Enzyme Delivery Systems and Methods of Preparation and Use

• US 20150150955A1
• Filed: 02/03/2015
• Published: 06/04/2015
• Est. Priority Date: 04/13/2009
• Status: Active Grant

• Current Assignee: Curemark LLC
• Original Assignee: Curemark LLC
• Inventors: Fallon, Joan M., Heil, Matthew
• Granted Patent: US 9,931,302 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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

1-59. -59. (canceled)

60. A pancreatin pellet consisting of pancreatin, which pellet contains no auxiliary substances and binding agents.

61. The pancreatin pellet according to claim 60, wherein the pellet is a micropellet.

62. The pancreatin pellet according to claim 60, wherein the pancreatin is obtained from the pancreas of a mammal.

69. The pancreatin pellet according to claim 60, wherein the pellet has a spherical, elliptical or drop-like shape, and wherein the diameter of the sphere or the shorter axis lies in the range of 0.4 to 0.8 mm.

63. A pancreatin pellet comprising a core and a coating, wherein the core consists of pancreatin.

64. The pancreatin pellet according to claim 63, wherein the coating comprises pancreatin.

65. The pancreatin pellet according to claim 63, wherein the coating comprises auxiliary substances and binding agents.

66. The pancreatin pellet according to claim 63, wherein the coating has a first inner layer which surrounds the core consisting of pancreatin, and a second, outer layer.

67. The pancreatin pellet according to claim 66, wherein the first layer comprises of auxiliary substances and binding agents.

68. The pancreatin pellet according to claim 66, wherein the second layer comprises a material that is resistant to gastric juices, and wherein the pellet has a drop-like or spherical shape.

70. A pharmaceutical composition, comprising a pharmacologically active quantity of pancreatin pellets which consist of pancreatin, which pellets contain no auxiliary substances and binding agents.

71. The pharmaceutical composition according to claim 70, in a dosage form that is suitable for oral administration.

72. A method of producing a pellet and/or micropellet consisting of pancreatin, which pellet contains no auxiliary substances and binding agents, comprising the steps of:

a.) comminuting the pancreases of pigs or cattle and conducting autolysis;

b.) obtaining a sieved filtrate by filtration of the intermediate product obtained in step a);

c.) precipitating the enzymes from the sieved filtrate;

d.) filtering the mixtures obtained in step c) to obtain a filter cake;

e.) grinding and vacuum-drying the filter cake until a residual moisture of 0.1 to 0.3% by weight is obtained, whereby the pancreatin product with 0.1 to 0.3% by weight of residual moisture constitutes the dried end product;

whereas the extrudable filter cake mass contains more residual moisture and/or organic solvent residues, which are of the order of 50%;

f.) thermally treating the filter cake at 80°

C. or at a temperature below 80°

C.;

g.) extruding the thermally treated filter cake having sufficient plasticity and having no additives and/or binding agents in order to form strands;

h.) spheronising the extrusion of step g) without additives and/or binding agents or auxiliary substances so as to obtain spherical, elliptical or drop-shaped pellets.

73. A digestive enzyme particle consisting of pancreatin, wherein the particle contains no additives, extenders, colorants, dyes, or flow enhancers.

74. The digestive enzyme particle according to claim 73, wherein the particle is about 105-425 pm in size.

75. The digestive enzyme particle according to claim 73, wherein the pancreatin is obtained from the pancreas of a mammal.

82. The digestive enzyme particle according to claim 73, wherein the particle has a round surface, and wherein the particle is about 105-425 μ

m in size.

76. A digestive enzyme preparation comprising a core and a coating, wherein the core consists of pancreatin.

77. The digestive enzyme preparation according to claim 76, wherein the coating comprises pancreatin.

78. The digestive enzyme preparation according to claim 76, wherein the coating comprises hypromellose phthalate, dimethicone 1000, and dibutyl phthalate, monoglycerides, or an emulsifiable lipid.

79. The digestive enzyme preparation according to claim 76, wherein the coating has a first inner layer which surrounds the core consisting of pancreatin, and a second, outer layer.

80. The digestive enzyme preparation according to claim 79, wherein the first layer comprises hypromellose phthalate, dimethicone 1000, and dibutyl phthalate, monoglycerides, or an emulsifiable lipid.

81. The digestive enzyme preparation according to claim 79, wherein the second layer comprises a material that is resistant to HCl present in the stomach, and wherein the digestive enzyme preparation has round surfaces and is free-flowing.

83. A pharmaceutical composition, comprising a therapeutically effective amount of digestive enzyme particles which consist of pancreatin, wherein the particles contain no additives, extenders, colorants, dyes, or flow enhancers.

84. The pharmaceutical composition according to claim 83, in a dosage form that is suitable for oral administration.

85. A method of producing a digestive enzyme preparation comprising digestive enzyme particles, wherein the particles contains no additives, comprising the steps of:

a.) obtaining unprocessed, raw enzyme preparation;

b.) screening or filtering uncoated particles to obtain particles of suitable size;

c.) obtaining sieved particles of suitable size and shape.