CN103933030A - Applications of ammonium pyrrolidine carbodithioic salt in preparation of drug for preventing decompression sickness caused by fast buoyant ascent escape - Google Patents
Applications of ammonium pyrrolidine carbodithioic salt in preparation of drug for preventing decompression sickness caused by fast buoyant ascent escape Download PDFInfo
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- CN103933030A CN103933030A CN201410187387.6A CN201410187387A CN103933030A CN 103933030 A CN103933030 A CN 103933030A CN 201410187387 A CN201410187387 A CN 201410187387A CN 103933030 A CN103933030 A CN 103933030A
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- ammonium pyrrolidine
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Abstract
The invention belongs to the field of medicine preparation, and particularly relates to applications of ammonium pyrrolidine carbodithioic salt in preparation of a drug for preventing decompression sickness caused by fast buoyant ascent escape. The ammonium pyrrolidine carbodithioic salt is dissolved in normal saline to prepare 25-125mg/mL of injection for use. The dose of ammonium pyrrolidine carbodithioic salt intraperitoneal injection is 80-120mg/kg, and the dose of ammonium pyrrolidine carbodithioic salt intravenous injection is 30-50mg/kg. The ammonium pyrrolidine carbodithioic salt is used at 20-35 minutes before fast buoyant ascent escape. The experiments show that the ammonium pyrrolidine carbodithioic salt can obviously inhibit the heart failure caused by myocardial fiber fracture due to bubbles so as to improve the cardiac function and lighten the injury and inflammation of the lung, so that the pathologic change caused by the decompression sickness can be lightened. Furthermore, the applications can provide experimental data for clinically more reasonably applying the ammonium pyrrolidine carbodithioic salt onto the decompression sickness caused by the fast buoyant ascent escape.
Description
Technical field
The invention belongs to medical preparation field, the particularly application of pyrrolidine dithio ammonium formate in preparing the medicine that prevents quick upward floating danger-removal to cause decompression sickness.
Background technology
One of main method of the submarine personnel underwater escape that quick upward floating danger-removal generally adopts as current various countries naval, it is that application no decompression diving principle is escaped danger ship person from large degree of depth accident ship.Because its equipment is simple, easy to implement the method, the degree of depth of escaping danger large, simple operation and other advantages, be that many countries adopt.But along with the intensification of the degree of depth, warship person allows high pressure open-assembly time is quite limited, if reason causes that open-assembly time is long because adjust blood pressure is improper etc., can there is serious decompression sickness.
The pathogeny of decompression sickness is that the gas being dissolved in body surpasses safety coefficient of supersaturation, and overflow in original place, forms bubble, and occluding vascular and compression organ-tissue, cause the dysfunctions such as a series of breathings, circulation and nervous system, and severe patient can cause death.The general method adopting for the treatment of for decompression sickness is again therapeutic compression both at home and abroad, and the prevention of decompression sickness is mainly taked according to the program of decompressing table, to carry out safety relief completely, carefully calculates diver's floating interval of floating dock and decompression time.But, because quick upward floating danger-removal mostly occurs at submarine accident, environment of living in makes the program of quick upward floating danger-removal be difficult to strict control, once and decompression sickness occurs, be difficult to carry out timely therapeutic compression again, therefore prepare a kind of medicine of the decompression sickness due to quick upward floating danger-removal process that effectively can prevent and be very important.
Pyrrolidine dithio ammonium formate is a kind of chemical compound, and molecular formula is C
5h
9nS
2, this molecule and salt thereof are widely used in multiple biochemical applications, comprise metal-chelating, and the aspects such as Inducible nitric oxide synthase are blocked and blocked to the inducing cell G1 phase.But this molecule studies confirm that and can be applicable to prevent decompression sickness, is not more used to prevent quick upward floating danger-removal to cause decompression sickness.
Summary of the invention
The object of this invention is to provide pyrrolidine dithio ammonium formate and cause the application in decompression sickness at prevention quick upward floating danger-removal, can significantly reduce the mortality rate that quick upward floating danger-removal causes decompression sickness, and alleviate the cardiopulmonary tissue injury that decompression sickness causes.
Technical scheme provided by the invention is pyrrolidine dithio ammonium formate to be caused to the medicine of decompression sickness for the preparation of prevention quick upward floating danger-removal.
Above-mentioned application, need to be dissolved in pyrrolidine dithio ammonium formate in normal saline, and the injection that is mixed with 25-125mg/mL is used.
The dosage of the lumbar injection of described pyrrolidine dithio ammonium formate is 80-120mg/kg, and intravenous dosage is 30-50mg/kg.Preferably, the dosage of the lumbar injection of described pyrrolidine dithio ammonium formate is 100mg/kg, and intravenous dosage is 40mg/kg.
Be 20-35 minute before quick upward floating danger-removal the service time of described pyrrolidine dithio ammonium formate.
Beneficial effect of the present invention is:
1, the invention provides the application of pyrrolidine dithio ammonium formate in preparing the medicine that prevents quick upward floating danger-removal to cause decompression sickness, experiment shows, pyrrolidine dithio ammonium formate can significantly suppress the heart failure that cardiac muscle fiber fracture that bubble causes causes, improve cardiac function, also can alleviate lung injury and inflammation, thereby alleviate the pathological change that decompression sickness causes, significantly improve the survival rate that quick upward floating danger-removal causes decompression sickness, alleviate the focus that quick upward floating danger-removal causes decompression sickness.
2, the present invention causes experimental data is provided in decompression sickness for more reasonably pyrrolidine dithio ammonium formate being applied in clinically to prevention quick upward floating danger-removal.
Accompanying drawing explanation
Fig. 1 is in embodiment 1, and rat quick upward floating danger-removal causes decompression sickness lung injury comparison diagram, and wherein scheming A is control rats pathologic figure, and amplification is 200 times; Figure B is pyrrolidine dithio ammonium formate prevention group lung tissue of rats pathology figure, and amplification is 200 times.
Fig. 2 is in embodiment 1, and rat quick upward floating danger-removal causes decompression sickness heart and injury comparison diagram.Wherein scheming A is the heart tissue pathology figure of control rats, and amplification is 200 times; Figure B is the heart tissue pathology figure of pyrrolidine dithio ammonium formate prevention group rat, and amplification is 200 times
Fig. 3 is in embodiment 2, and rabbit quick upward floating danger-removal causes decompression sickness lung injury comparison diagram, and wherein scheming A is the pathologic figure of matched group rabbit, and amplification is 200 times; Figure B is the pathologic figure of pyrrolidine dithio ammonium formate prevention group rabbit, and amplification is 200 times.
Fig. 4 is in embodiment 2, and rabbit quick upward floating danger-removal causes decompression sickness heart and injury comparison diagram, and wherein scheming A is the heart tissue pathology figure of matched group rabbit, and amplification is 200 times; Figure B is the heart tissue pathology figure of pyrrolidine dithio ammonium formate prevention group rabbit, and amplification is 200 times.
The specific embodiment
Below in conjunction with embodiment, the invention will be further described:
Experiment of the present invention pyrrolidine dithio ammonium formate used is purchased from Sigma company.
Embodiment 1
Experiment injectable drug: utilize normal saline, pyrrolidine dithio ammonium formate is mixed with to the solution of 25mg/ml, be prepared into injection.
Laboratory animal and grouping: 60 of male and healthy SD rats, body weight 220～250g, is purchased from Shanghai Slac Experimental Animal Co., Ltd..SD rat is divided into prevention group and matched group at random, 30 every group.
Experimental technique: prevention group is processed first 30 minutes, by lumbar injection pyrrolidine dithio ammonium formate solution (injected dose is 100mg/kg), matched group is processed first 30 minutes, by lumbar injection equal-volume normal saline, afterwards laboratory animal is placed in to quick upward floating danger-removal pressurization cabin, close hatch door, adopt self-editing computer automation quick upward floating danger-removal program, in 28 seconds, use the mode (doubling for every 7 seconds) of compressed air index multiplication to be forced into 1.6MPa, under high pressure, stop 242 seconds, in 50 seconds, be at the uniform velocity decompressed to normal pressure, deliver from vault carries out the detection analysis of experimental rat for 30 minutes.
Experiment finishes rear observation and finds, restless, the fast phenomenon of breast abdominal part fluctuating frequency that the rat of matched group occurs after deliver from vault, within 1 minute, occur dead, during to 5 minutes dead 15, after 10 minutes, survival rats breast abdominal part fluctuating frequency slows down, in 15 minutes dead 18 altogether, the mouth and nose of scratching after remaining 12 survival rats delivers from vault, nibble abdominal part performance, after progressively recover; After pyrrolidine dithio ammonium formate pretreated group rat deliver from vault, assemble together, movable few, breast abdominal part fluctuating Non Apparent Abnormality changes, and in 10 minutes, there is no death, and dead 3 altogether to 15 minutes, remaining 27 survival rats are progressively recovered normal activity.
Above-mentioned experiment shows, the mortality rate that rat quick upward floating danger-removal causes decompression sickness is 10%, and the mortality rate of control rats is 60%, illustrate that pyrrolidine dithio ammonium formate can significantly reduce the mortality rate that quick upward floating danger-removal causes decompression sickness, and can extend the time-to-live of rat after quick upward floating danger-removal, for follow-up therapeutic compression again provides favourable chance.
Experiment finishes rear observation and finds, the lung tissue of survival rats is detected and found, the wet dry weight ratio of quick upward floating danger-removal matched group is 6.6128 ± 0.2654 (mean+SD), and the wet dry weight ratio of pyrrolidine dithio ammonium formate prevention group is 5.2501 ± 0.5956 (mean+SD), p value >0.05, illustrates that the pretreatment of pyrrolidine dithio ammonium formate can significantly reduce the wet dry weight ratio of lung.
The pathologic inspection of survival rats is found, quick upward floating danger-removal causes the extensive damage of decompression sickness control rats alveolar structure and merges, and alveolar wall edema is obvious, has a liking for as seen her red liquid and erythrocyte and ooze out in alveolar space.Pyrrolidine dithio ammonium formate prevention group and quick upward floating danger-removal cause the comparison of decompression sickness matched group, and alveolar wall thickening degree obviously alleviates, and specifically as shown in Figure 1, wherein scheming A is control rats pathologic figure, and amplification is 200 times; Figure B is pyrrolidine dithio ammonium formate prevention group lung tissue of rats pathology figure, and amplification is 200 times.
The heart tissue pathologic finding of experimental rat is found, it is obvious that quick upward floating danger-removal causes rat cadavers cardiac muscle fiber edema, degeneration, the fracture of decompression sickness matched group, as shown in the A figure in Fig. 2, and the survival rats cardiac muscle fiber of pyrrolidine dithio ammonium formate prevention group only has slight edema, specifically as shown in the B figure in Fig. 2.
Embodiment 2
Experiment injectable drug: utilize normal saline, pyrrolidine dithio ammonium formate is mixed with to the solution of 120mg/mL, be prepared into injection.
Laboratory animal and grouping: 16 of male and healthy new zealand rabbits, body weight 2.6～3kg, is purchased from Shanghai Slac Experimental Animal Co., Ltd..Rabbit is divided into prevention group and matched group at random, 8 every group.
Experimental technique: prevention group is processed first 20 minutes, through auricular vein injection pyrrolidine dithio ammonium formate solution (injected dose is 40mg/kg), matched group is processed first 20 minutes, through auricular vein injection equal-volume normal saline, afterwards laboratory animal is placed in to quick upward floating danger-removal pressurization cabin, close hatch door, adopt self-editing computer automation quick upward floating danger-removal program, in 24 seconds, use the mode (doubling for every 7 seconds) of compressed air index multiplication to be forced into 1.1MPa, under high pressure, stop 240 seconds, in 33 seconds, be at the uniform velocity decompressed to normal pressure, deliver from vault is tested the detection analysis of rabbit for 30 minutes.
Experiment finishes rear observation to be found, quick upward floating danger-removal causes after decompression sickness matched group rabbit deliver from vault, in 10 minutes, 1 rabbit occur scratching mouth and nose, whole skin, the performance of screaming, and with two rear acroparalysis, in the time of 15 minutes, there is two rear acroparalysis in 2 rabbits, right hind paralysis appears in 1 rabbit; Movable few after prevention group rabbit deliver from vault, during to 15 minutes, only there is 1 rabbit to occur two rear acroparalysis, all the other rabbits progressively recovered normal activity in 30 minutes.Illustrate that the pretreatment of pyrrolidine dithio ammonium formate can significantly reduce the generation that quick upward floating danger-removal causes decompression sickness.
The pathologic inspection of rabbit is found, quick upward floating danger-removal causes the extensive damage of decompression sickness control rats alveolar structure and merges, and alveolar wall edema is obvious, and in alveolar space, visible a large amount of erythrocyte ooze out.Pyrrolidine dithio ammonium formate prevention group and quick upward floating danger-removal cause the comparison of decompression sickness matched group, rabbit alveolar wall, without obviously thickening, is oozed out without obvious erythrocyte, specifically as shown in Figure 3, wherein scheming A is matched group rabbit pathologic figure, and amplification is 200 times; Figure B is pyrrolidine dithio ammonium formate prevention group rabbit pathologic figure, and amplification is 200 times.
The heart tissue pathologic finding of rabbit is found, it is obvious that quick upward floating danger-removal causes decompression sickness matched group rabbit cardiac muscle fiber edema, degeneration, fracture, specifically as shown in the A figure in Fig. 4, and the survival rabbit cardiac muscle fiber of pyrrolidine dithio ammonium formate prevention group only has slight edema, but structure is normal, specifically as shown in the B figure in Fig. 4.
In sum, by above-mentioned experiment susceptible of proof, pyrrolidine dithio ammonium formate can significantly suppress the heart failure that cardiac muscle fiber fracture that bubble causes causes, and improves cardiac function, also can alleviate lung injury and inflammation, thereby alleviate the pathological change that decompression sickness causes.
The above is preferred embodiment of the present invention, but the present invention should not be confined to the disclosed content of this embodiment.So every, do not depart from the equivalence completing under spirit disclosed in this invention or revise, all falling into the scope of protection of the invention.
Claims (5)
1. the application of pyrrolidine dithio ammonium formate in preparing the medicine that prevents quick upward floating danger-removal to cause decompression sickness.
2. application according to claim 1, is characterized in that: the medicine that described prevention quick upward floating danger-removal causes decompression sickness is injection.
3. application according to claim 1 and 2, is characterized in that: pyrrolidine dithio ammonium formate is dissolved in normal saline, and the injection that is mixed with 25-125mg/mL is used.
4. application according to claim 1 and 2, is characterized in that: the dosage of the lumbar injection of described pyrrolidine dithio ammonium formate is 80-120mg/kg, and intravenous dosage is 30-50mg/kg.
5. application according to claim 1, is characterized in that: be 20-35 minute before quick upward floating danger-removal the service time of described pyrrolidine dithio ammonium formate.
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| CN201410187387.6A CN103933030B (en) | 2014-05-06 | 2014-05-06 | Ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness |
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| CN201410187387.6A CN103933030B (en) | 2014-05-06 | 2014-05-06 | Ammonium pyrrolidine dithiocarboxylate application in preparation prevention quick upward floating danger-removal causes the medicine of decompression sickness |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412139A (en) * | 2015-12-04 | 2016-03-23 | 中国人民解放军海军医学研究所 | Application of inosine in preparing medicine for preventing decompression sickness caused by fast buoyancy ascent escape |
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Non-Patent Citations (2)
| Title |
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| 王海涛: "极快速减压致大鼠肺损伤特点及机制的研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 03, 15 March 2008 (2008-03-15), pages 076 - 36 * |
| 王红嫚等: "PDTC对大鼠急性肺损伤TNF-α、IL-1β及核因子-κB蛋白表达的影响", 《中国老年学杂志》, vol. 33, 31 July 2013 (2013-07-31), pages 3116 - 3118 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412139A (en) * | 2015-12-04 | 2016-03-23 | 中国人民解放军海军医学研究所 | Application of inosine in preparing medicine for preventing decompression sickness caused by fast buoyancy ascent escape |
| CN105412139B (en) * | 2015-12-04 | 2018-01-16 | 中国人民解放军海军医学研究所 | Application of the inosine in preparing prevention quick upward floating danger-removal and causing the medicine of decompression sickness |
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