated animal is through intravenous injection equal-volume physiological 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.
B, C group row endotracheal intubation, trachea cannula is connected with animal respirator, adjust animal respirator, making its tidal volume is 30ml, respiratory rate is 30 beats/min, inhaling air oxygen concentration is 100%, and the speed of pressing 25ml/kg/h is through right lateral thigh ductus venosus input compound NaCl+Dopamine hydrochloride (hydrochloric dopamine 1.2mg/kg), continues infusion 2h. D, E group is pressed the speed of 25ml/kg/h through right lateral thigh ductus venosus input Benzylpenicillin sodium salt+compound NaCl+Dopamine hydrochloride (containing Benzylpenicillin sodium salt 20mg/kg, Dopamine hydrochloride 1.2mg/kg), continues infusion 2h. A group is pressed the speed of 25ml/kg/h through right lateral thigh ductus venosus input physiological saline, continues infusion 2h. Infusion starts after 30min, and C, E group give amyl ethyl quin ether through ear vein, and A, B, D group give equal-volume physiological 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.
Statistical method: arteriole caliber, arteriole flow velocity, point of intersect of the capillary network counting and CO2Tension force is measurement data, the one-way analysis of variance method that application SPSS11.0 software provides.
Statistical procedures: application SPSS10.0forwindows software carries out statistical procedures, all data with " mean ± standard deviation () " represent. The relatively employing one-way analysis of variance of many group sample averages: first each group of data are carried out to normal state inspection, while meeting normal distribution, adopt one-way analysis of variance (ONE-WAYANOVA), while not meeting, adopt non-parametric test (NonparametricTests). The concrete steps of every observation index and derivation parameter being carried out to statistical procedures are, before and after carrying out administration with the measured value of different observing times, self compare (intra-class variance analysis or non-parametric test), its percentage (after=administration, certain time point refers to target value/normal value or basic value, lower same) carries out between-group variance analysis or non-parametric test relatively judges its conspicuousness.P< 0.05 for difference has significant statistical significance,P< 0.01 has the statistical significance of highly significant for difference.
The variation of the each group of table 1 rabbit arteriole caliber (，n=10)
Note: B, C, D, E group compare with A group, *p<0.05，**p< 0.01; C group compares with B group,△ p<0.05，△△ p< 0.01; E group compares with D group,▲ p<0.05，▲▲ p<0.01。
The each group of table 2 rabbit arteriole change in flow (，n=10)
Note: B, C, D, E group compare with A group, *p<0.05，**p< 0.01; C group compares with B group,△ p<0.05，△△ p< 0.01; E group compares with D group,▲ p<0.05，▲▲ p<0.01。
The each group of table 3 rabbit point of intersect of the capillary network change in count (，n=10)
Note: B, C, D, E group compare with A group, *p<0.05，**p< 0.01; C group compares with B group,△ p<0.05，△△ p< 0.01; E group compares with D group,▲ p<0.05，▲▲ p<0.01。
The each group of table 4 rabbit CO2Tension variation (，n=10)
Note: B, C, D, E group compare with A group, *p<0.05，**p< 0.01; C group compares with B group,△ p<0.05，△△ p< 0.01; E group compares with D group,▲ p<0.05，▲▲ p<0.01。
Result shows: rabbit infect toxic shock still exist in the situation of microcirculation disorder through comprehensive treatment measures such as replenishment of blood content, application amyl ethyl quin ether hydrochloride can obviously expand capilary, reduce blood viscosity, significantly improve Rabbit Mesentery microcirculation disorder (p<0.01）。
Claims (2)
1. still there is the application in the medicine of microcirculation disorder through the comprehensive treatment measure of replenishment of blood content in the infection toxic shock that amyl ethyl quin ether hydrochloride causes at preparation treatment Neisseria meningitidis.
2. application according to claim 1, wherein, the administering mode of amyl ethyl quin ether hydrochloride is intramuscular injection and intravenously administrable.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1739511A (en) * | 2002-08-16 | 2006-03-01 | 成都力思特制药股份有限公司 | Application of penehyliclidine hydrochloride in preparing medicine |
| CN101461807A (en) * | 2009-01-15 | 2009-06-24 | 成都力思特制药股份有限公司 | Application of penehyclidine hydrochloride in preparing medicament for treating haemorrhagic shock |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1739511A (en) * | 2002-08-16 | 2006-03-01 | 成都力思特制药股份有限公司 | Application of penehyliclidine hydrochloride in preparing medicine |
| CN101461807A (en) * | 2009-01-15 | 2009-06-24 | 成都力思特制药股份有限公司 | Application of penehyclidine hydrochloride in preparing medicament for treating haemorrhagic shock |
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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. |