Background technology
(β-Carotene) is the typical case's representative in the carotenoid family to β-Hu Luobusu, be not only the important source of vitamin A in the body, and itself human body also being had the important physical function, it can prevent, delays and treat some disease, also can improve body's immunological function simultaneously.
The molecular formula of β-Hu Luobusu is C
40H
56, molecular weight is 536.88, its fusing point is 184 ℃, have 20 approximately surplus kind of isomer.It is water insoluble, methyl alcohol, ethanol, propylene glycol, glycerine, acid or alkali, is slightly soluble in vegetables oil, in aliphatics and aromatic hydrocarbon medium solvability is arranged, and is soluble in chlorinated hydrocarbon; Because its unsaturated structure makes it have the ability of stronger anti-oxidant activity and removing free radical, thereby has certain physiologically active.But,, make and its unstable chemcial property multiple side reactions such as oxygenolysis take place when illumination and heating easily also just because of its many double bond structures.
The solvability that β-Hu Luobusu the is limited and extreme susceptibility of oxidation hindered its direct application in fields such as food, feeds.Generally all β-Hu Luobusu is made the preparation of certain formulation in actual production, wherein activeconstituents exists with finely divided form, and can protect with anti-oxidant by protective colloid if desired, thereby realizes its application in every field.
WO91/06292 and WO94/19411 have introduced and have used colloidal mill that β-Hu Luobusu is ground to form the particulate of 2~10 μ m, and drying is made the carotenoid powder of water-dispersion then.But polishing efficient is low, energy consumption is big, and the carotenoid particle diameter is difficult to reach below the 1 μ m.
US3998753 has put down in writing the dispersible carotenoid preparation method of a kind of water, wherein the granularity of carotenoid is less than 1 μ m, this method is the solution that elder generation is made into carotenoid and other additives organic solvent, join then in the aqueous solution that contains gelatin, dispersion agent, stablizer, make system form emulsion through high speed shear; Remove organic solvent, spraying drying obtains required powder.
The method of the carotenoid powder of the preparation water-dispersion that EP-0065193 (or US4522743) is put down in writing; be that carotenoid was dissolved in 10 seconds in the mixable solvent of volatile water in 50~200 ℃; descend and the aqueous solution short mix that contains protective colloid in 0~50 ℃ then; carotenoid promptly with the size dispersion of<0.5 μ m in protective colloid; remove solvent, drying can get carotenoid powder.(pressure carries out 3.0~6.0MPa), under the high temperature (170~200 ℃) this arts demand, and to the equipment requirements height, operation, control difficulty are big at high-tension apparatus.
Based on the variety of issue that exists in the above-mentioned patent, the preparation method (patent publication No. CN1836652A) that we applied for a kind of water-dispersed carotenoid powder in 2005, this method is that the carotenoid coarse crystallization is dissolved in the halohydrocarbon or esters solvent that contains antioxidant, emulsifying agent, the solution of gained joins in the ethanol or Virahol of high-speed stirring with Sprayable, and carotenoid is separated out with the amorphous powder form of<2 μ m; Filter the carotenoid of separating out with filter membrane or sintering filter stick then, filter cake is with ethanol or washed with isopropyl alcohol, and filter is done; Filter cake is added again and contain in the aqueous solution of protective colloid, first stirring to pulp after homogenizing emulsifying then removes residual solvent, is made aqueous dispersions; With the spray method granulation of described dispersion liquid, obtain the preparation of water-dispersed carotenoid again through fluidized drying at last.
Though above-mentioned technology all has been applied in the actual production, but it is found that in the formulation preparation process, operation such as dissolving, precipitation, heating, pressurization can produce a considerable amount of cis-isomerides, finally causes in the formulation products content full cis-beta-carotene content not high.This problem is perplexing investigator all over the world all the time.
Because the chemical property of alltrans isomer is stable than other isomer, tiring in vivo is the highest, so the content that improves content full cis-beta-carotene in the preparation just means and improved its nutritive value to organism effectively.
Regrettably, add some antioxidant except mentioning routinely in the report before this, few about the report that improves alltrans content of isomer in the beta Carotene preparation product specially, only in Japanese Patent JP8119933, mention, under 110 ℃~120 ℃ with content full cis-beta-carotene, grease and Limonene heating, be made into the solution of 1-10%, then under the certain vacuum degree 100 ℃~110 ℃ reclaim Limonenes, then the grease that mainly contains the alltrans isomer is carried out follow-up preparation operations such as emulsification, finally obtain the beta Carotene preparation of high alltrans.By this method, make that the alltrans ratio of β-Hu Luobusu is brought up to more than 60% by about 30% in the final formulation products.
Mainly by this process of reclaim under reduced pressure Limonene, the cis β-Hu Luobusu transposition that makes a part add thermogenesis is a content full cis-beta-carotene to this method, thereby reaches the purpose that improves content full cis-beta-carotene content.But decompression precipitation process is destroyed the stable of β-Hu Luobusu grease system easily, can cause separating out coarse particle, directly influences the bioavailability of beta Carotene preparation.
Summary of the invention
The objective of the invention is problem, propose a kind of preparation method who is suitable for the high content full cis-beta-carotene preparation of widespread use at above-mentioned existence.
Concrete grammar is: be the β-Hu Luobusu of 1:0.01~0.1:50~500 with mass ratio; the combination antioxidant; the solvent that contains emulsifying agent; make solution at 30 ℃~60 ℃ following mixed dissolutions; join in the ethanol or Virahol of high-speed stirring with Sprayable then; β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m; after the filtration filter cake is joined in the water that is dissolved with auxiliary materials such as protective colloid in advance; carry out emulsification; remove residual solvent; spraying drying; obtain the beta Carotene preparation of high alltrans, the combination antioxidant is made up of category-A antioxidant and category-B antioxidant.
Described emulsifying agent is glycerin fatty acid ester or sapn.
Described solvent is ethyl acetate, normal hexane, sherwood oil, methylene dichloride, chloroform, toluene or their mixture.
Described category-A antioxidant is ethoxyquin, Quicifal, lecithin, Tyox B or their mixture.
Described category-B antioxidant is dl-alpha-tocopherol, mixed tocopherol, butylhydroxy toluene, butyl-4-methoxyphenol, 2,6-di-tert-butyl methyl phenol, tertiarybutylhydroquinone, p-Methoxyphenol, butylhydroxy anisole, butyl hydroxy anisol, gallic acid, methyl gallate, Progallin A, Tenox PG, Stabilizer GA 8, gallic acid octadecyl ester, 4-Sucrets or their mixture.
Advantage of the present invention is: 1) by adding the small number of combinations antioxidant corresponding to specific solvent, effectively suppress the isomerization in the processes such as dissolving, heating, emulsification, reduce the amount of cis-isomeride.2) this method technology is simpler, easy to operate.
Embodiment
The present invention is the β-Hu Luobusu of 1:0.01~0.1:50~500 with mass ratio; the combination antioxidant; the solvent that contains emulsifying agent; make solution at 30 ℃~60 ℃ following mixed dissolutions; join in the ethanol or Virahol of high-speed stirring with Sprayable then; β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m; after the filtration filter cake is joined in the water that is dissolved with auxiliary materials such as protective colloid in advance; carry out emulsification; remove residual solvent; follow-up preparation operation such as spraying drying; finally obtain the beta Carotene preparation of high alltrans, the combination antioxidant is made up of category-A antioxidant and category-B antioxidant.
The present invention is described in detail below in conjunction with embodiment.For the ease of comparative descriptions advantage of the present invention, we compare the contrast of example simultaneously, the unified dl-alpha-tocopherol that equates with combination antioxidant total amount among the embodiment that adds in comparative example, the ratio of the β-Hu Luobusu cis-trans-isomer in the last formulation products with high performance liquid chromatography detect [with methyl alcohol-acetonitrile-sherwood oil-water (volume ratio 35:55:10:1) is moving phase, under 30 ℃ in Agilent Zorbax Extend-C
18Detect in the post].
Embodiment 1
Under 30 ℃ the crystallization of 100g β-Hu Luobusu, 20g stearic acid monoglycerides, 1g ethoxyquin, 1g dl-alpha-tocopherol, 1.2g p-Methoxyphenol, 0.5g Progallin A, 0.6g butylhydroxy toluene and 0.7g4-Sucrets are dissolved in the mixed solvent of 1kg ethyl acetate and 4kg methylene dichloride and make solution.Join in the 20L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 93.4% alltrans isomer.
Comparative example 1
Under 30 ℃ the crystallization of 100g β-Hu Luobusu, 20g stearic acid monoglycerides and 5g dl-alpha-tocopherol are dissolved in the mixed solvent of 1kg ethyl acetate and 4kg methylene dichloride and make solution.Join in the 20L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 73.1% alltrans isomer.
Embodiment 2
Under 40 ℃ the crystallization of 100g β-Hu Luobusu, 20g Arlacel-80,0.3g Quicifal, 0.1g mixed tocopherol, 0.1g tertiarybutylhydroquinone, 0.1g butylhydroxy anisole 0.3g Stabilizer GA 8 and 0.1g gallic acid octadecyl ester are dissolved in the mixed solvent of 2kg normal hexane and 8kg chloroform and make solution.Join in the 20L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 92.7% alltrans isomer.
Comparative example 2
Under 40 ℃ the crystallization of 100g β-Hu Luobusu, 20g Arlacel-80 and 1g dl-alpha-tocopherol are dissolved in the mixed solvent of 2kg normal hexane and 8kg chloroform and make solution.Join in the 20L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 67.5% alltrans isomer.
Embodiment 3
Under 50 ℃ the crystallization of 100g β-Hu Luobusu, 15g Arlacel-60,1g Quicifal, 0.5g butyl-4-methoxyphenol, 0.4g butyl hydroxy anisol and 0.1g Tenox PG are dissolved in the mixed solvent of 10kg normal hexane and 40kg sherwood oil and make solution.Join in the 100L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 89.2% alltrans isomer.
Comparative example 3
Under 50 ℃ the crystallization of 100g β-Hu Luobusu, 15g Arlacel-60 and 2g dl-alpha-tocopherol are dissolved in the mixed solvent of 10kg normal hexane and 40kg sherwood oil, dissolve and make solution after 30 minutes.Join in the 100L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 70.1% alltrans isomer.
Embodiment 4
With the crystallization of 100g β-Hu Luobusu, 50g Arlacel-40,0.5g Tyox B, 1.2g2,6-di-tert-butyl methyl phenol, 0.4g gallic acid and 0.9g methyl gallate are dissolved in the mixed solvent of 20kg toluene and 20kg chloroform makes solution under 60 ℃.Join in the 80L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 88.4% alltrans isomer.
Comparative example 4
Under 60 ℃ the crystallization of 100g β-Hu Luobusu, 50g Arlacel-40 and 3g dl-alpha-tocopherol are dissolved in the mixed solvent of 20kg toluene and 20kg chloroform and make solution.Join in the 80L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 69.7% alltrans isomer.
Embodiment 5
Under 30 ℃ the crystallization of 100g β-Hu Luobusu, 20g stearic acid monoglycerides, 1g ethoxyquin and 3g p-Methoxyphenol be dissolved in the 20kg methylene dichloride and make solution.Join in the 40L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 95.3% alltrans isomer.
Comparative example 5
Under 30 ℃ the crystallization of 100g β-Hu Luobusu, 20g stearic acid monoglycerides and 4g dl-alpha-tocopherol be dissolved in the 20kg methylene dichloride and make solution.Join in the 40L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 72.7% alltrans isomer.
Embodiment 6
Under 40 ℃ the crystallization of 100g β-Hu Luobusu, 20g Arlacel-80,2g Quicifal, 4g butyl-4-methoxyphenol are dissolved in the 30kg normal hexane and make solution.Join in the 30L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 91.6% alltrans isomer.
Comparative example 6
Under 40 ℃ the crystallization of 100g β-Hu Luobusu, 20g Arlacel-80 and 6g dl-alpha-tocopherol are dissolved in the 30kg normal hexane, dissolve and make solution after 30 minutes.Join in the 30L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 77.4% alltrans isomer.
Embodiment 7
Under 50 ℃ the crystallization of 100g β-Hu Luobusu, 15g Arlacel-60,1g lecithin, 2g ethoxyquin and 5g butylhydroxy toluene are dissolved in the mixed solvent of 10kg normal hexane and 25kg sherwood oil and make solution.Join in the 50L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 89.1% alltrans isomer.
Comparative example 7
Under 50 ℃ the crystallization of 100g β-Hu Luobusu, 15g Arlacel-60 and 8g dl-alpha-tocopherol are dissolved in the mixed solvent of 10kg normal hexane and 25kg sherwood oil and make solution.Join in the 50L Virahol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 73.1% alltrans isomer.
Embodiment 8
With the crystallization of 100g β-Hu Luobusu, 50g Arlacel-40,5g Tyox B, 1g2,6-di-tert-butyl methyl phenol and 4g gallic acid are dissolved in the 45kg chloroform makes solution under 60 ℃.Join in the 50L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 90.9% alltrans isomer.
Comparative example 8
Under 60 ℃ the crystallization of 100g β-Hu Luobusu, 50g Arlacel-40,10g dl-alpha-tocopherol are dissolved in the 45kg chloroform, dissolve and make solution after 30 minutes.Join in the 50L ethanol of high-speed stirring with Sprayable then, β-Hu Luobusu is separated out with the amorphous powder form of<2 μ m.After the filtration filter cake is joined under high speed shear in the water that is dissolved with auxiliary materials such as protective colloid in advance, emulsification is after 0.5 hour, and heating up removes residual solvent, and last spraying drying obtains containing the beta Carotene preparation of 64.5% alltrans isomer.