CN114052008A - Preserving fluid and application thereof - Google Patents
Preserving fluid and application thereof Download PDFInfo
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- CN114052008A CN114052008A CN202111395499.7A CN202111395499A CN114052008A CN 114052008 A CN114052008 A CN 114052008A CN 202111395499 A CN202111395499 A CN 202111395499A CN 114052008 A CN114052008 A CN 114052008A
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- acid
- preservation solution
- preservation
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0221—Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- General Health & Medical Sciences (AREA)
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- Environmental Sciences (AREA)
- Biophysics (AREA)
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses a preservation solution which comprises one or more than two of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin. The invention also discloses application of the preservation solution. Compared with the prior art, the inventor adds the 5-aminolevulinic acid, the levocarnosine, the L-glutamic acid and the D-biotin into the preservation solution, carries out cold preservation on cells, tissues and/or organs, has high cell survival rate, can effectively reduce apoptosis caused by cold preservation-rewarming, stabilizes mitochondrial membrane potential, inhibits excessive generation of active oxygen free radicals of mitochondria, and effectively reduces mitochondrial damage caused by cold preservation-rewarming, thereby reducing ischemia reperfusion injury of donated tissue organs in the process of transplantation operation, and has great significance for the progress of organ transplantation preservation technology.
Description
Technical Field
The invention relates to the technical field of biology, in particular to a preservation solution for keeping cells alive, reducing in-vitro preservation damage and promoting tissue and organ recovery under the condition of no blood supply and application of the preservation solution.
Background
As early as the 20 th century, there was the first organ transplant surgery. Organ transplantation is the surgical or other placement of a healthy organ on a critically ill patient to allow continued functioning of the organ and thus the organ recipient to obtain a new life. For the excised healthy organs, the organs need to be perfused and immersed with a preservation solution to prevent organ necrosis and ischemic reperfusion injury. Ischemia-reperfusion refers to the occurrence of various toxic substances in the microcirculation in organs and tissues in an ischemic state and the resulting damage when organ and tissue are subjected to reperfusion. This damage may be a function of free radicals, such as the generation of ROS radicals, which cause damage.
The existing preservation solution can help to prevent cell swelling and reduce ROS generation during organ cryopreservation, has certain functions of reducing ischemic injury and promoting organ recovery, but still cannot achieve satisfactory effect on reducing ischemia-reperfusion injury, thereby limiting the safe time for organ preservation in vitro and possibly increasing the risk of organ injury during transplantation operation.
Disclosure of Invention
In order to solve the problems of the prior art, the present invention aims to provide a preservation solution which can keep cells alive without blood supply, is used for preserving cells, tissues and organs, can reduce the damage of human liver-like cells in the in vitro cold preservation-rewarming process, effectively reduces apoptosis caused by cold preservation-rewarming, reduces the mitochondrion membrane potential and the mitochondrial ROS, is applied to clinical organ transplantation preservation, can reduce ischemia reperfusion injury and reduce the risk of organ operation during the transplantation operation.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preservative solution comprises one or more of 5-aminolevulinic acid, levocarnosine, L-glutamic acid, and D-biotin.
Hibernating mode animals have extraordinary physiological characteristics that resist ischemia reperfusion injury and low temperature-rewarming injury, and during natural hibernation, when the core temperature drops sharply, no organ damage occurs in the face of drastic and rapid physiological changes. Outside of the hibernation season, hibernating animals are also able to sustain iatrogenic injuries such as ischemia-reperfusion injury that can lead to organ failure such as organ transplantation and myocardial infarction, and energy deprivation. Therefore, the inventor creatively operates liver cells of the hibernating animal to explore molecular mechanisms and metabolic regulation and control mechanisms of the liver cells in the cold adaptation and rewarming processes of the hibernating animal by taking the hibernating animal as a natural model, and finds that 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin are increased in the cold adaptation period of the hibernating species and decreased in the rewarming period, and human liver cells have no obvious difference in the substances above the cold adaptation period and the rewarming period. The inventor finds that if any one of the four substances, namely 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin, is added into the preservation solution, the liver-like cells of a human are preserved in a cold manner, the survival rate of the cells is high, the apoptosis caused by cold preservation-rewarming can be effectively reduced, the mitochondrial membrane potential and the mitochondrial ROS can be reduced, the mitochondrial damage caused by cold preservation-rewarming can be effectively reduced, and the ischemia-reperfusion injury can be reduced.
Optionally, the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is 200uM-1 mM.
Optionally, the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is 1 mM.
Optionally, the preservation solution is UW solution added with one or more of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin.
In one embodiment, the preservative solution comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide, and 1mM 5-aminolevulinic acid, and is adjusted to pH7.4 with sodium hydroxide and hydrochloric acid.
In one embodiment, the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 1mM L-carnosine, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
In one embodiment, the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, and 1mM potassium hydroxide, 5.61g/L, L-glutamic acid, and is adjusted to pH7.4 with sodium hydroxide and hydrochloric acid.
In one embodiment, the preservative solution comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, and 5.61g/L, D-biotin 1mM potassium hydroxide, and is adjusted to pH7.4 with sodium hydroxide and hydrochloric acid.
The invention also discloses application of the preservation solution, and the preservation solution is used for preserving isolated cells, tissues and/or organs.
In one embodiment, the preservation solution is used for preserving cells, tissues and/or organs ex vivo under cryogenic conditions, the cryogenic conditions being 2-8 ℃.
Compared with the prior art, the invention has the beneficial effects that:
the inventor adopts an innovative exploration mechanism to discover the obvious difference of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin in the cold preservation-rewarming period of hibernating animals and non-hibernating animals, and on the basis, the 5-aminolevulinic acid, the levocarnosine, the L-glutamic acid and the D-biotin are added into the preservation solution to carry out cold preservation on cells, tissues and/or organs, so that the cell survival rate is high, the apoptosis caused by cold preservation-rewarming can be effectively reduced, the mitochondrial membrane potential is stabilized, the generation of mitochondrial ROS is reduced, the mitochondrial injury caused by cold preservation-rewarming is effectively reduced, the ischemia-reperfusion injury is reduced, and the development of an organ transplantation preservation technology is of great significance.
Drawings
FIG. 1 is a graph showing the survival rate of cells restored to 37 ℃ for 2 hours after the cells are preserved at 4 ℃ for 24 hours by adding 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin of different concentrations to a cold preservation culture solution according to the invention;
FIG. 2 is a graph showing the change of apoptosis during freezing-rewarming processes of the control group medium and the experimental group medium supplemented with 5-aminolevulinic acid according to the invention;
FIG. 3 is a mitochondrial membrane potential diagram of a control group culture medium and an experimental group culture medium supplemented with 5-aminolevulinic acid during freezing-rewarming according to the invention;
FIG. 4 is a graph showing changes in mitochondrial ROS during freezing-rewarming in control and experimental media supplemented with 5-aminolevulinic acid according to the invention;
FIG. 5 is a diagram showing the change of tissue morphology and enzymology index during the rat liver cold preservation-rewarming process;
FIG. 6 is the diagram of the change of the apoptotic cells in the rat liver cold preservation-rewarming process.
Detailed Description
The invention is explained in more detail below with reference to specific embodiments and the drawing.
A preservative solution comprises one or more of 5-aminolevulinic acid, levocarnosine, L-glutamic acid, and D-biotin. The preserving fluid is prepared by adding one or more than two of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin into UW fluid. The preservation solution is used for cold preservation of cells, tissues and/or organs, has high cell survival rate, can effectively reduce apoptosis caused by cold preservation-rewarming, stabilizes mitochondrial membrane potential, reduces mitochondrial ROS generation, and effectively reduces mitochondrial damage caused by cold preservation-rewarming, thereby reducing ischemia-reperfusion injury. The temperature of cold storage is 2-8 ℃.
In an alternative embodiment, the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is from 200uM to 1 mM.
In an alternative embodiment, the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is 1 mM.
Example 1
A preservative solution comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 1mM 5-aminolevulinic acid, and the pH value is adjusted to 7.4 by sodium hydroxide and hydrochloric acid.
Example 2
A preservative solution comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 1mM L-carnosine, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
Example 3
A preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 1mM potassium hydroxide 5.61g/L, L-glutamic acid, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
Example 4
A preservative solution comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 5.61g/L, D-biotin (1 mM) potassium hydroxide, and the pH value is adjusted to 7.4 by sodium hydroxide and hydrochloric acid.
Example 5
A preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 200uM 5-aminolevulinic acid, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
Example 6
A preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 5.61g/L, L-200 uM potassium hydroxide, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
Example 7
A preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 5.61g/L, D-biotin 40uM potassium hydroxide, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
The inventor finds that the 5-aminolevulinic acid, the levocarnosine, the L-glutamic acid and the D-biotin can improve the in vitro cell survival rate, effectively reduce the apoptosis caused by cold storage-rewarming, stabilize the mitochondrial membrane potential and reduce the generation of mitochondrial ROS.
The cell survival rates were compared after 24h and 4 ℃ storage conditions by using a control group prepared by cold-storing human liver-like cells in a nutrient medium and an experimental group prepared by adding 5-aminolevulinic acid (200uM, 1mM, 5mM, 25mM), levocarnosine (10uM, 100uM, 1mM), L-glutamic acid (200uM, 1mM, 5mM, 25mM), and D-biotin (5uM, 40uM, 200uM, 1mM) at different concentrations to the control group and cold-storing the human liver-like cells in a nutrient medium. As shown in FIG. 1, it is understood from FIG. 1 that the groups to which 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin were added all improved the cell survival rate, and that the group to which 200uM-1mM 5-aminolevulinic acid, 1mM levocarnosine, 200uM-1mM L-glutamic acid or 40uM-1mM D-biotin was added was the most effective and the cell survival rate was the highest. Meanwhile, in the case of 5-aminolevulinic acid (5-ALA), 5-ALA is effective in reducing apoptosis caused by cold storage rewarming (as shown in FIG. 2), stabilizing mitochondrial membrane potential and reducing mitochondrial ROS production (as shown in FIGS. 3 and 4).
In the experiments, the nutrient medium was: hibernateTMMedium A (cat # GIBCO A1247501),10ug/ml transferrin, 3ng/ml human epidermal growth factor, 25.5ug/ml vitamin C, 10ug/ml insulin, 10uM hydrocortisone,10mg/ml bovine serum albumin.
In order to fully verify that the 5-ALA can effectively reduce mitochondrial injury caused by cold storage rewarming in cold storage. On this basis, the inventors applied it to rat liver cold preservation (as shown in fig. 5A). HE staining of rat liver tissue sections perfused at 48 hours of cold storage for 2 hours of rewarming revealed a significant improvement in liver tissue morphology in the UW fluid +5-ALA group compared to the UW fluid group (UW fluid is a clinical organ preservation fluid) (as shown in FIG. 5B). As shown in fig. 5C, the UW fluid +5-ALA group showed significantly lower enzymatic indicators for AST, ALT and LDH in the perfusate during 2 hours of perfusion than the UW fluid group. FIG. 6 shows a decrease in apoptotic cells in liver tissue of the UW fluid +5-ALA group.
In conclusion, the inventor adopts an innovative research method, takes induced pluripotent stem cells (TLGS iPSC) of a hibernating animal squirrel with thirteen strips as a model, utilizes liver-like cells differentiated by the TLGS iPSC to compare with similar liver-like cells differentiated by human embryonic stem cells (hESC), and finds that the liver-like cells differentiated by the TLGS iPSC show higher survival rate after cold preservation and rewarming, and mitochondria have membrane potential hyperpolarization stress reaction in the low-temperature rewarming process of the liver-like cells differentiated by the hESC, so that a large number of active oxygen Radicals (ROS) are generated. The metabolic products of hibernating animals and non-hibernating species during the cold storage-rewarming period are compared by utilizing metabonomics, differential metabolic products are found, and the 5-aminolevulinic acid, the levocarnosine, the L-glutamic acid and the D-biotin can reduce the generation of mitochondrial ROS and alleviate the damage of human liver-like cells in the cold storage-rewarming process in vitro. The metabolites are added into the preservation solution, and the UW solution added with 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin is verified to be capable of improving the in vitro cell survival rate, effectively reducing apoptosis caused by cold preservation-rewarming, stabilizing mitochondrial membrane potential and reducing the generation of mitochondrial ROS. The preservation solution is applied to in-vitro cell, tissue and/or organ preservation, can reduce ischemia reperfusion injury, and promotes development and application of organ transplantation technology.
It will be apparent to those skilled in the art that various other changes and modifications may be made in the above-described embodiments and concepts and all such changes and modifications are intended to be within the scope of the appended claims.
Claims (10)
1. A preservation solution is characterized in that: comprises one or more than two of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin.
2. The preservation solution according to claim 1, characterized in that: the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is 200uM-1 mM.
3. The preservation solution according to claim 2, characterized in that: the concentration of 5-aminolevulinic acid, levocarnosine, L-glutamic acid or D-biotin in the preservation solution is 1 mM.
4. The preservation solution according to claim 3, characterized in that: the preservation solution is UW solution added with one or more than two of 5-aminolevulinic acid, levocarnosine, L-glutamic acid and D-biotin.
5. The preservation solution according to claim 3, characterized in that: the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L potassium dihydrogen phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 1mM 5-aminolevulinic acid, and the pH value is adjusted to 7.4 by sodium hydroxide and hydrochloric acid.
6. The preservation solution according to claim 3, characterized in that: the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L monopotassium phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione, 5.61g/L potassium hydroxide and 1mM L-carnosine, and the pH value is adjusted to 7.4 by sodium hydroxide and hydrochloric acid.
7. The preservation solution according to claim 3, characterized in that: the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L potassium dihydrogen phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 1mM potassium hydroxide 5.61g/L, L-glutamic acid, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
8. The preservation solution according to claim 3, characterized in that: the preservative fluid comprises 50g/L hydroxyethyl starch, 35.83g/L lactobionic acid, 3.4g/L potassium dihydrogen phosphate, 1.23g/L magnesium sulfate heptahydrate, 17.83g/L raffinose, 1.34g/L adenosine, 0.136g/L allopurinol, 0.922g/L glutathione and 5.61g/L, D potassium hydroxide of 1mM, and is adjusted to pH7.4 by sodium hydroxide and hydrochloric acid.
9. Use of a preservation solution according to any one of claims 1 to 8, characterized in that: the preservation solution is used for preserving cells, tissues and/or organs in vitro.
10. Use according to claim 9, characterized in that: the preservation solution preserves isolated cells, tissues and/or organs at a temperature of 2-8 ℃.
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| CN202111395499.7A CN114052008A (en) | 2021-11-23 | 2021-11-23 | Preserving fluid and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111395499.7A CN114052008A (en) | 2021-11-23 | 2021-11-23 | Preserving fluid and application thereof |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH057619A (en) * | 1991-06-24 | 1993-01-19 | L Lyndstrom Richard | Serum- free therapeutic normal solution and method for preserving cornea using said solution |
| CN106110326A (en) * | 2011-10-12 | 2016-11-16 | 思佰益药业股份有限公司 | The one-tenth activity promoter of transplant organ |
| CN107148215A (en) * | 2014-05-30 | 2017-09-08 | 思佰益药业股份有限公司 | Organ preservative fluid |
| US20180070582A1 (en) * | 2015-04-03 | 2018-03-15 | Tx Innovations B.V. | Organ preservation composition |
| US20190082678A1 (en) * | 2015-06-09 | 2019-03-21 | President And Fellows Of Harvard College | Compositions and methods for tissue preservation at ambient or subnormothermic temperatures |
| WO2021190620A1 (en) * | 2020-03-27 | 2021-09-30 | 上海我武干细胞科技有限公司 | Cell preservation fluid and kit thereof |
-
2021
- 2021-11-23 CN CN202111395499.7A patent/CN114052008A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH057619A (en) * | 1991-06-24 | 1993-01-19 | L Lyndstrom Richard | Serum- free therapeutic normal solution and method for preserving cornea using said solution |
| CN106110326A (en) * | 2011-10-12 | 2016-11-16 | 思佰益药业股份有限公司 | The one-tenth activity promoter of transplant organ |
| CN107148215A (en) * | 2014-05-30 | 2017-09-08 | 思佰益药业股份有限公司 | Organ preservative fluid |
| US20180070582A1 (en) * | 2015-04-03 | 2018-03-15 | Tx Innovations B.V. | Organ preservation composition |
| US20190082678A1 (en) * | 2015-06-09 | 2019-03-21 | President And Fellows Of Harvard College | Compositions and methods for tissue preservation at ambient or subnormothermic temperatures |
| WO2021190620A1 (en) * | 2020-03-27 | 2021-09-30 | 上海我武干细胞科技有限公司 | Cell preservation fluid and kit thereof |
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