Brain-penetrating ligand and drug carrier

Patent metadata

Field	Value
Publication number	US-2022072150-A1
Application number	US-201917419068-A
Country	US
Kind code	A1
Filing date	Dec 27, 2019
Priority date	Dec 27, 2018
Publication date	Mar 10, 2022
Grant date	—

Abstract

An exemplary substance is provided that permeates the blood-brain barrier and shows a property of penetrating into the brain. Further, exemplary use of the substance as a drug carrier is provided for delivering into the brain, and a pharmaceutical composition containing the substance. Additionally, exemplary lactose-modified cyclodextrin or dendrimer/glucuronyl glucosyl-cyclodextrin is provided that permeates the blood-brain barrier and shows a property of penetrating into the brain. Exemplary blood-brain barrier permeable pharmaceutical composition is also provided which comprises a lactose-modified cyclodextrin or dendrimer/glucuronyl glucosyl-cyclodextrin, and a drug.

First claim

1 - 33 . (canceled)

34 . A method for treating or preventing a neurological disease or disorder comprising administering a composition comprising (i) a lactose-modified cyclodextrin or a derivative thereof and (i) a drug encapsulated in the lactose-modified cyclodextrin or a derivative thereof to a patient in need of administration of the drug into a brain.

35 . The method according to claim 34 , wherein the lactose-modified cyclodextrin or the derivative thereof is selected from a group consisting of a lactose-modified β-cyclodextrin, a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin, and a lactose-modified hydroxypropyl-β-cyclodextrin.

36 . The method according to claim 34 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

37 . The method according to claim 36 , wherein the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is one in which at least the dendrimer molecule is modified with lactose

38 . The method according to claim 36 , wherein a degree of substitution of cyclodextrin against dendrimer in the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is about 1 to 10.

39 . The method according to claim 34 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified hydroxypropyl-β-cyclodextrin.

40 . The method according to claim 34 , wherein a degree of substitution of lactose against cyclodextrin or dendrimer in the lactose-modified cyclodextrin or a derivative thereof is about 1 or more.

41 . The method according to claim 34 , wherein the neurological disease or disorder is selected from the group consisting of Alzheimer's disease, cerebral stroke, cerebral ischemia, dementia, muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis, cystic fibrosis, Angelman's syndrome, Riddle Syndrome, myasthenia gravis, spinal muscle atrophy, Down's syndrome, Parkinson's disease, Huntington's disease, schizophrenia, depression, Tauopathy disease, Pick's disease, Paget's disease, lysosome disease accompanied by brain damage, cancer, prion's disease, traumatic brain injury, and viral or bacterial central nervous system disorders.

42 . A carrier for a drug delivery into a brain comprising a lactose-modified cyclodextrin or a derivative thereof.

43 . The carrier for drug delivery according to claim 42 , wherein the lactose-modified cyclodextrin or the derivative thereof is selected from the group consisting of a lactose-modified β-cyclodextrin, a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin, and a lactose-modified hydroxypropyl-β-cyclodextrin.

44 . The carrier for drug delivery according to claim 42 , wherein the lactose-modified cyclodextrin or a derivative thereof is a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

45 . The carrier for drug delivery according to claim 42 , wherein the lactose-modified cyclodextrin or a derivative thereof is a lactose-modified hydroxypropyl-β-cyclodextrin.

46 . The carrier for drug delivery according to claim 42 , wherein a degree of substitution of cyclodextrin against dendrimer in the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is about 1 to 10.

47 . A pharmaceutical composition comprising:
a carrier for drug delivery into a brain, the carrier comprising a lactose-modified cyclodextrin or a derivative thereof; and a drug.

48 . The pharmaceutical composition according to claim 47 , wherein the pharmaceutical composition is provided for treating or preventing a neurological disease or disorder.

49 . The pharmaceutical composition according to claim 48 , wherein the neurological disease or disorder is selected from the group consisting of Alzheimer's disease, cerebral stroke, cerebral ischemia, dementia, muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis, cystic fibrosis, Angelman's syndrome, Riddle Syndrome, myasthenia gravis, spinal muscle atrophy, Down's syndrome, Parkinson's disease, Huntington's disease, schizophrenia, depression, Tauopathy disease, Pick's disease, Paget's disease, lysosome disease accompanied by brain damage, cancer, prion's disease, traumatic brain injury, and viral or bacterial central nervous system disorders.

50 . A brain-penetrating ligand for delivering a drug into a brain of subject, comprising:
lactose which is part of a molecule of the brain-penetrating ligand, wherein the brain-penetrating ligand has a binding affinity to a transporter or a receptor that recognizes a lactose expressed in brain endothelial cells.

51 . The brain-penetrating ligand according to claim 50 , wherein the brain-penetrating ligand is a lactose-modified cyclodextrin or a derivative thereof.

52 . The brain-penetrating ligand according to claim 51 , wherein the lactose-modified cyclodextrin or a derivative thereof is selected from the group consisting of a lactose-modified β-cyclodextrin, a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin, and a lactose-modified hydroxypropyl-β-cyclodextrin.

53 . The brain-penetrating ligand according to claim 51 , wherein the lactose-modified cyclodextrin or a derivative thereof is a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

54 . The brain-penetrating ligand according to claim 51 , wherein the lactose-modified cyclodextrin or a derivative thereof is a lactose-modified hydroxypropyl-β-cyclodextrin.

55 . The brain-penetrating ligand according to claim 51 , wherein a degree of substitution of the brain-penetrating lactose against cyclodextrin or dendrimer in the lactose-modified cyclodextrin or a derivative thereof is about 1 or more.

56 . A pharmaceutical composition comprising:
a brain-penetrating ligand for delivering a drug into a brain of subject, the brain-penetrating ligand comprising lactose which is part of a molecule of the brain-penetrating ligand, wherein the brain-penetrating ligand has a binding affinity to a transporter or a receptor that recognizes a lactose expressed in brain endothelial cells; and a drug.

57 . The pharmaceutical composition according to claim 56 , wherein the pharmaceutical composition is provided for treating or preventing a neurological disease or disorder.

58 . The pharmaceutical composition according to claim 57 , wherein the neurological disease or disorder is selected from the group consisting of Alzheimer's disease, cerebral stroke, cerebral ischemia, dementia, muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis, cystic fibrosis, Angelman's syndrome, Riddle Syndrome, myasthenia gravis, spinal muscle atrophy, Down's syndrome, Parkinson's disease, Huntington's disease, schizophrenia, depression, Tauopathy disease, Pick's disease, Paget's disease, lysosome disease accompanied by brain damage, cancer, prion's disease, traumatic brain injury, and viral or bacterial central nervous system disorders.

Assignees

• Univ Kumamoto Nat Univ Corp
• Japan Maize Prod

Inventors

• Arima Hidetoshi
• Motoyama Keiichi
• Higashi Taishi
• Onodera Risako
• Yokoyama Ryoma

Classifications

• C08B37/0012

  Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof · CPC title

• C08B37/0015

  Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P31/12

  Antivirals · CPC title

• 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