Enzyme delivery systems and methods of preparation and use

Patent metadata

Field	Value
Publication number	US-9415014-B2
Application number	US-201113193346-A
Country	US
Kind code	B2
Filing date	Jul 28, 2011
Priority date	Apr 13, 2009
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

This invention relates to coated digestive enzyme preparations and enzyme delivery systems and pharmaceutical compositions comprising the preparations. This invention further relates to methods of preparation and use of the systems, pharmaceutical compositions and preparations to treat persons having ADD, ADHD, autism, cystic fibrosis and other behavioral and neurological disorders.

First claim

What is claimed is:

1. A coated free-flowing particulate digestive enzyme preparation, comprising particles that comprise:
(a) a core comprising digestive enzymes, wherein the digestive enzymes comprise a protease, an amylase and a lipase; and
(b) a coating comprising an emulsifiable lipid, wherein the coating coats the core and the emulsifiable lipid emulsifies upon exposure to a solvent;
wherein the digestive enzymes are present in an amount of from 77.5-82.5% by weight of the particles, and
wherein the coating masks the taste and smell of the digestive enzymes.

2. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the coated free-flowing particulate digestive enzyme preparation provides a therapeutically effective amount of the digestive enzymes to treat a subject suffering from autism, Attention Deficit Disorder (ADD), or Attention Deficit Hyperactivity Disorder (ADHD).

3. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the core is from about 105 μm to about 425 μm.

4. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the core is sieved from about 40 mesh to about 140 mesh.

5. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the preparation is non-aerosolizable.

6. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid is selected from the group consisting of hydrogenated soy oil, hydrogenated castor wax, and carnauba wax.

7. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein about 80% of the digestive enzymes are released by 30 minutes in a dissolution test performed at pH 6.0.

8. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the coating consists essentially of the emulsifiable lipid that is one or more monoglycerides.

9. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid comprises monoglycerides.

10. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein at least 90% of the particles are sieved from about #40 to about #140 mesh in size.

11. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein less than 20%, or less than 15%, of the particles can be sieved through #100 mesh.

12. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid comprises at least one hydrophilic group and at least one hydrophobic group.

13. The coated free-flowing particulate digestive enzyme preparation of claim 12 , wherein the emulsifiable lipid is capable of forming a hydrophilic and hydrophobic interface.

14. The coated free-flowing particulate digestive enzyme preparation of claim 13 , wherein the interface is a micelle interface.

15. The coated free-flowing particulate digestive enzyme preparation of claim 13 , wherein the interface is a bilayer interface.

16. The coated free-flowing particulate digestive enzyme preparation of claim 12 , wherein the emulsifiable lipid is obtained from animal or vegetable origins.

17. The coated free-flowing particulate digestive enzyme preparation of claim 16 , wherein the emulsifiable lipid is selected from the group consisting of palm kernel oil, soybean oil, cottonseed oil, canola oil, poultry fat, hydrogenated soy oil, hydrogenated castor wax, and carnauba wax.

18. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid is hydrogenated, saturated or partially saturated.

19. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid consists of hydrogenated soy oil.

20. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid is selected from the group consisting of monoglycerides, diglycerides, fatty acids, esters of fatty acids, phospholipids, salts thereof, and combinations thereof.

21. The coated free-flowing particulate digestive enzyme preparation of claim 20 , comprising the esters of fatty acids, wherein the esters of fatty acids are selected from the group consisting of acetic acid esters of mono- and diglycerides, citric acid esters of mono- and diglycerides, lactic acid esters of mono- and diglycerides, polyglycerol esters of fatty acids, propylene glycol esters of fatty acids, and diacetyl tartaric acid esters of mono- and diglycerides.

22. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid is a food grade emulsifiable lipid.

23. The coated free-flowing particulate digestive enzyme preparation of claim 22 , wherein the food grade emulsifiable lipid comprises sorbitan monostearates, sorbitan tristearates, or calcium stearoyl lactylates.

24. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the core is processed by a technique selected from the group consisting of encapsulation, compression, extrusion and molding.

25. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein at least 75% of the particles are sieved from about #40 to about #80 mesh in size.

26. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the emulsifiable lipid comprises hydrogenated soy oil.

27. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the coating consists essentially of the emulsifiable lipid that is hydrogenated soy oil.

28. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the digestive enzymes have a protease activity of not less than 156 USP units/mg.

29. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein the core comprises the digestive enzymes present in an amount of 80% by weight of the particles.

30. The coated free-flowing particulate digestive enzyme of claim 1 , wherein at least 90% of the particles are from about 105 to about 425 μm.

31. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein less than 20% of the particles can be sieved through about 150 μm mesh.

32. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein less than 15% of the particles can be sieved through about 150 μm mesh.

33. The coated free-flowing particulate digestive enzyme preparation of claim 1 , wherein at least 75% of the particles are from about 180 to about 425 μm.

34. The coated free-flowing particulate digestive enzyme preparation of claim 1 or 27 , wherein the digestive enzymes are a pancreatin composition.

35. A pharmaceutical composition comprising a therapeutically effective amount of a coated free-flowing particulate digestive enzyme preparation, wherein the preparation comprises particles that comprise:
a core comprising digestive enzymes, wherein the digestive enzymes comprise a protease, an amylase and a lipase; and,
a coating comprising an emulsifiable lipid, wherein the coating coats the core and the emulsifiable lipid emulsifies upon exposure to a solvent;
wherein the digestive enzymes are p

Assignees

• Fallon Joan M
• Heil Matthew
• Curemark Llc

Inventors

• Fallon Joan M
• Heil Matthew

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P3/00

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