CN101045165A - Hydroxypropyl beta-cyclodextrin clathrate of astaxanthin, and its preparing method - Google Patents
Hydroxypropyl beta-cyclodextrin clathrate of astaxanthin, and its preparing method Download PDFInfo
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- CN101045165A CN101045165A CNA2007100220548A CN200710022054A CN101045165A CN 101045165 A CN101045165 A CN 101045165A CN A2007100220548 A CNA2007100220548 A CN A2007100220548A CN 200710022054 A CN200710022054 A CN 200710022054A CN 101045165 A CN101045165 A CN 101045165A
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Abstract
An inclusion compound of astaxanthin with hydroxypropyl-beta-cyclodextrin in mole ratio of 1: (1-100) features that part or all of astaxanthin moleculae are included in the cavities of hydroxypropyl-beta-cyclodextrin in order to improve the optical and thermal stability and water solubility of astaxanthin. It is prepared by deposition method, suspending method, or grinding method.
Description
Technical field
The present invention relates to the clathrate of the HP-of astaxanthin, and the preparation method of this clathrate.
Background technology
Astaxanthin extensively is present in the biosphere, particularly in the feather of the shrimp of aquatic animal, Eriocheir sinensis, fish and birds.Astaxanthin is a kind of important carotenoid, and its chemical name is: 3, and 3-dihydroxy-4,4 '-diketo-β-carotenoid, molecular formula (general formula) is: C
40H
52O
4, molecular weight 596.86.Experimental results show that astaxanthin be unique can be by the carotenoid of blood brain barrier, there are extremely strong antitumor, antioxygenic property (to be 10 times of beta-carotene, 500 times of vitamin E), and enhancing human body immunity power is arranged, resisting hypertension, multiple pharmacological effect such as control inflammation.Simultaneously, astaxanthin is again a kind of good coloring agent, can improve Aquatic product, poultry skin and fowl egg pigmentation, improve product quality, enhancing antibody produces, and improves animal immunizing power, be the main pigment of Fish such as salmon, also have important value aspect Aquatic product and the poultry farming.Natural astaxanthin is at present mainly as the raw material of human high-class healthy food, medicine; The feed additive of aquaculture, poultry farming; Cosmetics additive.Functional food, cosmetics and medical aspect have wide practical use.Because the height unsaturation and the water-insoluble of astaxanthin molecule, therefore extremely instability and bioavailability are relatively poor to photo-thermal, and these all become the technical bottleneck that it is used in field of medicaments.
At present, cyclodextrin inclusion technique has had application widely at food and field of medicaments.Experiment showed, that cyclodextrin and derivant thereof are the fine enclose materials of a class, mainly contain the application of following several aspects: the water solublity that increases medicine; Improve stability of drug; Promote drug absorption, improve bioavailability of medicament; Alleviate stimulation and the side effect of medicine to body; Carrier material as slow release and targeting preparation.In addition cyclodextrin can also make the liquid drug solidification, change medicine bad smell, reduce medicine volatilization loss, prevent the interaction of drug-drug, medicine-excipient or adjuvant in the preparation etc.The cyclodextrin derivative of developmental research at present reached hundreds of more than, but because these chemical compounds must satisfy water solublity well, the suitable little especially low many requirements such as nephrotoxicity of molecule inclusion characteristic, biological activity simultaneously, therefore, can be also few as cyclodextrin and derivant thereof that pharmaceutic adjuvant uses. what study morely at present is beta-schardinger dextrin-, HP-.
Clathration about beta-schardinger dextrin-and astaxanthin had bibliographical information (XiaolinChen, Rong Chen, Zhanyong guo, Cuiping Li, β-cyclodextrin.), result of study shows that astaxanthin can be by beta-cyclodextrin inclusion compound to The preparation and stability ofthe inclusion complex ofastaxanthin with, and the photo and thermal stability of formed clathrate greatly improves, but dissolubility does not have obvious improvement, and dissolubility is less than 0.5mg/ml.HP-is the neutral derivant of beta-schardinger dextrin-nonionicization, and it is in safety, and stabilisation, aspects such as medicament solubilization and technology for producing all have raising more significantly, and its advantage may be summarized to be: high water solublity (＞50g/100g H
2O); Strong enclose performance; Parmacodynamics-less activity; Renal function there is not influence; Can be used for non-oral formulation.China is through " 95 " research of technique, and HP-begins to produce as new pharmaceutic adjuvant.
Summary of the invention
The object of the present invention is to provide the clathrate and preparation method thereof of the HP-of astaxanthin,, improve the dissolubility of the astaxanthin that is insoluble in water to improve the stability of astaxanthin to photo-thermal.
Technical solution of the present invention is:
A kind of clathrate of HP-of astaxanthin is characterized in that: all or part of enclose of astaxanthin molecule is in the cavity of HP-, and the mol ratio of astaxanthin and HP-is 1: 1～100.
A kind of preparation method of clathrate of HP-of astaxanthin (coprecipitation) is characterized in that: HP-is made aqueous solution at 20～80 ℃, at N
2, H
2, or CO
2Under the protection of gas wherein the astaxanthin mole be equivalent to the astaxanthin solution of the organic solvent dissolution of HP-mole 1～1/100, stirring, the ultrasonic or 0.5～24h that refluxes, cooled and filtered, the dry clathrate that gets the HP-of astaxanthin; Described organic solvent is a kind of in ethanol, the acetone.
The clathrate of the HP-of the above-mentioned astaxanthin that obtains, also unreacted astaxanthin, dried in organic solvent eccysis filtering residue.
A kind of preparation method of clathrate of HP-of astaxanthin (outstanding turbid method), it is characterized in that: HP-is mixed with water, make into suspended substance or solution, add the astaxanthin that is equivalent to HP-mole 1～1/100 amount, mix, stir, ultrasonic or grind convection drying after 0.5～24 hour or through the clathrate of the HP-of filter pressing, washing, dry astaxanthin.
A kind of preparation method of clathrate of HP-of astaxanthin (polishing), it is characterized in that: HP-is put into colloid mill, ball mill or mortar, add entry and make it to become pastel, add the astaxanthin that is equivalent to HP-mole 1～1/100, mix, the common grinding 1～8 hour, convection drying or after filter pressing, washing, drying the clathrate of HP-of astaxanthin.
The beneficial effect that is brought after the invention process is: behind astaxanthin and HP-formation clathrate, because the inner chamber of HP-has wrapped up astaxanthin at molecular level, the photo and thermal stability that it has strengthened astaxanthin to the sterically hindered effect and the complexing of astaxanthin.
Because the hydrophilic hydroxyl that much is in the molecule exocoel is arranged in the HP-molecule, for hydrophobic astaxanthin, after its molecule enters the hydrophobicity inner chamber of HP-by the molecule self assembly, astaxanthin is by the hydrophilic shell of HP-, and its water solublity obtains significant increasing.
The experimental result of the clathrate of the HP-of the astaxanthin for preparing by mode of the present invention has also proved the deduction that cyclodextrin inclusion technique can strengthen the astaxanthin photo and thermal stability and improve its dissolubility.The light durability experiment of astaxanthin and cyclodextrin clathrate thereof shows, shine the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin and astaxanthin simultaneously with 4500Lx intensity light, with the high performance liquid chromatography is analysis means, calculates the content of astaxanthin remaining in 0-6 days samples, the results are shown in Table one.The result shows: astaxanthin content of 7 days under illumination descends obviously, and the stable content of astaxanthin in the clathrate.
The hydroxypropyl-beta-cyclodextrin inclusion light durability experimental result of table one astaxanthin
| Natural law | Illumination experiment (content astaxanthin) | |
| Astaxanthin | Astaxanthin/hydroxypropyl-beta-cyclodextrin inclusion | |
| 0 | 98.2％ | 16.8％ |
| 1 | 91.5％ | 16.7％ |
| 2 | 32.1％ | 16.4％ |
| 3 | 34.5％ | 16.6％ |
| 4 | 31.2％ | 16.4％ |
| 5 | 31.8％ | 16.5％ |
| 6 | 26.2％ | 16.5％ |
The heat stability of the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin also obviously increases.With astaxanthin, astaxanthin/hydroxypropyl-beta-cyclodextrin inclusion respectively as in 40 ℃ and the 60 ℃ of constant temperature ovens, with the high performance liquid chromatography is analysis means, investigate the influence of temperature by the content that detects remaining astaxanthin, the results are shown in Table two the stability of the clathrate of astaxanthin and HP-thereof.The result shows: astaxanthin is to thermoae instability, and intensive amount descended obviously in 7 days, and the content astaxanthin in the clathrate is stable.
The hydroxypropyl-beta-cyclodextrin inclusion high-temperature stability experimental result of table two astaxanthin
| Natural law | High temperature experiment (content astaxanthin) | |||
| 40℃ | 60℃ | |||
| Astaxanthin | Astaxanthin/hydroxypropyl-beta-cyclodextrin inclusion | Astaxanthin | Astaxanthin/hydroxypropyl-beta-cyclodextrin inclusion | |
| 0 | 98.2％ | 16.8％ | 98.2％ | 16.8％ |
| 1 | 84.6％ | 16.6％ | 81.4％ | 16.6％ |
| 2 | 58.2％ | 16.5％ | 51.7％ | 16.4％ |
| 3 | 50.2％ | 16.4％ | 47.2％ | 16.3％ |
| 4 | 43.8％ | 16.3％ | 38.5％ | 16％ |
| 5 | 41.9％ | 16.1％ | 27.9％ | 16.1％ |
| 6 | 23.9％ | 16.％ | 26.1％ | 16.1％ |
The present invention makes the water solubility of astaxanthin obtain significantly to increase, and the HP-of 10mg/ml makes the dissolubility of astaxanthin reach 3.7mg/ml, and solution is lavender.
Use the examination of infrared spectrum technology astaxanthin/hydroxypropyl-beta-cyclodextrin inclusion is characterized, the results are shown in accompanying drawing.
Description of drawings:
Accompanying drawing is astaxanthin, HP-, physical mixture, clathrate infrared scan collection of illustrative plates.
Astaxanthin is at 1652cm-1Be the stretching vibration of C=O, the superposeed characteristic peak of astaxanthin and cyclodextrin of the infared spectrum of physical mixture shows that mixture still has the characteristic of astaxanthin and cyclodextrin. Have no the characteristic absorption peak of astaxanthin in the infared spectrum of inclusion compound, also have no new absworption peak, show in the inclusion compound to produce without new chemical bond. New absworption peak can occur in the infared spectrum of general inclusion compound, showing has new chemical bond to produce; Reduction, displacement or the disappearance of medicine characteristic absorption peak or reduction, displacement or the disappearance of carrier characteristic absorption peak also can be arranged. Collection of illustrative plates among the present invention is the third situation, but since HP-β-CD free-OHs and association-vibration absorption peak of OHs is wider, a small amount of astaxanthin is not obvious on its impact in the inclusion compound, so inclusion compound collection of illustrative plates and HP-β-CD are basic identical.
The specific embodiment
Embodiment 1:
Get HP-, 110 ℃ are dried to constant weight, take by weighing 15g and place conical flask, and adding 50ml water is heated to HP-and dissolves fully, continues to be warming up to 70 ℃ (or 40 ℃, 80 ℃), feeds N in conical flask
2(or H
2, CO
2) not oxidized with the protective reaction thing; the astaxanthin of 0.5g is dissolved with 5ml ethanol (or acetone); be added to Dropping funnel; under stirring condition; dropwise splash in the flask that HP-is housed; continue to stir (or ultrasonic, reflow treatment) 8 hours; solution is concentrated into 20ml under vacuum condition; after cooling to room temperature; place 4 ℃ of cold preservations and spend the night, filter out precipitation, place 40 ℃ vacuum drying oven inner drying 4 hours again; can obtain the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin, product is the lavender powder.
Embodiment 2:
The clathrate powder that embodiment 1 is obtained washs with ethanol (or acetone) earlier, wash with water, and then vacuum drying gets the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin again.
Embodiment 3:
Under the room temperature 5g HP-is mixed with the pure water of 10ml, grind evenly, add 0.25g astaxanthin pressed powder, fully mix, grind (about 5～8 hours), ground again 1 hour when system changes even lavender pastel into by purple white content is alternate, 40 ℃ of vacuum dryings 4 hours fluffy lavender solid clathrates.
Embodiment 4:
Under the room temperature 10 gram HP-are mixed, stirred with 50 milliliters of pure water, make into suspended substance, add 1 gram astaxanthin pressed powder, fully mix, logical nitrogen, insulated and stirred (or ultrasonic, milled processed) is about more than 12 hours, and system is even lavender, stir slowly cooling down, placement is spent the night, and filters out precipitation, with 5 milliliters of alcohol flushing precipitations, place 40 ℃ vacuum drying oven inner drying 4 hours again, can obtain the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin.
Embodiment 5:
Take by weighing the 20g HP-, put into the ball milling cylinder (or colloid mill, mortar) of ball mill, add about 10ml water, grind and make into pasty state; Take by weighing the 1g astaxanthin, pour in the mortar; Mixed liquor ground 2 hours, obtained the homogeneous dope, filtered, and 40 ℃ of vacuum dryings 4 hours take out to grind and get final product.
Embodiment 6:
Get HP-, take by weighing 15g and place conical flask, adding 50ml water is heated to HP-and dissolves fully, feeds CO in conical flask
2Not oxidized with the protective reaction thing; astaxanthin powder with 0.5g; under stirring condition, slowly add and be equipped with in the flask of HP-, continue to stir 8 hours; solution is concentrated into 20ml under vacuum condition; after cooling to room temperature, place 4 ℃ of cold preservations and spend the night, filter out precipitation; place 40 ℃ vacuum drying oven inner drying 4 hours again, can obtain the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin.
Embodiment 7:
Under the room temperature 10 gram HP-are mixed, stirred with 50 milliliters of pure water, make into suspended substance, add 1 gram astaxanthin pressed powder, fully mix, logical nitrogen, insulated and stirred is about more than 12 hours, and system is even lavender, stirs down slowly cooling, placement is spent the night, filter out precipitation, place 40 ℃ vacuum drying oven inner drying 4 hours, can obtain the hydroxypropyl-beta-cyclodextrin inclusion of astaxanthin.
Claims (5)
1, a kind of clathrate of HP-of astaxanthin is characterized in that: all or part of enclose of astaxanthin molecule is in the cavity of HP-, and the mol ratio of astaxanthin and HP-is 1: 1～100.
2, the preparation method of the clathrate of the HP-of the described astaxanthin of a kind of claim 1 is characterized in that: HP-is made aqueous solution at 20～80 ℃, at N
2, H
2, or CO
2Under the protection of gas wherein the astaxanthin mole be equivalent to the astaxanthin solution of the organic solvent dissolution of HP-mole 1～1/100, stirring, the ultrasonic or 0.5～24h that refluxes, cooled and filtered, the dry clathrate that gets the HP-of astaxanthin; Described organic solvent is a kind of in ethanol, the acetone.
3, the preparation method of the clathrate of the HP-of astaxanthin according to claim 2, it is characterized in that: the clathrate of the HP-of the astaxanthin that obtains, also unreacted astaxanthin, dried in organic solvent eccysis filtering residue.
4, the preparation method of the clathrate of the HP-of the described astaxanthin of a kind of claim 1, it is characterized in that: HP-is mixed with water, make into suspended substance or solution, add the astaxanthin that is equivalent to HP-mole 1～1/100 amount, mix, stir, ultrasonic or grind convection drying after 0.5～24 hour or through the clathrate of the HP-of filter pressing, washing, dry astaxanthin.
5, the preparation method of the clathrate of the HP-of the described astaxanthin of a kind of claim 1, it is characterized in that: HP-is put into colloid mill, ball mill or mortar, add entry and make it to become pastel, add the astaxanthin that is equivalent to HP-mole 1～1/100, mix, the common grinding 1～8 hour, convection drying or after filter pressing, washing, drying the clathrate of HP-of astaxanthin.
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| CN110876742A (en) * | 2019-11-14 | 2020-03-13 | 广州家安化妆品有限公司 | Pharmaceutical composition for repairing skin injury and application thereof |
| CN111518659A (en) * | 2020-04-10 | 2020-08-11 | 云南爱尔康生物技术有限公司 | Astaxanthin wine and preparation method thereof |
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| CN102343100B (en) * | 2011-10-15 | 2013-01-09 | 成都大学 | Method for quickly preparing rutin inclusion compound |
| CN107858259A (en) * | 2017-11-15 | 2018-03-30 | 荆楚理工学院 | A kind of vinegar and processing method for reducing blood lipid |
| CN110075000A (en) * | 2019-04-19 | 2019-08-02 | 山东省药学科学院 | A kind of hydroxytyrosol inclusion compound and its preparation method and application |
| CN110876742A (en) * | 2019-11-14 | 2020-03-13 | 广州家安化妆品有限公司 | Pharmaceutical composition for repairing skin injury and application thereof |
| CN111518659A (en) * | 2020-04-10 | 2020-08-11 | 云南爱尔康生物技术有限公司 | Astaxanthin wine and preparation method thereof |
| CN112791001A (en) * | 2020-12-18 | 2021-05-14 | 南京理工大学 | Preparation method of astaxanthin liposome |
| CN112791001B (en) * | 2020-12-18 | 2023-09-29 | 南京理工大学 | Preparation method of astaxanthin liposome |
| CN112891319A (en) * | 2021-02-01 | 2021-06-04 | 浙江工业大学 | Preparation method of quick-release astaxanthin nanoparticles |
| CN113208967A (en) * | 2021-05-24 | 2021-08-06 | 山东药品食品职业学院 | Composition with skin care function and preparation method thereof |
| CN114701723A (en) * | 2022-03-24 | 2022-07-05 | 徐亲成 | Vehicle-mounted passive vacuum insulation box suitable for long-time and long-distance transportation |
| CN115428942A (en) * | 2022-08-12 | 2022-12-06 | 大连工业大学 | Liver-targeting astaxanthin compound and preparation method and application thereof |
| CN115595020A (en) * | 2022-10-12 | 2023-01-13 | 云南电网有限责任公司电力科学研究院（Cn） | Moss inhibiting paint and its preparation method |
| CN115595020B (en) * | 2022-10-12 | 2024-04-09 | 云南电网有限责任公司电力科学研究院 | Moss inhibition coating and preparation method thereof |
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