Substance-containing vesicle, and production method therefor
|発明の名称 （英語）||Substance-containing vesicle, and production method therefor|
|発明の概要（英語）||Provided is a mono-disperse agglomerate of a substance-containing vesicle filled with a substance at a concentration higher than conventionally possible. A mixed solution, in which a target substanceis included in an aqueous medium, is mixed with a mono-disperse 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.|
It is well known, for level-one structure through a carefully controlled high molecular self-assembly, and to obtain microcapsules can be formed. Due to this design of the microcapsules can be diversified molecules, at the same time it is presented to the performance of the new polymer-specific properties, as drug delivery systems were investigated (Drug Delivery System: DDS) carriers, the use of a biomaterial · functional material or the like.
In Patent Document 1 (JP Patent No.8-188541 A) are, according to the present invention such as a human portion of the population, there is disclosed: a block copolymer having a non-charged segment and the charged segment formed electrostatic self-assembly of a polymer micelle bound drug carrier.
In the Non-Patent Document 1(Schlaad H.et al.,Macromolecules,2003,36 (5), 1417-1420), discloses: manufactured by poly (1,2-butadiene) blocks and poly (methyl cesium acrylate) block with a block copolymer composed of polystyrene block and a poly (1-methyl-4-vinyl pyridine iodide) block copolymer self-assembly to form a block will be referred to as polymersomes of the microcapsule.
In Patent Document 2 (Pamphlet of International Publication No. 2006/118260) are, according to the present invention such as a human portion of the population, there is disclosed: a hydrophilic segment and a cationic segment having uncharged of the 1st block copolymers (such as PEG-poly cation or the like), and the amino acids with uncharged hydrophilic segments and anion sub-segment of the 2nd block copolymers (such as PEG-polyanion and the like) to form a self-assembly of the microcapsules.
In the Non-Patent Document 2(Anraku Y.et al.,J.Am.Chem.Soc.,2010,132 (5), 1631-1636), according to the present invention or the like is of a portion of the population, there is disclosed: a hydrophilic segment and a chargeable segment having a non-charged block copolymers (such as PEG-poly cation or the like), a copolymer of opposite charge to the charged segment and a band (such as a polyanion and the like) to form a self-assembly of the microcapsules.
It is generally considered a self-assembled with a polymer obtained by using microcapsules containing void portions thereof various kinds, loaded with various substances. (With respect to the overview, see Non-Patent Document 3(H.Nyin et al.Soft Matter,2006,2,940-949) and Non-Patent Document 4 ("liposomes applied new launch", Kazunari Akiyoshi et al. ed., NTS, 2005)).
As in the preparation of the microcapsules encapsulating material in a gap (hereinafter may be referred to as "microcapsule encapsulating material" case) of the method, represented as: which contains the encapsulated substance (hereinafter may be referred to as "encapsulated substance" case) which is the polymer of the membrane component, or a pre-formed polymer film are mixed together, are self-assembled, and to the formation of microcapsules is carried out while the substance in the method of the gap to be filled (hereinafter may be referred to as "simultaneous mixing method" in the case). As a specific example, there may be mentioned an emulsion polymerization method (see Non-Patent Document 5(F.Szoka,Jr et al.,Proc.Natl.Acad.Sci.USA,1978 75 (9) 4194-4198)), lipid organic solution dropping method (see Non-Patent Document 6(Batzri,S.et al.,Biochim.Biophys Acta 1973,298,1015-1019) ) and the like.
However, at the same time in the mixing method, there are encapsulated by the presence of the substance to affect self-assembly of the formed microcapsules, the microcapsules are formed of blocks, or even if the microcapsule formation but in gap un-encapsulated substance. In addition, in the case of hazardous organic solvents to be used when forming a film is large, there are also becomes complex, an organic solvent is present at the same time by the encapsulating material is susceptible to damage due to a problem. Furthermore, it is difficult to form a uniform particle size, structure of the microcapsules, in order to ensure that such a uniform particle size, structure has to be increased and the other steps, there is also a problem of easily becomes complex processes. Thus, the present method has poor generality, as a manufacturing method of the microcapsule encapsulating of each species is not practical.
On the other hand, in the hollow particles as the primary method used in the coating material, there will be encapsulated substance is introduced into the space of the hollow particles after the prior art, so as to enclose, method of the load (hereinafter may be referred to as [post-carrying method] case) (see Non-Patent Document 7(W.Tong et al.J.Phys.Chem.B,2005,109,13159-13165)), has also been considered such a method is applied to the microcapsules.
However, in the case of the rear loading method is applied to the microcapsules, it is sought to traverse the empty microcapsule film, will become encapsulated substance into the void portions. For example, it is envisioned that empty , the film is relaxed, a gap of the film from the creation of the encapsulated substance introduced into the void portions after penetration, the film is shrunk and prevent separation of the encapsulated substance method, or a hole is formed in the , through the aperture will become encapsulated substance into the void portions are, blocking the hole and prevent separation of the method or the like is encapsulated material, however any one of which is an extremely complex, is very unfavorable for practical use. In addition, taking into account the load is enclosing or encapsulating material, causing the particle size of microcapsules are available now, a disorder of the structure is a high probability, so it is not practicable.
In addition, the lipid bilayer of the liposome or the like with respect to the microcapsule membrane, also reports on lipid bilayer method or the like is fitted on the channel proteins (see Non-Patent Document 8(Ranquin A,Versees W,Miere W,Steyaert J,GelderPV.Therapeutic Nanoreactors: Combining Chemistry and Biology in a NovelTriblock Copolymer Drug Delivery System.Nano Lett.2005; 5:2220-4)), however the procedure still is extremely complex, and the versatility is extremely low, or not practical.
Against the above background technology, the present invention or the like is proposed quite unexpected findings: the presence of a target substance encapsulated in the it through, mixed in an aqueous medium having both film and the method of the gap formed in a membrane enclosed (rather "post-carrying method"), 1st and the 2nd through self-assembly of the polymer and which, it is possible to easily and efficiently produced in the void (internal aqueous phase) of the target substance is encapsulated in a microcapsule encapsulating material, wherein, having a non-charged hydrophilic block comprising as membrane is charged and 1st 1st polymer block of a block copolymer, and has a band and the 1st 2nd opposite charge on the charge on the charge block of a block of the 2nd polymer, and is applied for a patent (Patent Document 3: pamphlet of International Publication No. 2011/145745).
Prior Art Document
Patent Document 1: JP Patent No.8-188541 A
Patent Document 2: pamphlet of International Publication No. 2006/118260
Patent Document 3: pamphlet of International Publication No. 2011/145745
Non-Patent Document: 1Schlaad H.et al.,Macromolecules,2003,36 (5), 1417-1420
Non-Patent Document: 2Anraku Y.et al.,J.Am.Chem.Soc.,2010,132 (5), 1631-1636
Non-Patent Document: 3H.Nyin et al.Soft Matter,2006,2,940-949
Non-patent Document: "development of a new Liposome Application" 4, Kazunari Akiyoshi, Shigeru Tsujii, NTS, Non-Patent Document 2005: 5F.Szoka,Jr.et al.,Proc.Natl.Acad.Sci.USA,1978 75 (9) 4194-4198
Non-Patent Document: 6Batzri,S.et al.,Biochim.Biophys Acta 1973,298,1015-1019 Non-Patent Document: 7W.Tong et al.,J.Phys.Chem.B,2005,109,13159-13165
Non-Patent Document: 8Ranquin A et al.,Nano Lett.2005,5:2220-4
1. An adsorbent material encapsulated microcapsules, characterized in,
It comprises an uncharged hydrophilic block comprises as a block polymer of the 1st and 1st charged blocks of the polymer, and, has a 1st 2nd charged blocks of opposite charge of the charged polymer film formation of the 2nd block of the microcapsules, and the microcapsule-encapsulated adsorbent material particles, 1st and 2nd adsorbed on the adsorbent material particles at least one of the polymer.
2. Absorbent material during the encapsulating microcapsule according to claim 1, characterized in, 1st and a 2nd/or polymer is cross-linked.
3. In the microcapsule encapsulated adsorbent material according to claim 1, characterized in, adsorbent material particles are silica particles.
4. An adsorbent material encapsulated in the microcapsule according to claim 1, characterized in, particles having an average particle diameter of 40 nm-10 μm adsorbent material.
5. Absorbent material during the encapsulating microcapsule according to claim 1, characterized in, on the adsorbent material particles to surface treatment.
6. In the microcapsule encapsulated adsorbent material according to claim 1, characterized in, particulate adsorbent capable of adsorbing a small molecule compound.
7. Method for producing a microcapsule encapsulating an adsorbent material, characterized in,
In the film formation of the microcapsule encapsulating the adsorbent material particles; wherein film having uncharged hydrophilic block and comprising as 1st charged blocks of the block copolymer of the 1st polymer, and has a 1st 2nd charged with opposite charges charged blocks of the block of the 2nd polymer;
(A) of the 1st and the 2nd polymer either of the adsorbent material particles are mixed, adsorbed on the adsorbent material pellet;
(B) the step (a) 1st or 2nd polymer with a mixture of the other of the mixing is continued, the adsorbent material particles consisting of the 1st and the 2nd polymer is formed around the film formation of the microcapsules, the microcapsules encapsulating a step of making an adsorbent material.
8. In the method according to claim 7, characterized in, this method also includes
(C): cross-linking step (b) of the 1st and the 2nd step of the polymer/or in the microcapsules.
9. In the method according to claim 7, characterized in, adsorbent material particles are silica particles.
10. In the method according to 7, characterized in, adsorbent material particles have an average particle diameter of 40 nm-10 μm.
11. In the method according to claim 7, characterized in, this method further comprises the step of adsorbent material particles to surface treatment.
12. In the method according to claim 7, characterized in, small molecule compounds adsorbed on the adsorbent material particles.
13. One drug delivery system of claim 1-6 in any one microcapsules.
|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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