Intravenous administration of citrulline during surgery

Patent metadata

Field	Value
Publication number	US-10525026-B2
Application number	US-201615197209-A
Country	US
Kind code	B2
Filing date	Jun 29, 2016
Priority date	Jun 29, 2015
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

Abstract

A method for administering citrulline to a patient during surgery without filtration of the hemolysis.

First claim

What is claimed is:

1. A method for maintaining pulmonary vascular tone in a patient undergoing cardiopulmonary bypass surgery for a cardiac defect, wherein the cardiopulmonary bypass surgery utilizes filtration, the method comprising:
(a) administering about 100-300 mg/kg citrulline to the patient at the initiation of the surgery;
(b) administering about 100-300 μmol/L citrulline to the patient via the hemoconcentration replacement fluid during the surgery;
(c) administering a citrulline bolus of about 10-30 mg/kg about 15-45 minutes after decannulation from cardiopulmonary bypass, and,
(d) infusing citrulline into the patient after the surgery for about 6-48 hours at about 5-15 mg/kg/hour,
wherein the patient's plasma citrulline level is raised above 100 μmol/L.

2. The method of claim 1 , wherein the cardiac defect is associated with excess pulmonary blood flow, atrial septal defect, large arterial septal defect, ventricular septal defect, large unrestrictive ventricular septal defect, single ventricle lesion, partial atrioventricular septal defect, complete atrioventricular septal defect, or ostium primum atrial septal defect.

3. The method of claim 1 , wherein the surgery comprises an arterial switch procedure or Glenn and Fontan procedures.

4. The method of claim 1 , wherein the bolus of citrulline at the initiation of the surgery in step (a) is about 150 mg/kg of citrulline.

5. The method of claim 1 , wherein the citrulline in step (b) is added at about 200 μmol/L.

6. The method of claim 1 , wherein the citrulline bolus is administered about 30 minutes after the surgery.

7. The method of claim 1 , wherein the citrulline bolus in step (c) is about 20 mg/kg citrulline.

8. The method of claim 1 , wherein a citrulline bolus in step (c) is administered about 30 minutes after decannulation from cardiopulmonary bypass.

9. The method of claim 1 , wherein citrulline infusion in step (d) is infused into the patient for about 48 hours at about 9 mg/kg/hour.

10. The method of claim 1 , wherein the patient is less than about 6 years old, less than 10 days old, at risk for persistent pulmonary hypertension (PPHN), at risk for acute lung injury, or a combination thereof.

11. The method of claim 1 , wherein the patient's plasma citrulline level is raised to 100 μmol/L to 300 μmol/L for about 48 hours after surgery.

12. The method of claim 1 , wherein the citrulline infusion is started within 5-10 minutes of the citrulline bolus in step (c).

13. The method of claim 1 , wherein the surgery is completed within 4 hours as measured from completion of step (a) to initiation of step (d).

Assignees

• Univ Vanderbilt

Inventors

• Summar Marshall L
• Barr Frederick E

Classifications

• A61K31/198 Primary

  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 title

• A61M1/3666

  Cardiac or cardiopulmonary bypass, e.g. heart-lung machines · CPC title

• A61K9/0019

  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 title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title