Solid compositions of triglycerides and uses thereof

Patent metadata

Field	Value
Publication number	US-2016243071-A1
Application number	US-201414419601-A
Country	US
Kind code	A1
Filing date	Nov 14, 2014
Priority date	Nov 14, 2013
Publication date	Aug 25, 2016
Grant date	—

Abstract

The present invention includes solid compositions of triglycerides with one or more fatty acids, such as triheptanoin and glycerol phenylbutyrate, and therapeutic use thereof. The solid compositions can be prepared by spray-drying or other processes.

First claim

What is claimed is:

1 . A solid composition comprising triglycerides with one or more fatty acids as an active ingredient and a solid substance;
wherein the active ingredient has purity greater than 95% and the solid composition comprises at least about 50% by weight the triglycerides.

2 . The solid composition of claim 1 , wherein the one or more fatty acids are one or more odd-numbered carbon fatty acids selected from the group consisting of C5, C7, C9, C11, C13, C15, and any combinations thereof; and wherein the active ingredient has purity greater than 98%.

3 . The solid composition of claim 2 , wherein the triglycerides comprise triheptanoin oil.

4 . The solid composition of claim 1 , wherein the one or more fatty acids are one or more phenylalkanoic acids and/or phenylalkenoic acids.

5 . The solid composition of claim 4 , wherein the triglycerides comprise a compound of formula (I):

wherein R 1 , R 2 , and R 3 are independently H,

and n is zero or an even number from 2-24 and m is an even number from 2-24, with the proviso that at least one of R 1 , R 2 , and R 3 is other than H.

6 . The solid composition of claim 5 , wherein the compound is glycerol phenylbutyrate.

7 . The solid composition of any one of claims 1 - 6 , which comprises at least about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, or about 90% of the active ingredient by weight of the composition.

8 . The solid composition of any one of claims 1 - 7 , wherein the solid substance comprises a solid carrier.

9 . The solid composition of claim 8 , wherein the solid carrier is a fumed silica.

10 . The solid composition of claim 8 , wherein the solid carrier is selected from the group consisting of SiO 2 , TiO 2 , Al 2 O 3 , zeolites, Cab-O-Sil, and combinations thereof.

11 . The solid composition of any of the preceding claims, wherein the solid substance further comprises one or more sustained release polymers.

12 . The solid composition of claim 11 , wherein the sustained release polymer is a film-forming, water insoluble polymer.

13 . The solid composition of claim 12 , wherein the film-forming, water insoluble polymer is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose propionate (lower, medium or higher molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate), poly(isobutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate), poly(ethylene), poly(ethylene) low density, poly(ethylene) high density, poly(propylene), poly(ethylene oxide), poly(ethylene terephthalate), poly(vinyl isobutyl ether), poly(vinyl acetate), poly(vinyl chloride) or polyurethane, or mixtures thereof.

14 . The solid composition of claim 13 , wherein the film-forming, water insoluble polymer is cellulose acetate.

15 . The solid composition of claim 11 , wherein the one or more sustained release polymer comprises one or more pH dependent polymers.

16 . The solid composition of claim 15 , wherein the pH dependent polymer is selected from a group consisting of a methyl acrylate-methacrylic acid copolymer, a cellulose acetate succinate, a hydroxy propyl methyl cellulose phthalate, a hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), a polyvinyl acetate phthalate (PVAP), a methyl methacrylate-methacrylic acid copolymer, alginate and stearic acid, and any combinations thereof.

17 . The solid composition of any of the preceding claims, which is in form of a powder.

18 . The solid composition of claim 17 , which comprises, by weight of the composition,
about 50% to about 80% of the active ingredient; about 10% to about 30% of the solid carrier; and about 10% to about 30% of the sustained release polymer.

19 . The solid composition of claim 18 , wherein the active ingredient, the solid carrier, and the sustained release polymer are in a weight ratio of about 2:1:1.

20 . The solid composition of claim 17 , wherein the powder comprises particles having an average diameter of less than about 10 micron.

21 . The solid composition of claim 20 , wherein the particles have an average diameter of less than about 9 microns, less than about 8 microns, less than about 7 microns, less than about 6 microns, less than about 5 microns, less than about 4 microns, less than about 3 microns, less than about 2 microns, less than about 1000 nm, less than about 900 nm, less than about 800 run, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 290 nm, less than about 280 nm, less than about 270 nm, less than about 260 nm, less than about 250 nm, less than about 240 nm, less than about 230 nm, less than about 220 nm, less than about 210 nm, less than about 200 nm, less than about 190 nm, less than about 180 nm, less than about 170 nm, less than about 160 nm, less than about 150 nm, less than about 140 nm, less than about 130 nm, less than about 120 nm, less than about 110 nm, less than about 100 nm, less than about 90 nm, less than about 80 nm, less than about 70 nm, less than about 60 nm, less than about 50 nm, less than about 40 nm, less than about 30 nm, less than about 20 nm, less than about 10 nm, less than about 9 nm, less than about 8 nm, less than about 7 nm, less than about 6 nm, or less than about 5 nm.

22 . A solid composition comprising a plurality of solid particles, each particle comprising triglycerides with one or more fatty acids as an active ingredient adsorbed onto a solid substance;
wherein the active ingredient has purity greater than 95% and the solid composition comprises at least about 50% by weight the triglycerides.

23 . The solid composition of claim 22 , wherein the one or more fatty acids are one or more odd-numbered carbon fatty acids selected from the group consisting of C5, C7, C9, C11, C13, C15, and any combinations thereof; and wherein the active ingredient has purity greater than 98%.

24 . The solid composition of claim 23 , wherein the triglycerides comprise triheptanoin oil.

25 . The solid composition of claim 22 , wherein the one or more fatty acids are one or more phenylalkanoic acids and/or phenylalkenoic acids.

26 . The solid composition of claim 25 , wherein the triglycerides comprise a compound of formula (I):

wherein R 1 , R 2 , and R 3 are independently H,

and n is zero or an even number from 2-24 and m is an even number from 2-24, with the proviso that at least one of R 1 , R 2 , and R 3 is other than H.

27 . The solid composition of claim 26 , wherein the compound is glycerol phenylbutyrate.

28 . The solid comp

Assignees

• Klopp John
• Morris Gabrielle
• Kakkis Emil
• Ultragenyx Pharmaceutical Inc

Inventors

• Klopp John
• Morris Gabrielle
• Kakkis Emil
• Jungles Steven

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61K31/23 Primary

  of acids having a carboxyl group bound to a chain of seven or more carbon atoms · CPC title

• A61K9/1611

  Inorganic compounds · CPC title