# US 2021/0330754 A1 · Self-assembling oxygen carrier compositions

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- Number: US 2021/0330754 A1
- Document ID: US20210330754A1
- Status: Published application
- Kind: A1
- Application number: 17/238,809
- Filed: 2021-04-23
- Published: 2021-10-28
- Earliest claimed: 2020-04-23
- Assignees: KaloCyte, Inc.
- Applicants: KaloCyte, Inc.
- Inventors: Dipanjan Pan; Allan Doctor; Phil Spinella
- Web page: https://patentgrep.com/patent/US20210330754A1

## CPC

- A61K 38/42: Haemoglobins; Myoglobins
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/1277: Preparation processes; Proliposomes
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- C07F 9/10: Phosphatides, e.g. lecithin
- C07F 9/106: {Adducts, complexes, salts of phosphatides}
- 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)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Synthetic blood substitutes and methods for making them. A lipid-amphiphile blood-substitute precursor compound having a hydrophobic fatty acid/acyl moiety, a hydrophilic head moiety including a phosphate group, and a pH responsive moiety. The lipid-amphiphile precursor is configured to self-assemble from a solution mixture of phospholipid and cholesterol in the presence of hemoglobin and an allosteric effector into a hybrid-vesicle resulting from the combined self-assembly of both the amphiphilic lipid-oligomer and the lipids into an advanced vesicular structure containing a hemoglobin/allosteric effector payload.

## Claims

### Claim 1

A lipid-amphiphile precursor compound having the formula:
or a salt or tautomer thereof, wherein:
R1 is a hydrophobic group;
R2 is an amine containing group; and
R3 is chosen from

### Claim 2 (depends on 1)

A compound according to claim 1, wherein R1 is (CH2)lCH3; and l is an integer between 10 and 16, inclusive.

### Claim 3 (depends on 2)

A compound according to claim 2, wherein R1 is (CH2)lCH3; and l is an integer between 10 and 16, inclusive.

### Claim 4 (depends on 3)

A compound according to claim 3, wherein l is 14.

### Claim 5 (depends on 1)

A compound according to claim 1, wherein:
R2 is chosen from (CHR5)mR6 and (CHR5)mNR7(CH2)nR6;
each R5 is independently chosen from H and N(R7)2;
at most one R5 is not H;
R6 is chosen from N(R8)2 and N═C(NHR8)2;
each R7 is independently chosen from H and alkyl;
each R8 is chosen from H and alkyl;
m is an integer between 2 and 6, inclusive; and
n is an integer between 2 and 6, inclusive.

### Claim 6 (depends on 5)

A compound according to claim 5, wherein each R5 is independently chosen from H and NHCH3; and at most one R5 is not H.

### Claim 7 (depends on 5)

A compound according to claim 5, wherein R6 is chosen from N(R8)2 and N═C(NH2)2.

### Claim 8 (depends on 1)

A compound according to claim 1, wherein R2 is chosen from

### Claim 9 (depends on 1)

A compound according to claim 1, wherein R3 is

### Claim 10 (depends on 1)

A compound according to claim 1, wherein R1 is (CH2)14CH3.

### Claim 11 (depends on 1)

A composition comprising:
(a) a phospholipid;
(b) cholesterol
(c) an oxygen carrier;
(d) a lipid-amphiphile precursor according to claim 1; and
(e) an allosteric effector.

### Claim 12 (depends on 11)

A composition according to claim 11, wherein the oxygen carrier is hemoglobin (Hb).

### Claim 13 (depends on 11)

A composition according to claim 11, wherein the allosteric effector is selected from the group consisting of 2,3-DPG, RSR-13, inositol phosphate, inositol hexaphosphate (IP6), phytic acid, and guanosine triphosphate.

### Claim 14 (depends on 11)

A composition according to claim 11, which self assembles into a vesicle having a amphiphilic lipid bi-layer membrane and a payload comprising said oxygen carrier and said allosteric effector.

### Claim 15 (depends on 11)

A composition according to claim 11 further comprising a reducing agent.

### Claim 17 (depends on 15)

A composition according to claim 15, wherein said reducing agent is selected from leucomethylene blue, n-benzoyl-leucomethylene blue, and methylene blue.

### Claim 18 (depends on 1)

A method for making a synthetic oxygen carrier, comprising:
preparing a composition comprising
(a) a phospholipid;
(b) cholesterol;
(c) an oxygen carrier;
(d) a lipid-amphiphile precursor according to claim 1; and
(e) an allosteric effector.
allowing said composition to self-assemble into a vesical having a lipid bilayer outer membrane and a payload comprising said oxygen carrier and said allosteric effector; and
lyophilizing said self-assembled vesicle.

### Claim 18 (depends on 17)

A method according to claim 17, wherein said composition further includes a reducing agent selected from the group consisting of methylene blue, n-benzoyl-leucomethylene blue, and leucomethylene blue.

### Claim 19 (depends on 11)

A composition according to claim 11, wherein said composition is lyophilized.

### Claim 20 (depends on 19)

A method for preparing a synthetic oxygen carrier, comprising reconstituting a lyophilized composition according to claim 19.