JPH04128201A - Solution for preserving organ - Google Patents

Abstract

PURPOSE:To obtain a stable, inexpensive and excellent solution for preserving organs, having a specific osmotic pressure and pH and containing Na<+>, K<+>, H2PO, HPO <->, anions of carbonic acid or an organic acid, gluconate anions, mannitol and hydroxyethylated starch. CONSTITUTION:A solution which is an aqueous solution, having 310-410mOsm/l osmotic pressure at pH7.1-7.7 and containing 10-30mg equiv. (preferably 15-25mg equiv.) Na<+>, 70-140mg equiv. (preferably 100-140mg equiv.) K<+>, 20-35mg equiv. (preferably 20-30mg equiv.) H2PO and HPO <->, 5-15mg equiv. anions of carbonic acid or a 2-3C organic acid, 80-110mg equiv. (preferably 85-105mg equiv.) gluconate anions, 5-30g (preferably 10-20g) mannitol and 30-80g (preferably 50-70g) hydroxyethylated starch, and used for preserving organs. The average molecular weight of the hydroxyethylated starch is 200000-900000 daltons and substitution degree thereof is 0.4-0.8. The resultant solution is excellent in effects on preservation of transplanting organs.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a solution for preserving organs for transplantation.

[Conventional technology]

One of the most commonly used organ preservation solutions in Europe and the United States is Euro-Collins, which contains potassium chloride, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium carbonate, and glucose.
s) There is a liquid. However, this solution has the problem that it cannot be said to have a sufficient protective effect against degeneration of organ cells, and that the time required to maintain organ viability is short.

Recently, electrolyte solutions and UW solutions have been developed that contain sodium lactobionate and raffinose as impermeable agents, hydroxyethyl starch as a colloid osmotic agent, and further contain adenosine, insulin, etc. in consideration of cellular energy metabolism. (Japanese Unexamined Patent Publication No. 1-246201) was developed. Although this UW solution is currently used as a useful solution for preserving organs, it is expensive because it contains insulin and the like, and has drawbacks in its pharmaceutical stability.

[Problem to be solved by the invention]

An object of the present invention is to provide a stable and inexpensive solution that is excellent in protecting against cell degeneration of organs for transplantation.

[Means for Solving the Problems] As a result of extensive research into the desirable selection and composition range of electrolytes, osmotic pressure regulators, and colloid osmotic pressure, the present inventors have found that:
We were able to complete the present invention which achieves the intended purpose.

That is, the organ preservation solution of the present invention has an osmotic pressure of 310
~410 mOsm/12, pH 7.1-7
．． This is an aqueous solution of No. 7, which is characterized by containing the following components within the following composition range.

N a "10-30 milligram equivalent" 70-140 milligram equivalent H1PO,- and HPO4-20-35 milligram equivalent anion of carbonic acid or organic acid having 2-3 carbon atoms gluconate anion mannitol hydroxyethyl starch 5-15 80- 110 5-30 30-80 Milligram equivalent Milligram equivalent Gram Gram The composition range of a more preferred embodiment of the present invention is as follows.

　　　　　 “Na” K” ozpoa- and) IPO.

Anion of carbonic acid or an organic acid having 2 to 3 carbon atoms Gluconate anion Mannitol Composition range in 11 15 to 25 Milligram equivalent 100 to 140 Milligram equivalent 20 to 30 Milligram equivalent 5 to 15 Milligram equivalent 85 to 105 Milligram equivalent 10 to 20 grams Among the above components, the organic acid anion having 2 to 3 carbon atoms is acetic acid,
Anions such as lactic acid are preferred.

Moreover, hydroxyethyl starch has a degree of substitution of 0.4 to 0.
8, with an average molecular weight of about 200,000 to 9
00,000 daltons is preferred, and more preferably about 350,000-$100,000 daltons.

In producing the solution of the present invention, the electrolytes used are sodium and potassium salts of phosphoric acid, carbonic acid, organic acids having 2 to 3 carbon atoms, and gluconic acid. The combination of salts is arbitrary.

The solution of the present invention can be easily manufactured according to a known method for manufacturing an infusion solution.

[Example 1] Sodium gluconate was added to 800 m of distilled water at about 60°C.
18g, potassium gluconate 20.25g, potassium dihydrogen phosphate 0.885g, dipotassium hydrogen phosphate 3.
22 g, mannitol 16.4 g and hydroxyethyl starch (average molecular weight 609,500 daltons, degree of substitution 0.5
8) After dissolving 60g, add 0.8g of sodium bicarbonate.
4g and distilled water were added to bring the total amount to 12. This was immediately filtered, filled into a glass bottle, sealed, and steam sterilized to give an osmotic pressure of 401 mOs/I! A solution for organ preservation with a pH of 7.59 was obtained.

[Test Example 1] The protective effect of the following test solution on isolated rat liver was investigated.

(1) Composition of Nylow Collins liquid component 11 KCI
15 mmolKHz PO415m
mol Kt HP Oa 42.5 s*ol
Na HCOs 10 m5ol Dextrose 35 g (2) U W Liquid Potassium Lactobionate KHl PO.

M g S Oa aOH Raffinose + uio1 Junmong O1 Rinsol @mol Adenosine 5 m5ol glutathione 3 Sunmong o1 insulin
100 υ Bacterium 0.
5 Jli! Dexamethasone 81g Allopurinol 1mlHydroxyethyl starch 50g (average molecular weight 200,000~
300,000 daltons, degree of substitution 0.4-0.7) Osmotic pressure 325 505 m/iip
H7,4 (3) HPO to the organ preservation solution KH2PO4 of Example 1.

potassium gluconate sodium gluconate NaHCO.

Mannitol 6.5 Sheath mole 01 18.5-Mole o1 86.55 no1 10, Owa■ o1 10, Ome+o1 90.0 +u+ol Hydroxyethyl starch 60 g (average molecular weight 6
09500 Dalton, degree of substitution 0.4-0.7) Osmotic pressure 401 Gos candy 71p
H7,59 10-12 week old Wistar male rats (5 rats per group)
After anesthetizing with ether, bentoharbital 101
mg/kg was injected intraperitoneally and the abdomen was opened. The liver was first perfused with lactated Ringer's solution, then sufficiently reperfused with the test solution, and then immersed in the test solution. The liquid temperature during perfusion and immersion was 4±2°C. After soaking for 3 hours, a portion of the left lobe of the liver was collected, fixed with formalin, stained with HE to prepare a specimen, and observed with an optical microscope.

Boiled 221 (1) Group using Nielow-Collins solution Slight disturbance of hepatocyte arrangement and swelling of cells were observed in the central vein area and around Glisson's sheath. In addition, localized expansion of the jigsoid (sinusoid) was observed.

(2) LIW fluid use group The condition remained almost normal except for slight dilation of the jigsoid in the central venous region and slight changes in the 3rd to 4th rows of hepatocytes under the capsule.

(3) Almost no difference was observed between the group using the organ preservation solution in Example 1 and the UW liquid group.

That is, it was found that the organ preservation solution of Example 1 and the LJW solution exhibited equivalent protection against hepatocyte degeneration and were superior to the Nylow-Collins solution.

〔Effect of the invention〕

According to the present invention, it is possible to provide a stable and inexpensive solution that has an excellent preservation effect on organs for transplantation.

Patent applicant: Morishita Pharmaceutical Co., Ltd. Same Ajinomoto Co., Inc.

Claims (2)

[Claims] (1) Osmotic pressure is 310-410 mOsm/l, pH is 7
．． 1 to 7.7, the solution for organ preservation is characterized by containing the following components within the following composition range. Composition range in 1 liter of ingredients Na^+10-30 milligram equivalents K^+70-140 milligram equivalents H_2PO_4^- and HPO^-^-20-35 milligram equivalents Anion of carbonic acid or an organic acid having 2-3 carbon atoms 5-15 milligrams equivalent gluconate anion 80-110 milligrams equivalent mannitol 5-
30 grams hydroxyethyl starch 30-80 grams (2) The average molecular weight of hydroxyethyl starch is 20,000
0 to 900,000 daltons, degree of substitution 0.4 to 0.8
The organ preservation solution according to claim 1.