# US 12,599,605 B2 · Uric acid liposomes

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- Number: US 12,599,605 B2
- Document ID: US12599605B2
- Status: Granted
- Kind: B2
- Application number: 18/693,714
- Filed: 2022-10-25
- Published: 2024-11-28
- Granted: 2026-04-14
- Earliest claimed: 2021-10-29
- Assignees: Hospital Clinic De Barcelona; Fundació De Recerca ClíNic Barcelona-Institut D'Investigacions BiomèDiques August Pii Sunyer; Agencia Estatal Consejo Superior de Investigaciones Cientificas, M.P.
- Applicants: Hospital Clinic De Barcelona; Fundació De Recerca ClíNic Barcelona-Institut D'Investigacions BiomèDiques August Pi I Sunyer; Agencia Estatal Consejo Superior De Investigaciones CientíFicas, M.P.
- Inventors: Angel Chamorro Sánchez; Ana María Planas Obradors; Pedro Ramos Cabrer
- Web page: https://patentgrep.com/patent/US12599605B2

## CPC

- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 9/1278: Post-loading, e.g. by ion or pH gradient
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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

## Abstract

The present invention relates to liposomes that encapsulate uric acid, methods for its preparation and uses of said liposomes.

## Claims

### Claim 1

Liposome that encapsulates uric acid, uric acid salts, or combinations thereof, wherein said liposome has a lipid bilayer comprising double-chain phospholipids and positively charged cholesterol, wherein said liposome is unilamellar.

### Claim 2 (depends on 1)

The liposome according to claim 1, wherein the encapsulated amount of uric acid is between 6*10−20 and 6*10−18 moles per liposome.

### Claim 3 (depends on 1)

The liposome according to claim 1, wherein said liposome has a hydrodynamic diameter measured by Dynamic Light Scattering (DLS) in water at a temperature of 25° C. of between 80 and 140 nm.

### Claim 4 (depends on 1)

The liposome according to claim 1, wherein said liposome has a positively charge surface and a Z potential measured by Dynamic Light Scattering (DLS) at a temperature of 25° C. greater than 0 and lower than 15 mV.

### Claim 5 (depends on 1)

The liposome according to claim 1, wherein between 2.5% and 10% molar of the double-chain phospholipids are phospholipids with one or more polyethylene glycol chains attached to a polar head that hinder the opsonization of blood liposomes attached to a polar head of said phospholipids; and between 90 and 97.5% molar of the double chain phospholipids are phospholipids with no polyethylene glycol attached to a polar head of said phospholipids.

### Claim 6 (depends on 5)

The liposome of claim 5, wherein:
said double chain phospholipids with one or more polyethylene glycol chains attached to a polar head are selected from 16:0 PEG2000 PE (or 1,2 dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000]), 18:0 PEG2000 PE (or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000]), 18:0 PEG5000 PE (or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-5000]) or combinations thereof; and
said double chain phospholipids without polyethylene glycol attached to a polar head are selected from DSPC (18:0 PC or 1,2-distearoyl-sn-glycero-3-phosphocholine), DPPC (16:0 PC or 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine)), 17:0 PC (or 1,2-diheptadecanoyl-sn-glycero-3-phosphocholine) or combinations thereof.

### Claim 7 (depends on 1)

The liposome according to claim 1, wherein said positively charged cholesterol is dimethylaminoethane-carbamoyl-cholesterol (DC-cholesterol) hydrochloride.

### Claim 8 (depends on 7)

The liposome according to claim 7, comprising a molar fraction ratio between double chain phospholipids and DC-cholesterol between 0.6:0.4 and 0.75:0.25.

### Claim 9

A method for the manufacture of liposomes that encapsulate uric acid, uric acid salts, or combinations thereof, said method comprising the steps of:
a) preparing a solution comprising lithium and/or potassium ions in water;
b) adjusting said solution to a pH value between 10 and 11;
c) adding uric acid, uric acid salts, or combinations thereof, in which the lithium and/or potassium ions are present in an molar amount that is at least twice than of uric acid, keeping the pH in the range of 10-11 to obtain a complete dissolution;
d) lowering the pH to a value between 7.2 and 7.4 to obtain a uric acid solution;
e) forming a lipid film;
f) rehydrating the lipid film formed in step e) with the uric acid solution of step d) to obtain liposomes;
g) extruding the obtained liposomes in step f) using the lithium and/or potassium ions solution of step a) as solvent; and
h) filtering the obtained liposomes in step g) using the lithium and/or potassium ions solution of step a) as solvent,
wherein steps e) to h) are carried out free of calcium ions.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a liposome according to claim 1 and at least one pharmaceutically acceptable excipient.

### Claim 11 (depends on 10)

A medicine comprising the pharmaceutical composition according to claim 10.

### Claim 12 (depends on 10)

A method for improving and/or treating cerebrovascular disease comprising administering the pharmaceutical composition according to claim 10 to a patient in need thereof.

### Claim 13 (depends on 1)

A medicine comprising the liposome according to claim 1.

### Claim 14 (depends on 1)

A method for improving and/or treating cerebrovascular disease comprising administering the liposome according to claim 1 to a patient in need thereof.