CN105878051A - Honeycomb hyaluronic acid and preparation method thereof - Google Patents

Honeycomb hyaluronic acid and preparation method thereof Download PDF

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CN105878051A
CN105878051A CN 201510037950 CN201510037950A CN105878051A CN 105878051 A CN105878051 A CN 105878051A CN 201510037950 CN201510037950 CN 201510037950 CN 201510037950 A CN201510037950 A CN 201510037950A CN 105878051 A CN105878051 A CN 105878051A
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hyaluronic acid
molecular weight
ha
salt
honeycomb
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CN 201510037950
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Chinese (zh)
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郭学平
刘建建
杨莹莹
高钧
耿凤
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华熙福瑞达生物医药有限公司
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Abstract

The invention relates to honeycomb hyaluronic acid and a preparation method thereof. The hyaluronic acid, after dissolved in water, is represented as a regular honeycomb structure. The honeycomb hyaluronic acid consists of high-molecular-weight hyaluronic acid or salt thereof and low-molecular-weight hyaluronic acid or salt thereof; and the honeycomb hyaluronic acid can be prepared by the following ways: conducting alcohol precipitation under an alkaline condition, washing and drying in a vacuum environment, so that the honeycomb hyaluronic acid is obtained. Compared with hyaluronic acid of the prior art, the hyaluronic acid is better in water replenishing and moisturizing effects.

Description

蜂巢状透明质酸及其制备方法 The method of preparing honeycomb hyaluronic acid, and

技术领域 FIELD

[0001] 本发明属于护肤品领域,更具体而言,本发明涉及一种蜂巢状透明质酸及其制备方法。 [0001] The present invention belongs to the field of skin care products, and more particularly, the present invention relates to a method for preparing hyaluronic acid and honeycomb.

背景技术 Background technique

[000引透明质酸曲aluronic acid,简称HA),是由(1 一;3)-2-己醜氨基-2-脱氧-目-D-葡萄糖-(1 一4)-0-目-D-葡糖醒酸双糖重复单位所组成的直链多聚糖,分子式为(C14肥INOlDn。其广泛存在于皮肤、眼玻璃体、软骨和关节滑液等许多结缔组织中,起到保湿、营养和修复等生理作用。 [000 cited hyaluronic song aluronic acid, referred to as HA), is composed of (a 1; 3) -2 OX-2-deoxy - Head -D- glucose - (1 - 4) -D mesh -0- - a linear polysaccharide consisting of gluconic acid wake disaccharide repeating unit, the formula (C14 fat which INOlDn widely present in many connective tissues of the skin, vitreous, synovial fluid and cartilage, and the like, play a moisturizing, nutrient. and repair and other physiological effects.

[0003] 通常,高分子量HA( > l,〇〇〇kDa)可W在皮肤表面形成一层生物膜,起到紧致肌肤,降低真皮、表皮水分蒸发的作用,但是由于其分子量太大,难W透过表皮,因此,深层补水作用较差;低分子量HA(lkDa~l,000kDa)能渗入表皮,增加皮肤弹性,营养皮肤,延缓皮肤衰老,但是低分子量HA降低水分蒸发性能较差。 [0003] Generally, high molecular weight HA (> l, 〇〇〇kDa) W can be formed in the surface of the skin layer of the biofilm, play a compact skin, decreased dermal, epidermal, evaporation effects, but because of its large molecular weight is W transdermally difficult, and therefore, deep water effect is poor; low molecular weight HA (lkDa ~ l, 000kDa) can penetrate the skin, increasing skin elasticity, skin nutrients, delay skin aging, but poor low-molecular weight HA to reduce water evaporation performance.

[0004] CN 101500535A公开了一种护肤品,其中包含高分子量的HAα00邸a-500邸a)与低分子量的HA(8KDa - lOOKDa),但是,该产品是由高、低分子量的HA简单混合后得到的。 [0004] CN 101500535A, discloses a skin care products, which comprises a high molecular weight di HAα00 a-500 Di a) a low molecular weight HA (8KDa - lOOKDa), however, the product is a simple mixture of HA high and low molecular weight after get.

[0005] CN 101450028A公开了一种护肤品,其中包含高分子量的HAO2600邸a)与低分子量的HA(<10KDa),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0005] CN 101450028A, discloses a skin care products, which comprises a high molecular weight di HAO2600 a) a low molecular weight HA (<10KDa), similarly, the product is also a high, low molecular weight HA obtained by simple mixing after.

[0006] CN 102905677A公开了一种护肤品,其中包含高分子量的HA(>1000邸a)与低分子量的HA(<1000KDa),同样,该产品是也由高、低分子量的HA简单混合后得到的。 After the [0006] CN 102905677A, discloses a skin care products, wherein the HA (> 1000 Di a) a high molecular weight and low molecular weight HA (<1000KDa), similarly, the product is also a high, a low molecular weight simply mixing the HA owned.

[0007] US 2011/0077737A1公开了一种透明质酸聚合物的组合物,其中包含高分子量的HA(2000邸a-5000邸a)与低分子量的HA(300邸a-800邸a),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0007] US 2011 / 0077737A1 discloses a hyaluronic acid polymer composition, wherein the HA (2000 a-5000 Di Di a) a high molecular weight and low molecular weight HA (300 a-800 Di Di a), Similarly, the product is also a high, the simple mixing of a low molecular weight HA obtained.

[0008] US 2011/0118206A1公开了一种透明质酸聚合物的组合物,其中包含高分子量的HA(1000邸a-4000邸a)与低分子量的HA(200邸a-990邸a),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0008] US 2011 / 0118206A1 discloses a hyaluronic acid polymer composition, wherein the HA (1000 a-4000 Di Di a) a high molecular weight and low molecular weight HA (200 a-990 Di Di a), Similarly, the product is also a high, the simple mixing of a low molecular weight HA obtained.

[0009] 特表2011-513481公开了一种透明质酸聚合物的组合物,其中包含高分子量的HA巧00邸a-3000邸a)与低分子量的HA(0. 5邸a-50邸a),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0009] Unexamined 2011-513481 discloses a composition comprising a hyaluronic acid polymer, wherein the HA comprises a molecular weight Di Qiao 00 a-3000 Di of a) with a low molecular weight HA (0. 5 a-50 Di Di a), similarly, the product is also a high, the simple mixing of a low molecular weight HA obtained.

[0010] FR 2924606A公开了一种透明质酸聚合物的组合物,其中包含高分子量的HA(1500邸a-1800邸a)与低分子量的HA(250邸a-450邸a),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0010] FR 2924606A discloses a hyaluronic acid polymer composition, wherein the HA comprises a molecular weight (a-1800 1500 Di Di a) a low molecular weight HA (250 a-450 Di Di a), similarly, the product is also made high, the simple mixing of a low molecular weight HA obtained.

[0011] 特开2007-297460公开了一种透明质酸聚合物的组合物,其中包含高分子量的HA (〉500邸a)与低分子量的HA巧邸a-20邸a),同样,该产品是也由高、低分子量的HA简单混合后得到的。 [0011] Laid-Open 2007-297460 discloses a composition comprising a hyaluronic acid polymer, wherein HA (> 500 Di a) a high molecular weight and low molecular weight HA Qiao Di Di a-20 a), similarly, the the product is also high, the simple mixing of a low molecular weight HA obtained.

[0012] 本领域已知的是,如果将高分子量HA和低分子量HA简单的物理混合,由于HA 的线性大分子特性,分子之间容易缠绕;同时,由于分子之间的相互作用(氨键、水桥作用等),高分子HA还可能会阻碍低分子HA的皮肤透过性,不利于充分发挥其深层补水、营养肌肤的作用。 [0012] is known in the art, if a high molecular weight and low molecular weight HA HA simple physical mixing, due to the characteristics of the linear macromolecule HA easily entangled molecules; the same time, due to the interaction (between the ammonia molecule bonds , water bridge effect, etc.), polymers of low molecular weight HA HA may also hinder the permeability of the skin, it is not conducive to their full deep water, the role of nutrition skin. HA为线性大分子,稀溶液中,HA分子在水溶液中由于分子内氨键的作用,呈单螺旋状态;当HA达到一定浓度时,HA分子之间具有相互作用,形成双螺旋结构;浓度更高时可形成网状结构。 HA is a linear macromolecules, in dilute solution, in an aqueous solution of the HA molecule by the action of the ammonia molecule bonds, form a single spiral state; when a certain concentration of HA, having interaction between the HA molecules form a double helix structure; concentration is more when the network structure can be formed high.

[0013] 综上所述,单纯高分子和低分子的HA都不能发挥出其最大的功效,而高分子量HA 和低分子量HA简单的物理混合复配,混合之后由于分子间相互作用,高分子量HA可能会阻碍低分子量HA的皮肤透过性,也会降低补水和保水效果。 [0013] In summary, a simple and low-molecular HA polymer can not play its maximum effect, and then the high molecular weight and low molecular weight HA HA simple physical mixing of the compound, since the intermolecular interaction mixing, a high molecular weight low molecular weight HA HA may hinder skin permeability will reduce replenishment and water retention effect.

发明内容 SUMMARY

[0014] 为了克服W上技术问题,本发明人经过创造性劳动,发现了一种制备HA的新方法,该方法通过将高分子量HA和低分子量HA在一定条件下进行配制,从而提供了一种蜂巢状HA。 [0014] In order to overcome the technical problems W, the present invention is inventive labor, found a novel process for preparing the HA, by the method of high molecular weight and low molecular weight HA HA formulated under conditions, thereby providing a honeycomb HA. 该方法包括将高分子量HA和低分子量HA混合,在一定条件下使HA分子聚集成网状结构并进行醇沉析出,通过该技术制备的HA能快速溶于水,并且溶于水后呈规则的蜂巢状,故命名为"蜂巢状HA"。 The method comprises mixing a high molecular weight and low molecular weight HA HA, HA under certain conditions that the aggregated molecules into a network structure The precipitated and alcohol, the technique for preparing the HA can quickly dissolved in water, and soluble in water in a regular honeycomb, so named for the "honeycombed the HA."

[0015] 在一个实施方案中,本发明提供透明质酸,该透明质酸的特征在于其溶于水后呈规则的蜂巢状结构。 [0015] In one embodiment, the present invention provides a hyaluronic acid, wherein the form of hyaluronic regular honeycomb structure after it is dissolved in water.

[0016] 在另一个实施方案中,本发明涉及透明质酸,其特征在于其溶于水后呈规则的蜂巢状结构,并且是由高分子量透明质酸或其盐和低分子量透明质酸或其盐配制而成。 [0016] In another embodiment, the present invention relates to hyaluronic acid, which is honeycomb-like regular structure after it is dissolved in water, and high molecular weight hyaluronic acid or a hyaluronic acid or salt thereof and low molecular weight salt preparation.

[0017] 在再一个实施方案中,在本发明的"透明质酸"中,所述高分子量透明质酸或其盐的分子量为lOOOkDa~3000kDa,低分子量透明质酸或其盐的分子量为IkDa~500kDa,优选高分子量HA的分子量为lOOOkDa~2000kDa,低分子量HA分子量5kDa~400kDa,更优选高分子量HA分子量为lOOOkDa~ISOOkDa,低分子量HA分子量5kDa~200kDa。 [0017] In a further embodiment, the "hyaluronic acid" in the present invention, the high molecular weight hyaluronic acid or salt thereof has a molecular weight lOOOkDa ~ 3000kDa, low molecular weight hyaluronic acid or salt thereof has a molecular weight IkDa ~ 500kDa, preferably high molecular weight HA has a molecular weight lOOOkDa ~ 2000kDa, low molecular weight HA molecular 5kDa ~ 400kDa, more preferably a molecular weight of the high molecular weight HA lOOOkDa ~ ISOOkDa, low molecular weight HA molecular 5kDa ~ 200kDa.

[0018] 在另一个实施方案中,在本发明的"透明质酸"中,所述高分子量透明质酸或其盐和低分子量透明质酸或其盐的配比为重量百分比为1:9~9:1,优选3:7~7:3,更优选3:7。 [0018] In another embodiment, the "hyaluronic acid" in the present invention, the high molecular weight hyaluronic acid or salt thereof and low molecular weight hyaluronic acid or a salt weight percentage ratio of 1: 9 ~ 9: 1, preferably 3: 7 to 7: 3, more preferably 3: 7.

[0019] 在另外一个实施方案中,本发明涉及制备本发明的蜂巢状HA的方法,该方法包括下列步骤: [0019] In another embodiment, the present invention relates to a process for preparing a honeycomb HA of the invention, the method comprising the steps of:

[0020] A、将高、低分子量HA溶于纯化水,揽拌均匀; [0020] A, the high and low molecular weight HA is dissolved in purified water, mix well embrace;

[0021] B、加入氯化钢揽拌均匀; [0021] B, mix well embrace chloride added steel;

[0022] C、用无机碱或盐调节抑至碱性; [0022] C, with an inorganic base or basic salt thereof adjusted to a suppression;

[0023] D、揽拌下,用醇溶剂进行醇沉; [0023] D, embrace the mix, alcohol precipitation with an alcohol solvent;

[0024] E、过滤,对剩余沉淀物进行脱盐; [0024] E, filtration, desalting the remaining precipitate;

[00巧]F、沉淀物用脱水溶剂脱水后干燥即得。 [00 Qiao] F, the precipitate was dried to obtain the dehydrating solvent.

[0026] 步骤B中采用的氯化钢的浓度不是关键的,但优选重量百分比为1%~5%的氯化钢。 The chloride concentration in the steel [0026] Step B employed is not critical, but is preferably 1% by weight to 5% steel chloride.

[0027] 步骤C中采用的无机碱或盐不是关键的,只要能够将抑调至碱性即抑〉7即可,优选所述无机碱或盐选自氨氧化钢、碳酸钢、碳酸氨钢和己酸钢,更优选为氨氧化钢。 [0027] Step C using an inorganic base or salt is not critical, as long as can be suppressed suppression was made basic i.e.> 7, and is preferably an inorganic base or salt is selected from the ammoxidation of steel, steel carbonate, ammonium carbonate steel hexanoate steel, steel and more preferably from ammonia oxidation.

[0028] 步骤D中采用的醇沉溶剂不是关键的,但是,优选体积百分比为95%的己醇或甲醇,更优选体积百分比为95%的己醇。 [0028] Step D alcohol precipitation solvent employed is not critical, however, the percentage is preferably 95% by volume of hexanol or methanol, and more preferably 95% by volume percentage hexanol.

[0029] 步骤E中采用的脱盐溶剂不是关键的,但是优选体积百分比为75%~80%的己醇或甲醇,更优选体积百分比为75 %~80 %的己醇。 [0029] Step E desalting solvent employed is not critical, but is preferably a volume percentage of 75% to 80% hexanol or methanol, and more preferably a volume percentage of 75% to 80% hexanol.

[0030] 步骤F中采用的脱水溶剂不是关键的,只要能够使沉淀物脱水并容易挥发即可, 优选无水己醇或甲醇或丙丽,更优选己醇。 [0030] Step F dehydrating solvent employed is not critical, as long as the precipitate was dehydrated and volatile, and preferably anhydrous methanol or propan-hexanol or Li, and more preferably hexanol.

附图说明 BRIEF DESCRIPTION

[0031] 图1为本发明蜂巢状HA溶于水后分子聚集状态。 Molecular aggregation state dissolved in water honeycomb HA [0031] FIG. 1 of the present invention.

[0032] 图2为高分子量HA溶于水后分子聚集状态。 [0032] FIG. 2 is a state where molecules aggregate molecular weight HA is dissolved in water.

[0033] 图3为低分子量HA溶于水后分子聚集状态。 [0033] FIG. 3 is a low molecular weight HA molecules dissolved in water aggregate state.

[0034] 图4为高低分子量HA物理混合物溶于水后分子聚集状态。 [0034] FIG. 4 is a physical mixture of high and low molecular weight HA molecules dissolved in water aggregate state.

[0035] 原子力显微镜的参数如下;Multimode Nanoscope VIII,探针是XSC11,扫描模式是scanasyst,扫描速度是IHz,分辨率是512X 512。 [0035] The following parameters of the atomic force microscope; Multimode Nanoscope VIII, the probe is XSC11, scan mode is scanasyst, the scanning speed was IHz, resolution is 512X 512.

具体实施方式 detailed description

[0036] 为了更好的理解本发明,下面结合具体实施例来进一步说明。 [0036] For a better understanding of the invention, in conjunction with the following specific examples further illustrate. 但是本发明不仅限于W下具体实施例。 However, the present invention is not limited to the specific embodiments of the W.

[0037] 实施例1 [0037] Example 1

[003引50g本发明蜂巢状HA,投料配比如下: [003 primers of the present invention honeycomb 50g HA, the following charge ratio:

[0039] 高分子量HA (30ί)0 kDa)受g 低分子量HA (1 kl)a) 45g 氣化锅50.5g 纯化水5000 ml [0039] High molecular weight HA (30ί) 0 kDa) by g low molecular weight HA (1 kl) a) 45g gasification boiler 50.5g Purified water 5000 ml

[0040] 制备本发明蜂巢状HA的步骤: [0040] The step of preparing the honeycomb of the present invention, HA:

[0041] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0041] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比1% 氯化钢,揽拌均匀。 Was added 1% by weight of steel chloride, olive mix evenly. 用碳酸钢溶液迅速将体系抑调节至8,揽拌下,滴加两倍体积的体积百分比为95%甲醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比75%甲醇洗涂Η次,再用无水甲醇脱水,真空干燥即得。 The system was quickly suppressed steel carbonate solution was adjusted to 8 with, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% methanol, precipitated completely, the supernatant was removed by filtration, a white precipitate percentage of 75% by volume methanol washcoated Η times, dried over anhydrous methanol dehydration, and dried in vacuo to obtain.

[004引实施例2 [Example 2 004 Primer

[0043] 50g本发明蜂巢状ΗΑ,投料配比如下: [0043] 50g of the present invention is a honeycomb ΗΑ, the following charge ratio:

[0044] 高分子量HA yOOO kDa) 45g 低分子量HA 口00 kDa) 5g 氯化铜252.5g 纯化水S㈱0 ml [0044] High molecular weight HA yOOO kDa) 45g of low molecular weight HA port 00 kDa) 5g of copper chloride 252.5g purified water S㈱0 ml

[0045] 制备本发明蜂巢状HA的步骤: [0045] The step of preparing the honeycomb of the present invention, HA:

[0046] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0046] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比为5%的氯化钢,揽拌均匀。 Was added 5% by weight of chlorinated steel embrace mix well. 用氨氧化钢溶液迅速将体系抑调节至13,揽拌下,滴加两倍体积的体积百分比为95%的己醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比为80%的己醇洗涂Η次,再用无水己醇脱水,烘干即得。 The rapid growth suppression was adjusted with ammonia solution to the oxidation of the steel 13, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% hexyl alcohol, completely precipitated, supernatant was removed by filtration, a white precipitate was washed with 80 volume percent of % hexanol washcoating Η times, dried over anhydrous dehydration and drying to obtain.

[0047] 实施例3 [0047] Example 3

[0048] 50g本发明蜂巢状ΗΑ,投料配比如下: [0048] 50g of the present invention is a honeycomb ΗΑ, the following charge ratio:

[0049] 高分子量Η A 口000 kDa) 15g 低分子量HA巧kOa) 35g 氯化钥Wig 纯化水5000ml [0049] The molecular weight Η A port 000 kDa) 15g of low molecular weight HA Qiao kOa) Wig chloride key 35g purified water 5000ml

[0050] 制备本发明蜂巢状HA的步骤: [0050] The step of preparing the honeycomb of the present invention, HA:

[0051] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0051] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比为2 %的氯化钢,揽拌均匀。 Was added 2% by weight of chlorinated steel embrace mix well. 用碳酸氨钢溶液将体系抑调节至8,揽拌下,滴加两倍体积的体积百分比为95%的己醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比为75% 的己醇洗涂Η次,再用丙丽脱水,自然风干即得。 Carbonate steel ammonia solution was adjusted to 8 suppression system, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% hexyl alcohol, completely precipitated, supernatant was removed by filtration, a white precipitate was washed with 75% volume percent hexanol washcoating Η times and then with propan-Li dehydration, to obtain dry naturally.

[0052] 实施例4 [0052] Example 4

[005引50g本发明蜂巢状ΗΑ,投料配比如下: [005 50g primer of the present invention is a honeycomb ΗΑ, the following charge ratio:

[0054] 高分子量HA(lOOOkDa) 35g 低分子量Η A (400 kDa) 15g [0054] High molecular weight HA (lOOOkDa) 35g of low molecular weight Η A (400 kDa) 15g

[00 巧] 氯化铺151.5g 统化水5000ml [00 Qiao] chlorination system laid 151.5g of water 5000ml

[0056] 制备本发明蜂巢状HA的步骤: [0056] The step of preparing the honeycomb of the present invention, HA:

[0057] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0057] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比为3 %的氯化钢,揽拌均匀。 Was added 3% by weight of chlorinated steel embrace mix well. 用己酸钢溶液将体系抑调节至8,揽拌下,滴加两倍体积的体积百分比为95%的己醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比为80%的己醇洗涂Η次,再用无水己醇脱水,真空干燥即得。 Steel with a solution of hexanoic acid suppression system was adjusted to 8, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% hexyl alcohol, completely precipitated, supernatant was removed by filtration, a white precipitate with 80% by volume hexanol washcoating Η times, dried over anhydrous hexanol dehydration, and dried in vacuo to obtain.

[00则实施例5 [Example 5 00

[005引50g本发明蜂巢状ΗΑ,投料配比如下: [005 50g primer of the present invention is a honeycomb ΗΑ, the following charge ratio:

[0060] 高分子量HA "500 kDa) 15g 低分子量HA巧kDa) 35g 氯化铜50.5g 纯化水5000ml [0060] High molecular weight HA "500 kDa) 15g of low molecular weight HA Qiao kDa) 35g copper chloride 50.5g Purified water 5000ml

[0061] 制备本发明蜂巢状HA的步骤: [0061] The step of preparing the honeycomb of the present invention, HA:

[0062] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0062] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比为1 %的氯化钢,揽拌均匀。 Was added 1% by weight of chlorinated steel embrace mix well. 用氨氧化钢溶液将体系抑调节至9. 5,揽拌下,滴加两倍体积的体积百分比为95%的己醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比为80%的己醇洗涂Η次,再用无水己醇脱水,真空干燥即得。 Ammonia solution with iron oxide growth suppression was adjusted to 9.5, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% hexyl alcohol, completely precipitated, the supernatant was removed by filtration, a white precipitate of the volume percentage 80% of coating Η hexanol washed twice, dehydrated with anhydrous hexanol, and dried in vacuo to obtain.

[0063] 实施例5所得ΗΑ在水溶液的分子聚集形态如图1所示。 [0063] 5 obtained in Example 1 ΗΑ molecule aggregates form aqueous FIG. 本发明所得ΗΑ,溶于水后,原子力显微镜扫描可见,分子聚集成规则的蜂巢状。 The resulting present invention ΗΑ, dissolved in water, visible scanning atomic force microscopy, molecules aggregate into a honeycomb rules.

[0064] 实施例6 [0064] Example 6

[006引50g本发明蜂巢状ΗΑ,投料配比如下: [006 50g primer of the present invention is a honeycomb ΗΑ, the following charge ratio:

[0066] 高分子量HA (1000 kDa) 25g 低分子量ha片00 kDa) 25g 氯化铜2筑•雖纯化水5000ml [0066] High molecular weight HA (1000 kDa) 25g ha sheet of low molecular weight 00 kDa) 25g cupric chloride • building although 5000ml purified water

[0067] 制备本发明蜂巢状HA的步骤: [0067] The step of preparing the honeycomb of the present invention, HA:

[0068] 将高、低分子量HA溶于5000ml纯化水,溶解后继续揽拌比。 [0068] The high and low molecular weight HA was dissolved in 5000ml of purified water and continue to mix embrace than dissolved. 加入重量百分比为5 %的氯化钢,揽拌均匀。 Was added 5% by weight of chlorinated steel embrace mix well. 用氨氧化钢溶液迅速将体系抑调节至10. 5,揽拌下,滴加两倍体积的体积百分比为95%的己醇,沉淀析出完全,过滤除去上清液,白色沉淀物用体积百分比为80%的己醇洗涂Η次,再用无水己醇脱水,抽真空干燥即得。 The rapid growth suppression was adjusted with ammonia solution to oxidation of the steel 10.5, embrace the mix, the percentage by volume twice the volume of the dropwise addition of 95% hexyl alcohol, completely precipitated, supernatant was removed by filtration, the volume percentage of the white precipitate 80% wash coating Η times hexanol, dehydrated with anhydrous hexanol, evacuated and dried in vacuo to obtain.

[0069] 将该方法制备的蜂巢状ΗΑ与非蜂巢状ΗΑ进行功效学试验,评价补水和保水性能, [0069] The prepared honeycomb ΗΑ ergonomics test methods and non honeycomb ΗΑ, moisturizing and water retention property evaluation,

具体实施方式见对比实施例1。 DETAILED DESCRIPTION See Comparative Example 1. 本发明的有益效果: Advantageous effects of the invention:

[0070] 本发明在醇沉之前将溶液抑调节至碱性,使分子的螺旋半径减小,分子拓展度降低,使ΗΑ达到较高浓度,ΗΑ分子间的疏水区域相互作用,聚集成蜂巢状结构,同时该溶液体系还具有较低的粘性,利于醇沉淀。 [0070] The present invention prior to ethanol precipitation the solution was adjusted to suppress basic molecular helix radius is reduced, reducing the degree of molecular expand the ΗΑ reach higher concentrations, the hydrophobic region between ΗΑ intermolecular interactions, gathered into a honeycomb structure, while the system further has a low solution viscosity, is conducive to alcohol precipitation.

[0071] 通过该工艺制备的"蜂巢状ΗΑ"既具有高分子量ΗΑ良好的长久保水和隔离侵害作用,又具有低分子量ΗΑ深层补水保湿和营养修复的作用;同时相比于高分子量ΗΑ和低分子量ΗΑ的简单物理混合,该发明的ΗΑ其在水溶液中具有亲体仿生的蜂巢状结构,溶解更快, 利于透气,具有更好的补水和保水作用。 [0071] prepared by the process "honeycomb ΗΑ" both good high molecular weight ΗΑ long water retention and isolation against the action, but also has a deep effect of low molecular weight ΗΑ hydrating and nutrition repair; while compared to the high molecular weight ΗΑ and low ΗΑ simple physical mixing of the molecular weight, ΗΑ the invention in an aqueous solution having a parent body of the honeycomb structure biomimetic, dissolve more quickly, conducive breathable, have better water retention and replenishment.

[0072] 本发明的有益效果具体通过下面的功效试验体现。 [0072] Advantageous effects of the present invention is particularly embodied by the following test efficacy.

[007引对比实施例1 ;蜂巢状ΗΑ与非蜂巢状ΗΑ功效学评价。 [Comparative Example 1 Primer 007; ΗΑ a honeycomb effect and non ΗΑ Evaluation of honeycomb.

[0074] 测试样品4组,A组为低分子量HA(200kDa),Β组为高分子量HA(lOOOkDa),C组为高低分子量HA (与蜂巢HA所用HA分子量相同)按重量百分比5:5物理混合均匀,D组为实施例6所制备的蜂巢HA,测试样品为HA浓度0. 5%的水溶液。 [0074] The test samples four groups, A group of low molecular weight HA (200kDa), Β group of high molecular weight HA (lOOOkDa), group C is a low molecular weight HA (the honeycomb HA used in the same HA molecular weight) weight percent 5: 5 Physical mixed, honeycomb group D prepared in Example HA. 6, the test sample is an aqueous solution of HA of 0.5% concentration.

[0075] 试验采用自身对照法,受试者32名,在受试者左、右手臂前臂屈侧标记试验区域, 共四个测试区域,每个测试区域4cmX 4cm,标记为A、B、C、D。 [0075] The self-control method using the test subject 32, subject the left and right arm flexor forearm marked test area, a total of four test areas, the test areas each 4cmX 4cm, labeled A, B, C , D. 四个测试区域滴加相应样品并轻轻拍打使其吸收。 Four test areas corresponding samples added dropwise and gently pat to absorb. 使用Corneometer CM825、Co;rneometer TM300测定涂抹前及涂后30min、lh、3h、化时各区域内的皮肤水分含量和皮肤水分流失量。 Using Corneometer CM825, Co; rneometer TM300 measured before spread 30min, lh, 3h, when the moisture content of the skin and skin water loss and after application of each of the regions. 数据处理公式如下: Data processing formula is as follows:

[0076] [0076]

[0077] [0077]

Figure CN105878051AD00081

[0078] 试验结果见表1和表2,表中数值为32名受试者的平均值。 [0078] The results in Table 1 and Table 2, values ​​in the table are mean of 32 subjects.

[0079] 表1 ;蜂巢状HA与非蜂巢状HA样品涂抹后皮肤水分含量增加率(% ) [0079] Table 1; HA honeycomb skin moisture content and the increasing rate of the non-HA honeycomb sample applicator (%)

[0080] [0080]

Figure CN105878051AD00082

[0081] 表1中数值为涂抹#品后4涂抹W皮中水为、含量i加的百分比。 [0081] The values ​​in Table 1 apply to W 4 # skin after application of product in water, the percentage content of i is incremented. 数值越大表明皮肤涂抹样品后含水量增加越高,样品补水效果越好。 A greater value increases the water content of a sample of skin after application, the better the effect of water samples.

[0082] 表2 ;蜂巢状HA与非蜂巢状HA样品涂抹后皮肤水分流失增加率(% ) [0082] Table 2; honeycomb HA after HA Non sample applicator honeycomb skin water loss rate (%)

[0083] [0083]

Figure CN105878051AD00083

[0084] 表2中,负号表示涂抹样品后较涂抹前皮肤水分流失减少I,即,绝对值越大表明涂抹样品后水分流失减少的越多,样品保水效果越好。 In [0084] Table 2, compared with a negative sign indicates the applicator after applying the sample to reduce the water loss of the skin before I, i.e., the larger the absolute value of the smear sample showed more reduction of water loss, the better the water retention effect of the sample.

[0085] 由试验结果可见,A组低分子量HA 30min内补水效果较好,但皮肤水分散失率最大,保水效果差;B组高分子量HA瞬时补水效果最差,但是由于在皮肤表面形成保护膜,皮肤水分散失率小,保水效果较好;C组高低分子量HA物理混合后,补水和保水相对都较好, 但是依然劣于蜂巢状HA ;D组蜂巢状HA无论是补水还是保水效果,都是四组中最好的。 [0085] The test results can be seen, A group of the low molecular weight HA pay better for 30 min, but the maximum rate of skin water loss, poor water retention; Group B molecular weight HA replenishment worst instantaneous, but by forming a protective film on the skin surface , small skin water loss rate, water retention is better; group C LMW physical mixing HA, moisturizing and water retention opposing are better, but still inferior to the honeycomb HA; group D honeycomb HA either replenishment or water retention effect are It is the best of the four groups. 对比实施例2 ;不同配比的高低分子量HA制备的蜂巢状HA功效学评价。 Comparative Example 2; Evaluation of Low Molecular Weight HA ergonomics of different ratio of HA prepared honeycomb.

[0086] 测试样品5组,分别为不同配比的高低分子量HA所制备的蜂巢状HA。 [0086] Group 5 test samples were prepared for the different ratio of LMW HA HA honeycomb. 其中分组和高低分子量HA配比如表3所示。 And wherein the LMW HA with packet such as shown in Table 3. 蜂巢状HA的制备条件如实施例3所述。 Honeycomb HA preparation conditions as described in Example 3. 巧IJ试样品为总HA浓度0.5 %的水溶液。 Qiao IJ test sample of an aqueous solution of 0.5% of the total HA concentration.

[0087] 表3不同配比的蜂巢状HA配方 [0087] TABLE 3 different HA formulation ratios of honeycomb

[0088] [0088]

Figure CN105878051AD00091

[0090] 试验采用自身对照法,受试者32名,在受试者左、右手臂前臂屈侧标记试验区域, 共五个测试区域,每个测试区域4cmX 4cm,标记为A、B、C、D、E。 [0090] The self-control method using the test subject 32, subject the left and right arm flexor forearm marked test area, a total of five test zones, each test zone 4cmX 4cm, labeled A, B, C , D, E. 每个测试区域滴加相应样品并轻轻拍打使其吸收。 Each respective sample was added dropwise and the test area to absorb pat. 使用Corneometer CM825、Co;rneomete;r TM300测定涂抹前及涂后30min、lh、3h、化时各区域内的皮肤水分含量和皮肤水分流失量。 Using Corneometer CM825, Co; rneomete; r TM300 measured before spread 30min, lh, 3h, when the moisture content of the skin and skin water loss and after application of each of the regions.

[0091] 试验结果见表4和表5,表中数值为32名受试者的平均值。 [0091] The results in Table 4 and Table 5, values ​​in the table is the average of the 32 subjects.

[009引表4不同配比的蜂巢状HA样品涂抹后皮肤水分含量增加率(% ) [Table 009 cited increasing rate of skin moisture content after the honeycomb HA samples different ratio applicator 4 (%)

[0093] [0093]

Figure CN105878051AD00092

[0094] 表4中数值为涂抹#品后4涂抹W皮中水为、含量i加的百分比。 [0094] The values ​​in Table 4 apply to W 4 # skin after application of the product water, the percentage content of i is incremented. 数值越大表明皮肤涂抹样品后含水量增加越高,样品补水效果越好。 A greater value increases the water content of a sample of skin after application, the better the effect of water samples.

[0095] 表5不同配比的蜂巢状HA样品涂抹后皮肤水分流失增加率(% ) [0095] Table 5 after the applicator honeycomb HA samples different ratio of skin water loss rate (%)

[0096] [0096]

Figure CN105878051AD00101

[0097] 表5中,负号表示涂抹样品后较涂抹前皮肤水分流失减少I,即,绝对值越大表明涂抹样品后水分流失减少的越多,样品保水效果越好。 [0097] Table 5, compared with a negative sign indicates the applicator before the sample after the application of the skin to reduce moisture loss I, i.e., the larger the absolute value of the smear sample showed more reduction of water loss, the better the water retention effect of the sample.

[009引由试验结果可见,涂抹B组样品后,皮肤水分含量增加率最高,说明B组样品补水效果最好(表4);同时皮肤水分流失减少的最高,说明B组样品保水效果最好(表5)。 [009 cited seen from the test results, the smear sample group B, maximum rate of increase skin moisture content, Group B described replenishment of the best samples (Table 4); while the maximum decrease in skin water loss, water retention sample group B described best (table 5). 目P, 蜂巢状HA中高、低分子量HA配比为重量百分比3:7时,补水和保水效果都最好。 P mesh, honeycomb HA of high and low molecular weight HA 3 percentage ratio: 7, moisturizing and water retention effects are best.

Claims (10)

  1. 1. 透明质酸,其特征在于该透明质酸溶于水后呈规则的蜂巢状结构。 1. hyaluronic acid, hyaluronic acid, characterized in that the honeycomb structure as a rule dissolved in water.
  2. 2. 根据权利要求1所述的"透明质酸",其特征还在于该透明质酸由高分子量透明质酸或其盐和低分子量透明质酸或其盐配制而成。 The claim "hyaluronic acid" according to 1, further characterized in that the hyaluronic acid of high molecular weight hyaluronic acid or a salt thereof and low molecular weight hyaluronic acid or salt thereof formulated.
  3. 3. 根据权利要求2所述的"透明质酸",其中所述高分子量透明质酸或其盐的分子量为1000 kDa~3000kDa,低分子量透明质酸或其盐的分子量为IkDa~500kDa,优选高分子量HA的分子量为1000 kDa~2000kDa,低分子量HA分子量5kDa~400kDa,更优选1¾分子量HA分子量为1000 kDa~1500kDa,低分子量HA分子量5kDa~200kDa。 3. The claim "hyaluronic acid" of claim 2, wherein the molecular weight of the high molecular weight hyaluronic acid or salt thereof is 1000 kDa ~ 3000kDa, the molecular weight of the low molecular weight hyaluronic acid or salt thereof is IkDa ~ 500kDa, preferably molecular weight HA molecular weight of 1000 kDa ~ 2000kDa, low molecular weight HA molecular 5kDa ~ 400kDa, more preferably a molecular weight of HA 1¾ molecular weight 1000 kDa ~ 1500kDa, low molecular weight HA molecular 5kDa ~ 200kDa.
  4. 4. 根据权利要求2所述的"透明质酸",其中所述高分子量透明质酸或其盐和低分子量透明质酸或其盐的配比为重量百分比为1:9~9:1,优选3:7~7:3,更优选3:7。 According to claim "hyaluronic acid" of claim 2, wherein the high molecular weight hyaluronic acid or salt thereof and low molecular weight hyaluronic acid or a salt weight percent ratio of from 1: 9 to 9: 1, preferably 3: 7 to 7: 3, more preferably 3: 7.
  5. 5. 根据权利要求2 - 4中任一项所述的"透明质酸",其中所述配制在碱性条件下进行。 According to any one of the 4 "hyaluronic acid", wherein the formulation is performed under basic conditions - as claimed in claim 2.
  6. 6. 根据权利要求9所述的"透明质酸",其中所述碱性条件为用无机碱或盐调节pH至8 - 13,优选pH 为9. 5 - 10. 5。 The claim "hyaluronic acid" 9, wherein the basic pH condition is adjusted with an inorganic base or salt to 8 - 13 and preferably a pH of 9.5 - 10.5.
  7. 7. 根据权利要求5-6中任一项所述的"透明质酸",其中所用的无机碱或盐选自氢氧化钠、碳酸钠、碳酸氢钠和乙酸钠,优选氢氧化钠。 According to any one of claims 5-6, "hyaluronic acid", wherein the inorganic base used or salt thereof selected from sodium hydroxide, sodium carbonate, sodium bicarbonate and sodium acetate, preferably sodium hydroxide claims.
  8. 8. 根据权利要求2 - 7中任一项所述的"透明质酸",其中所述配制还包括醇沉的步骤。 According to claim 2--7 of any one of "hyaluronic acid", wherein the formulation further comprises a step of alcohol precipitation.
  9. 9. 根据权利要求8所述的"透明质酸",其中所述醇沉采用体积百分比为95%的乙醇或甲醇进行,优选体积百分比为95%的乙醇。 According to claim "hyaluronic acid" according to 8, wherein the alcohol precipitation percent by volume of 95% ethanol or methanol, preferably a volume percentage of 95% ethanol.
  10. 10. 制备权利要求1所述的"透明质酸"的方法,该方法包括以下步骤: A、 将高、低分子量的HA溶于纯化水,搅拌均匀; B、 加入重量百分比为1%~5%的氯化钠搅拌均匀; C、 用无机碱或盐调节pH至碱性; D、 搅拌下,用体积百分比为95%的乙醇或甲醇醇沉; E、 滤出沉淀物,用体积百分比为75%~80%的乙醇或甲醇洗涤; F、 沉淀物用无水乙醇或甲醇或丙酮脱水后干燥即得。 The method of "hyaluronic acid" 10. The preparation according to claim 1, the method comprising the steps of: A, the high and low molecular weight HA is dissolved in purified water, stir; B, 1% by weight was added to 5 stir% NaCl; C, the pH was adjusted to a salt with an inorganic base or basic; D, under stirring, with a percentage of 95% by volume of ethanol or methanol, ethanol precipitation; E, the precipitate was filtered off, the volume percentage of washed with 75% to 80% ethanol or methanol; F, the precipitate was dried to obtain anhydrous ethanol or methanol or acetone dehydration.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101704905A (en) * 2009-09-28 2010-05-12 安徽丰原发酵技术工程研究有限公司 Method for extracting hyaluronic acid
US20110118206A1 (en) * 2008-08-04 2011-05-19 Allergan Industrie, Sas Hyaluronic acid based formulations
CN104059166A (en) * 2013-03-21 2014-09-24 上海昊海生物科技股份有限公司 Method for preparing oligomeric hyaluronic acid by hyaluronic acid broth
CN104225677A (en) * 2013-06-13 2014-12-24 山东省生物药物研究院 Cross-linked hyaluronic acid cell-scaffold material and preparation method and application

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110118206A1 (en) * 2008-08-04 2011-05-19 Allergan Industrie, Sas Hyaluronic acid based formulations
CN101704905A (en) * 2009-09-28 2010-05-12 安徽丰原发酵技术工程研究有限公司 Method for extracting hyaluronic acid
CN104059166A (en) * 2013-03-21 2014-09-24 上海昊海生物科技股份有限公司 Method for preparing oligomeric hyaluronic acid by hyaluronic acid broth
CN104225677A (en) * 2013-06-13 2014-12-24 山东省生物药物研究院 Cross-linked hyaluronic acid cell-scaffold material and preparation method and application

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