Reperfusion with omega-3 glycerides promotes protection of donor organs for transplantation

A technology of diglyceride and triglyceride, which is applied in the preservation, application of human or animal body, and medical preparations containing active ingredients, etc., can solve problems such as acute and chronic rejection reactions

Inactive Publication Date: 2018-07-27
THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ischemia-reperfusion injury of organs preserved in prior art solutions often results in delayed graft function and predisposes to acute and chronic rejection of the transplanted organ or tissue

Method used

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  • Reperfusion with omega-3 glycerides promotes protection of donor organs for transplantation
  • Reperfusion with omega-3 glycerides promotes protection of donor organs for transplantation
  • Reperfusion with omega-3 glycerides promotes protection of donor organs for transplantation

Examples

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preparation example Construction

[0152] The preparation of such n-3 glyceride infused emulsions is known in the art. The omega-3 lipid based infusion emulsions according to the present invention are oil-in-water (o / w) emulsions in which the external continuous phase is a purified or sterilized infusion buffer for storing organs / tissues. Such n-3 glyceride emulsions can be obtained by standard methods, ie by mixing the oil components followed by emulsification and sterilization. The pH of the lipid emulsion can be adjusted to a physiologically acceptable value, preferably a pH of about 6.0 to about 9.0, more preferably about 6.5 to about 8.5. Auxiliaries and additives can be added to the oil mixture prior to emulsification or prior to sterilization.

[0153] The omega-3 glyceride infusion emulsions according to the invention can be prepared by known standard methods. Typically, the lipids, emulsifiers and other adjuvants and additives are first mixed and then topped up with water to disperse. The water may ...

Embodiment 1

[0202] Example 1: Materials and methods

[0203] All studies were performed according to protocols approved by Columbia University's Institutional Animal Care and Use Committee (IACUC) and evaluated and certified in accordance with the Institute's Guidelines for the Care of Laboratory Animals.

[0204] General Method for Preparation of Diglycerides (DG) and Triglycerides (TG)

[0205] Phospholipid-stabilized n-3 (DG and / or TG) emulsions are usually prepared from fish oils DG and / or TG (synthetic oils can also be used) and egg yolk phospholipids. In one embodiment, the amount of n-3 oil in the infused emulsion is as low as 0.05%

[0206]Each emulsion contained the required amount of n-3 oil (diglyceride or triglyceride), usually emulsified with 1.2 g egg yolk lecithin and 2.5 g glycerin per 100 mL water. The lipids of the emulsion were mixed in doubly distilled water (30 g of water) and dispersed for 10 min by means of an ULTRA-TURRAX (Janke and Kunkel KG, Staufen, West Ger...

Embodiment 2

[0211] Example 2: In Vitro Ischemia and Reperfusion of Emulsions Infused with n-3 Glycerides

[0212] A. Materials and methods

[0213] Experiments performed and modified for use with mouse hearts 1,2 . C57BL6 mice weighing 25-30 g and aged 12-14 weeks were anesthetized by injection of ketamine / xylazine protease inhibitor (cocktail) [80 mg / kg and 10 mg / kg, respectively]. The heart was rapidly removed, followed by retrograde perfusion through the aorta in a non-circulatory mode using an isovolumic perfusion system by the Langendorff technique (LT) using a Krebs-Henseleit buffer containing the following components (in mM): 118NaCl, 4.7KCl, 2.5CaCl 2 , 1.2MgCl 2 , 25NaHCO 3 , 5 glucose, 0.4 palmitate, 0.4 BSA and 70mU / l insulin. Maintain the perfusion pressure pO in the oxygenation chamber 2 >600mmHg.

[0214] Evidence in support of the methods and products of the present invention has been established by an in vitro model using rapidly removed hearts from 12-14 week ol...

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Abstract

It was found that isolated organs and tissues perfused / reperfused with perfusion buffer supplemented with omega-3 glyceride oil maintained a higher level of function relative to perfusion / reperfused without omega-3 glyceride oil. Ex vivo reperfusion of isolated hearts with n‑3 triglyceride perfusion emulsion after induction of ischemia maintained normal heart rate and normal LVDP and showed significantly reduced arrhythmias compared with control hearts. Furthermore, test hearts reperfused with n‑3 oil triglyceride emulsions showed downregulation of creatine kinase levels and upregulation of certain beneficial proteins, including the antiapoptotic gene marker Bcl‑2.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application 61 / 806,391, entitled "Reperfusion with Omega-3 Glycerides Promotes Protection of Donor Organs for Transplantation," filed March 28, 2013, which is hereby incorporated its entire contents. [0003] Statement of Government Interest [0004] This invention was made with government support under grant HL40404 from the National Institutes of Health. The government has certain rights in this invention. Background technique [0005] The present invention provides a preservation solution for storing an organ while awaiting transplantation, which prolongs the vitality of the organ and reduces damage to the cells of the organ. The present invention also provides methods of organ preservation to prolong the maximum lifespan of an organ prior to or during transplantation. [0006] Over the years, substantial research progress has been made in understanding cellular...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A01N1/02
CPCA01N1/0226A61K31/202
Inventor R·J·德克尔鲍姆R·拉马萨米
Owner THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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