# US 11,439,661 B2 · Ophthalmic compositions

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- Number: US 11,439,661 B2
- Document ID: US11439661B2
- Status: Granted
- Kind: B2
- Application number: 16/911,833
- Filed: 2020-06-25
- Published: 2020-12-31
- Granted: 2022-09-13
- Earliest claimed: 2019-06-28
- Assignees: Alcon Inc.
- Applicants: Alcon Inc.
- Inventors: Steve Yun Zhang; Richard Charles Breitkopf; Daqing Wu; Junhao Ge; Maria F. Gubitosi Raspino; Augustine Twum Kumi; Wei Liang
- Web page: https://patentgrep.com/patent/US11439661B2

## CPC

- A61K 31/80: Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
- A61P 27/02: Ophthalmic agents
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 31/015: carbocyclic
- A61K 31/07: Retinol compounds, e.g. vitamin A (retinoic acids A61K31/203)
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K 31/593: 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
- A61K 31/736: Glucomannans or galactomannans, e.g. locust bean gum, guar gum
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- 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 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61P 27/04: Artificial tears; Irrigation solutions
- 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 invention is generally related to topical ophthalmic compositions comprising: from about 0.05 w/v % to about 5 w/v % of galactomannan polymer; a cis-diol and about 0.5 w/v % to about 10 w/v % of a hydrophilic copolymer which comprises (a) arylborono-containing repeating units each having a boronic acid, (b) repeating units of at least one phosphorylcholine-containing vinylic monomer, and (c) acrylic monomeric units of at least one acrylic monomer having 3 to 16 carbon atoms, the ophthalmic composition is substantially free of a borate for improving lubrication, hydration and drug delivery property.

## Claims

### Claim 1

An ophthalmic composition, comprising: from about 0.05 w/v % to about 5 w/v % of galactomannan polymer; a cis-diol and about 0.5 w/v % to about 10 w/v % of a hydrophilic copolymer which comprises (a) arylborono-containing repeating units each having a boronic acid, (b) repeating units of at least one phosphorylcholine-containing vinylic monomer, and (c) acrylic monomeric units of at least one acrylic monomer having 3 to 16 carbon atoms, the composition is substantially free of a borate.

### Claim 2 (depends on 1)

The ophthalmic composition of claim 1, wherein said at least one arylborono-containing vinylic monomer is a vinylic monomer of formula (II) in which:
R1 is H, NO2, F, Cl, or CF3; Q is a monovalent radical of
L is a direct bond, a C1-C4 alkylene divalent radical, a divalent radical of
in which Y1 is CH(OH) or a C1-C4 alkylene divalent radical, Y2 is a C1-C4 alkylene divalent radical, and Ro is H or a C1-C4 alkyl.

### Claim 3 (depends on 2)

The ophthalmic composition of claim 2, wherein said at least one arylborono- containing vinylic monomer is selected from the group consisting of 3-vinylphenylboronic acid, 4-vinylboronic acid, 3-(meth)acrylamidophenylboronic acid, 4-(meth)acrylamidophenylboronic acid, and combinations thereof.

### Claim 4 (depends on 1)

The ophthalmic composition of claim 1, wherein the phosphorylcholine-containing vinylic monomer is selected from the group consisting of (meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine, 4-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate, 2-[(meth)acryloylamino]ethyl-2′-(trimethylammonio)-ethylphosphate, 3-[(meth)acryloylamino]propyl-2′-(trimethylammonio)ethylphosphate, 4-[(meth)acryloylamino]butyl-2′-(trimethylammonio)ethylphosphate, 5-((meth)acryloyloxy)pentyl-2′-(trimethylammonio)ethyl phosphate, 6-((meth)acryloyloxy)hexyl-2′-(trimethylammonio)-ethylphosphate, 2-((meth)acryloyloxy)ethyl-2′-(triethylammonio)ethylphosphate, 2-((meth)acryloyloxy)ethyl-2′-(tripropylammonio)ethylphosphate, 2-((meth)acryloyloxy)ethyl-2′-(tri butylammonio)ethyl phosphate, 2-((meth)acryloyloxy)propyl-2′-(trimethylammonio)-ethylphosphate, 2-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate, 2-((meth)acryloyloxy)pentyl-2′-(trimethylammonio)ethylphosphate, 2-((meth)acryloyloxy)hexyl-2′-(trimethylammonio)ethyl phosphate, 2-(vinyloxy)ethyl-2′-(trimethylammonio)ethylphosphate, 2-(allyloxy)ethyl-2′-(trimethylammonio)ethylphosphate, 2-(vinyloxycarbonyl)ethyl-2′-(trimethylammonio)ethyl phosphate, 2-(allyloxycarbonyl)ethyl-2′-(trimethylammonio)-ethylphosphate, 2-(vinylcarbonylamino)ethyl-2′-(trimethylammonio)ethylphosphate, 2-(allyloxycarbonylamino)ethyl-2′-(trimethylammonio)ethyl phosphate, 2-(butenoyloxy)ethyl-2′-(trimethylammonio)ethylphosphate, and combinations thereof.

### Claim 5 (depends on 1)

The ophthalmic composition of claim 1, wherein said at least one at least one acrylic monomer is selected from the group consisting of a C1-C12 alkyl (meth)acrylate, a hydroxy-substituted C2-C12 alkyl (meth)acrylate, a carboxy-substituted C2-C12 alkyl (meth)acrylate, an NH2-substituted C2-C12 alkyl (meth)acrylate, a methylamino-substituted C2-C12 alkyl (meth)acrylate, a dimethylamino-substituted C2-C12 alkyl (meth)acrylate, an ethylamino-substituted C2-C10 alkyl (meth)acrylate, a diethylamino-substituted C2-C8 alkyl (meth)acrylate, a C2-C12 alkyl (meth)acrylamide, a hydroxy-substituted C2-C12 alkyl (meth)acrylamide, a carboxy-substituted C2-C12 alkyl (meth)acrylaide, an NH2-substituted C2-C12 alkyl (meth)acrylamide, a methylamino-substituted C2-C12 alkyl (meth)acrylamide, a dimethylamino-substituted C2-C12 alkyl (meth)acrylamide, an ethylamino-substituted C2-C10 alkyl (meth)acrylamide, a diethylamino-substituted C2-C8 alkyl (meth)acrylamide, ethylene glycol (meth)acrylate, di(ethylene glycol) (meth)acrylate, tri(ethylene glycol) (meth)acrylate, tetra(ethylene glycol) (meth)acrylate, ethylene glycol methyl ether (meth)acrylate, di(ethylene glycol) methyl ether (meth)acrylate, tri(ethylene glycol) methyl ether (meth)acrylate, tetra(ethylene glycol) methyl ether (meth)acrylate, and combinations thereof. (meth)acrylamide, N,N-dimethyl (meth)acrylamide, N-vinylpyrroli-done (NVP), N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (meth)acrylamide, N-2-hydroxylethyl (meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl (meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide, 2-hydroxyethyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, glycerol methacrylate (GMA), di(ethylene glycol) (meth)acrylate, tri(ethylene glycol) (meth)acrylate, tetra(ethylene glycol) (meth)acrylate, poly(ethylene glycol) (meth)acrylate having a number average molecular weight of up to 1500, poly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, ethylene glycol methyl ether (meth)acrylate, di(ethylene glycol) methyl ether (meth)acrylate, tri(ethylene glycol) methyl ether (meth)acrylate, tetra(ethylene glycol) methyl ether (meth)acrylate, C1-C4-alkoxy poly(ethylene glycol) (meth)acrylate having a weight average molecular weight of up to 1500, methoxy-poly(ethylene glycol)ethyl (meth)acrylamide having a number average molecular weight of up to 1500, allyl alcohol, vinyl alcohol, and combinations thereof.

### Claim 6 (depends on 1)

The ophthalmic composition of claim 1, wherein the hydrophilic copolymer comprises (a) from about 1% to about 20% by mole of the arylborono-containing repeating units, (b) from about 60% to about 98% by mole of repeating units of at least one phosphorylcholine-containing vinylic monomer, and (c) from about 1% by mole to about 20% by mole of acrylic monomeric units of at least one acrylic monomer having 3 to 16 carbon atoms, provided that the sum of the mole percentages of components (a), (b) and (c) and other components not listed above is 100%.

### Claim 7 (depends on 1)

The ophthalmic composition according to claim 1, wherein the phosphate-modified galactomannan polymer is present in the ophthalmic composition at a concentration of from about 0.05 to about 3 w/v %.

### Claim 8 (depends on 1)

The ophthalmic composition according to claim 1, wherein the phosphate-modified galactomannan polymer is present in the ophthalmic composition at a concentration of from about 0.1 to about 1.0 w/v %.

### Claim 9 (depends on 1)

The ophthalmic composition according to claim 1, wherein the phosphate-modified galactomannan polymer is present in the ophthalmic composition at a concentration of from about 0.15 to about 0.25 w/v %.

### Claim 10 (depends on 1)

The ophthalmic composition of claim 1, wherein the composition has a pH value between 6.5 to 8.5.

### Claim 11 (depends on 1)

The ophthalmic composition of claim 1, wherein the ophthalmic composition comprises at least one cis-diol compound at a concentration that reduces (inhibits) cross-linking of the galactomannan polymer by the hydrophilic copolymer.

### Claim 12 (depends on 11)

The ophthalmic composition of claim 11, wherein the cis-diol compound is present at a concentration of from about 0.5 to about 5.0 w/v %.

### Claim 13 (depends on 11)

The ophthalmic composition according to claim 11, wherein the cis-diol compound is sorbitol, mannitol, propylene glycol, or combinations thereof.

### Claim 14 (depends on 1)

The ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises at least one demulcent selected from the group consisting of glycerin, polyvinyl pyrrolidone, polyethylene oxide, polyethylene glycol, polyethyleoxide-polybutyleneoxide block copolymer, polyethyleneoxide-polypropyleneoxide block copolymer, propylene glycol, polyacrylic acid, and combinations thereof.

### Claim 15 (depends on 14)

The ophthalmic composition of claim 14, wherein said at least one demulcent demulcent is propylene glycol and polyethylene glycol 400.

### Claim 16 (depends on 1)

The ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises an anesthetic drug, a glaucoma therapeutics, a pain reliever, an anti-hypertensive agent, a neuro-protective agent, muco-secretagogue, an angiostatic agent, an anti-angiogenesis agent, a growth factor, an immunosuppressant agent, an anesthetic drug, an anti-infective agent, an antiviral agent, an anti-inflammatory agent, an anti-angiogenesis agent, an anti-myopia agent, an anti-allergy agent, a dopaminergic antagonist, a protein, an anti-microbial, or combinations.

### Claim 17 (depends on 1)

The ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises a cooling agent, an antioxidant, a nutriceutical, or combinations thereof.

### Claim 18 (depends on 1)

The ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises omega-3 fatty acid, omega-6 fatty acid, vitamin A, vitamin D, vitamin E, tocopherols, vitamin K, beta-carotene, or combinations thereof.

### Claim 19 (depends on 1)

The ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises less than 0.1% W/V of borate.