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Polymer based transplant preservation solution

A solution and organ preservation technology, applied in the field of polyglycerol, can solve problems such as damage to the kidney function of direct donors and negative effects of application

Active Publication Date: 2016-09-21
李沙丹 +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the addition of hydroxyethyl starch (HES) to the UW solution negatively affected its use in cryopreservation of organs, especially those derived from deceased donors
Hetastarch is commonly used as a colloid for volume resuscitation in critically ill patients, but recently, its safety has been questioned; fluid resuscitation using hydroxyethyl starch is associated with coagulopathy, pruritus, and acute kidney injury (Hartog and Reinhart, 2009; Perner et al.,2012; Perner et al.,2011; Schortgen et al.,2001; Winkelmayer et al.,2003), and after transplantation, impaired renal function of the direct donor and after transplantation, impaired renal function of the direct donor renal function (Cittanova et al., 1996)

Method used

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  • Polymer based transplant preservation solution
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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0109] Example 1: Cold storage of isolated hearts with HPG solution reduces tissue damage

[0110] To demonstrate the cold storage process of donor organs by measuring the LDH release of donor tissues at different time points to compare the damage caused by preservation of isolated mouse hearts with HPG solution and UW solution. Beneficial effect of medium HPG solution compared to UW solution (0.2 mL / organ, 4°C) in preventing cold ischemic injury. Such as figure 1 As shown in A, the longer the cold storage time in UW solution and HPG solution, the more the amount of LDH released by the damaged tissue or necrotic cells of the organ in the supernatant, but the amount of LDH in HPG solution was significantly lower than that in UW solution in the amount. Compared with the amount of LDH in the UW group increased from 1.15±0.22 at 2h to 2.46±0.24 at 24h, in the HPG group, the amount of LDH increased from 0.75±0.43 at 2h to 1.71±0.55 at 24h (Pfigure 1 B). Ethidium bromide (which s...

example 2

[0111] Example 2: Functional recovery of hearts in syngeneic recipients is accelerated with less tissue damage after cold storage with HPG solution

[0112] To further examine whether the enhanced protective effect of HPG solution on donated organs could be translated into post-transplant functional recovery, hearts of B6 mice that had been refrigerated with HPG solution (5 mL / organ) at 4°C for 24 hours were heterotopically transplanted into syngeneic B6 mice. Similar experiments were performed on hearts stored in UW solution. The function of the graft was checked at 15min and 24h after the operation. Such as figure 2 As shown, at two time points, the graft function clinical score of the transplanted heart pretreated with HPG solution was significantly higher than that of the heart pretreated with UW solution. At 15min (P<0.0001), compared to the average score of 2.292 in the UW solution group, the average score of the HPG solution group was 3.542. At 24h, compared to the ...

example 3

[0115] Example 3: Prolonged survival time of transplanted hearts after cold storage with HPG solution

[0116] During clinical transplantation, donor organs are mostly transplanted into allogeneic recipients, and these allografts need to survive immunosuppressive therapy. To test whether HPG solution is superior to UW solution under this condition, donor hearts from B6 mice were preserved with HPG solution and UW solution (5 mL / organ) for 24 h at 4 °C. Stored hearts were transplanted into heterotopically transplanted allogeneic BALB / c mice, which received daily CsA treatment after surgery. Such as Figure 5 As shown, allografts preserved in HPG solution survived longer compared to UW solution. In the UW solution group, only one graft survived for 3 days, and the remaining grafts survived within 24 hours. In contrast, in the HPG group, three grafts survived to the end of the experiment (20 days) in recipients treated with CsA (P=0.0175, log-rank test) and maintained their fu...

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Abstract

Provided are transplant preservation solutions comprising a polygiycerol wherein the polygiycerol is of a raoleculax weight between about 0.15 kDa and about 3.99 kDa, methods and uses thereof as well as kits providing said transplant preservation solutions.

Description

technical field [0001] The present invention relates to the field of polyglycerol. In particular, the present invention relates to polyglycerol-based preservation solutions for transplantation and their use. Background technique [0002] Irrigation and storage of donor organs with cold preservation solution is a common approach to reduce ischemic injury during donor organ harvesting. To this end, various storage solutions and various storage techniques have been developed with varying degrees of success, including modern perfusion techniques. Transplantation of kidneys from donors exceeding the standard will lead to delayed recovery of graft function. At present, these donors exceeding the standard are washed and stored with UW solution, Celsior solution, and HTK solution (Agarwal et al., 2006 ; Montalti et al., 2005; Stevens et al., 2009). [0003] The different preservation solutions differ to a large extent in composition, but generally they are aimed at preventing cel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N1/02A61K35/12
CPCA61K35/12A01N1/021A01N1/0226
Inventor 捷亚成哲.克瓦肯德杜杜才干唐纳德.布鲁克斯阮以壯
Owner 李沙丹
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