CN103933030B - Ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness - Google Patents
Ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness Download PDFInfo
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- CN103933030B CN103933030B CN201410187387.6A CN201410187387A CN103933030B CN 103933030 B CN103933030 B CN 103933030B CN 201410187387 A CN201410187387 A CN 201410187387A CN 103933030 B CN103933030 B CN 103933030B
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- ammonium pyrrolidine
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- upward floating
- dithiocarboxylate
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Abstract
The invention belongs to field of medicine preparation, particularly to ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness, be dissolved in physiological saline by ammonium pyrrolidine dithiocarboxylate, the injection being configured to 25 125mg/mL uses.The dosage of the lumbar injection of this ammonium pyrrolidine dithiocarboxylate is 80 120mg/kg, and intravenous dosage is 30 50mg/kg.The use time of this ammonium pyrrolidine dithiocarboxylate is before quick upward floating danger-removal 20 35 minutes.The experiment proves that, ammonium pyrrolidine dithiocarboxylate can significantly inhibit the cardiac muscle fibre that bubble causes and rupture the heart failure caused, and improves heart function, also can alleviate lung injury and inflammation, thus alleviate the pathological change that decompression sickness is caused.And the present invention causes to provide experimental data in decompression sickness at prevention quick upward floating danger-removal for the most more reasonably being applied by ammonium pyrrolidine dithiocarboxylate.
Description
Technical field
The invention belongs to field of medicine preparation, particularly to ammonium pyrrolidine dithiocarboxylate in preparation prevention quickly
Float escape danger cause decompression sickness medicine in application.
Background technology
Quick upward floating danger-removal is as the main side of the commonly used submarine personnel underwater escape of naval of current various countries
One of method, it is that application no deceompression diving principle makes ship person escape danger from big degree of depth accident ship.Due to its equipment
Simply, easy to implement the method, the degree of depth of escaping danger big, simple operation and other advantages, has been that many countries use.But along with
The intensification of the degree of depth, the high pressure open-assembly time that warship person is allowed is fairly limited, if reason is drawn owing to pressure regulation is improper etc.
Rise open-assembly time long, then serious decompression sickness can occur.
The gas that the pathogenesis of decompression sickness is dissolved in body exceedes safety coefficient of supersaturation, overflows in original place
Go out, form bubble, occluding vascular and compression organ-tissue, cause a series of breathing, circulation and nerve
The dysfunctions such as system, severe patient may result in death.Both at home and abroad for the general side used for the treatment of of decompression sickness
Method is repressurization treatment, and the prevention of decompression sickness is mainly taked to carry out safety fully according to the program of decompression table and subtracted
Pressure, the most carefully calculates floating interval of floating dock and the decompression time of diver.But, owing to quick upward floating danger-removal is many
Occurring at submarine accident, local environment makes the program of quick upward floating danger-removal be difficult to strict control, and reduces pressure
Disease once occurs, and is difficult to carry out repressurization treatment timely, therefore prepares one and effectively can prevent quickly
The medicine of the decompression sickness escaped danger caused by process that floats is very important.
Ammonium pyrrolidine dithiocarboxylate is a kind of chemical compound, and molecular formula is C5H9NS2, this molecule and salt thereof
Being widely used in multiple biochemical applications, including metal-chelating, induction is blocked and blocked to the inducing cell G1 phase
The aspects such as nitricoxide synthase.But this molecule do not have research confirmation can be applicable to prevent decompression sickness, more not by
It is used for preventing quick upward floating danger-removal to cause decompression sickness.
Summary of the invention
It is an object of the invention to provide ammonium pyrrolidine dithiocarboxylate and cause decompression sickness at prevention quick upward floating danger-removal
In application, quick upward floating danger-removal can be significantly reduced and cause the death rate of decompression sickness, and alleviate decompression sickness and caused
Cardiopulmonary tissue damage.
The technical scheme that the present invention provides is to be used for ammonium pyrrolidine dithiocarboxylate preparing prevention floating upward quickly
Escape danger and cause the medicine of decompression sickness.
Above-mentioned application, needs to be dissolved in physiological saline ammonium pyrrolidine dithiocarboxylate, is configured to
The injection of 25-125mg/mL uses.
The dosage of the lumbar injection of described ammonium pyrrolidine dithiocarboxylate is 80-120mg/kg, intravenous
Dosage is 30-50mg/kg.Preferably, the dosage of the lumbar injection of described ammonium pyrrolidine dithiocarboxylate is
100mg/kg, intravenous dosage is 40mg/kg.
The use time of described ammonium pyrrolidine dithiocarboxylate is before quick upward floating danger-removal 20-35 minute.
The invention have the benefit that
1, the invention provides ammonium pyrrolidine dithiocarboxylate and cause decompression sickness at preparation prevention quick upward floating danger-removal
Medicine in application, experiment shows, ammonium pyrrolidine dithiocarboxylate can significantly inhibit the heart that bubble causes
The heart failure that muscle fibre fracture causes, improves heart function, also can alleviate lung injury and inflammation, thus
Alleviate the pathological change that decompression sickness is caused, significantly improve quick upward floating danger-removal and cause the survival rate of decompression sickness, slow
Solve quick upward floating danger-removal and cause the focus of decompression sickness.
2, the present invention is for the most more reasonably applying ammonium pyrrolidine dithiocarboxylate at prevention floating upward quickly
Cause decompression sickness of escaping danger provides experimental data.
Accompanying drawing explanation
Fig. 1 is in embodiment 1, and rat quick upward floating danger-removal causes decompression sickness lung injury comparison diagram, Qi Zhongtu
A is control rats pathologic figure, and multiplication factor is 200 times;Figure B is pyrrolidines dithiocarbonic acid
Ammonium prevention group lung tissue of rats pathology figure, multiplication factor is 200 times.
Fig. 2 is in embodiment 1, and rat quick upward floating danger-removal causes decompression sickness heart injury comparison diagram.Wherein scheme
A is the heart tissue pathology figure of control rats, and multiplication factor is 200 times;Figure B is pyrrolidines two sulphur generation
The heart tissue pathology figure of ammonium formate prevention group rat, multiplication factor is 200 times
Fig. 3 is in embodiment 2, and rabbit quick upward floating danger-removal causes decompression sickness lung injury comparison diagram, wherein schemes A
For the pathologic figure of control group rabbit, multiplication factor is 200 times;Figure B is pyrrolidines dithiocarbonic acid
The pathologic figure of ammonium prevention group rabbit, multiplication factor is 200 times.
Fig. 4 is in embodiment 2, and rabbit quick upward floating danger-removal causes decompression sickness heart injury comparison diagram, wherein schemes A
For the heart tissue pathology figure of control group rabbit, multiplication factor is 200 times;Figure B is that pyrrolidines two sulphur is for first
The heart tissue pathology figure of acid ammonium prevention group rabbit, multiplication factor is 200 times.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described:
Ammonium pyrrolidine dithiocarboxylate used by the experiment of the present invention is purchased from Sigma company.
Embodiment 1
Experiment injection medicine: utilize physiological saline, ammonium pyrrolidine dithiocarboxylate is configured to 25mg/ml
Solution, be prepared as injection.
Animal used as test and packet: male and healthy SD rat 60, body weight 220~250g, be purchased from Shanghai this
Rec animal used as test Co., Ltd.SD rat is randomly divided into prevention group and control group, often group 30.
Experimental technique: prevention group processes first 30 minutes, molten by lumbar injection ammonium pyrrolidine dithiocarboxylate
Liquid (injection dosage is 100mg/kg), control group processes first 30 minutes, by lumbar injection equal-volume physiology
Salt solution, is placed in quick upward floating danger-removal pressurization cabin afterwards by animal used as test, closes hatch door, uses self-editing computer certainly
Dynamicization quick upward floating danger-removal program, used the mode of compressed air index multiplication (within every 7 seconds, to turn in 28 seconds
One times) it is forced into 1.6MPa, stop 242 seconds under high pressure, be at the uniform velocity decompressed to normal pressure in 50 seconds, go out cabin 30
Minute carry out the detection analysis of experimental rat.
It has been observed that the rat of control group occurs restless, thorax abdomen fluctuating frequency speed after going out cabin after experiment terminates
Phenomenon, death i.e. occurred in 1 minute, to when 5 minutes dead 15, survival rats chest and abdomen after 10 minutes
Portion's fluctuating frequency slows down, and is total to dead 18 in 15 minutes, and remaining 12 survival rats are scratched after going out cabin
Mouth and nose, nibble belly performance, after progressively recover;After ammonium pyrrolidine dithiocarboxylate pretreated group rat goes out cabin
Assembling together, movable few, thorax abdomen fluctuating Non Apparent Abnormality changes, and does not has death, to 15 in 10 minutes
Minutes dead 3 altogether, remaining 27 survival rats progressively recover normal activity.
Above-mentioned experiment shows, it is 10% that rat quick upward floating danger-removal causes the death rate of decompression sickness, and control group is big
The death rate of mouse is 60%, illustrates that ammonium pyrrolidine dithiocarboxylate can significantly reduce quick upward floating danger-removal and cause decompression
The sick death rate, and the time-to-live of rat after can extending quick upward floating danger-removal, control for follow-up repressurization
Treat and provide favourable chance.
It has been observed that the lung tissue of survival rats is detected discovery after experiment terminates, quick upward floating danger-removal compares
The wet dry weight ratio of group is 6.6128 ± 0.2654 (mean+SD), and ammonium pyrrolidine dithiocarboxylate
The wet dry weight ratio of prevention group is 5.2501 ± 0.5956 (mean+SD), p value > 0.05, pyrrole is described
Cough up the pretreatment of alkane dithiocarbonic acid ammonium and can significantly reduce lung wet dry weight ratio.
Pathologic inspection to survival rats finds, quick upward floating danger-removal causes decompression sickness control rats lung
Bubble structure extensive damage is merged, and alveolar wall oedema is obvious, in alveolar space visible addicted to her red liquid and red carefully
Born of the same parents are oozed out.Ammonium pyrrolidine dithiocarboxylate prevention group causes decompression sickness control group with quick upward floating danger-removal and compares, greatly
Mouse alveolar wall thickened degree substantially alleviates, and the most as shown in Figure 1, wherein figure A is control rats lung tissue
Pathology figure, multiplication factor is 200 times;Figure B is that ammonium pyrrolidine dithiocarboxylate prevention group lung tissue of rats is sick
Reason figure, multiplication factor is 200 times.
Finding the heart tissue pathologic finding of experimental rat, quick upward floating danger-removal causes the dead of decompression sickness control group
Die rat heart muscle fiber oedema, sex change, fracture is obvious, as shown in the A in Fig. 2 schemes, and pyrrolidines two sulphur
Survival rats cardiac muscle fibre for ammonium formate prevention group only has slight oedema, specifically as shown in the B in Fig. 2 schemes.
Embodiment 2
Experiment injection medicine: utilize physiological saline, ammonium pyrrolidine dithiocarboxylate is configured to 120mg/mL
Solution, be prepared as injection.
Animal used as test and packet: male and healthy new zealand rabbit 16, body weight 2.6~3kg, be purchased from Shanghai this
Rec animal used as test Co., Ltd.Rabbit is randomly divided into prevention group and control group, often group 8.
Experimental technique: prevention group processes first 20 minutes, injects ammonium pyrrolidine dithiocarboxylate through auricular vein
Solution (injection dosage is 40mg/kg), control group processes first 20 minutes, injects equal-volume through auricular vein
Physiological saline, is placed in quick upward floating danger-removal pressurization cabin afterwards by animal used as test, closes hatch door, uses self-editing electricity
Brain automation quick upward floating danger-removal program, the mode of use compressed air index multiplication (every 7 seconds in 24 seconds
Double) it is forced into 1.1MPa, stop 240 seconds under high pressure, be at the uniform velocity decompressed to normal pressure in 33 seconds, go out cabin
Within 30 minutes, carry out the detection analysis of experimental rabbit.
It has been observed that quick upward floating danger-removal causes after decompression sickness control group rabbit goes out cabin after experiment terminates, 10 minutes
In, there is scratch mouth and nose, whole skin, performance of screaming in 1 rabbit, and with double hind limb paralysis, 15 points
Zhong Shi, there is double hind limb paralysis in 2 rabbits, and 1 rabbit occurs that right hind is paralysed;Prevention group rabbit goes out cabin
Rear activity is few, only has 1 rabbit and double hind limb paralysis occur during to 15 minutes, and remaining rabbit is in 30 minutes
Progressively recover normal activity.Illustrate that ammonium pyrrolidine dithiocarboxylate pretreatment can significantly reduce quick upward floating danger-removal
Cause the generation of decompression sickness.
Pathologic inspection to rabbit finds, quick upward floating danger-removal causes decompression sickness control rats alveolar knot
Structure extensive damage is merged, and alveolar wall oedema is obvious, and in alveolar space, visible a large amount of red blood cells ooze out.Pyrrolidines
Dithiocarbonic acid ammonium prevention group causes decompression sickness control group with quick upward floating danger-removal and compares, and rabbit alveolar wall is without substantially
Thicken, ooze out without obvious red blood cell, concrete as it is shown on figure 3, wherein scheming A is control group rabbit lung tissue
Pathology figure, multiplication factor is 200 times;Figure B is ammonium pyrrolidine dithiocarboxylate prevention group rabbit lung tissue disease
Reason figure, multiplication factor is 200 times.
Finding the heart tissue pathologic finding of rabbit, quick upward floating danger-removal causes decompression sickness control group rabbit cardiac muscle
Fiber oedema, sex change, fracture are obvious, specifically as shown in the A in Fig. 4 schemes, and pyrrolidines dithiocarbonic acid
The survival rabbit cardiac muscle fibre of ammonium prevention group only has slight oedema, but structure is normal, concrete as in Fig. 4
Shown in B figure.
In sum, by above-mentioned experiment it can be confirmed that ammonium pyrrolidine dithiocarboxylate can significantly inhibit bubble
The heart failure that the cardiac muscle fibre fracture caused causes, improves heart function, also can alleviate lung injury and inflammation
Disease, thus alleviate the pathological change that decompression sickness is caused.
The above is presently preferred embodiments of the present invention, but the present invention should not be limited to this embodiment institute
Disclosure.So every without departing from the equivalence completed under spirit disclosed in this invention or amendment, all fall
Enter the scope of protection of the invention.
Claims (5)
1. ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness.
Application the most according to claim 1, it is characterised in that: described prevention quick upward floating danger-removal causes decompression
Sick medicine is injection.
Application the most according to claim 1 and 2, it is characterised in that: ammonium pyrrolidine dithiocarboxylate is molten
In physiological saline, the injection being configured to 25-125mg/mL uses.
Application the most according to claim 1 and 2, it is characterised in that: described ammonium pyrrolidine dithiocarboxylate
The dosage of lumbar injection be 80-120mg/kg, intravenous dosage is 30-50mg/kg.
Application the most according to claim 1, it is characterised in that: making of described ammonium pyrrolidine dithiocarboxylate
It it is before quick upward floating danger-removal 20-35 minute with the time.
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