Enzyme delivery systems and methods of preparation and use

• US 10,098,844 B2
• Filed: 10/23/2015
• Issued: 10/16/2018
• Est. Priority Date: 04/13/2009
• Status: Active Grant

• Current Assignee: Curemark LLC
• Original Assignee: Curemark LLC
• Inventors: Fallon, Joan M., Heil, Matthew
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): Dutt, Aditi
• Application Number:
  US14/921,896
• Publication Number:
  US 20160045576A1
• Time in Patent Office: 1,089 Days
• Field of Search: None
• CPC Class Codes: A23L 33/17 Amino acids, peptides or proteins
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61J 15/00 Feeding-tubes for therapeutic purposes
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/48 acting on peptide bonds (3.4)
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 38/54 Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/009 Sachets, pouches characterised by the material or function of the envelope with gastric retention A61K9/0065; sachets which are not administered but function merely as a container are classified according to the content, e.g. sachets comprising powder for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5063 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/5015
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 : 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 Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Y 301/01003 : Triacylglycerol lipase (3.1.1.3)
• CPC Class Codes: C12Y 302/01 : Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
• CPC Class Codes: C12Y 304/21001 : Chymotrypsin (3.4.21.1)
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1. A method of preparing a coated controlled-release digestive enzyme preparation having enhanced flow properties, the method comprising:

(a) screening uncoated digestive enzyme particles to obtain screened digestive enzyme particles of a suitable size for coating, wherein the digestive enzyme particles comprise digestive enzymes, and wherein the digestive enzymes comprise a protease, an amylase, and a lipase; and

(b) coating the screened digestive enzyme particles with a lipid to form coated digestive enzyme particles, wherein the coated digestive enzyme particles comprise a core that comprises the digestive enzymes and a coating that comprises the lipid, and wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of from about 75% to about 85% by weight.

2. The method of claim 1, wherein screening uncoated digestive enzyme particles comprises sieving the uncoated digestive enzyme particles with a #40 USSS mesh and a #140 USSS mesh.

3. The method of claim 1, wherein the lipid comprises a hydrogenated soy oil.

4. The method of claim 1, wherein coating comprises a spray process.

5. The method of claim 1, wherein the lipid comprises a sorbitan monostearate, a sorbitan tristearate, or a calcium stearoyl lactylate.

6. A method of preparing a coated controlled-release digestive enzyme preparation, the method comprising:

(a) obtaining digestive enzyme particles ranging from about 105 to 450 microns in size, wherein the digestive enzyme particles comprise digestive enzymes, and wherein the digestive enzymes comprise a protease, an amylase, and a lipase; and

(b) coating the digestive enzyme particles with a lipid to form coated digestive enzyme particles, wherein the coated digestive enzyme particles comprise a core that comprises the digestive enzymes and a coating that comprises the lipid, and wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of from about 75% to about 85% by weight.

7. The method of claim 6, wherein obtaining digestive enzyme particles ranging from about 105 to 450 microns in size comprises sieving the digestive enzyme particles with a #40 USSS mesh and a #140 USSS mesh.

8. The method of claim 6, wherein the lipid comprises a hydrogenated soy oil.

9. The method of claim 6, wherein coating comprises a spray process.

10. The method of claim 6, wherein the lipid comprises a sorbitan monostearate, a sorbitan tristearate, or a calcium stearoyl lactylate.

11. A method of preparing a coated controlled-release digestive enzyme preparation, the method comprising:

(a) blending a lipid with one or more additives to obtain a lipid blend;

(b) obtaining screened digestive enzyme particles, wherein the screened digestive enzyme particles comprise digestive enzymes, and wherein the digestive enzymes comprise a protease, an amylase, and a lipase;

(c) coating the screened digestive enzyme particles with the lipid blend in a spray process to form coated digestive enzyme particles, wherein the coated digestive enzyme particles comprise a core that comprises the digestive enzymes and a coating that comprises the lipid blend, and wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of from about 75% to about 85% by weight; and

(d) adjusting batch and oil temperatures during the spray process at periodic time intervals, whereby optimal spray conditions are maintained during said spray process.

12. The method of claim 11, wherein the screened digestive enzyme particles are a size ranging from about 105 to about 450 microns.

13. The method of claim 11, wherein obtaining screened digestive enzyme particles comprises sieving the digestive enzyme particles through a #40 USSS mesh and through a #140 USSS mesh.

14. The method of claim 11, wherein obtaining screened digestive enzyme particles comprises sieving the digestive enzyme particles through a #40 USSS mesh and through a #80 USSS mesh.

15. The method of claim 11, wherein at least 90% of the screened digestive enzyme particles are sieved from about #40 USSS mesh to about #80 USSS mesh in size.

16. The method of claim 11, wherein at least 75% of the screened digestive enzyme particles are sieved from about #40 USSS mesh to about #80 USSS mesh in size.

17. The method of claim 11, wherein obtaining screened digestive enzyme particles comprises sieving the digestive enzyme particles to obtain screened digestive enzyme particles that are from about 105 to about 450 microns in size.

18. The method of claim 11, wherein a temperature of the lipid blend is maintained at about 110°

F. before coating the screened digestive enzyme particles.

19. The method of claim 11, wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of about 75% by weight.

20. The method of claim 11, wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of about 77.5% by weight.

21. The method of claim 11, wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of about 80% by weight.

22. The method of claim 11, wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of about 82.5% by weight.

23. The method of claim 11, wherein the digestive enzymes are present in the coated digestive enzyme particles in an amount of about 85% by weight.

24. The method of claim 11, wherein the lipid comprises a sorbitan monostearate, a sorbitan tristearate, or a calcium stearoyl lactylate.

25. The method of claim 11, wherein the lipid comprises at least one hydrophilic group and at least one hydrophobic group.

26. The method of claim 11, wherein the lipid comprises an animal lipid or a vegetable lipid.

27. The method of claim 11, wherein the lipid is selected from the group consisting of palm kernel oil, cottonseed oil, canola oil, poultry fat, hydrogenated castor wax, and carnauba wax.

28. The method of claim 11, wherein the lipid is hydrogenated, saturated, or partially saturated.

29. The method of claim 11, wherein the lipid is selected from the group consisting of monoglycerides, diglycerides, fatty acids, esters of fatty acids, phospholipids, salts thereof, and a combination thereof.

30. The method of claim 29, 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.