Isolated nanosheet and production method thereof

Patent metadata

Field	Value
Publication number	US-11957796-B2
Application number	US-201917258953-A
Country	US
Kind code	B2
Filing date	Jul 10, 2019
Priority date	Jul 11, 2018
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present invention provides isolated nanosheets each of which includes a plurality of pseudo-polyrotaxanes and which are easily isolated without adhering to each other. The present invention provides an isolated nanosheet including a plurality of pseudo-polyrotaxanes each having one or more first cyclic molecules and a linear molecule included in a cavity or cavities of the first cyclic molecules in a skewered manner, wherein the linear molecules include, as part thereof, first linear molecules each having an ionizable group that ionizes in water or an aqueous solution.

First claim

The invention claimed is:

1. An isolated nanosheet comprising a plurality of pseudo-polyrotaxanes and/or polyrotaxanes each having one or more first cyclic molecules and one or more linear molecules included in a cavity of at least one of the one or more first cyclic molecules in a skewered manner,
wherein the one or more linear molecules include, as part thereof, first linear molecules each having an ionizable group that ionizes in water or an aqueous solution,
each of the first linear molecules is (i) a linear molecule including a linear polymer formed of only one type of repeating unit or (ii) a block copolymer including at least three blocks,
when each of the first linear molecules is (i) the linear molecule including the linear polymer formed of only one type of repeating unit, the linear polymer includes polyethylene glycol (PEG) and at least one of the first cyclic molecules is a cyclodextrin,
when each of the first linear molecules is (i) the linear molecule including a linear polymer formed of only one type of repeating unit, the inclusion ratio of the pseudo-polyrotaxanes and/or the polyrotaxanes is at least 95% when the specified inclusion ratio is set to 100%,
when each of the first linear molecules is (ii) the block copolymer including at least three blocks, the block polymer includes PEO-PPO-PEO and at least one of the first cyclic molecules is a cyclodextrin, and
when each of the first linear molecules is (ii) the block copolymer including at least three blocks, the inclusion ratio of the pseudo-polyrotaxanes and/or the polyrotaxanes is at least 10% when the specified inclusion ratio is set to 100%.

2. The isolated nanosheet according to claim 1 , wherein the first linear molecules each have the ionizable group at or near at least one end thereof.

3. The isolated nanosheet according to claim 1 , wherein the first linear molecules each have the ionizable group at or near each of both ends thereof.

4. The isolated nanosheet according to claim 1 , wherein the ionizable group is at least one kind selected from the group consisting of a carboxyl group, an amino group, a sulfo group, a phosphoric acid group, a trimethylamine hydrochloride group, a trimethylamine hydrochloride group, a dimethylamino group, a diethylamino group, a methylamino group, an ethylamino group, a pyrrolidine group, a pyrrole group, an ethyleneimine group, a piperidine group, a pyridine group, a pyrylium ion group, a thiopyrylium ion group, a hexamethyleneimine group, an azide group, an imidazole group, a pyrazole group, an oxazole group, a thiazole group, an imidazoline group, a morpholine group, a thiazine group, a triazole group, a tetrazole group, a pyridazine group, a pyrimidine group, a pyrazine group, an indole group, a benzimidazole group, a purine group, a benzotriazole group, a quinoline group, a quinazoline group, a quinoxaline group, a pteridine group, a carbazole group, a porphyrin group, a chlorin group, a choline group, an adenine group, a guanine group, a cytosine group, a thymine group, a uracil group, a dissociated thiol group, a dissociated hydroxy group, an azido group, a pyridine group, a carbamic acid, a guanidine, a sulfenic acid, a urea, a thiourea, a peroxy acid, and analogs and derivatives thereof.

5. The isolated nanosheet according to claim 1 , wherein each of the first linear molecules is (i) the linear molecule including the linear polymer formed of only one type of repeating unit, the linear polymer includes polyethylene glycol (PEG), and at least one of the first cyclic molecules is a cyclodextrin.

6. The isolated nanosheet according to claim 1 , wherein each of the first linear molecules is (ii) the block copolymer including at least three blocks, the block polymer includes PEO-PPO-PEO, and at least one of the first cyclic molecules is a cyclodextrin.

7. The isolated nanosheet according to claim 1 , further comprising a second cyclic molecule, wherein none of the one or more linear molecules are included in the second cyclic molecule in a skewered manner.

8. The isolated nanosheet according to claim 7 , wherein the second cyclic molecule has a first substance included by a cavity thereof.

9. The isolated nanosheet according to claim 7 , comprising at least two first cyclic molecules, wherein at least one of the first cyclic molecules is the cyclodextrin, and wherein the other one or more first cyclic molecules and the second cyclic molecule are each selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, a crown ether, a pillararene, a calixarene, a cyclophane, a cucurbituril, and derivatives thereof.

10. The isolated nanosheet according to claim 1 , further comprising a second substance.

11. The isolated nanosheet according to claim 1 ,
wherein the one or more linear molecules are each a copolymer having a configuration represented by: “a moiety formed of polyethylene glycol (PEG)-a moiety formed of polypropylene glycol (PPG)-a moiety formed of PEG,” and
wherein the one or more first cyclic molecules are each β-cyclodextrin.

12. The isolated nanosheet according to claim 1 ,
wherein the one or more linear molecules are each a triblock copolymer formed only of a configuration represented by: “a moiety formed of polyethylene glycol (PEG)-a moiety formed of polypropylene glycol (PPG)-a moiety formed of PEG,” and
wherein the one or more first cyclic molecules are each β-cyclodextrin.

13. The isolated nanosheet according to claim 1 , wherein the isolated nanosheet has a thickness of from 0.5 nm to 100 nm.

14. The isolated nanosheet according to claim 1 ,
wherein the one or more linear molecules includes a moiety formed of polyethylene glycol (PEG) and/or a moiety formed of polypropylene glycol (PPG), and
wherein the one or more first cyclic molecules are each selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and derivatives thereof.

15. The isolated nanosheet according to claim 1 ,
wherein the one or more linear molecules include polyethylene glycol (PEG) and/or polypropylene glycol (PPG), and
wherein the one or more first cyclic molecules are each selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and derivatives thereof.

16. A material comprising the isolated nanosheet of claim 1 .

17. A pharmaceutical carrier and/or a pharmaceutical vehicle comprising the isolated nanosheet of claim 1 .

18. The pharmaceutical carrier and/or the pharmaceutical vehicle according to claim 17 , wherein the isolated sheet is configured to adhere to a target site.

19. A pharmaceutical disintegrant and/or a pharmaceutical binder comprising the isolated nanosheet of claim 1 .

20. A pharmaceutical comprising:
a pharmaceutically acceptable active ingredient; and
the isolated nanosheet of claim 1 .

21. A pharmaceutical comprising:
a pharmaceutically acceptable active ingredient; and
a pharmaceutical carrier and/or a pharmaceutical vehicle including the isolated nanosheet of claim 1 .

Assignees

• Univ Tokyo

Inventors

• Ito Kohzo
• Maeda Rina
• Uenuma Shuntaro

Classifications

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• A61K9/7007 Primary

  Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence) · CPC title

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• A61K31/4704

  2-Quinolinones, e.g. carbostyril · CPC title

• A61K31/5415

  ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam · CPC title