Brain-penetrating ligand and drug carrier

Patent metadata

Field	Value
Publication number	US-12246071-B2
Application number	US-201917419068-A
Country	US
Kind code	B2
Filing date	Dec 27, 2019
Priority date	Dec 27, 2018
Publication date	Mar 11, 2025
Grant date	Mar 11, 2025

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

The invention claimed is:

1. A method for treating 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 the derivative thereof to a patient in need of administration of the drug into a brain,
wherein the lactose-modified cyclodextrin or the derivative thereof is selected from a group consisting of a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin and a lactose-modified hydroxypropyl-β-cyclodextrin.

2. The method according to claim 1 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

3. The method according to claim 2 , wherein the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is one in which at least the dendrimer molecule is modified with lactose.

4. The method according to claim 2 , wherein a degree of substitution of cyclodextrin against dendrimer in the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is about 1 to 10.

5. The method according to claim 1 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified hydroxypropyl-β-cyclodextrin.

6. The method according to claim 1 , 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.

7. The method according to claim 1 , 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.

8. A carrier for a drug delivery into a brain comprising a lactose-modified cyclodextrin or a derivative thereof,
wherein the lactose-modified cyclodextrin or the derivative thereof is selected from a group consisting of a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin and a lactose-modified hydroxypropyl-β-cyclodextrin.

9. The carrier for drug delivery according to claim 8 , wherein the lactose-modified cyclodextrin or the derivative thereof is the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

10. The carrier for drug delivery according to claim 8 , wherein the lactose-modified cyclodextrin or the derivative thereof is the lactose-modified hydroxypropyl-β-cyclodextrin.

11. The carrier for drug delivery according to claim 9 , wherein a degree of substitution of cyclodextrin against dendrimer in the lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin is about 1 to 10.

12. 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,
wherein the lactose-modified cyclodextrin or the derivative thereof is selected from the group consisting of a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin, and a lactose-modified hydroxypropyl-β-cyclodextrin.

13. The pharmaceutical composition according to claim 12 , wherein the pharmaceutical composition is provided for treating or preventing a neurological disease or disorder.

14. The pharmaceutical composition according to claim 13 , 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.

15. A brain-penetrating ligand for delivering a drug into a brain of subject, comprising a lactose-modified cyclodextrin or a derivative thereof, wherein the lactose-modified cyclodextrin or the derivative thereof is selected from the group consisting of a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin, and a lactose-modified hydroxypropyl-β-cyclodextrin.

16. The brain-penetrating ligand according to claim 15 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin.

17. The brain-penetrating ligand according to claim 15 , wherein the lactose-modified cyclodextrin or the derivative thereof is a lactose-modified hydroxypropyl-β-cyclodextrin.

18. The brain-penetrating ligand according to claim 15 , wherein a degree of substitution of lactose against cyclodextrin or dendrimer in the lactose-modified cyclodextrin or the derivative thereof is about 1 or more.

19. A pharmaceutical composition comprising:
a brain-penetrating ligand for delivering a drug into a brain of subject, the brain-penetrating ligand comprising a lactose-modified dendrimer/glucuronyl glucosyl-β-cyclodextrin or a lactose-modified hydroxypropyl-β-cyclodextrin; and
a drug.

20. The pharmaceutical composition according to claim 19 , wherein the pharmaceutical composition is provided for treating or preventing a neurological disease or disorder.

21. The pharmaceutical composition according to claim 20 , 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

• C08B37/0015

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

• 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

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title