KR830000629B1 - Manufacturing method of perfusion preservation liquid of transplant organ - Google Patents

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Description

Manufacturing method of perfusion preservation liquid of transplant organ

The present invention relates to a method for producing a perfusion liquid for preserving an organ to be transplanted, and more particularly to a method for preparing a perfusion preservation liquid containing a conversion ringer solution, albumin and perfluorocarbon emulsifier into a basic salt solution.

Recent advances in technology to preserve organs for transplantation are remarkable. In particular, advances in technology for preserving the kidneys have contributed greatly to the growth of graft-extracted kidneys. Advances in this technology are largely due to the development of perfusion fluids. For example, clinical preservation methods for transplantation of kidneys fall into two broad categories. One is cold storage by immersion [Lancet, 2, 1219-1222 (1969)] and the other is low temperature continuous perfusion [Lancet, 2, 536 (1967)]. In fact, the former is used for short term preservation, while the latter is used for long term preservation. Perfusion preservation is important for the growth of transplanted cadaveric kidneys, ie, for longer retention.

Since most kidneys are provided by a person who died in a car accident, the measures to be taken between the time of the accident and the time of transplantation are: Preparation for transportation and kidney transplantation. For this reason it is necessary to preserve the kidneys provided as long as possible. Indeed, as part of the study of transplanted cadaveric kidneys, many attempts have been made to preserve cadaveric kidneys for a long time. One of the primary goals of this attempt is the development and improvement of perfusion.

A widely used low temperature continuous perfusion method is the result of studies by Belzers [Lancet 536 (1967)]. They succeeded in preserving the kidneys of the dogs for 72 hours using freeze-precipitated plasma, followed by freezing and dissolving, and using fibringan-free plasma as the perfusate.

Toledo-Pereyra in 1974 [Surg, Gynecol. Obstet, 138, 901 to 905 (1974) developed a new perfusion solution of lyoprecipitated plasma treated with silica gel, which removes lipoproteins of fibrinogen that are still present in conventional lyoprecipitated plasma. For example, the triglyceride value is reduced by one third. There is a great risk of embolism during perfusion of conventional cryoprecipitated plasma, which is due to residual fibrinogen, lipoprotein or neutral fat. However, the risk is greatly reduced by using cryoprecipitated plasma treated with silica gel developed by Joledo-Pereyla. These cryoprecipitated plasmas still have several problems. First, the manufacturing process has not yet been fully established, and the composition of the prepared plasma is not constant, so it is difficult to obtain a formulation having a constant protein content and a constant electrolyte composition. Second, there remains a risk of fat embolism during perfusion due to incomplete removal of insoluble fat. In order to eliminate this risk, it was necessary to use an expensive membrane oxygenator. Third, an important and essential issue is the lack of proper inactivation of hepatitis viruses that are feared of hepatitis virus infection. Cryoprecipitated plasma has excellent perfusion fluids for kidney preservation and various drawbacks described above.

In order to overcome the above-mentioned problems of cryoprecipitated plasma, attempts have been made when using albumin solution as a perfusate, and animal experiments have been successful. Grundmans [Transpl., 17, 299 305 (1974)] successfully perfused the kidneys of dogs with 6% albumin solution to preserve kidneys for 96 hours. Their perfusate is devoid of Krebs Ringer's solution containing 6% (W / V) human albumin. Dog kidneys, which had been perfused for 96 hours at low temperature, were autografted and had a spliced survival of more than 80%. This demonstrates that albumin solution is an excellent perfusate when compared to lysed plasma.

Long-term preservation of the kidneys requires perfusion with a constant colloidal osmotic pressure, a suitable electrolyte composition, and a certain amount of oxygen at low temperatures. When stored at low temperatures, the kidney consumes much less oxygen than at room temperature, but a certain amount of oxygen is required to maintain its function. Classical studies by Levy [American Journal Physiology 197, 1111-1114, (1959)] show that the oxygen consumption of kidneys at 8-10 ° C. is about 3 μl / g / min, which corresponds to about 20% of the consumption at room temperature. Thus, in preserving the kidneys, it is common to perfuse the kidneys with a perfusate that supplies oxygen.

Saturated perfluorinated organic compounds (hereinafter referred to as PFCs) are liquids capable of dissolving significant amounts of oxygen and function as oxygen carriers when used in the form of emulsions. Research into artificial blood using the above-described properties of PFC emulsions is progressing.

Emulsions function well as oxygen carriers in vivo or in vitro (in excorporeal systems such as perfusion systems), suggesting that PFC emulsions can be beneficially used as oxygen carriers in kidney preservation. In addition to being a good solvent for oxygen, PFC is physiologically inert and does not present a problem of direct toxicity to tissues. Therefore, the use of this as a perfusate for preservation of the kidneys does not cause toxicity problems. The study of kidney preservation using PFC emulsions has begun very recently, starting with studies by Proceedings of Symposium on Perfluorochemical Artificial Blood, Kyoto 1976, 187-201. They were perfused with rabbit kidney by FC-43 emulsion (perfluorotributylamine emulsion) for 9 hours at room temperature and examined the vitality of kidney by physiological method.

Kidneys perfused with FC-43 emulsion had better preservation of mitochondrial function and higher activity values of glycolysis and staphyloenzyme compared to control perfused with Ringer's solution. This indicates that the supply of oxygen by FC-43 has an effective effect on preserving function by perfused kidneys. However, the above-mentioned people focused their efforts on physiology only and did not study preserved kidney transplants. Results of transplantation of the kidneys preserved with perfusate containing PFC emulsions were reported by Bercowitz. [J. Surg. Res., 20, 595-600 (1976). He was perfused for 24 hours in a PFC emulsion containing albumin and freeze-precipitated plasma at low temperature. The preserved kidneys were autografted and the junction survival rate was examined. The survival rate was 100% in 5 cases. On the other hand, 62% of the 8 cases survived in the perfusion solution containing no FC-43 emulsion, indicating that the FC-43 system is very beneficial.

The two reports cited show that it is an effective perfusate for kidney preservation at low temperature and room temperature. However, the retention periods described in the two reports are not sufficient for the actual use of the conservation method. In particular, FC-43 emulsion-containing albumin was not safe enough to produce a generalized formulation.

Under the circumstances described above, the present inventors conducted a study on perfusate containing PFC-43 for organ storage of transplant organs, particularly kidneys. The result of this study is the completion of the present invention.

It is an object of the present invention to provide an effective organ preservation method of PFC perfusate and organs for transplantation.

Perfusion liquid for preservation of the organ for transplantation mainly containing the modified Ringer's solution containing 8-20 meq / l of potassium ion, albumin and emulsified liquid saturated perfluorinated carbon compound, and the organ for transplantation using the perfusion liquid It provides a preservation method by perfusion.

The basic Ringer's solution used in the converted Ringer's solution of the present invention is not particularly limited, and may be a conventional one, and a converting solution of lock, tie rod, ole, Hank or Krebs may be used. The conversion according to the present invention is to increase the concentration of potassium ions from the usual 4 to 6 meq / l to 8 to 20 meq / l (preferably 8 to 15 meq / l). This increase in concentration was adapted to further approach the potassium concentration of the extracellular fluid. By selecting such potassium ion concentration, it is possible to greatly increase the survival rate of the conjugate for a long time in preservation of organs, especially kidneys, by perfusion. The conversion ringer solution of the present invention has an osmotic pressure of 290 to 300 mOsm / L and a pH of 7.1 to 7.7 (at 20 ° C). Table 1 also shows the composition of the converted special Ringer's solution of the present invention and that of normal plasma which is the prototype of the conventional Ringer's solution.

TABLE 1

Organ perfusion solution of the present invention is prepared by mixing the PFC emulsion, albumin and the converted Ringer's solution in the converted Ringer's solution so that the concentration of PFC and albumin has a determined value, respectively.

PFC emulsions used in the present invention are prepared from liquid perfluorocarbon compounds based on oxygen absorption capacity by known methods as described, for example, in US Pat. Nos. 3958014, 3911138, 3962439 or German patent application DT-OS 2630586. These patents include emulsifying perfluorinated carbon compounds using monolipides as emulsifiers (US Pat. No. 3,958,014), or emulsifying C _8-22 fatty acids with adjuvant phospholipids as emulsifiers (U.S. Pat. Or using a polyoxyethylene-polyoxypropylene copolymer (molecular weight 2,000-20,000) as a nonionic emulsifier (US Pat. No. 3,911,138), or polyoxyethylene alkyl ether or polyoxy alkyl allyl ether as the emulsifier or the aforementioned fatty acids, A stable emulsion suitable for preparing artificial blood by emulsifying a perfluorinated carbon compound using a warm emulsifier and the aforementioned auxiliary emulsifier together is described.

The perfluorinated carbon compound to be emulsified is a saturated perfluorinated carbon compound having 9 to 12 carbon atoms that does not adversely affect organs or tissues, and some or all of the carbons are combined with at least one saturated alicyclic ring, nitrogen atom and / or oxygen atom. Together form a heterocycle or an aliphatic tertiary amine with a nitrogen atom or an aliphatic ether with one or more oxygen atoms.

The first group of perfluorinated carbon compounds used in the present invention are, for example, perfluorinated alkanes such as perfluorinated decane and perfluorinated detanes, perfluorinated cycloalkanes or perfluorinated (alkylcycloalkanes), perfluorinated (methylpropylcyclohexane) , Perfluorine (C _3-4 alkylcyclohexane) such as perfluorine (butylcyclohexane), perfluorine (trimethylcyclohexane), perfluorine (ethylpropylcyclohexane) and perfluorine (pentylcyclohexane); And perfluorine decalin, such as perfluorine (methyldecarin) and perfluorine (dimethyldecarin).

The second group includes, for example, perfluorine (alkyltetrahydropyran) such as perfluorine (butyl tetrahydropyran), perfluorine (pentyltetrahydropyran) and perfluorine (hexyltetrahydropyran); Perfluoro (alkyltetrahydrofuran) Perfluorine (N-pentylpiperidine) such as perfluorine (pentyltetrahydrofuran) perfluorine (hexyltetrahydrofuran) and perfluorine (heptylhydrofuran) ), Perfluorine (N-hexyl pyridine), perfluorine (N-alkylpiperidine) such as perfluorine (N-butylpiperidine) and perfluorine (N-pentylmorpholine), perfluorine (N -Hexyl morpholine) and perfluorine (N-alkyl morpholine) such as perfluorine (N-heptylmorpholine).

The third group is, for example, perfluorine containing trifluorine (tributylamine), perfluorine (diethylhexylamine), perfluorine (dipropylbutylamine) and perfluorine (diethylcyclohexylamine) (3). Tertiary amines; Perfluorine (3,8-dioxa-2,9-dimethyldecane) or perfluorine (tetramethylene glycol diisopropylether), perfluorine (3,7-dioxa-2,8-dimethylnonane) or perfluoro Perfluorine (alkylene) such as bovine (trimethylene glycol diisopropylether) and perfluorine (4,6-dioxa-5,5-dimethylnoic acid) or perfluorine (isopropylene glycoldi-n-propylether) Perfluorine (dioxaalkane) which is glycol dialkyl ether).

The emulsion prepared by PFC in the conversion Ringer's solution has a particle size of 0.05-0.3μ, PFC 10-50% (W / V), emulsifier 2.0-5% (W / V), and co-emulsifier 0.1-1.0% (W) if necessary. / V) and can be stored in a stable state for a long time. The perfusate for transplant organ preservation was obtained by mixing the above-described PFC emulsion, bovine or human albumin, and the above-mentioned converted Ringer's solution, and the resultant solution was 7.5-12.5% (W / V) of PFC and 1-8% of albumin. Contains (W / V). If necessary, drugs such as procaine hydrochloride, heparin, phenoxabenzamine, insulin, dexamethasone (decadron), methylprednisolone, antibiotics and urokinase can be added. The limit of PFC concentration given above is to ensure post-transplant conjugation survival of organs preserved by perfusion of liquid. Albumin concentrations within the aforementioned limits are suitable to control colloidal osmotic pressure so that perfusion can maintain physiological appearance. Preservation of the organ to be transplanted is performed with oxygenation using conventional equipment. For example, 400 ml of 25% (W / V) PFC emulsion, 360 ml of conversion Ringer's solution and 240 ml of 25% (W / V) human albumin are mixed together to a total of 1 liter. The resulting mixture is placed in a perfusate reservoir and perfused to the organ to be transplanted. At this time, only mixed gas (oxygen 95-98% and CO ₂ 5-2%) or oxygen is supplied with a film-like or bubble-type oxygen generator. The circulation rate of the perfusate is 15-50 ml / g (newly) / hour, and the perfusate provides oxygen at 95% O ₂ -5% CO ₂ at a flow rate of 30-1500 ml / min. If necessary, the aforementioned drug may be added to the perfusate without impairing the perfusate. In preservation by perfusion, the pulsation pump may be recycled, and the perfusate may be placed in the arterial reservoir of the long-term preservation apparatus. For long-term storage, it is desirable to clean the perfusion solution appropriately. The perfusion solution of the present invention can be used not only for perfusion preservation but also for general surgical field.

The method of the present invention can preserve the organ very safely for a long time until transplantation. Due to the extremely high conjugation survival rate, the method can be commercially successful in organ transplantation in the real world of medicine.

Next, the Example which manufactures each component of this perfusion liquid, and the process of manufacturing perfusion liquid are described as an Example next. The symbol "% (W / V)" in the specification and claims of this application is the amount of the ratio by weight (g) of material to 100 ml of liquid.

Production Example 1

Preparation of Fullocarbon Emulsion

In 8 L of the converted Ringer's solution (described later), 300 g of the polyoxyethylene-polyoxypropylene copolymer (molecular weight 8,350) was dissolved, and then 3 kg of perfluorinated decarin was added. The mixture is stirred in a mixer to form a coarse emulsion. This is placed in a reservoir of a jet-type emulsifier (Monton-Gaurin-type homogenizer) to circulate the emulsion. Emulsification is carried out at 35 ± 5 ° C. under a pressure of ²⁰⁰ to 500 kg / cm ² . The concentration of perfluorinated decalin in the resultant microemulsion was 31.3% (W / V) and the average particle size was 0.09∼0.1μ as measured by centrifugal sedimentation. After 6 months of storage at 4 ° C. the emulsion showed no condensation of the particles and no change in average particle size.

Preparation of Albumin Solution

Commercially available human serum albumin is dissolved in a conversion ringer solution at a concentration of 25% (W / V) by the method described below.

Preparation of Conversion Ringer's Solution

The converted Ringer's solution was dissolved in distilled water at the ratio of NaCl 6.51, MgSO ₄ 0.4, KCl ^- 0.8, NaHCO ₃ 0.24, Na ₂ HPO ₄ 0.14 and Glucose 6.0 (unit is g / l) to form a solution having the following electrolyte composition. ^{Na + 112, K + 11,} Mg ++ 7, Cl-118, HCO 3 - 3,

_{^{HPO 4 - 2, SO 4 -}} 7 , and glucose 33 (unit: meq / ℓ Im).

Mixing of the component liquids

Mix 570 ml of the conversion Ringer's solution and 330 ml of carbon into the pool and stir thoroughly. The mixture is sterilized by heating to 115 ° C. for 12 minutes in a sterilizer. The sterilized mixture is mixed with 100 ml of albumin solution passed through a bacterial strainer. The resulting mixed solution is stored in a cool place at 1 to 10 ° C. and used as a perfusion solution for long-term storage for transplantation, if necessary.

Production Example 2

Preparation of Perfluorocarbon Emulsions

To 8 L of the converted Ringer's solution, 330 g of polyoxyethylene octyl ether having an average molecular weight of 3,500 was dissolved, and 40 g of soy phospholipid and 2 g of potassium oleate were added thereto. The mixture is suspended by stirring in a mixer, and the suspension is mixed with 3 kg of perfluorinated (tributylamine) and stirred in the mixer to prepare a coarse emulsion. This is further emulsified in the same manner as in Example 1. The fine emulsion thus obtained is sterilized by heating at 115 ° C. for 12 minutes in a rotary sterilizer. The concentration of perfluorinated carbon was 29.7% (W / V). There was no agglomeration of particles even after 5 months storage at 4 ° C.

Mixing of component liquids

100 ml of 550 ml of the converted Ringer's solution used in Preparation Example 1 and 350 ml of the pullocarbon emulsion were mixed and the mixed liquid was stored in a cool place at 1 to 10 ° C. When necessary, it is used as a perfusate for organ preservation for transplantation.

Production Example 3

The method of Preparation Example 1 was prepared using perfluorinated methylpropylcyclehexane instead of perfluorinated decalin. The obtained perfusate has properties similar to those obtained in Production Example 1.

Production Example 4

Perfluoro butylcyclohexane, perfluorotrimethylcyclohexane, perfluoroethylpropylcyclohexane, perfluoromethyldecarine, perfluorohexyl tetrahydropyran, perfluoropentyltetra Hydrofuran, perfluorine heptyl tetrahydrofuran and perfluorine decane are prepared. The obtained perfusate has properties similar to those obtained in Production Example 1.

Production Example 5

Perfluorinated N, N-dibutylmonomethylamine, perfluorinated N, N-diethylpentylamine, perfluorinated N, N-dipropylbutylamine, perfluorinated tripropyl instead of perfluorinated decalin by the method of Example 1 Amines, perfluorinated N, N-diethylcyclohexylamine, perfluorinated N-pentylpiperidine, perfluorinated N-hexylpiperidine, perfluorinated N-butylpiperidine, perfluorinated-N-pentylmorpholine, Perfluoro N-hexyl morpholine and perfluoro N-heptyl morpholine are prepared respectively. The obtained perfusate was similar in properties to that obtained in Production Example 1.

Production Example 6

Prepared using perfluorotributylamine instead of perfluorinated decalin by the method of Preparation Example 1. The obtained perfusate was similar to that obtained in Preparation Example 1.

Production Example 7

The preparation of Example 1 was carried out using polyoxyethylene-polyoxypropylene having a molecular weight of 15,800 instead of a copolymer having a molecular weight of 8,350. The obtained perfusate was similar in properties to that obtained in Production Example 1.

The following is a comparative experiment in which the effectiveness of the perfusion preservation solution of the present invention was performed in animal experiments in transplantation of kidneys preserved by perfusion. Conjugation survival or mortality is determined by removing the settled kidney at the opposite site and then observing the function of the conjugated kidney. In the following table, "fast function" means urination was observed within 2 days after resection of the contralateral site, and "late function" means no urination was observed within 2 days after resection of the contralateral site, but the renal function gradually improved after that. Urination is observed and thus the animal survived. "Necrosis" means that the tissue in the kidney region transplanted before resection of the renal site died (stopped), and "ATN" (acute glomerulone necrosis) was reversed. Acute renal failure after site resection means that the animal suffered from death due to urinary obstruction, loss of appetite and frequent vomiting.

Experimental Example 1

Optimal PFC Concentration of Preservative

Increasing the PFC concentration in the PFC emulsion increases the oxygen carrying capacity of the emulsion, while increasing the viscosity at low temperatures is essential to determine the optimal PFC concentration for perfusion. In order to determine the optimal PFC concentration during perfusion, a series of different PFC concentration perfusion solutions are prepared using a converted Collins solution (MCS) using a basic salt solution. [Th Lanct, 2, 1219-1222 (1969)] This is most conjugated to low temperature preservation of organs, and is close to the electrolyte composition of extracellular fluid. The amount of carbon emulsion is varied with the pulley obtained in Example 2 and added to the MCS so that the PFC concentrations in the perfusate are 5,7.5, 10, 12.5 and 15% (W / V). The experiment was performed using kidneys of transplanted dogs at 300-500 ml / g oxygen-containing gas (O 95%, CO ₂ 5%) for 24 hours at a flow rate of 15-18 ml / g / hour at 5 ° to 8 ° C. Preserve oxygen at minute flow rate. Conserved kidneys are autografted using five dogs per group. Seven opposite normal kidneys are excised on day 7 after autografting and each survival date is calculated. If the dog survives more than 4 weeks, the splicing survival rate is determined to be positive. Two weeks later, BUN (blood urea nitrogen) and creatinine levels remained normal in the dog and urinary tracts were observed. From the data obtained, the optimum PFC concentration in the perfusate is determined.

The experiment was conducted in a usual manner according to the following steps.

Anesthesia: Pentovalbital sodium (30mg / kg intravenous) haloethane and oxygen administered into the bronchus

Incision of the central abdominal cavity

Left Kidney Resection

Cannulation (Urinary, Renal Vein and Vein)

Cold M.C.S. Or wash with cold Ringer lactate

Perfusion circuit connection: Permeate at 5-8 ℃ for 24 or 2 hours while supplying oxygen and preservation washing (M.C.S. or Ringer's lactate solution)

Automatic transplantation into the femoral cavity

Shortly after, resection of opposite site

Effect of PFC Concentration on Perfusion Fluid on Conjugate Survival

TABLE 2

* Survival: Survive 4 weeks or more

** A.T.N. (Acute glomerular necrosis)

The obtained results are shown in Table 2.

As shown in Table 2, the junction survival rate is high at the PFC concentration of 7.5-12.5% (W / V). When PFC concentrations exceeded 12.5% (W / V) and reached 15% (W / V), hematuria was observed in all cases of blood flow after transplantation. Two dogs that survived for more than two weeks had hematuria for several days after cutting the other kidney, but recovered and survived. From the above results, it can be concluded that the perfusion solution with the PFC concentration of 10% (W / V) was most effective for perfusion preservation of the resected kidney.

Experimental Example 2

Basic salt solution:

Preservation experiments by low-temperature, long-term perfusion were performed to select a suitable basic salt solution. The salt solution tested was M.C.S., Ringer's solution described above, and the conversion Ringer's solution (M.R.S.) prepared in Preparation Example 1. Preservative perfusion solution was added to the perfluorinated carbon compound emulsion of Preparation Example 2 and bovine serum albumin was added to the salt solution so that the PFC concentration was 10% (W / V) and the albumin concentration was 6% (W / V). Perfusion is performed on 5 kidneys (5 per group) at 5 to 8 ° C. according to the method of Experimental Example 1. After transplantation and blood flow begins, tests for blood movement through the kidneys, intestines of light kidneys, and symptoms appearing after resection of the contralateral kidney on day 7 after transplantation are performed. The perfusate is circulated at a rate of 15-18 mL / g / hour without regeneration for 72 hours of perfusion (total amount 2,000 mL). Except for the use of M.R.S. as the basic saline solution, the transplantation result was very poor, and almost all experimental animals died of acute renal failure within 10 days after contralateral nephrectomy. On the other hand, when M.R.S. was used as the basic salt solution, all animals were recovered without exception.

Experimental Example 3

Effect of albumin concentration in the perfusion solution on the kidney of the dog: The perfusion solution used in this experiment was obtained by adding 10% PFC emulsion to the converted Ringer's solution, which was prepared using the PFC emulsion prepared in Preparation Example 6, and the human albumin was used. Each contains different concentrations. The kidneys were perfused at 5 to 8 ° C. for 72 hours while supplying oxygen at a flow rate of 300 to 500 ml / min with the oxygen-containing gas used in Experimental Example 1, and then transplanted automatically as in Experimental Example 1. The flow rate of perfusion is maintained at 15-18 ml / g / hour. Opposite nephrectomy is performed 1 week after automatic transplantation.

The results are shown in Table 3.

TABLE 3

Experimental Example 4

Perfusion of the kidney for prolonged transplantation at low temperatures:

Kidney transplant experiments in dogs were performed in a similar manner to Experimental Example 1. Each kidney is preserved for one week while being perfused at a rate of 15-18 mg / g / hour perfusion rate while supplying oxygen to the gas at a flow rate of 300 to 500 ml / min at 5 to 8 ° C. The perfusate was prepared using the MRS of Preparation Example 1 as the basal salt solution and the serum albumin of bovine and the PFC emulsion of Example 2 or the PFC emulsion prepared in a similar manner as in Preparation Example 2 (but instead of perfluorine tributylamine Perfluorinated decalin). Albumin and PFC concentrations in the perfusate were 6% (W / V) and 10% (W / V), respectively. After perfusion and preserved for one week, the kidney is automatically transplanted as in Experiment 1. One week after autografting, the other side of the kidney is excised and the symptoms are observed. As a result, in Table 4, the blood system of creatinine and BUN of surviving animals became normal after 3 weeks.

TABLE 4

Experimental Example 5

Transplant experiments were performed in a similar manner to Experimental Example 1 using the kidneys of dogs.

Each elongation feeds oxygen at a rate of 300-500 ml / min for a mixed gas (O ₂ 95% -CO ₂ 5%) while feeding 12 or 24 hours 18 at a flow rate of 40-50 ml / g / hour. It saves at -22 degreeC. The perfusate is prepared by using the MRS of Preparation Example 1 as the basic salt solution and adding the PFC emulsion of Preparation Example 2 and bovine serum albumin. Perfusates had concentrations of 10% (W / V) and 6% (W / V) of PFC and albumin, respectively. Kidneys are autografted after 12 or 24 hours retention. One week after the autograft, the kidney on the other side is excised and the symptoms are observed. Table 5 shows the results of the above experiment and the comparative experiment using MCS as the control and base salt solution without PFC.

TABLE 5

Claims (1)

By mixing a stable emulsion of Ringer's solution, albumin and perfluorinated carbon compounds with an increased amount of potassium ions of 8-20 meq / l, albumin concentrations of 1-8% (W / V) and perfluorocarbon compounds of 7.5-12.5% ( A method for producing a liquid for perfusion preservation of an organ for transplantation containing W / V).