# US 9,750,241 B2 · Blood substitute composition and method of use

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,750,241 B2
- Document ID: US9750241B2
- Status: Granted
- Kind: B2
- Application number: 15/460,843
- Filed: 2017-03-16
- Published: 2017-06-29
- Granted: 2017-09-05
- Earliest claimed: 2013-05-03
- Assignees: Washington University
- Applicants: Washington University
- Inventors: Gregory M. Lanza; Dipanjan Pan; Allan Doctor; Philip C. Spinella
- Web page: https://patentgrep.com/patent/US9750241B2

## CPC

- A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients
- A61K 9/0026: {Blood substitute; Oxygen transporting formulations; Plasma extender}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 38/063: {Glutathione}
- A61K 38/42: Haemoglobins; Myoglobins
- A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04)
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

The present disclosure provides oxygen-carrying nanoparticles, methods of making the nanoparticles, and methods of using the nanoparticles to carry oxygen in blood.

## Claims

### Claim 1

A method for providing oxygen to an organ ex vivo, the method comprising perfusing an organ with an effective amount of an oxygen-carrying nanoparticle, wherein the nanoparticle has a substantially bi-concaved disc shape and comprises an aqueous core, a bi-layered shell comprising an amphiphilic polymer, and a payload; and wherein
the bi-layered shell has a hydrophilic outer layer, a hydrophilic inner layer, and a hydrophobic region between the hydrophilic outer layer and the hydrophilic inner layer;
the amphiphilic polymer comprises a branched, amine-containing polymer linked to a lipid; and
the payload comprises an oxygen-carrying agent, an allosteric effector, and a reducing agent.

### Claim 2 (depends on 1)

The method of claim 1, wherein the amphiphilic polymer comprising the hydrophilic outer layer of the shell is derivatized with polyethylene glycol, such that the particle has a zeta potential of about −15 mV to about +15 mV.

### Claim 3 (depends on 1)

The method of claim 1, wherein the average diameter of the nanoparticle is from about 150 nm to about 300 nm, and the average height of the nanoparticle is from about 30 nm to about 80 nm.

### Claim 4 (depends on 1)

The method of claim 1, wherein the oxygen-carrying agent is synthetic hemoglobin or naturally occurring hemoglobin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the allosteric effector is selected from the group consisting of 2,3-diphosphoglycerate (2,3-DPG), inositol hexaphosphate (IHP), pyridoxal-phosphate (PLP), and 2-[4-[[(3,5-dimethylanilino carbonyl]methyl]-phenoxy]-2-methylpropionic acid.

### Claim 6 (depends on 1)

The method of claim 1, wherein the reducing agent is selected from the group consisting of leucomethylene blue, glutathione and ascorbate.

### Claim 7 (depends on 1)

The method of claim 1, wherein the nanoparticle comprises about 3000 to about 10,000 hemoglobin molecules.

### Claim 8 (depends on 1)

The method of claim 1, wherein the nanoparticle comprises about 20% to about 60% (w/v) hemoglobin or about 30% to about 60% (w/v) hemoglobin.

### Claim 9 (depends on 1)

The method of claim 1, wherein the nanoparticle limits the oxidation of hemoglobin to about 10% or less of the total concentration of hemoglobin in the nanoparticle.

### Claim 10 (depends on 1)

The method of claim 1, wherein the branched, amine-containing polymer is selected from the group consisting of a polyethyleneimine branched polymer, a PAMAM dendrimer, a star polymer, and a graft polymer.