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Substance containing vesicle and production method therefor NEW

外国特許コード F170009166
整理番号 AF12-14WO
掲載日 2017年9月12日
出願国 インド
出願番号 DEL86812015
公報番号 8681/DELNP/2015
出願日 平成27年9月22日(2015.9.22)
公報発行日 平成28年7月22日(2016.7.22)
国際出願番号 JP2014055186
国際公開番号 WO2014133172
国際出願日 平成26年2月28日(2014.2.28)
国際公開日 平成26年9月4日(2014.9.4)
優先権データ
  • 特願2013-041186 (2013.3.1) JP
  • 特願2013-176068 (2013.8.27) JP
発明の名称 (英語) Substance containing vesicle and production method therefor NEW
発明の概要(英語) (IN2015DN08681)
Provided is a monodisperse agglomerate of a substance-containing vesicle filled with a substance-at a concentration higher than conventionally possible.
A mixed solution, in, which a target substance is included in an aqueous medium, is mixed with a monodisperse agglomerate of a crosslinked vesicle comprising a prescribed polymer which includes a first polymer, i.e. a block copolymer having uncharged hydrophilic segments and first charged segments, and a second polymer having second charged segments carrying a charge opposite to that of the first charged segments, and in which the first polymer and/or the second polymer are/is crosslinked.
As a result, the crosslinked vesicle is made to contain the target substance.
特許請求の範囲(英語) [claim1]
1. (Amended) A "monodisperse population of substance-encapsulating crosslinked vesicles, each of the substance-encapsulating crosslinked vesicles comprising: a crosslinked membrane comprising a"first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged, segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the first charged segment, the first and/or the second polymer(s) being crosslinked;
an inner aqueous phase surrounded by the crosslinked membrane;
and a target substance encapsulated in the Inner aqueous phase, wherein the concentration of the target substance encapsulated in the inner aqueous phase is higher than 5mg/mL and high enough to prevent formation of a monodisperse population of substance-encapsulating non-crosslinked vesicles each encapsulating the target substance when a monodisperse population of vacant non-crosslinked vesicles is mixed with a mixture liquid containing the target substance in an aqueous medium at the same concentration as the concentration of the substance-encapsulating crosslinked vesicle in the inner aqueous phase, wherein the monodisperse population of vacant non-crosslinked vesicles differs from the monodisperse population of substance-encapsulating crosslinked vesicles only in that the first and/or the second polymer(s) is(are) not crosslinked and that the target substance is not encapsulated.
[claim2]
2. The monodisperse population of substance-encapsulating crosslinked vesicles according to claim 1, having a polydispersity index of 0.2 or lower.
[claim3]
3. (Amended) The monodisperse population of substance-encapsulating crosslinked vesicles according to claim 1 or 2, wherein the weight-average molecular weight of the target substance is between 10000 and 40000.
[claim4]
4. The monodisperse population of substance-encapsulating crosslinked vesicles according to claim 2, wherein the first and/or the second polymer(s) is(are) crosslinked with one or more crosslinking bonds selected from the group consisting of a crosslinking bond formed between cationic groups, a crosslinking bond formed between anionic groups, and a crosslinking bond formed between a cationic group and an anionic group, and the molar ratio of the cationic groups and/or anionic groups forming crosslinking bonds to the cationic groups and/or anionic groups' contained in the crosslinked membrane is 35% or more.
[claim5]
5. A substance-encapsulating crosslinked vesicles comprising: a crosslinked membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the first charged segment, the first and/or the second polymer(s) being crosslinked;
an inner aqueous phase surrounded by the crosslinked membrane;
and a first target substance and a second target substance encapsulated in the inner aqueous phase, the first target substance having a smaller molecular weight than the molecular weight of the second target substance, wherein the first target substance is more stable than when the first target' substance is contained in the inner aqueous phase in the absence of the second target substance.
[claim6]
6. The substance-encapsulating crosslinked vesicle according to claim 5, wherein the second target substance is a clouding agent.
[claim7]
7. A method of producing a substance-encapsulating vesicle, comprising mixing a monodisperse population of vacant crosslinked vesicles with a mixture liquid containing the target substance in an aqueous medium to form a monodisperse population of substance-encapsulating crosslinked vesicles, wherein each of the vacant crosslinked vesicles comprises: a crosslinked membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the first charged segment, the first and/or the second polymer(s) being crosslinked;
and an inner aqueous phase surrounded by the crosslinked membrane, wherein the inner aqueous phase does not contain the target substance, and wherein each of the substance-encapsulating crosslinked vesicles comprises: the crosslinked membrane comprising the first polymer and the second polymer, the first and/or the second polymer(s) being crosslinked;
and the inner aqueous phase surrounded by the crosslinked membrane, wherein the inner aqueous phase contains the target substance.
[claim8]
8. The method according to claim 7, wherein the monodisperse population of vacant crosslinked vesicles, the monodisperse population of substance-encapsulating crosslinked vesicles, the monodisperse population of vacant non-crosslinked vesicles, and the monodisperse population of substance-encapsulating non-crosslinked vesicles each have a poiydispersity index of 0.2 or less.
[claim9]
9. The method according to claim 7 or 8, wherein the weight-average molecular weight of the target substance is between 10000 and 40000, and the concentration of the target substance in the mixture liquid' is more than 5mg/mL.
[claim10]
10. The method according to claim 9, wherein both i-n tb, e vacant crosslinked vesicles and the substance-encapsulating crosslinked vesicles, the first and/or the second polymer(s) is(are) crosslinked' with one or more crosslinking bonds selected from the group consisting of a crosslinking bond formed between cationic groups, a crosslinking bond formed between anionic groups, and a crosslinking bond formed between a cationic group and an anionic group, and the molar ratio of the cationic groups and/or anionic groups forming crosslinking bonds to the cationic groups and/or anionic groups contained in the crosslinked membrane is 35% or more.
[claim11]
11. The method according to any one of claims 7 to 10, further comprising: reacting the monodisperse population of substance-encapsulating crosslinked vesicles with a crosslinker which can react with the first and/or the second polymer(s).
[claim12]
12. A method of producing a substance-encapsulating vesicle, comprising: mixing a first substance-encapsulating crosslinked vesicle, which encapsulates a first substance, with a mixture liquid containing a second target substance in an aqueous medium to form a second substance-encapsulating crosslinked vesicle, which encapsulates the first substance, wherein the first substance-encapsulating crosslinked vesicle comprises: a crosslinked membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the first charged segment, the first and/or the second polymer(s) being crosslinked;
and an inner aqueous phase surrounded by the crosslinked membrane, wherein the inner aqueous phase contains the first target substance, and wherein the second substance-encapsulating crosslinked vesicle comprises: the crosslinked membrane comprising the first polymer and the second polymer, the first and/or the second polymer(s) being crosslinked;
and the inner aqueous phase surrounded by the crosslinked membrane, wherein the inner aqueous phase contains;
the first and second substances.'
[claim13]
13. The method according to claim 12, wherein a monodisperse population of the first substance-encapsulating crosslinked vesicles is used to thereby produce a monodisperse population of the second substance-encapsulating crosslinked vesicles.
[claim14]
14. The method according to claim 13, wherein the concentration of the second target substance contained in the mixture liquid is high enough to prevent formation of a monodisperse population of substance-encapsulating non-crosslinked vesicles each encapsulating both the first and second target substances when a monodisperse population of first non-crosslinked vesicles is mixed with the mixture liquid, wherein the monodisperse population of first substance-encapsulating non-crosslinked vesicles differs from the monodisperse population of first substance-encapsulating crosslinked vesicles only in that the first and/or the second polymer(s) is(are) not crosslinked.
[claim15]
15. The method according to any one of claims 12 to 14, further comprising forming the first substance-encapsulating crosslinked vesicle by contacting a vacant crosslinked vesicle a mixture liquid containing the first target substance in an aqueous medium, wherein the vacant crosslinked vesicle comprises a crosslinked membrane comprising: the first and second polymers wherein the first and/or the second polymer(s) is(are) crosslinked;
and an.inner aqueous phase surrounded by the crosslinked membrane, wherein the inner aqueous phase does not - contain the first and second target substances;
and if necessary, reacting the vesicle with a crosslinker which can react with the first and/or the second polymer(s).
[claim16]
16. The method according to claim 15, wherein a monodisperse population of the vacant crosslinked vesicles is used to thereby produce a monodisperse population of the first substance-encapsulating crosslinked vesicles.
[claim17]
17. The method according to claim 16, wherein the concentration of the first target substance contained in the mixture liquid is high enough to inhibit the formation of a monodisperse population of substance-encapsulating non-crosslinked vesicles containing the first target substance when a monodisperse population of vacant non-crosslinked vesicles is mixed with the mixture liquid, wherein the monodisperse population of vacant non-Crosslinked vesicles differs from the monodisperse population of vacant crosslinked vesicles only in that the first and/or the second polymer(s) are not crosslinked.
[claim18]
18. The method according to any one of claims 12 to 17, wherein the second target substance is a clouding agent.
J
[claim19]
19. An adsorbent-encapsulating vesicle comprising: a vesicle composed of a membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of. the first charged segment;
and an adsorbent particle encapsulated in the vesicle, wherein at least either the first polymer or the second..polymer is adsorbed by the adsorbent particle.
[claim20]
20. The adsorbent-encapsulating vesicle according to claim 19, wherein the first and/or second polymer(s) is(are) crosslinked.
[claim21]
21. The adsorbent-encapsulating vesicle according to claim 19 or 20, wherein the adsorbent particle is a silica particle.
[claim22]
22. The adsorbent-encapsulating vesicle according to any one of claims 19 to 21, wherein the adsorbent particle has an average particle size of between 40nm and 10 m.
[claim23]
23. The adsorbent-encapsulating vesicle according to any one of claims 19 to 22, wherein the adsorbent particle has been surface-treated..
[claim24]
24. The adsorbent-encapsulating vesicle according to any one of claims 19 to 23, wherein a low-molecular compound is adsorbed by the adsorbent particle.
[claim25]
25. A method of producing an adsorbent-encapsulating vesicle comprising a vesicle composed of a membrane comprising a first polymer, which is block' copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the first charged segment, and an adsorbent particle encapsulated in the vesicle, said method comprising the steps of: (a) mixing one of the first and second polymers with the adsorbent particle, to have the one of-the first and second polymers adsorbed by the adsorbent particle;
and (b) further mixing the mixture from step (a) with the other of the first and second polymers to form a vesicle composed of a membrane comprising the first and second polymers around the adsorbent particle, thereby forming the adsorbent-encapsulating vesicle.
[claim26]
26. The method according to claim 25, further comprising: (c) crosslinking the first and/or the second polymer (s) contained in the vesicle from step (b)
[claim27]
27. The method according to claim 25 or 26, wherein the adsorbent particle is a silica particle.
[claim28]
28. The method according to any one of claims 25 to 27, wherein the adsorbent particle has an average particle size of between 40nm and 10pm.
[claim29]
29. The method according to any one of claims 25 to 28, further comprising the step of surface-treating the adsorbent particle.
[claim30]
30. The method according to any one of claims 25 to 29, wherein a low-molecular compound is adsorbed by the adsorbent particle.
[claim31]
31. (Amended) A method of producing a substance-encapsulating vesicle comprising: a vesicle composed of a membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment having a charge opposite to the charge of the 'first charged segment, the first and/or the second polymer(s) being crosslinked;
and a target substance encapsulated by the vesicle, said method comprising the steps of: (a) preparing an enzyme-encapsulating vesicle comprising a vesicle composed of a membrane containing the first and second polymers and an enzyme encapsulated in the vesicle, wherein the vesicle can convert a precursor, which has a higher water-solubility than the. target substance, into the target substance;
and (b) introducing the precursor into the enzyme-encapsulating vesicle under conditions which exhibit a lower solubility for the target substance than for the precursor such that the enzyme converts the precursor into the target substance to thereby cause the target substance to precipitate and be encapsulated in the enzyme-encapsulating vesicle, thereby forming the substance-encapsulating vesicle, wherein said method further comprises crosslinking the first and/or the second polymer(s) of the enzyme-encapsulating-vesicle before step (b), and wherein the low-water-solubility substance is encapsulated at a concentration exceeding the solubility of the low-water-solubility substance to the inner aqueous phase.
[claim32]
32. The method according to claim 31, wherein the introduction of the precursor into the enzyme-encapsulating vesicle in step (b) is carried out by mixing the enzyme-encapsulating vesicle with an aqueous solution of the precursor.
[claim33]
33. (Amended) The substance-encapsulating vesicle produced by the method according to claim 31 or 32.
[claim34]
34. (Amended) A low-water-solubility substance-encapsulating vesicle comprising: a vesicle composed of a membrane comprising a first polymer, which is block copolymer having an uncharged hydrophilic segment and a first' charged segment, and a second polymer, which has a, second charged segment having a charge opposite to the charge of the first charged segment, the first and/or the second polymer(s) being crosslinked;
a low-water-solubility substance encapsulated in the vesicle, wherein the low-water-solubility substance can be converted from a precursor, which has a higher water-solubility than the target substance;
and an enzyme encapsulated in the vesicle, wherein the enzyme can convert the precursor into the low-water-solubility substance wherein the low-water-solubility substance is encapsulated at a concentration exceeding the solubility of the low-water-solubility substance to the inner aqueous phase.
[claim35]
35. (Amended) A drug delivery system comprising the monodisperse population of vesicles according to any one of claims 1 to 4 and/or the vesicles according to any one of claims 5, 6, 19 to 22, and 33.
[claim36]
36. A method of delivering a drug to a subject, comprising the steps of: (a) preparing an enzyme-encapsulating vesicle comprising a vesicle composed of a membrane comprising a, first polymer, which is block copolymer having an uncharged 'hydrophilic segment and a first charged segment, and a second polymer, which, has a second charged-segment having a charge opposite to "the charge of the first charged segment, 'and an enzyme' which can convert a precursor of the drug into the drug;
and (b) forming the drug by introducing the precursor into the enzyme-encapsulating vesicle at a predetermined position in the subject such that the enzyme converts the precursor into the drug.
[claim37]
37. (Amended) The method according to claim 36, wherein the precursor has a lower water-solubility than the drug, and the precursor is introduced into the enzyme-encapsulating vesicle in-step (b) under conditions which exhibit a lower solubility for the drug than for the precursor.
[claim38]
38. The method according, to claim 36 or 37, wherein step (b) further comprises allowing the drug to precipitate and be encapsulated in the enzyme- encapsulating vesicle, thereby forming a drug-encapsulating vesicle.
  • 出願人(英語)
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • 発明者(英語)
  • KATAOKA Kazunori
  • KISHIMURA Akihiro
  • ANRAKU Yasutaka
  • GOTO Akinori
国際特許分類(IPC)
参考情報 (研究プロジェクト等) CREST Establishment of Innovative Manufacturing Technology Based on Nanoscience AREA
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