JP2014076971A5 - - Google Patents
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- JP2014076971A5 JP2014076971A5 JP2012226108A JP2012226108A JP2014076971A5 JP 2014076971 A5 JP2014076971 A5 JP 2014076971A5 JP 2012226108 A JP2012226108 A JP 2012226108A JP 2012226108 A JP2012226108 A JP 2012226108A JP 2014076971 A5 JP2014076971 A5 JP 2014076971A5
- Authority
- JP
- Japan
- Prior art keywords
- composite particles
- chitosan
- concentration
- hyaluronan
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000011246 composite particle Substances 0.000 description 12
- 229920001661 Chitosan Polymers 0.000 description 9
- 229920002674 hyaluronan Polymers 0.000 description 8
- 229940099552 Hyaluronan Drugs 0.000 description 7
- KIUKXJAPPMFGSW-MNSSHETKSA-N Hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000007979 citrate buffer Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- MAKUBRYLFHZREJ-JWBQXVCJSA-M sodium;(2S,3S,4R,5R,6R)-3-[(2S,3R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylate Chemical compound [Na+].CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@H](O)[C@H]1O MAKUBRYLFHZREJ-JWBQXVCJSA-M 0.000 description 4
- 239000007993 MOPS buffer Substances 0.000 description 3
- 229940010747 Sodium Hyaluronate Drugs 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K 2qpq Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Inorganic materials [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Description
＜試験例１＞
表１に示す割合で、種々の分子量のヒアルロン酸ナトリウムとキトサン（３４．３ｋＤ
ａ）を用いて、複合粒子を作製した。
すなわち、溶媒として、クエン酸緩衝液（クエン酸濃度が１ｍＭ、ｐＨ６．５）、ＰＢＳ（ｐＨ６．５、ＰＢＳの組成は、［ＫＣｌ］＝２．７ｍＭ、［ＫＨ２ＰＯ４］＝１．５ｍＭ、［ＮａＨ２ＰＯ４・７（Ｈ２ Ｏ）］＝８．１ｍＭ、［ＮａＣｌ］＝１３７ｍＭ）、又はＭＯＰＳ（１０ｍＭ、ｐＨ６．５）を用いて、ヒアルロン酸ナトリウム溶液とキトサン溶液を調製し、キトサン溶液を撹拌しながら、キトサン溶液にヒアルロン酸溶液を滴下した。
表１に、得られた複合粒子の粒子径と、複合粒子の表面電荷を示す。
複合粒子の平均粒子径は、Zetasizer Nano-ZS ZEN3600, Malvern社（動的光散乱法）を用いて測定した。
複合粒子の表面電荷は、Zetasizer Nano-ZS ZEN3600, Malvern社（レーザードップラー法）を用いて測定した。
<Test Example 1>
Sodium hyaluronate and chitosan (34.3 kD) of various molecular weights in the proportions shown in Table 1.
Composite particles were prepared using a).
That is, as a solvent, a citrate buffer (citrate concentration is 1 mM, pH 6.5), PBS (pH 6.5, the composition of PBS is [ KCl] = 2.7 mM, [KH 2 PO 4 ] = 1.5 mM. , [NaH 2 PO 4 · 7 (H 2 O )] = 8.1 mM, [NaCl] = 137 mM), or MOPS (10 mM, pH 6.5) to prepare a sodium hyaluronate solution and a chitosan solution, While stirring the chitosan solution, the hyaluronic acid solution was added dropwise to the chitosan solution.
Table 1 shows the particle diameter of the obtained composite particles and the surface charge of the composite particles.
The average particle size of the composite particles was measured using Zetasizer Nano-ZS ZEN3600, Malvern (dynamic light scattering method).
The surface charge of the composite particles was measured using Zetasizer Nano-ZS ZEN3600, Malvern (Laser Doppler method).
上記表に示す通り、溶媒としてＭＯＰＳを用いて、ヒアルロナン濃度１７２μｇ／ｍＬ程度、キトサン濃度８３．５μｇ／ｍＬ程度で作製したＮｏ．１〜４では、作製された複合粒子の平均粒子径は１８０ｎｍよりも大きいものであった。特に１３００ｋＤａの分子量の大きいヒアルロナンを用いた場合には、２００ｎｍより大きい平均粒子径となった。
なお、溶媒としてＭＯＰＳを用いた場合でも、ヒアルロナン濃度とキトサン濃度を小さくすることにより（Ｎｏ．５〜１０）、粒子径を小さくすることが可能であった。
一方、溶媒としてクエン酸緩衝液を用いて、Ｎｏ．１〜４と同様のヒアルロナン濃度とキトサン濃度で作製したＮｏ．１６と１８は、平均粒子径が有意に５０ｎｍ程度小さくなった。また、高濃度の溶液を用いて作製したＮｏ．１５も、１５０ｎｍ以下の微粒子であった。さらに、Ｎｏ．１１〜１４を見るとわかるように、クエン酸緩衝液を用いることにより、ヒアルロン酸ナトリウムの分子量が大きくなっても、作製される複合粒子の粒子径はほとんど増大しないことが分かった。
なお、ＰＢＳを用いたＮｏ．１９は、凝集が起こり、複合粒子が形成されなかった。
これにより、クエン酸緩衝液を用いてヒアルロナンとキトサンの複合粒子を製造することにより、小さな径の複合粒子を製造することができることが分かった。特に、高分子量のヒアルロナンを用いて、ナノサイズの複合粒子を製造することができることが分かった。
また、クエン酸緩衝液を用いることにより、他の緩衝液を用いる場合に比べて高濃度のヒアルロナン及びキトサンを含む溶液から複合粒子を製造することができるため、用いる溶媒の量を低減でき、製造効率の向上、コスト削減の観点からも効果的であることが分かった。
As shown in the above table, No. 1 prepared using MOPS as the solvent and having a hyaluronan concentration of about 172 μg / mL and a chitosan concentration of about 83.5 μg / mL. In 1-4, the average particle diameter of the produced composite particles was larger than 180 nm. In particular, when hyaluronan having a large molecular weight of 1300 kDa was used, the average particle size was larger than 200 nm.
Even when MOPS was used as the solvent, it was possible to reduce the particle size by reducing the hyaluronan concentration and chitosan concentration (Nos. 5 to 10).
On the other hand, no citrate buffer was used as a solvent. No. 1 prepared with the same hyaluronan concentration and chitosan concentration as in Nos. 1-4. In 16 and 18, the average particle size was significantly reduced by about 50 nm. In addition, No. 1 prepared using a high concentration solution. 15 was also a fine particle of 150 nm or less. Furthermore, no. As can be seen from FIGS. 11 to 14, it was found that by using a citrate buffer, the particle diameter of the composite particles produced hardly increases even when the molecular weight of sodium hyaluronate is increased.
No. using PBS. In No. 19, aggregation occurred and composite particles were not formed.
Thus, it was found that composite particles having a small diameter can be produced by producing composite particles of hyaluronan and chitosan using a citrate buffer. In particular, with reference to hyaluronan Rona emissions of high molecular weight, it was found that it is possible to produce composite particles of nanosize.
In addition, by using a citrate buffer, composite particles can be produced from a solution containing high concentrations of hyaluronan and chitosan as compared to the case of using other buffers, so that the amount of solvent used can be reduced and produced. It was found that it is effective from the viewpoint of efficiency improvement and cost reduction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012226108A JP6120397B2 (en) | 2012-10-11 | 2012-10-11 | Method for producing nanoparticles containing chitosan and hyaluronan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012226108A JP6120397B2 (en) | 2012-10-11 | 2012-10-11 | Method for producing nanoparticles containing chitosan and hyaluronan |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014076971A JP2014076971A (en) | 2014-05-01 |
| JP2014076971A5 true JP2014076971A5 (en) | 2015-10-29 |
| JP6120397B2 JP6120397B2 (en) | 2017-04-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012226108A Active JP6120397B2 (en) | 2012-10-11 | 2012-10-11 | Method for producing nanoparticles containing chitosan and hyaluronan |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6120397B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101662146B1 (en) * | 2014-10-23 | 2016-10-05 | 주식회사 마이크로젠 | Manufacturing method of chitosan-amino acid nano composite |
| JP6812100B2 (en) | 2015-12-15 | 2021-01-13 | ロレアル | Combination of polyion complex particles with hydrophilic or water-soluble UV shield |
| JP6921476B2 (en) * | 2015-12-15 | 2021-08-18 | ロレアル | Combination of polyion complex particles with non-polymeric acids with two or more acid dissociation constants |
| JP7176836B2 (en) | 2017-06-13 | 2022-11-22 | ロレアル | Composition containing polyion complex particles and oil |
| EP4018998A4 (en) * | 2019-08-21 | 2023-09-27 | Shiseido Company, Ltd. | Cosmetic |
| CN115645377A (en) * | 2022-11-04 | 2023-01-31 | 华东理工大学 | Preparation method of volatile essential oil-encapsulated nano-scale natural polyelectrolyte aggregate |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3283288B2 (en) * | 1991-03-08 | 2002-05-20 | 電気化学工業株式会社 | Bioactive peptide preparation |
| JPH06100468A (en) * | 1992-09-25 | 1994-04-12 | Kibun Food Chemifa Co Ltd | Sustained release composition |
| JP4234803B2 (en) * | 1997-10-27 | 2009-03-04 | 久光製薬株式会社 | Pharmaceutical composition with controlled drug release rate |
| JP4250740B2 (en) * | 2002-06-03 | 2009-04-08 | 宮崎県 | Fine particles containing naturally-derived polysaccharide and method for producing the same |
| ES2226567B1 (en) * | 2003-06-20 | 2006-07-01 | Universidad De Santiago De Compostela | NANOPARTICULAS OF HIALURONIC ACID. |
| JP2006241321A (en) * | 2005-03-03 | 2006-09-14 | Yoshinobu Fukumori | Method for producing chitosan nanoparticle, chitosan particle, coating composition, sustained release preparation, and injection |
| JP2009537604A (en) * | 2006-05-24 | 2009-10-29 | アドヴァンスド イン ヴィトロ セル テクノロジーズ ソシエダッド アノニマ | Chitosan and hyaluronan nanoparticles for administration of active molecules |
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2012
- 2012-10-11 JP JP2012226108A patent/JP6120397B2/en active Active
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