Classifications

• • 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
• • 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

Definitions

• the present invention relates to additives for organ preservation solutions for the protection of biological transplants of all kinds (tissues, blood vessels, organs) after their explantation and during their storage or during their transport, against ischemic inflammatory reactions (eg edema and / or oxidative or hydrolytic cell damage) which are triggered by the temporary cessation of blood flow.
• ischemic inflammatory reactions eg edema and / or oxidative or hydrolytic cell damage
• This is achieved by admixing certain flavonoids of the flavonol group, in particular quercetin glucuronide and / or kaolin glucuronide, to the respective preservation solutions.
• PAF and LTB 4 promote the adhesion of the platelets and PMN at the respective endothelium.
• adherent leukocytes can damage the endothelium by releasing aggressive compounds (eg, proteolytic enzymes, oxygen radicals, hypochlorous acid, etc.), and activated platelets on the surface become catalysing fibrin formation by binding and arranging the coagulation cascade, it occurs on the wall and in the lumen of affected blood vessels to inflammatory reactions, which Cause formation of thrombi.
• aggressive compounds eg, proteolytic enzymes, oxygen radicals, hypochlorous acid, etc.
• microcirculatory inflammatory processes there is a mass accumulation of white blood cells within and around the smallest veins (postcapillary venules) that can induce extensive inflammatory edema in organs. Furthermore, there is a high probability that arterioles adjacent to the venous barrier and numerous mediators of inflammation will constrict in the vicinity, thereby severely limiting local perfusion. In addition, there is a risk of intravascular thrombosis.
• grafts are tissues, individual blood vessels, organs or parts of the body of the human body taken from a donor organism for the purpose of implantation into an acceptor organism
• the acceptor organism may be the donor organism or another organism.
• Inflammatory processes in the sense of the present invention are components of the immune system which are acute or chronically induced defense processes involving not only the breakdown of foreign substances, foreign cells, foreign tissues or transplanted body parts that have entered a body, but also the destruction of the body's own structures, cells, tissue and tissue Body parts can come. These directly cell-damaging processes are mediated by the activity of defensive hydrolytic enzymes, oxidants, and phagocytes of the immune system. At the same time, cell aggregation, thrombotic and edematous processes develop, which in the sense of ischemic disorders can have a pathogenetic effect on the affected body regions.
• blood vessels are all blood-flushed regions in the human organism, including, in particular, the heart, veins and venules, as well as arteries and arterioles.
• flavonol compounds are substances having a 3-hydroxyflavone structure, in particular those having free hydroxyl groups
• Preferred flavonols are derivatives of quercetin and camphor oil
• Particularly preferred flavonol compounds in the context of the present invention are quercetin glucuronide and warfarin glucuronide, in particular quercetin-3 O-.beta.-D-glucuronide and kaempferol-3-O-.beta.-D-glucuronide.
• veins are the smallest veins with a cross section of 10-30 ⁇ m, which are located in the circulatory system postcapillary.
• “Arterioles” in the sense of the present invention are smallest arteries with a cross section of 10-50 ⁇ m.
• Inner surface of a transplant in the context of the present invention relates to the luminal surface of the blood vessels of the transplant, which are perfused after removal from the donor organism with suitable preservation solution from the outside.
• Outer surface of a graft in the context of the present invention relates to the surface of the graft, which is visible to the viewer from the outside with the naked eye.
• the process of transplantation can be divided into three phases:
• the graft is surgically removed from the donor organism.
• the first stimuli are triggered, which then can further promote the inflammatory physiological cascades.
• the transplant In the second phase, the transplant is in the state of ischemia during its storage in appropriate preservation solution, i. it is no longer flowed through by blood, because it is outside of a supplying organism.
• This second or ischemic phase is extremely critical for the further behavior of the graft. If the inflammation cascades induced in the first phase are allowed to run their course, severe complications can occur during the ischemic storage of the graft, which jeopardize the success of the entire transplantation.
• the ischemic phase there is a particularly simple possibility of specifically acting on the graft in order to attenuate or even prevent exactly the cascade reactions described leading to inflammation. This is the concern of the present invention.
• the graft is implanted into the acceptor organism.
• This phase is also known as the reperfusion phase, as the graft flows through blood again becomes.
• the reperfusion phase as the graft flows through blood again becomes.
• the ischemic organ is finally perfused with blood again, it often leads to the greatest damage to the graft.
• the present invention uses the described knowledge to suppress the described inflammatory processes and their triggers by treatment of grafts taken from the donor organism with flavonol compounds, in particular Quercetinglucuronid and Kämpferolglucuronid, in the phase of ischemia or the preoperative storage and thus after implantation and reperfusion Transplants in the acceptor organism avoid the complications described above, such as blockages of freshly implanted bypasses and the like.
• the explanted organs (heart, lungs, kidneys, etc.) are best rinsed with optimized heparin-anticoagulated preservative solutions at room temperature prior to explantation in situ, to which Quercetinglucuronide has been added up to the final concentration of 100 ⁇ M.
• the organs are placed in fresh, analogously substituted preservation solution and at 4 ° C. cooled. In this condition, the organs can be stored for up to 12 hours and then transplanted.
• mice Female guinea pigs (250-33Og) were used as heart donors. After decapitating the animals, their hearts were explanted and placed in a Langendorff apparatus (self-construction). The perfusion under normal conditions was retrograde via the aorta under a constant pressure of 60 mm Hg for 3 min (mode 1). For perfusion, 37 ° C-warm Krebs-Henseleit bicarbonate buffer (KHM) was used without the addition of quercetiglucuronide (QG), which was fumigated with carbogen before use. After cannulation of the left atrium was switched to the working mode (mode 2) with a preload of lOmmHg and an afterload of 60mmHg.
• KHM 37 ° C-warm Krebs-Henseleit bicarbonate buffer
• QG quercetiglucuronide

Landscapes

• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• Environmental Sciences (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• General Health & Medical Sciences (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Physiology (AREA)
• Biophysics (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
• Saccharide Compounds (AREA)
• Materials For Medical Uses (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=40651377

Family Applications (1)

Country Status (6)

Families Citing this family (5)

Family Cites Families (19)

• 2008
  • 2008-03-06 DE DE102008012908A patent/DE102008012908A1/de not_active Withdrawn
• 2009
  • 2009-03-03 WO PCT/EP2009/052503 patent/WO2009109574A2/de active Application Filing
  • 2009-03-03 CA CA2718810A patent/CA2718810C/en not_active Expired - Fee Related
  • 2009-03-03 US US12/919,563 patent/US8795956B2/en active Active
  • 2009-03-03 EP EP09717445A patent/EP2249639A2/de not_active Ceased
  • 2009-03-03 JP JP2010549126A patent/JP2011527985A/ja active Pending

Non-Patent Citations (2)

Also Published As

Similar Documents

Legal Events