CN104083353B - N-acetylcystein is in the application of preparing in the medicine that prevents quick upward floating danger-removal to cause decompression sickness - Google Patents
N-acetylcystein is in the application of preparing in the medicine that prevents quick upward floating danger-removal to cause decompression sickness Download PDFInfo
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- CN104083353B CN104083353B CN201410321315.6A CN201410321315A CN104083353B CN 104083353 B CN104083353 B CN 104083353B CN 201410321315 A CN201410321315 A CN 201410321315A CN 104083353 B CN104083353 B CN 104083353B
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Abstract
The invention belongs to medical preparation field, particularly N-acetylcystein, in the application of preparing in the medicine that prevents quick upward floating danger-removal to cause decompression sickness, is dissolved in N-acetylcystein in physiological saline, and the injection that is mixed with 50-500mg/mL uses. The dosage of the lumbar injection of this N-acetylcystein is 150-1000mg/kg, and intravenous dosage is 200-500mg/kg. Be 16-60 minute before quick upward floating danger-removal the service time of this N-acetylcystein. Of the present inventionly experiment showed, that N-acetylcystein can significantly suppress cardiac muscle fibre that bubble the causes heart failure causing that ruptures, improve heart function, also can alleviate lung injury and inflammation, thereby alleviate the pathological change that decompression sickness causes. And the present invention causes experimental data is provided in decompression sickness for more reasonably N-acetylcystein being applied in clinically to prevention quick upward floating danger-removal.
Description
Technical field
The invention belongs to medical preparation field, particularly N-acetylcystein is at preparation prevention floating upward quicklyEscape danger and cause the application in the medicine of decompression sickness.
Background technology
The main side of the submarine personnel underwater escape that quick upward floating danger-removal generally adopts as naval of current various countriesOne of method, it is that application no deceompression diving principle is escaped danger ship person from large degree of depth accident ship. Due to its equipmentSimply, easy to implement the method, the degree of depth of escaping danger large, simple operation and other advantages, has been that many countries adopt. But along withThe intensification of the degree of depth, the high pressure open-assembly time that warship person allows is quite limited, if reason is drawn because pressure regulation is improper etc.Rise open-assembly time long, can there is serious decompression sickness.
The pathogenesis of decompression sickness is that the gas being dissolved in body exceedes safety coefficient of supersaturation, overflows in original placeGo out, form bubble, occluding vascular and compression organ-tissue, cause a series of breathings, circulation and nerveThe dysfunctions such as system, severe patient can cause death. The side generally adopting for the treatment of decompression sickness both at home and abroadMethod is again therapeutic compression, and the prevention of decompression sickness is mainly taked completely to carry out safety according to the program of decompression table and subtractedPress, carefully calculate diver's floating interval of floating dock and decompression time. But, because quick upward floating danger-removal is manyOccur in submarine accident, environment of living in makes the program of quick upward floating danger-removal be difficult to strict control, and decompressionOccur once sick, be difficult to carry out timely therapeutic compression again, therefore prepare one and effectively can prevent fastThe escape danger medicine of the decompression sickness due to process of floating is very important.
Acetylcysteine (N-acetylcysteine, NAC) molecular formula is C5H9NO3S, is L-half Guang ammoniaThe acetyl compound of acid, it contains active-SH base, is often used to clinically eliminate the phlegm, also for saving secondThe hepatotoxicity wind agitation reaction that acylamino-phenol causes. In recent years there is more bibliographical information NAC to supply with body as a kind of sulfydryl,Or a kind of antioxidant, has removing free radical, regulate the effect such as metabolic activity of cell, breathing (asThe diseases such as treatment chronic obstructive pulmonary, pulmonary interstitial fibrosis), cardiovascular (hypertension cardiac remodeling), nerveIn the Clinical and experimental study of system (promoting dopamine to discharge) and AIDS, all there is application. But this molecule does not haveStudies confirm that and can be applicable to prevent decompression sickness, be 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 N-acetylcystein causes in decompression sickness at prevention quick upward floating danger-removalApplication, can significantly reduce quick upward floating danger-removal and cause the death rate of decompression sickness, and alleviate the heart that decompression sickness causesLung injury.
Technical scheme provided by the invention is for the preparation of prevention quick upward floating danger-removal by N-acetylcysteinCause the medicine of decompression sickness.
Above-mentioned application, need to be dissolved in N-acetylcystein in physiological saline, is mixed with 50-500mg/mLInjection use. Preferably, N-acetylcystein is dissolved in physiological saline, is mixed withThe injection of 200-300mg/mL uses.
The dosage of the lumbar injection of described N-acetylcystein is 150-1000mg/kg, intravenousDosage is 200-500mg/kg. Preferably, the dosage of the lumbar injection of described N-acetylcystein is500-1000mg/kg, intravenous dosage is 400mg/kg.
Be 15-60 minute before quick upward floating danger-removal the service time of described N-acetylcystein.
Beneficial effect of the present invention is:
1, the invention provides N-acetylcystein prevents quick upward floating danger-removal to cause the medicine of decompression sickness in preparationApplication in thing, experiment shows, it is disconnected that N-acetylcystein can significantly suppress the cardiac muscle fibre that bubble causesSplit the heart failure causing, improve heart function, also can alleviate lung injury and inflammation, thereby alleviate decompressionThe sick pathological change causing, significantly improves quick upward floating danger-removal and causes the survival rate of decompression sickness, alleviate fast onLift-off danger causes the damage of decompression sickness.
2, the present invention is for being more reasonably applied in N-acetylcystein clinically prevention quick upward floating danger-removalCause experimental data is provided in decompression sickness.
Brief description of the drawings
Fig. 1 is in embodiment 1, rat quick upward floating danger-removal under different N-acetylcysteine dosageCause decompression sickness lung injury comparison diagram, wherein scheming A is physiology saline control group lung tissue of rats pathology figure, putsLarge multiple is 200 times; Figure B is N-acetylcystein 250mg/kg prevention group lung tissue of rats pathology figure,Multiplication factor is 200 times; Figure C is N-acetylcystein 500mg/kg prevention group lung tissue of rats pathologyFigure, multiplication factor is 200 times; Figure D is N-acetylcystein 1000mg/kg prevention group lung tissue of ratsPathology figure, multiplication factor is 200 times.
Fig. 2 is in embodiment 1, rat quick upward floating danger-removal under different N-acetylcysteine dosageCause decompression sickness heart injury comparison diagram. Wherein scheming A is the heart tissue pathology figure of physiology saline control group rat,Multiplication factor is 200 times; Figure B is the heart tissue of N-acetylcystein 250mg/kg prevention group ratPathology figure, multiplication factor is 200 times; Figure C is the N-acetylcystein 500mg/kg prevention group rat heartDirty histopathology figure, multiplication factor is 200 times; Figure D is N-acetylcystein 1000mg/kg prevention groupRat heart histopathology figure, multiplication factor is 200 times.
Fig. 3 is in embodiment 3, and rabbit quick upward floating danger-removal causes decompression sickness lung injury comparison diagram, wherein schemes AFor the pathologic figure of lumbar injection control group rabbit, multiplication factor is 200 times; Figure B is acetyl half GuangThe pathologic figure of propylhomoserin 300mg/kg prevention group rabbit, multiplication factor is 200 times; Figure C ear edge is quietThe pathologic figure of arteries and veins injection control group rabbit, multiplication factor is 200 times; Figure D is A SixintaiThe pathologic figure of 400mg/kg prevention group rabbit, multiplication factor is 200 times.
Fig. 4 is in embodiment 3, and rabbit quick upward floating danger-removal causes decompression sickness heart injury comparison diagram, wherein schemes AFor the pathology figure of heart tissue of lumbar injection control group rabbit, multiplication factor is 200 times; Figure B is acetyl half GuangThe pathology figure of heart tissue of propylhomoserin 300mg/kg prevention group rabbit, multiplication factor is 200 times; Figure C ear edge is quietThe pathology figure of heart tissue of arteries and veins injection control group rabbit, multiplication factor is 200 times; Figure D is A SixintaiThe pathology figure of heart tissue of 400mg/kg prevention group rabbit, multiplication factor is 200 times.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described:
Experiment of the present invention N-acetylcystein used is purchased from Sigma company, N-acetylcystein injectionLiquid is purchased from Hangzhou Minsheng Medcine Co., Ltd.
Embodiment 1
Experiment injectable drug: utilize physiological saline, N-acetylcystein is mixed with to 250mg/ml'sSolution, is prepared into injection.
Animal used as test and grouping: 40 of male and healthy SD rats, body weight 220～260g, be purchased from Shanghai thisRec animal used as test Co., Ltd. By SD rat be divided at random acetylcysteine 250mg/kg prevention group,Acetylcysteine 500mg/kg prevention group, acetylcysteine 1000mg/kg prevention group and physiological salineControl group, 10 every group.
Experimental technique: prevention group is processed first 60 minutes, by lumbar injection N-acetylcystein solution (notePenetrate dosage and be respectively 250mg/kg, 500mg/kg and 1000mg/kg), control group is processed 60 minutes, logicalCross lumbar injection equal-volume physiological saline, afterwards animal used as test is placed in to quick upward floating danger-removal pressurization cabin, closeHatch door, adopts self-editing computer automation quick upward floating danger-removal program, uses compressed air index in 28 secondsThe mode (doubling for every 7 seconds) of multiplication is forced into 1.6MPa, stops 242 seconds under high pressure, even in 50 secondsSpeed is decompressed to normal pressure, and deliver from vault carries out the detection analysis of experimental rat for 30 minutes.
Experiment finishes rear observation to be found, the rat of physiological saline control group occurs after deliver from vault restless, chest bellyThe frequently phenomenon of speed that rises and falls, 2 minutes, 5 minutes, 6 minutes each dead 1, after 8 minutes, 1 paralysis is alsoAnd state difference, the mouth and nose of scratching, nibbles belly performance after remaining 6 survival rats delivers from vault, but afterwards byStep is recovered; After N-acetylcystein 250mg/kg prevention group rat deliver from vault, also occur that restless, chest belly risesVolt is the phenomenon of speed frequently, and each dead 1 in 4 minutes and 6 minutes, 1 paralysis after 6 minutes, remaining 7Rat progressively recovers normal activity; General after N-acetylcystein 500mg/kg prevention group rat deliver from vaultState is good, and dead 1 in 14 minutes, after 15 minutes, there is 1 state difference, observe to dead after 188 minutesDie, remaining 8 rats progressively recover normal activity; N-acetylcystein 1000mg/kg prevention group is largeAfter mouse deliver from vault, flock together, movable few, there is the rat observation of 3 state difference to have 1 after 234 minutesDeath, all the other 2 are progressively recovered, and all the other 7 rats progressively recovered normal activity in 30 minutes.
Above-mentioned experiment shows, along with the increase of N-acetylcystein dosage, can progressively to reduce rat quickFloating is escaped danger and is caused the M & M of decompression sickness, and heavy decompression sickness M & M is from 40% and 30%All be reduced to 10%, and time-to-live of rat after can significant prolongation quick upward floating danger-removal, for follow-upPressurization and complex treatment provide favourable chance.
The pathologic inspection of survival rats is found, quick upward floating danger-removal causes decompression sickness control rats lungBubble structure extensive damage is merged, and has a liking for as seen her red liquid and red blood cell and ooze out in alveolar space. N-acetyl halfCystine prevention group and the comparison of physiological saline control group, along with the increase of dosage, alveolar wall thickeningDegree alleviates gradually, and specifically as shown in Figure 1, wherein scheming A is control rats pathologic figure, amplifiesMultiple is 200 times; Figure B is N-acetylcystein 250mg/kg prevention group lung tissue of rats pathology figure,Multiplication factor is 200 times; Figure C is N-acetylcystein 500mg/kg prevention group lung tissue of rats pathologyFigure, multiplication factor is 200 times; Figure D is N-acetylcystein 1000mg/kg prevention group lung tissue of ratsPathology figure, multiplication factor is 200 times.
The heart tissue pathologic finding of experimental rat is found, quick upward floating danger-removal causes the dead of decompression sickness control groupThe rat heart muscle fiber oedema, sex change, fracture of dying is obvious, as shown in the A figure in Fig. 2; And various dose N-The survival rats cardiac muscle fibre of acetylcysteine prevention group only has slight oedema, concrete as the B-D in Fig. 2Shown in figure, wherein, figure B is the heart tissue pathology of N-acetylcystein 250mg/kg prevention group ratFigure, multiplication factor is 200 times; Figure C is N-acetylcystein 500mg/kg prevention group rat heart groupKnit pathology figure, multiplication factor is 200 times; Figure D is N-acetylcystein 1000mg/kg prevention group ratHeart tissue pathology figure, multiplication factor is 200 times.
Embodiment 2
Experiment injectable drug: A Sixintai (acetylcysteine injection, 20ml, 4g).
Animal used as test and grouping: 40 of male and healthy SD rats, body weight 220～260g, be purchased from Shanghai thisRec animal used as test Co., Ltd. By SD rat be divided at random acetylcysteine 150mg/kg prevention group,Acetylcysteine 300mg/kg prevention group, acetylcysteine 600mg/kg prevention group and physiological saline pairAccording to group, 10 every group.
Experimental technique: prevention group is processed first 60 minutes, by lumbar injection acetylcysteine injection (notePenetrate dosage and be respectively 150mg/kg, 300mg/kg and 600mg/kg), physiological saline control group processes front 60Minute, by lumbar injection equal-volume physiological saline, afterwards animal used as test is placed in to quick upward floating danger-removal pressurizationCabin, closes hatch door, adopts self-editing computer automation quick upward floating danger-removal program, uses compression in 28 secondsThe mode (doubling for every 7 seconds) of air index multiplication is forced into 1.6MPa, under high pressure, stops 242 seconds,In 50 seconds, be at the uniform velocity decompressed to normal pressure, after deliver from vault, observe the incidence of Rat 24 h.
Experiment finishes rear observation to be found, the rat of physiological saline control group occurs after deliver from vault restless, chest bellyThe frequently phenomenon of speed that rises and falls, 4 minutes, 5 minutes, 10 minutes each dead 1,1 paralysis after 15 minutesAnd state difference, observes to dead after 268 minutes, the mouth and nose of scratching after remaining 6 survival rats delivers from vault,Nibble belly performance, but progressively recover afterwards; N-acetylcystein 150mg/kg prevention group rat deliver from vaultAfter also there is restless, the chest belly phenomenon of speed frequently that rises and falls, in 3 minutes, 7 minutes and 12 minutes each dead 1Only, remaining 7 rats progressively recover normal activity; N-acetylcystein 300mg/kg prevention group is largeAfter mouse deliver from vault, general state is good, and dead 1 in 7 minutes and 8 minutes, after 15 minutes, there is 1 state difference,Observe to dead after 246 minutes, remaining 7 rats progressively recover normal activity; N-acetylcysteinMovable few after 600mg/kg prevention group rat deliver from vault, to observe and had 1 death after 298 minutes, all the other are 9 years oldRat progressively recovered normal activity, no abnormality seen afterwards in 30 minutes.
Above-mentioned experiment shows, when acetylcysteine injection volume, can significantly to reduce rat at 300mg/kg quickFloating is escaped danger and is caused the death rate of decompression sickness, especially in the time of acetylcysteine injection volume 600mg/kg, deadThe rate of dying is down to 10% from 40%, illustrates that N-acetylcystein can significantly reduce quick upward floating danger-removal and cause decompression sicknessThe death rate, and can extend the time-to-live of rat quick upward floating danger-removal from the time-to-live, forFollow-up pressurization again and complex treatment provide favourable chance.
Embodiment 3
Experiment injectable drug: utilize physiological saline, N-acetylcystein is mixed with to 500mg/mL'sSolution, is prepared into injection; A Sixintai (acetylcysteine injection, 20ml, 4g).
Animal used as test and grouping: 32 of male and healthy new zealand rabbits, body weight 2.3～2.7kg, is purchased from ShanghaiThis Rec animal used as test Co., Ltd. Rabbit is divided into acetylcysteine 300mg/kg prevention group (abdomen at randomChamber injection), lumbar injection control group, A Sixintai 400mg/kg prevention group (intravenous injection) and ear edge quietArteries and veins injection control group, 8 every group.
Experimental technique: acetylcysteine 300mg/kg prevention group is processed first 30 minutes, through lumbar injection N-Acetylcysteine solution (ID is 300mg/kg), lumbar injection control group is processed first 30 minutes,Through lumbar injection equal-volume physiological saline, A Sixintai 400mg/kg prevention group is processed first 15 minutes, through earEdge intravenous injection A Sixintai (ID is 400mg/kg), auricular vein injection control group processes front 15Minute, through auricular vein injection equal-volume physiological saline, afterwards animal used as test is placed in to quick upward floating danger-removal and addsBallasting, closes hatch door, adopts self-editing computer automation quick upward floating danger-removal program, in 24 seconds, uses and pressesThe mode (doubling for every 7 seconds) of contracting air index multiplication is forced into 1.1MPa, under high pressure, stops 240 seconds,In 33 seconds, be at the uniform velocity decompressed to normal pressure, deliver from vault carries out the detection analysis of experimental rabbit for 30 minutes.
Experiment finishes rear observation to be found, after lumbar injection control group rabbit deliver from vault, and 2 minutes and 3 minutes each 1Rabbit occur scratching mouth and nose, whole skin, dead after screaming, 15 minutes time, 2 rabbits occur two afterAcroparalysis; The activity of acetylcysteine 300mg/kg prevention group is few, within 6 minutes, has 1 rabbit to occur two hind legsParalysis, all the other 7 rabbits progressively recovered normal activity in 30 minutes; Auricular vein injection control group rabbitMovable few after deliver from vault, in 1 minute, 11 minutes, 12 minutes and 16 minutes two hind legs of each 1 rabbit appearanceParalysis, all the other 4 are progressively recovered; The activity of acetylcysteine 400mg/kg prevention group is few, within 1 minute, has 1Rabbit occur two after acroparalysis, all the other 7 rabbits progressively recovered normal activity in 30 minutes. N-is describedAcetylcysteine pretreatment can significantly reduce quick upward floating danger-removal and cause the generation of decompression sickness.
The pathologic inspection of rabbit is found, lumbar injection control group and auricular vein injection control groupRat all shows alveolar structure extensive damage, can measure red blood cell and ooze out in alveolar space. Acetylcysteine300mg/kg prevention group and A Sixintai 400mg/kg prevention group homophase are answered control group comparison, alveolar space structureMore complete, ooze out without obvious red blood cell, specifically as shown in Figure 3, wherein scheme A and C and be respectively abdominal cavity notePenetrate control group and auricular vein injection control group rabbit pathologic figure, multiplication factor is 200 times; Figure BBe respectively acetylcysteine 300mg/kg prevention group and A Sixintai 400mg/kg prevention group rabbit with figure DPathologic figure, multiplication factor is 200 times.
The heart tissue pathologic finding of rabbit is found to lumbar injection control group and auricular vein injection control groupRabbit cardiac muscle fibre oedema, sex change are obvious, and the survival rabbit cardiac muscle fibre of N-acetylcystein prevention groupOnly have slight oedema and hyperemia, but structure is normal, specifically as shown in Figure 4, wherein scheming A is lumbar injectionThe pathology figure of heart tissue of control group rabbit, multiplication factor is 200 times; Figure B is acetylcysteine 300mg/kgThe pathology figure of heart tissue of prevention group rabbit, multiplication factor is 200 times; Figure C auricular vein injection control group rabbitThe pathology figure of heart tissue of son, multiplication factor is 200 times; Figure D is A Sixintai 400mg/kg prevention group rabbitThe pathology figure of heart tissue of son, multiplication factor is 200 times.
Comparative example 1
Experiment injectable drug: utilize physiological saline, nitre Pu Na; Phentolamine.
Animal used as test and grouping: 24 of male and healthy new zealand rabbits, body weight 2.3～2.7kg, is purchased from ShanghaiThis Rec animal used as test Co., Ltd. By rabbit be divided at random nitre Pu Na prevention group, phentolamine prevention group andPhysiological saline control group, 8 every group.
Experimental technique: nitre Pu Na prevention group is processed first 15 minutes, through auricular vein injection sodium nitroprusside solution (notePenetrating dosage is 2.5mg/kg), phentolamine prevention group is processed first 15 minutes, appropriate through auricular vein injection phenolLamine solution (ID is 2mg/kg), control group is processed first 15 minutes, through bodies such as auricular vein injectionsLong-pending physiological saline, is placed in animal used as test quick upward floating danger-removal pressurization cabin afterwards, closes hatch door, adopts self-editingComputer automation quick upward floating danger-removal program was used the mode of compressed air index multiplication (every in 24 secondsWithin 7 seconds, double) be forced into 1.1MPa, under high pressure, stop 240 seconds, in 33 seconds, be at the uniform velocity decompressed to normal pressure,The incidence of 30 minutes observation experiment rabbit decompression sicknesses of deliver from vault.
Lazy moving and ears week of the large rabbit of equal observable in 5 minutes after the above two kinds of expansion blood vessel medicines of auricular vein injectionEnclose blood vessel dilatation, after simulation quick upward floating danger-removal, observe and find, after nitre Pu Na prevention group rabbit deliver from vault, 2 pointsIn clock, 1 rabbit whole skin, dead after screaming that occurs scratching, respectively has 1 rabbit for 6 minutes and 10 minutesThere is two rear acroparalysis in son, within 15 minutes, right hind paralysis appears in 1 rabbit; Phentolamine prevention group rabbitAfter deliver from vault, within 1 minute and 2 minutes, respectively there is 1 rabbit death, within 8 minutes, have 1 rabbit to occur two hind leg paralysissParalysis; After physiological saline control group rabbit deliver from vault, 2 minutes time, have 1 rabbit death, 4 minutes, 6 minutes andWithin 9 minutes, respectively there is 1 to occur two lower limb paralysis. Illustrate that expanding blood vessel pretreatment cannot prevent quick upward floating danger-removal to causeThe generation of decompression sickness.
In sum, by above-mentioned experiment susceptible of proof, N-acetylcystein can significantly suppress bubble to be causedThe cardiac muscle fibre heart failure causing that ruptures, improve heart function, also can alleviate lung injury and inflammation,Thereby alleviate the pathological change that decompression sickness causes. And owing to there are some researches show that N-acetylcystein has expansionOpen the effect of blood vessel, all can not prevent decompression by two kinds of expansion blood vessel medicine nitre Pu Na of independent use and phentolamineSick generation, therefore illustrates that N-acetylcystein is not or is not only to prevent to subtract by hemangiectasisPress sick generation.
The above is preferred embodiment of the present invention, but the present invention should not be confined to this embodiment instituteDisclosed content. Do not depart from the equivalence or the amendment that under spirit disclosed in this invention, complete so every, all fallEnter the scope of protection of the invention.
Claims (5)
1.N-acetylcysteine is in the application of preparing in the medicine that prevents quick upward floating danger-removal to cause decompression sickness.
2. application according to claim 1, is characterized in that: described prevention quick upward floating danger-removal causes decompressionSick medicine is injection.
3. application according to claim 1 and 2, is characterized in that: N-acetylcystein is dissolved in to lifeIn reason salt solution, the injection that is mixed with 50-500mg/mL uses.
4. application according to claim 1, is characterized in that: the abdominal cavity note of described N-acetylcysteinThe dosage of penetrating is 150-1000mg/kg, and intravenous dosage is 200-500mg/kg.
5. application according to claim 1, is characterized in that: when the use of described N-acetylcysteinBetween be 15-60 minute before quick upward floating danger-removal.
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| CN108042516B (en) * | 2018-01-30 | 2020-09-22 | 中国人民解放军第二军医大学 | Application of R, S-1,3-butanediol acetoacetic acid diester in preparation of drugs for preventing or treating decompression sickness |
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| CN102949381A (en) * | 2011-08-17 | 2013-03-06 | 上海市第六人民医院 | Application of ethanol in drug treating acute decompression sickness |
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| CN102949381A (en) * | 2011-08-17 | 2013-03-06 | 上海市第六人民医院 | Application of ethanol in drug treating acute decompression sickness |
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| A New Measure of Decompression Sickness in the Rat;Peter Buzzacott et al;《BioMed Research International》;20140525;第2014卷;http://dx.doi.org/10.1155/2014/123581 * |
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