# US 9,517,202 B2 · Phospholipid depot

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

- Number: US 9,517,202 B2
- Document ID: US9517202B2
- Status: Granted
- Kind: B2
- Application number: 13/523,860
- Filed: 2012-06-14
- Published: 2012-12-13
- Granted: 2016-12-13
- Earliest claimed: 2009-12-18
- Assignees: Latitude Pharmaceuticals, Inc.
- Applicants: Andrew Xian Chen; Hailiang Chen
- Inventors: Andrew Xian Chen; Hailiang Chen
- Web page: https://patentgrep.com/patent/US9517202B2

## CPC

- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- 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)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/4174: Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/727: Heparin; Heparan
- A61K 38/1816: {Erythropoietin [EPO]}
- A61K 38/215: {IFN-beta}
- A61K 38/26: Glucagons
- A61K 38/27: Growth hormone [GH], i.e. somatotropin
- A61K 38/28: Insulins
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 17/00: Drugs for dermatological disorders
- C07K 16/241: {Tumor Necrosis Factors}
- C07K 2317/21: from primates, e.g. man
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention is directed to phospholipid compositions and methods of preparation of phospholipid depots that are injectable through a fine needle. The phospholipid depots prepared by the methods described herein comprise nanometer-sized phospholipid particles and exhibit a higher degree of structural order compared to compositions prepared by other methods.

## Claims

### Claim 1

An nanoemulsion based injectable one-phase gel composition, comprising:
about 30% to about 60% by weight of phospholipid based on the total weight of the gel, wherein the phospholipid is a member selected from the group consisting of a lecithin, phosphatidylcholine or a mixture thereof;
0.1% to 65% by weight based on the total weight of the gel;
10% to 50% by weight of an oil based on the total weight of the gel, wherein the phospholipid comprising particles are stacked together and have an average particle size of about 30 nm to about 100 nm in diameter;
and wherein the composition has an increased degree of order as shown by an increase in the Scherrer crystalline domain size over a composition containing the same quantities of the same components but prepared by a process without forming a nanodispersion and the discrete phospholipid particles; is extrudable or injectable through a 25 G, ½ inch long needle from a 1 cc syringe at an extrusion rate of 2 cc/min by an applied force of no more than 12 pounds.

### Claim 2 (depends on 1)

The gel composition of claim 1, further comprising a pharmacologically active agent having concentration of no more than 20% by weight of the final gel composition.

### Claim 3 (depends on 2)

The gel composition of claim 2, wherein the pharmacologically active agent is a heat-sensitive pharmacologically active agent.

### Claim 4 (depends on 2)

The gel composition of claim 2, wherein the pharmacologically active agent is a protein or peptide.

### Claim 5 (depends on 2)

The gel composition of claim 2, wherein the pharmacologically active agent is a member selected from the group consisting of an insulin, an insulin analog, a crystalline insulin with zinc and/or protamine, an NPH insulin, and a combination thereof.

### Claim 6 (depends on 5)

The gel composition of claim 5, wherein the phospholipid comprises 30% to 40% by weight based on the total weight of the gel.

### Claim 7 (depends on 1)

The gel composition of claim 1, wherein the phospholipid is a lecithin.

### Claim 8 (depends on 1)

The gel composition of claim 1, wherein the oil is selected from the group consisting of a synthetic oil, a vegetable oil, a medium chain oil, ethyl oleate, fatty acid, vitamin E, vitamin E succinate, cholesterol, or a mixture thereof.

### Claim 9 (depends on 1)

The gel composition of claim 1, further comprising one or more sugars selected from the group consisting of sucrose, dextrose, lactose, glucose, trehalose, maltose, mannitol, sorbitol, glycerol, amylose, starch, amylopectin, or a mixture thereof.

### Claim 10 (depends on 1)

The gel composition of claim 1, further comprising one or more non-aqueous solvents selected from the group consisting of ethanol, propylene glycol, glycerol, sorbitol, polyethylene glycol, ethyl oleate, or a mixture thereof.

### Claim 11 (depends on 1)

The gel composition of claim 1, further comprising a functional pharmaceutical excipient selected from the group consisting of an acidifying agent, an alkalizing agent, a pH buffering agent, a metal ion chelator, an antioxidant, a preservative, a tonicity/osmotic pressure modifier, a condensing agent, a solubilizing agent, or a mixture thereof.

### Claim 12 (depends on 1)

The gel composition of claim 1, where the gel composition has a small-angle X-ray scattering diffractogram of FIG. 10 and a lattice d spacing of 67 Å and 33 Å.

### Claim 13 (depends on 1)

The gel composition of claim 1, wherein the gel has an increase in the Scherrer crystalline domain size over a composition containing the same quantities of the same components but prepared by a process without forming a nanodispersion and the discrete phospholipid particles having a diameter of 30-100nm; and (2) a small-angle X-ray scattering diffractogram of FIG. 10 and a lattice d spacing of 67 Å and 33 Å.

### Claim 14

An injectable one-phase gel composition, comprising about 30% to about 60% by weight of phospholipid, wherein the phospholipid is a member selected from the group consisting of a lecithin, phosphatidylcholine or a mixture thereof based on the total weight of the gel;
10% to 50% by weight of an oil based on the total weight of the gel; and
0.1% to 65% by weight water based on the total weight of the gel, wherein said composition is prepared by a process comprising:
i mixing one or more phospholipid(s) and water to form a primary dispersion;
ii homogenizing the primary dispersion to form a nanodispersion with an average particle size of about 30 nm to about 100 nm in diameter;
iii passing the nanodispersion through a filter; and
iv removing the excessive water to obtain a one-phase gel composition comprising (a) discrete phospholipid particles that are stacked together and have an average particle size of about 30 nm to about 100 nm in diameter; (b) an increased degree of order as shown by an increase in the Scherrer crystalline domain size over a composition containing the same quantities of the same components but prepared by a process without forming a nanodispersion and the discrete phospholipid particles of (a); and (c) is extrudable or injectable through a 25 G ½ inch long needle from a 1 cc syringe at an extrusion rate of 2 cc/min by an applied force of no more than 12 pounds.