# US 2010/0167260 A1 · Use of N-Piperidine Derivative Compositions for Protecting Biological Systems

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- Number: US 2010/0167260 A1
- Document ID: US20100167260A1
- Status: Published application
- Kind: A1
- Application number: 12/161,232
- Filed: 2007-01-18
- Published: 2010-07-01
- Earliest claimed: 2006-01-19
- Assignees: Medestea Research & Production S.p.A.
- Inventors: Gianfranco Merizzi; Antonio Soleti
- Web page: https://patentgrep.com/patent/US20100167260A1

## CPC

- A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients
- A01N 1/10: Preservation of living parts
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS

## Abstract

The present invention relates to compositions and the use of such compositions in the formulation of preservation solutions for protecting mammalian (including human) biological systems such as biotechnological preparations (including recombin 10d3 ant proteins), organs, tissues (including whole blood and blood derivatives such platelets and plasma) and cells (including red blood cells, pancreatic ss-cells, stem cells and germ cells) from oxidative damage occurring, for example, during the different phases of transplantation and surgery. More particularly, this invention relates to a method for protecting and/or enhancing viability of mammalian biotechnological preparations/cells/tissues/organs during isolation (or harvesting), preservation (or storage), expansion (or colture), transplantation and surgery by using compositions containing effective amount of antioxidant cyclic (bis)-hydroxylamines derived from N-piperidine. Data supplied from the esp@cenet database—Worldwide

## Claims

### Claim 1

A method for preserving and/or enhancing the viability ex vivo of a mammalian biological system, comprising contacting said biological system with a preservation solution comprising a compound of formula:
in which:
R1, R2, R3 and R4 are, independently of one another, hydrogen or alkyl having from 1 to 6 carbon atoms, R6 is oxyl or hydroxyl, and R5 is
in which R1, R2, R3 and R4 are, independently of one another, hydrogen or alkyl having from 1 to 6 carbon atoms, R7 is oxyl or hydroxyl, and n is a whole number from 2 to 14; or a physiologically acceptable salt of said compound.

### Claim 2 (depends on 1)

A method according to claim 1, in which R1, R2, R3 and R4 are, independently of one another, an alkyl having from 1 to 3 carbon atoms and R5 is:
in which R1, R2, R3 and R4 are, independently of one another, an alkyl having from 1 to 3 carbon atoms, R7 is oxyl or hydroxyl, and n is a whole number from 6 to 10.

### Claim 3 (depends on 1)

A method according to claim 1, in which the compound is of formula
in which R6 and R7 are identical or different and are selected from oxyl and hydroxyl.

### Claim 4 (depends on 1)

A method according to claim 1, in which the biological systems are biotechnological preparations such as recombinant proteins, organs such as heart, liver, pancreas, kidney, lung, intestine, trachea as well as amputated organs such as digits, tissues such as skin/muscle flaps, whole blood, blood derivatives such as platelets and plasma, and cells such as red blood cells, pancreatic islet cells, stem cells and germ cells.

### Claim 5 (depends on 1)

A method according to claim 1, in which the compounds are under the form of physiologically acceptable salts, said salts being either chloride, fumarate and maleate.

### Claim 6 (depends on 1)

A method according to claim 1, in which said compound is present in the preservation solution in an antioxidant effective amount, preferably in the range of from 0.001 to 50 mM.

### Claim 7 (depends on 1)

A method according to claim 1, wherein said compound is added to a standard commercially available preservation solution that is either Celsior solution, University of Wisconsin solution (UW-1), Modified University of Wisconsin solution (UW-2), Krebs-Henseleit solution, St. Thomas 1 (STH-1) and 2 (STH-2) solution, Collins solution, Euro-Collins solution (EC), Lactated Ringer's solution, Columbia University solution, Stanford solution (STF), Lyon Preservation solution (LYPS), Bretschneider solution (HTK), RMBM solution, ET-Kioto solution, CMV-1 solution, Polysol solution, NaCl solution.

### Claim 8 (depends on 1)

A method according to claim 1, in which said compound is used in combination with desferoxamine preferably within the range of from 0.01 to 55 mM and, if not already present, Na+, preferably at the final concentration within the range of from 0.1 to 200 mM, and K+, preferably at the final concentration within the range of from 0.2 to 220 mM.

### Claim 9 (depends on 1)

A method according to claim 1, in which said compound is comprised in an isotonic aqueous buffer solution comprising desferoxamine, within the range of from 0.01 to 55 mM, Na+, within the range of from 0.1 to 200 mM, and K+, within the range of from 0.2 to 220 mM.

### Claim 10 (depends on 1)

A method according to claim 1, wherein the biological system is contacted with the preservation solution by infusion, immersion, flushing, perfusion or culture.

### Claim 11

An aqueous saline-based solution for the preservation of biological materials, particularly for storage, perfusion and reperfusion ex vivo of mammalian organs, comprising: an effective antioxidant amount of a compound of formula (I) or (III) or a physiological acceptable salt thereof; and a preservative or antioxidant compound selected from trolox derivatives of vitamin E (Trolox C), allopurinol, deferoxamine, indaindoles, catalase, peroxidase, superoxide dismutase, glutathione, N-acetylcysteine, nytroxides, ginkolides, coenzyme Q, β-carotene, cyanidol and mixtures thereof.

### Claim 12 (depends on 11)

A solution according to claim 11, further comprising a physiologically acceptable amount of an ion selected from sodium, potassium, calcium, magnesium, mono- and bi-acidic phosphate, bicarbonate, chloride and mixtures thereof, preferably a mixture of at least four of said ions.

### Claim 13 (depends on 12)

A solution according to claim 12, further comprising a carbohydrate source.

### Claim 14 (depends on 11)

A solution according to claim 11, having a pH of from 7.4 to 8.5.

### Claim 15 (depends on 11)

A solution according to claim 11, comprising desferoxamine, preferably in the concentration of from 0.01 to 55 mM.

### Claim 16 (depends on 11)

A solution according to claim 11, further comprising sodium ions preferably from 0.1 to 200 mM and potassium ions preferably from 0.2 to 220 mM.
