US5145684A — Surface modified drug nanoparticles

Claim 1

Independent Claim 57 words

Particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier adsorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm.

Claim 2

Dependent Claim 57 words

Particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier adsorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm.

Claim 3

Dependent Claim 16 words

The particles of claim 1 having an effective average particle size of less than 250 nm.

Claim 4

Dependent Claim 16 words

The particles of claim 1 having an effective average particle size of less than 100 nm.

Claim 5

Dependent Claim 80 words

The particles of claim 1 wherein said drug substance is selected from analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, contrast media, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immuriological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin, prostaglandins, radio-pharmaceuticals, sex hormones, anti-allergic agents, stimulants, sympathomimetics, thyroid agents, vasodilators and xanthines.

Claim 6

Dependent Claim 12 words

The particles of claim 1 wherein said drug substance is a steroid.

Claim 7

Dependent Claim 75 words

Particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier absorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm, wherein said drug substance is selected from the group consisting of Danazol, 5α,17α,-1'-(methylsulfonyl)-1'H-pregn-20-yno-[3,2-c]-pyrazol-17-ol, piposulfam, piposulfan, camptothecin, and ethyl-3,5-diacetamido-2,4,6-triiodobenzoate.

Claim 8

Dependent Claim 75 words

Particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier absorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm, wherein said drug substance is selected from the group consisting of Danazol, 5α,17α,-1'-(methylsulfonyl)-1'H-pregn-20-yno-[3,2-c]-pyrazol-17-ol, piposulfam, piposulfan, camptothecin, and ethyl-3,5-diacetamido-2,4,6-triiodobenzoate.

Claim 9

Dependent Claim 79 words

The particles of claim 1 wherein said surface modifier is selected from the group consisting of gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glyceryl monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene caster oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidol silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethycellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, and polyvinylpyrrolidone.

Claim 10

Dependent Claim 40 words

The particles of claim 1 wherein said surface modifier is selected from the group consisting of polyvinylpyrrolidone, an ethylene oxide-propylene oxide block copolymer, lecithin, an alkyl aryl polyether sulfonate, gum acacia, sodium dodecylsulfate, and a dioctylester of sodium sulfosuccinic acid.

Claim 11

Dependent Claim 40 words

Particles consisitng essentially of 80-40% by weight of crystalline danazol having polyvinyl pyrrolidone adsorbed on the surface thereof in an amount of 20-60% by weight and sufficient to maintain an effective average particle size of less than about 100 nm.

Claim 12

Dependent Claim 40 words

Particles consisitng essentially of 80-40% by weight of crystalline danazol having polyvinyl pyrrolidone adsorbed on the surface thereof in an amount of 20-60% by weight and sufficient to maintain an effective average particle size of less than about 100 nm.

Claim 13

Dependent Claim 45 words

Particles consisting essentially of 99.9-10% by weight of crystalline 5α, 17α,-1'-(methylsulfonyl)-1'H-pregn-20-yno-pyrazol-17-ol having an ethylene oxide propylene-oxide block copolymer adsorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm.

Claim 14

Dependent Claim 45 words

Particles consisting essentially of 99.9-10% by weight of crystalline 5α, 17α,-1'-(methylsulfonyl)-1'H-pregn-20-yno-pyrazol-17-ol having an ethylene oxide propylene-oxide block copolymer adsorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm.

Claim 15

Dependent Claim 16 words

A stable dispersion consisting essentially of a liquid dispersion medium and the particles of claim 1.

Claim 16

Dependent Claim 11 words

The dispersion of claim 11 wherein said dispersion medium is water.

Claim 17

Dependent Claim 23 words

The dispersion of claim 11 wherein said dispersion medium is selected from the group consisting of safflower oil, ethanol, t-butanol, hexane and glycol.

Claim 18

Dependent Claim 15 words

A pharmaceutical composition comprising the particles of claim 1 and a pharmaceutically acceptable carrier therefor.

Claim 19

Dependent Claim 24 words

A method of treating a mammal comprising the step of administering to the mammal an effective amount of the pharmaceutical composition of claim 14.

Claim 20

Dependent Claim 70 words

A method of preparing the particles of claim 1 comprising the steps of dispersing a drug substance in a liquid dispersion medium and wet grinding said drug substance in the presence of rigid grinding media having an average particle size of less than 3 mm and a surface modifier to reduce the particle size of said drug substance to an effective average particle size of less than about 400 nm.

Claim 21

Dependent Claim 77 words

A method of preparing the particles of claim 1 comprising the steps of dispersing a drug substance in a liquid dispersion medium, wet grinding said drug substance in the presence of rigid grinding media having an average particle size of less than 3 mm, thereafter contacting said drug substance with a surface modifier by mixing said surface modifier with said dispersion medium to form particles having an effective average particle size of less than about 400 nm.

Claim 22

Dependent Claim 25 words

The method of claim 17 further including the step of subjecting the dispersion medium containing said drug substance and said surface modifier to ultrasonic energy.

Claim 23

Dependent Claim 19 words

The method of claim 16 wherein said grinding media have an average particle size of less than 1 mm.

Claim 24

Dependent Claim 18 words

The method of claim 16 wherein said grinding media have a density greater than 3 g/cm 3 .

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1995-09-08	1996-03-09	1996-09-08	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1999-09-08	2000-03-09	2000-09-08	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2003-09-08	2004-03-09	2004-09-08	$7700.00	Window Closed / Lapsed

Surface modified drug nanoparticles

Abstract

Inventors

Bibliographic Details

Claims Analysis

References Cited (Backward Citations)

USPTO Annuity & Maintenance Windows

Assigned Categories & Tags

Assign Category Tag