COMPOSITION COMPRISING NOR-ADRENALINE AND A NET INHIBITOR FOR ADMINISTERING TO A BRAIN-DEAD, HEART-BEATING POTENTIAL ORGAN DONOR

• US 20110270215A1
• Filed: 12/30/2009
• Published: 11/03/2011
• Est. Priority Date: 12/30/2008
• Status: Abandoned Application

• Current Assignee: Xvivo Perfusion AB
• Original Assignee: Vivoline Medical AB (Xvivo Perfusion AB)
• Inventors: Steen, Stig
• Application Number:
  US13/142,727
• Publication Number:
  US 20110270215A1
• Time in Patent Office: Days
• US Class Current: 604/500
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/172 electrical or electronic A61M5/16804, A61M5/16831 take precedence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A composition, an infusion solution, a method for treatment, and a kit for intravascular administration for treatment of a brain-dead, heart-beating, respirated, potential organ donor. The composition has a non-adrenaline and NET inhibitor for noradrenaline. The NET inhibitor may be cocaine or an analogue thereof or a tricyclic antidepressant. The composition may in addition include adrenaline, hydrocortisone, thyroxin, insulin, triiodotyronine, dopamine, a vasopressor agent, such as desmopressin, and methylprednisolone. The ratio between the NET inhibitor and nor-adrenaline is about 1:1. The composition may be dissolved in pure water, Ringer'"'"'s acetate solution or physiological sodium chloride solution. The composition is infused in such an amount as to maintain a mean arterial pressure of about 60 mmHg. The composition may be infused by a pump at a rate of about 1.7 ml/hour decreasing dose-dependent to about 0.4 ml/hour after 24 hours.

Claims

1. A composition for intravascular administration for treatment of a brain-dead, heart-beating, respirated potential organ donor, comprising:

nor-adrenaline and a NET inhibitor.

2. The composition according to claim 1, wherein the NET inhibitor is cocaine or a stimulating analogue thereof.

3. The composition according to claim 1, wherein the NET inhibitor is at least one tricyclic antidepressant included in the group comprising:

Amitriptyline (ELAVIL);

Clomipramine (ANAFRANIL);

Doxepin (ADAPIN, SINEQUAN);

Imipramine (TROFANIL);

Trimipramine (SURMONTIL);

Amoxapine (ASENDIN);

Desipramine (NORPRAMIN);

Maprotinile (LUDIOMIL);

Nortriptyline (PAMELOR); and

Protriptyline (VIVACTIL).

5. The composition according to claim 1, wherein the NET inhibitor is at least one agent included in the group comprising:

Venlafaxin (EFFEXOR);

Atomexetine (WELLBUTRIN);

Duloxetine (CYMBALTA);

Mirtacapine (REMERON);

Norclomipramine;

Oxaprotiline;

Lofepramine;

Reboxetine;

Maprotiline;

Nomifensine;

Doxepin;

Mianserin;

Viloxazine;

Mirtazapine; and

Nisoxetine.

6. The composition according to claim 1, further comprising at least one of:

adrenaline, hydrocortisone, thyroxin, insulin, triiodotyronine, dopamine, a vasopressor agent, such as desmopressin, and methylprednisolone.

7. The composition according to claim 1, wherein the NET inhibitor is present in an amount of 0.2 to 5 times of the amount of nor-adrenaline.

8. The composition according to claim 1, wherein a ratio between cocaine and nor-adrenaline is about 1:

1.

9. An infusion solution comprising the composition according to claim 1 and a pharmaceutically acceptable medium, such as pure water, Ringer'"'"'s acetate solution or physiological sodium chloride solution.

10. The infusion solution according to claim 9, wherein said composition is dissolved in the pharmaceutically acceptable medium in an amount of about 1 mg of noradrenaline, and about 1 mg of cocaine in about 50 ml of fluid.

11. A method for treatment of a brain dead, heart-beating, respirated potential organ donor, comprising:

infusion of the infusion solution according to claim 9, in an amount sufficient for maintaining a mean arterial pressure of about 60 mmHg.

12. A kit for intravenous administration for treatment of a brain dead, heart-beating, respirated potential organ donor, comprising

an infusion bag comprising an infusion solution according to claim 9, an infusion pump for pumping the infusion solution to a needle inserted into the vascular system of the donor for controlling the amount of infusion solution entered into the donor and tubings for interconnecting the bag, pump and needle.

13. The kit according to claim 12, comprising several sets of infusion bags, infusion pumps and tubings.

14. The kit according to claim 12, further comprising a computer for controlling the pump or pumps, whereby the computer is operated according to a predetermined control strategy.

15. A method of infusing a solution into the circulation system of a brain dead, heart-beating, respirated potential organ donor, comprising:

determining that the donor is brain dead;

continuing or initating respiration for oxygenation of the blood;

infusion of an infusion solution according to claim 9;

controlling the infusion by means of a computer.