CN101496512A - Organ preservative fluid and preparation method thereof - Google Patents
Organ preservative fluid and preparation method thereof Download PDFInfo
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- CN101496512A CN101496512A CNA2008100334257A CN200810033425A CN101496512A CN 101496512 A CN101496512 A CN 101496512A CN A2008100334257 A CNA2008100334257 A CN A2008100334257A CN 200810033425 A CN200810033425 A CN 200810033425A CN 101496512 A CN101496512 A CN 101496512A
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Abstract
The invention relates to a preservation solution for organs, tissues or cells of human bodies or animals. The organ preservation solution comprises sodium citrate, potassium citrate, magnesium sulfate, sodium dihydrogen phosphate, sodium hydroxide, adenosine, arginine, tryptophan, mannitol, tetramethylpyrazine hydrochloride and other components. The organ preservation solution can be used for cooling, lavaging and preserving the organs of the human bodies or the animals, can effectively preserve human in vitro kidneys for 48 hours and animal in vitro kidneys for 72 hours, can prevent ischemia-reperfusion injury, and has great value for clinical application.
Description
Technical field:
The present invention relates to medical science, be specifically related to a kind of preservation liquid that is used for human body or animal organ, tissue or cell, particularly a kind of preservation liquid that is used for human body or animal organ.
Background technology:
Organ transplant is the major progress of 20th century physianthropy science, has begun since clinical practice from the sixties in 20th century, and transplantation medicine has obtained the development of advancing by leaps and bounds.At present, the whole world has surpassed 700,000 examples (inferior) at the transplanting sum in the field of kidney, liver, heart, pancreas and bone-marrow transplantation, and the longest organ transplant recipients of surviving is nearly half a century.Organ transplant has become one of main direction of 21 century medical development, is that treatment organ failure in whole latter stage effectively effects a radical cure means.Yet any clinical organ transplant at first will have high-quality donor, and this is the prerequisite and the basic guarantee of organ transplant success, therefore, being kept at this significance arranged of organ, it is the foundation stone of organ transplant.And the basic goal that organ is preserved is to reduce the various damages that ischemic causes isolated organ to greatest extent, makes isolated organ preserve effective vigor, transports, joins type and operation so that finish, and makes transplant organ rapid restore funcitons after operation.
Closely during the last ten years, Chinese organ transplant quantity has leapt to the first place, Asia, but clinically except kidney is preserved, liquid is preserved in the preservation of organs such as liver, the heart and pancreas still dependence on import.The import organ preservative fluid costs an arm and a leg, for the patient who carries out organ transplant has increased heavy financial burden.As the last common stage of all types ephrosis development, ESRD (ESRD) is the disease of serious threat human health.According to the statistics of 1994 2000000 urban populations, the incidence of disease of Chinese ESRD is about 568/ hundred ten thousand, and it is about 600,000 to suffer from the patient, and patient's number is with the speed increment more than 10% in recent years.
The carrying out on a large scale of China's kidney transplant work starts from eighties of last century beginning of the eighties at the end of the seventies, and its important motive force is that height oozes succeeding in developing of potassium citrate purine (HCA) kidney preserving liquid.This preservation liquid can effectively be preserved kidney 57 hours.Over more than 20 year, this preservation liquid is carried out organ transplant in the whole nation medical institutions are used widely.Brought into play important function in the kidney transplant field.
HCA liquid prescription composition (every 1000ml) and important technological parameters are as follows: K
+Be 80mmoL, Na
+Be 80mmoL, MgSO
4For 41mmoL, citrate are that 55mmoL, mannitol are that 30.2mmoL, adenosine purine phosphate are that 0.38mmoL, pH value are 7.14, osmotic pressure is 380mOsm/L.
The main feature of HCA kidney preserving liquid has: 1, osmotic pressure height prevents that the effect of edema is stronger; 2, contain the adenosine purine, for cell provides the certain energy substrate: 3, contain magnesium sulfate, help stabilizing cell membrane: 4, cheap, public's acceptance is higher.
But this preservation liquid also has weak point: 1, magnesium sulfate concentration is higher, easily separates out under the low temperature, is deposited in to preserve in liquid and the kidney blood vessel to cause tissue injury; 2, it is right not contain efficient buffer, and the pH value is unstable, is not enough to prevent cell acidify when long-time (more than the 24h) preserves kidney; 3, contain more biochemical preparation, purity is not enough.Therefore, when HCA liquid preservation liquid kidney reached more than 24 hours in clinical practice is used, the generation of post-transplantation kidney significantly raise.
Folkert doctor O.Belzer leader's in 1987 experiment group of U.S. WISCONSIN university has successfully developed a kind of low temperature organ preservative fluid, it is UW (UNIVERSITY OF WISCONSIN) organ preservative fluid, it has improved the effect that simple hypothermia perfusion musical instruments used in a Buddhist or Taoist mass official preserves, can preserve pancreas or kidney 72 hours, liver can be preserved and reach 24 hours.The composition of UW liquid is: HES 50g/L, lactic acid (lactone) 35.83g/L, potassium dihydrogen phosphate 3.4g/L, magnesium sulfate (MgSO
47H2O) 1.23g/L, raffinose 17.83g/L, adenosine 1.34g/L, allopurinol 0.136g/L, total glutathione 0.922g/L, potassium hydroxide 5.61g/L, pH value be 7.4, insulin 40 units, benzyl penicillin 200,000 units, dexamethasone 16mg.Though the increasingly extensive in the world application of UW liquid, its prescription liquid exists as viscosity higher, thereby cooling rate is slow; Potassium content is too high, and the improper use meeting causes cardiac arrest in the art, and price is very expensive, is not suitable for widespread usage.
Summary of the invention:
It is a kind of safe in utilization, effective, quality controllable that the technical problem to be solved in the present invention is to provide, and height oozes, contains the abundant energy substrate, inexpensive organ preservative fluid and preparation method thereof.
The invention provides a kind of organ preservative fluid.
Organ preservative fluid of the present invention is made up of the composition of following weight proportion: (every 1000ml)
Sodium citrate 2.0g～50.0g
Potassium citrate 3.0g～50.0g
Magnesium sulfate 0.1g～8.0g
Arginine 0.02g～4.0g
Tryptophan 0.05g～5.0g
Ligustrazine Hydrochloride 0g～6.0g
Osmotic pressure regulator 5.0g～80.0g
PH value buffering is to 0.1g～60.0g
Energy substrate 0.1g～20.0g.
The pH value of organ preservative fluid of the present invention is 5.0～9.5, osmotic pressure value is 320～420mOsm/L.
Another object of the present invention has provided the preparation method of above-mentioned organ preservative fluid, may further comprise the steps:
1, dense joining: dissolve potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, adenosine, arginine, tryptophan, mannitol and sodium hydroxide with proper amount of water for injection respectively, add water for injection to 80% of cumulative volume, add medical charcoal (0.05% w/v of cumulative volume), fully stir, take off charcoal to clear liquid;
2, rare joining: add the Ligustrazine Hydrochloride of formula ratio in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration;
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: to be detected qualified after, with soup through 0.2 μ m membrane filtration;
4, embedding: streamline on the soup is carried out embedding;
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet; Set sterilising conditions: 115 ℃, 30 minutes or sterilization in 121 ℃, 15 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Organ preservative fluid of the present invention can be used in human body or animal organ's cooling, lavation and preservation, and as kidney, effectively depositary's Dispersing Monkey Kidney Cell in Tissue Culture is 48 hours, animal 72 hours, and can prevent ischemical reperfusion injury.
The characteristics of organ preservative fluid of the present invention are:
1, owing to is that intracellular fluid type (hyperkalemia hyponatremia) is preserved liquid, similar to ion concentration inside and outside the cell, the inside and outside ion exchange of cell reduces between storage life, energy consumption reduces, recover to stride film cation gradient and cell function when helping pouring into rapidly, most importantly the intracellular fluid type is preserved the low Na of liquid again
+To obviously reduce Na
+The interior stream of ion reduces Na in the cell
+The gathering of ion can stop the generation of edema.
2, raw materials used being easy to get in the prescription, low price.
3, added adenosine and tryptophan (L-tryptophan) substrate in the prescription, for the reparation and the activation energy utilization of reperfusion injury provides condition, for the cell under the anoxia condition provides enough energy as energy (ATP).
4, added Ligustrazine Hydrochloride in the prescription, can remove oxygen radical, anti peroxidation of lipid improves the SOD activity, and therefore the balanced action that suppresses platelet aggregation and activation and keep TXA2/PGI2 has the effect of outstanding anti-blood reperfusion injury.Pharmacological research proves that Ligustrazine Hydrochloride also has the expansion arteriole and improves microcirculation and brain blood flow, produces the effect of antithrombotic form and thrombus dissolving.Also have the calcium antagonistic effect simultaneously, can suppress the absorption of cells in-vitro, the cellular damage of having avoided intracellular calcium overload to cause calcium ion.
5, added arginine (L-arginine) in the prescription, arginine is the generation substrate of NO in the body, and under NO synzyme (NOS) and co-factor effect thereof, arginine N end guanidine radicals deamination is oxidized to NO, and this path becomes " L-arginine: NO path ".NO is a kind of fat-soluble very strong small molecule active nitrogen free radical, and the energy freedom is by cell membrane and alleviate ischemical reperfusion injury, and effective histocyte apoptosis.
6, reduced magnesium sulfate (MgSO in the prescription
4Concentration 7H2O) reduces its separating out under cryogenic conditions.
7, add mannitol in the prescription and be used to adjust osmotic pressure, made the solution osmotic pressure value maintain 320～420mOsm/L, can effectively prevent oedema.
8, it is right to have added phosphate buffer in the prescription, makes the pH value of solution value stabilization between 5.5～9.5, helps the loss cell that prevents that rapid acidifying causes under the weary oxygen metabolism of cell.
9, do not have incompatibility between organ preservative fluid component of the present invention, preparation technology is simple, can stand the high-temperature sterilization of 115 ℃, 30 minutes or 121 ℃, 15 minutes, and stable and controllable for quality, using method is simple.
Animal (dog) experiment shows that organ preservative fluid of the present invention can effectively preserve kidney 72 hours, the preservation quality of kidney significantly is better than HCA liquid, and works as with the UW liquid phase.
Embodiment:
Below in conjunction with embodiment the present invention is described in further detail, but should understands the scope that the scope of protection of the invention is not limited only to these embodiment.
Embodiment 1
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, adenosine, arginine, tryptophan, mannitol and the sodium hydroxide of 500ml, add water for injection to 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.65, osmotic pressure value is 370mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: 115 ℃, 30 minutes, the sterilization cabinet entered automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 2
Prescription:
The preparation method:
1, dense joining: with 500ml water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, adenosine, arginine, tryptophan, sorbierite and sodium hydroxide, add water for injection to 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.61, osmotic pressure value is 366mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: 115 ℃, 30 minutes, the sterilization cabinet entered automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 3
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, adenosine, arginine, tryptophan, mannitol and the sodium hydroxide of 500ml, add water for injection to 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.89, osmotic pressure value is 377mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 121 ℃, 15 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 4
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, sodium hydrogen phosphate, adenosine, arginine, tryptophan and the mannitol of 500ml, add water for injection to 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.72, osmotic pressure value is 373mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 121 ℃, 15 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 5
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, adenosine, arginine, tryptophan and the mannitol of 500ml, add water for injection to 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.79, osmotic pressure value is 368mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 115 ℃, 30 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 6
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, potassium dihydrogen phosphate, adenosine, arginine, tryptophan, mannitol and the sodium hydroxide of 500ml, add water for injection to about 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 8.12, osmotic pressure value is 386mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 115 ℃, 30 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 7
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, potassium dihydrogen phosphate, sodium hydrogen phosphate, adenosine, arginine, tryptophan and the mannitol of 500ml, add water for injection to about 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.87, osmotic pressure value is 365mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 115 ℃, 30 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Embodiment 8
Prescription:
The preparation method:
1, dense joining: with water for injection dissolving potassium citrate, sodium citrate, magnesium sulfate, potassium dihydrogen phosphate, sodium hydrogen phosphate, adenosine, arginine, tryptophan and the mannitol of 500ml, add water for injection to about 80% of cumulative volume, add medical charcoal 0.5g, fully stir, take off charcoal to clear liquid.
2, rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration.
3, the pH value and the osmotic pressure value of rare dosing of checking procedure 2: the pH value is 7.83, osmotic pressure value is 362mOsm/L.With soup through 0.2 μ m membrane filtration.
4, embedding: streamline on the soup is carried out embedding.
5, sterilization: the semi-finished product that embedding is good are sterilized in the sterilization cabinet.Set sterilising conditions: sterilization in 115 ℃, 30 minutes, the sterilization cabinet enters automatic program, and sterilization is offerd for sale after finishing, and obtains finished product.
Animal experiment:
Organ preservative fluid (to call " this organ preservative fluid " in the following text) with embodiment 1 preparation is an example, and its application in kidney transfer operation is studied.Adopt simple lavation cooling dog kidney autoplastic transplantation model, with HCA liquid and UW liquid is contrast, dog is divided into A (HCA liquid 48h), the B (organ preservative fluid that embodiment 1 provides, to call " this organ preservative fluid " in the following text, 48h), 6 groups of C (UW liquid 48h), D (HCA liquid 72h), E (this organ preservative fluid 72h), F (UW liquid 72h) etc., 10 every group.
The foundation of animal model: choose the female hybrid dog of 13～17kg, 12h fasting before the art is anaesthetized with 3% amobarbital 30mg/kg intraperitoneal injection.After anaesthetizing successfully, get median abdominal incision, be about 12cm downwards, cut abdomen from xiphoid-process.Free left kidney and kidney arteriovenous, ureter cut off ureter, are about 8cm, at renal vein and arteria renalis root respectively with its cut-out.Take out kidney immediately and place preservation liquid (0 ℃) 200mL that respectively organizes appointment to pour into kidney, be pale asphyxia, specify preservation liquid to place the kidney bag together with 500mL in kidney, under 0～4 ℃ of condition, store until kidney through the arteria renalis.Constriction experiment animal kidney arteriovenous and ureter remnant are closed abdomen respectively.Postoperative is given preface Ceftriaxone Sodium 1g drip-feed immediately.Behind the 72h, same experimental dog is by anaesthetizing with quadrat method, open the abdominal cavity by former otch, and extend to downwards above the pubis, ilium outer arteriovenous in free right side is taken out kidney, and renal vein and vena iliaca externa are with 7-0prelene vascular anastomosis line end side-to-side anastomosis, the arteria renalis and arteria iliaca externa end to end anastomosis, thoroughly hemostasis behind the open blood flow.Cut bladder, self retaining catheter.The double J pipe of the built-in F4.5 of ureter coincide with 5-0 catgut and bladder.Cut the right kidney of experimental dog subsequently, close abdomen, operation finishes.Postoperative gives fluid infusion (every day 10% glucose 500mL, equilibrium liquid 500mL) and antibiotic (Ceftriaxone Sodium 1g) begins to take food voluntarily until laboratory animal.Renal function index changed before and after postoperative detect to be transplanted, and phlebotomized on 3rd and to measure the serum creatinine value.60 days clinical follow phases, the animal that reaches 60 days is considered as long-term surviving.
Experimental result is as follows:
1, Apoptosis testing result between cortex renis low temperature storage life:
Preserve the same day this organ preservative fluid group and HCA group, UW liquid group Apoptosis be in similar low-level, the apoptotic index no significant difference.With the prolongation of holding time, the incidence of renal cortical cell apoptosis increases, and there is difference in the different liquid group apoptosis rates of preserving of same time point, and the 1st, 2, the 3 day HCA liquid group of preserving at low temperature is significantly higher than this organ preservative fluid (P＜0.05).And low temperature is preserved each time point, and UW liquid group and this organ preservative fluid group apoptotic index change similar, two groups of differences with insignificance (P〉0.05).
The influence (n=10) that different preservation liquid wither to renal cortical cell between table 1 low temperature storage life
Annotate: * represents to compare significant difference with this organ preservative fluid group, P＜0.05; UW liquid group and this organ preservative fluid group do not have significant difference, P〉0.05.
2, mitochondria respiratoring control rate (RCR) measurement result:
Along with the low temperature holding time prolongs, the cortex renis mitochondria respiratoring control rate descends with the prolongation of holding time.Each time point that low temperature is preserved, this organ preservative fluid group cortex renis RCR organizes apparently higher than HCA, mitochondria function difference remarkable (P＜0.05) between two groups; This organ preservative fluid group cortex renis preservation RCR on the same day can reach 3.08 ± 0.41, near normal value, and HCA liquid group RCR has dropped to below 3.0: this organ preservative fluid group RCR descends gradually between storage life, reduce to 2.68 ± 0.27 after three days, and the ratio that HCA liquid group RCR value descends is very fast, after three days only be between 2.06 ± 0.32, two groups the RCR value all there were significant differences at each time point, and this organ preservative fluid group and UW liquid group do not have significant difference at each time point.
3, the dog time-to-live:
The dog time-to-live after table 2 kidney transplant
The result is as seen: A group and B and C group have significant difference, B group and C group there was no significant difference; D group and E and F group have significant difference, E group and F group there was no significant difference;
4, serum creatinine pH-value determination pH result:
Respectively organize dog serum creatinine value (μ mol/L) before and after table 3 kidney transplant
Annotate: data are x ± s in the table, and the S-N-K variance analysis shows that A group and B and C group have significant difference, B group and C group there was no significant difference; D group and E and F group have significant difference, E group and F group there was no significant difference.
The concrete proportioning example of the various embodiments described above by exemplifying, and in the kidney transplant process of dog, compare with HCA liquid and UW liquid with this organ preservative fluid for preparing, the result shows that this organ preservative fluid obviously is better than HCA liquid to kidney preservation aspect, does not have significant difference with UW liquid preservation effect.But above-mentioned example is not to a kind of restriction of the present invention, and when specifically implementing, the internal organs that described organ preservative fluid can substitute in the multiple important organ transfer operation that UW liquid is applied to comprise kidney, liver, pancreas, heart etc. are preserved.
Claims (6)
1, a kind of organ preservative fluid is characterized in that this organ preservative fluid is made up of following components by weight ratio: every 1000ml
Sodium citrate 2.0g～50.0g
Potassium citrate 3.0g～50.0g
Magnesium sulfate 0.1g～8.0g
Arginine 0.02g～4.0g
Tryptophan 0.05g～5.0g
Ligustrazine Hydrochloride 0g～6.0g
Osmotic pressure regulator 5.0g～80.0g
PH value buffering is to 0.1g～60.0g
Energy substrate 0.1g～20.0g.
2, organ preservative fluid according to claim 1 is characterized in that: described osmotic pressure regulator is selected from mannitol or sorbierite; Preferred mannitol.
3, organ preservative fluid according to claim 1 is characterized in that: described pH value buffering is to being selected from sodium dihydrogen phosphate/sodium hydrogen phosphate, potassium dihydrogen phosphate/dipotassium hydrogen phosphate, potassium dihydrogen phosphate/sodium hydroxide, sodium dihydrogen phosphate/sodium hydroxide or sodium hydrogen phosphate/potassium dihydrogen phosphate; Preferably phosphoric acid sodium dihydrogen/sodium hydroxide, the amount of wherein every 1000ml phosphoric acid sodium dihydrogen are that the amount of 0.5g～60.0g, sodium hydroxide is 0.05g～50.0g.
4, organ preservative fluid according to claim 1 is characterized in that: described energy substrate is selected from adenosine or guanosine, preferred adenosine.
5, organ preservative fluid according to claim 1, the pH value that it is characterized in that described organ preservative fluid is 5.0～9.5; Osmotic pressure value is 320～420mOsm/L.
6, a kind of preparation method of organ preservative fluid as claimed in claim 1 is characterized in that this method may further comprise the steps:
(1) dense joining: dissolve potassium citrate, sodium citrate, magnesium sulfate, sodium dihydrogen phosphate, adenosine, arginine, tryptophan, mannitol and sodium hydroxide with water for injection respectively, add water for injection to 80% of cumulative volume, the 0.05%w/v medical charcoal that adds cumulative volume, fully stir, take off charcoal to clear liquid;
(2) rare joining: add Ligustrazine Hydrochloride in above-mentioned concentrated wiring liquid, benefit adds to the full amount of water for injection, and fully stirs, with soup footpath 0.45 μ m membrane filtration;
(3) the pH value and the osmotic pressure value of the rare dosing of checking procedure (2), to be detected qualified after, with soup through 0.2 μ m membrane filtration;
(4) embedding: the soup that will detect after qualified carries out embedding;
(5) sterilization: the semi-finished product that embedding is good are sterilized described sterilising conditions in the sterilization cabinet: 115 ℃, 30 minutes or sterilization in 121 ℃, 15 minutes obtain finished product.
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