WO2012083571A1 - 一种高生物利用度的类胡萝卜素油悬浮液及其制备方法 - Google Patents
一种高生物利用度的类胡萝卜素油悬浮液及其制备方法 Download PDFInfo
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
- A23D9/007—Other edible oils or fats, e.g. shortenings, cooking oils characterised by ingredients other than fatty acid triglycerides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
Definitions
- the present invention relates to a carotenoid crystal in which a carotenoid crystal is suspended in a vegetable oil by direct fogging, thereby obtaining an oil suspension dosage form having good fluidity and high bioavailability. It belongs to the field of biochemical industry.
- Carotenoids are widely found in nature. In 1831, Wachenroder crystallized carbohydrates for the first time from carrot roots and named them as “carotene”. Later, Berzelius isolated yellow polarities from autumn leaves. Pigment, and named. “Lutein”; With the development of biophysical technology, people have separated a series of natural pigments by chromatography and named it “carotenoids”. They have a common chemical structural feature, and the center of the molecule is a polyisoprene long chain with polyene bonds. Many derivatives are produced by cyclization at the end, addition of oxygen, or rotation and isomerization of bonds. At present, there are about 600 known carotenoid members.
- Carotenoids belong to the class of terpenoids and are a general term for carotenoids and xanthophylls.
- a hydrocarbon carotenoid which does not contain an oxygen atom in a molecule is called a carotenoid group; a derivative containing an oxygen functional group (such as a hydroxyl group, an epoxy group, a methoxy group, a ketone group, a hydroxyl group, etc.) and an ester thereof in the molecule It is called the lutein family.
- beta-carotene can be fully synthesized, or obtained by fermentation or culture of salt algae. Extraction of natural substances such as palm oil; lycopene may be derived from natural sources such as from tomato or fermented, or fully synthetic; lutein is an exception in these carotenoids, due to structural asymmetry, currently It is only synthesized from plants and is not synthesized at high cost.
- These six carotenoids are similar in molecular structure. They are a class of hydrocarbons and their oxidized derivatives. They are composed of 8 isoprenoid units, but there are subtle differences in the two terminal six-membered rings. .
- beta-carotene which is a good vitamin A based on the amount of vitamin A in the body
- beta-carotene can be automatically decomposed to supplement vitamin A deficiency.
- Lutein and zeaxanthin are isomers, the only difference being that the position of a double bond on one of the six-membered ring ends is different. They are the only carotenoids present on the retina of the human eye, and they are selective.
- the ground is deposited in the macular area and the entire retina, with the highest density around the fovea of the macula and the peripheral portion of the retina gradually decreasing. These macular pigments can effectively prevent the oxidation reaction on the retina. It has an important protective effect on the retina.
- Lycopene has a good effect on the prevention and treatment of prostate diseases. Astaxanthin also has important anti-tumor and cancer-preventing effects. This is why many epidemiological studies have confirmed that regular and regular consumption of carotenoid-containing fruits and vegetables can reduce the risk of chronic diseases, including cardiovascular disease, while also having the beneficial effect of preventing cancer.
- the particle size of the active ingredient in the carotenoid oil suspension directly determines the bioavailability of the soft capsules made from the oil suspension in the human body.
- the diameter is allowed to reach the micron or even nanometer level, so that it has a higher bioavailability after being filled into the soft capsule.
- an important factor in the intake of carotenoids via soft capsules is the inability to carry too much harmful organic solvents, which requires that the carotenoids are exposed to the organic solvent with as few steps as possible before being filled into soft capsules, and There are certain steps to remove the organic solvent that is introduced during processing so that it meets the safety requirements for human consumption.
- the temperature of carotene crystals rises, especially when the carotenoid particle size is finely ground, the temperature rise phenomenon is more obvious, and the increase of temperature will inevitably cause degradation of carotenoids, which are easily oxidized. Loss, so it is not advisable to prepare a carotenoid oil suspension by grinding.
- a method for preparing a carotenoid oil suspension is disclosed in US Pat. No. 6,936,279, the disclosure of which is incorporated herein by reference in its entirety, in which the carotenoid is mixed with a water-insoluble solvent, and then mixed with the vegetable oil and atomized under a nitrogen stream to collect the mist. After the solution is recovered, the solvent is recovered to obtain a carotenoid oil suspension.
- the present invention seeks to find a way to prepare a carotenoid oil suspension having a higher bioavailability.
- the carotenoid particles in the oil suspension obtained in this route are very fine, and the average particle size is generally less than 5 ⁇ m, which is easily absorbed by the human body, and the obtained organic solvent has almost no residue, and has good safety, and this The process has high industrial production efficiency and is suitable for continuous operation.
- the object of the present invention is to conveniently obtain a carotenoid oil suspension by an efficient method, in which no additional process is required to superfine the carotenoid crystal, but the carotenoid is directly dissolved in the organic solvent.
- the organic solvent in the carotenoid solution is removed under vacuum in the process, and the volatilization of the organic solvent causes the carotenoid to precipitate in an amorphous form, and the carotenoid precipitated under high-speed stirring.
- the crystals do not re-aggregate and make the particle size larger, which ensures that the carotenoid particles in the final oil suspension are fine enough to be absorbed and utilized by the human body. Has a high bioavailability.
- a method of preparing a carotenoid oil suspension comprising the steps of:
- step a) mixing the carotenoid with an organic solvent, heating to completely dissolve it to obtain a carotenoid solution; preferably, the heating temperature in step a) is 40 ° C ⁇ 6 (TC ;
- the carotenoid solution described in the step a) is atomized into the high-speed stirring vegetable oil solution, and at the same time, the organic solvent generated during the atomization is recovered in a vacuum environment, and the organic solvent is simultaneously recovered after the atomization is completed.
- the carotenoid oil suspension contains carotenoid crystals having an average particle diameter of less than 5 ⁇ m.
- the carotenoid is at least one selected from the group consisting of ⁇ -carotene, lutein, zeaxanthin, lycopene, canthaxanthin and astaxanthin.
- the organic solvent is a water-soluble organic solvent or a water-insoluble organic solvent
- the water-soluble organic solvent is acetone, tetrahydrofuran or isopropanol
- the water-insoluble organic solvent is chloroform, toluene or ethyl acetate.
- the vegetable oil solution is a mixture of one or more of edible vegetable oils of soybean oil, corn oil, sunflower oil, rapeseed oil, peanut oil, and safflower oil.
- the vegetable oil solution further comprises an antioxidant, the antioxidant being one or more of mixed tocopherol, synthetic tocopherol, hydrazine, ethoxyquin, ascorbyl palmitate or other edible antioxidants. mixture.
- an antioxidant being one or more of mixed tocopherol, synthetic tocopherol, hydrazine, ethoxyquin, ascorbyl palmitate or other edible antioxidants. mixture.
- the vegetable oil solution further comprises an organic solvent which is less toxic or non-toxic,
- an organic solvent which is less toxic or non-toxic.
- the carotenoid solution is atomized into the high speed stirred vegetable oil solution, it is heated and kept at 30 ° C to 70 ° C, and evacuated to maintain a negative pressure state.
- the present invention provides a carotenoid oil suspension comprising the edible carotenoid crystals and vegetable oils prepared by the method and having an average particle diameter of less than 5 ⁇ m. Solution.
- the carotenoid is at least one selected from the group consisting of ⁇ -carotene, lutein, zeaxanthin, lycopene, canthaxanthin and astaxanthin.
- a vegetable oil solution is also included, and the vegetable oil solution is a mixture of one or more of edible vegetable oils of soybean oil, corn oil, sunflower oil, rapeseed oil, peanut oil, and safflower oil.
- the vegetable oil solution further comprises an antioxidant, the antioxidant being one or more of mixed tocopherol, synthetic tocopherol, hydrazine, ethoxyquin, ascorbyl palmitate or other edible antioxidants. mixture.
- the process disclosed in the present invention is suitable for industrial scale continuous operation, high production efficiency, and no additional process for grinding carotenoid crystals, which reduces the degradation of carotenoids during the preparation of the oil suspension.
- the recyclable organic solvent is simultaneously vacuumed during the atomization of the carotenoid crystals without the need for special steps to remove the organic solvent residue.
- the precipitated carotenoid amorphous crystals can be prevented from re-aggregating, thereby ensuring carotenoid particles in the final product oil suspension.
- the particle size is small, and the average particle size is generally less than 5 ⁇ m.
- Figure 1 shows a schematic diagram of the preparation process of a carotenoid oil suspension.
- the carotenoid crystals are mixed with a certain proportion of organic solvent, heated to completely dissolve, and then the carotenoid solution is atomized from the bottom of the reaction vessel R1 through a high-speed rotating nozzle into the vegetable oil, which may be included in the vegetable oil.
- Certain antioxidants such as tocopherol, natural mixed tocopherol, BHT, ascorbyl palmitate, etc., it is important that high-speed stirring can effectively prevent the precipitation of amorphous carotenoid crystals from re-aggregating during atomization. The particle size becomes coarse.
- the R1 reactor is in a vacuum state, and on one side, the organic solvent after spraying can be volatilized and recovered in time, and on the other hand, the carotenoid crystal can be precipitated in an amorphous form in time.
- the organic solvent is recovered in tanks V01 and V02 after passing through two-stage condensers E1 and E2 and can be recycled.
- the organic solvent used in the process may be water-soluble, such as acetone, tetrahydrofuran, ethanol, isopropanol or the like, or may be water-insoluble, such as dichloromethane, toluene, ethyl acetate or the like.
- the ratio of the organic solvent to the crystal can be adjusted, and only the carotenoid is required to be completely dissolved in the solvent.
- the vegetable oil in the process may be any of various edible vegetable oils or mixtures thereof, such as sunflower oil, soybean oil, rapeseed oil, corn oil, peanut oil, safflower oil, etc., depending on the production requirements.
- the mass ratio of vegetable oil to carotenoid crystals in the reactor can be adjusted depending on the concentration of carotenoids required in the final oil suspension. And, as needed, part of the vegetable oil can be placed in the reactor R1, and the other part has The solvent and carotenoid crystals are mixed and dissolved.
- a certain amount of other organic solvent may be mixed in the vegetable oil, for these organic solvents, It is required to have low toxicity and a boiling point higher than the boiling point of the organic solvent used to dissolve the carotenoid crystals.
- Organic solvents suitable for this type are ethanol, isopropanol, isobutyl acetate and the like.
- the effective concentration of carotenoids in the oil suspension in the final product can be adjusted according to the production needs, and can be between 5% and 50%.
- the carotenoids mentioned in the present invention include all kinds of carotenoids which are industrially produced for human consumption, including natural and synthetic sources, such as ⁇ -carotene, lutein, lycopene, canthaxanthin, corn yellow. Quality, astaxanthin, etc. or a mixture thereof.
- natural and synthetic sources such as ⁇ -carotene, lutein, lycopene, canthaxanthin, corn yellow. Quality, astaxanthin, etc. or a mixture thereof.
- the organic solvent in the lutein solution volatilizes in a vacuum environment, and the lutein crystals can be precipitated in an amorphous manner in time, but due to the high-speed stirring, the precipitated lutein amorphous crystals do not re-aggregate and the particle size It becomes thicker, so the average particle size of lutein crystals in the final product oil suspension is about 2 ⁇ , and no solvent residue is detected, which is very beneficial to the absorption and utilization of the human body.
- the high-speed shear stirring is started, and the prepared ⁇ -carotene solution is atomized by a high-speed rotating nozzle to a high-speed stirring vegetable oil solution.
- the organic solvent tetrahydrofuran in the ⁇ -carotene solution is atomized to encounter a vacuum. After the environment, it will be volatilized immediately. After passing through the heat exchangers E01 and ⁇ 02, it will be cooled to the storage tanks V01 and V02 and can be recycled.
- the tetrahydrofuran is also recovered. Then, the mixture in the reaction vessel was heated to 70 ° C, and the anhydrous ethanol was recovered in vacuo.
- the mixture of R1 in the reaction vessel was filled to obtain 200 kg of a ⁇ -carotene oil suspension, wherein the ⁇ -carotene content was 50.0%.
- the organic solvent in the ⁇ -carotene solution volatilizes in a vacuum environment, and the ⁇ -carotene crystal can be precipitated in an amorphous manner in time, but due to the presence of high-speed stirring, the precipitated ⁇ -carotene amorphous crystal does not crystallize.
- Re-aggregation makes the particle size coarser, so the average particle size of the ⁇ -carotene crystal in the final product oil suspension is about 3 ⁇ , which is very advantageous for improving the bioavailability in the human body. No solvent residue was detected in the product.
- zeaxanthin crystals were weighed and mixed well with 1200 kg of methylene chloride, and the mixture was heated to 40 ° C and stirred to dissolve to obtain a zeaxanthin solution.
- 300 kg of isopropanol was added to the reaction vessel, and the temperature was raised to Keep warm at 30 ° C and evacuate to maintain a negative pressure.
- the high-speed shear stirring is started, and the prepared zeaxanthin solution is atomized by a high-speed rotating nozzle to a high-speed stirring vegetable oil solution.
- the organic solvent dichloromethane in the zeaxanthin solution is atomized to encounter a vacuum. After the environment, it will be volatilized immediately. After passing through the heat exchangers E01 and E02, it will be cooled to the storage tanks V01 and V02 and can be recycled. After the zeaxanthin solution is atomized, the chloroform is also recovered. Then, the mixture in the reaction vessel was heated to 80 ° C, and isopropanol was recovered in vacuo.
- the mixture of R1 in the reaction vessel was filled to obtain 300 kg of a zeaxanthin oil suspension, wherein the zeaxanthin content was 20.0%.
- the average particle size of zeaxanthin crystals in the final product oil suspension is around 2.5 ⁇ , which is very beneficial to the improvement of bioavailability in human body.
- the organic solvent in the lycopene solution volatilizes in a vacuum environment, and the lycopene crystals can be precipitated in an amorphous manner in time, but due to the high-speed stirring, the precipitated lycopene amorphous crystals do not re-aggregate and the particle size Thickening, so the average particle size of lycopene crystals in the final product oil suspension is about 5 ⁇ , which is beneficial to the absorption and utilization of the human body.
- the heat exchangers E01 and E02 are cooled to the tanks V01 and V02 and can be recycled. After the atomization of the astaxanthin solution is completed, the toluene is simultaneously recovered, and the R1 mixture in the reaction vessel is filled with shrimp.
- the oil suspension is 200 kg, wherein the astaxanthin content is 20.0%.
- the organic solvent in the astaxanthin solution volatilizes in a vacuum environment, and the astaxanthin crystals can be precipitated in an amorphous manner in time, but due to the presence of high-speed stirring, the precipitated astaxanthin amorphous crystals do not re-aggregate and the particle size It becomes thicker, so the average particle size of astaxanthin crystals in the final product oil suspension is about 4 ⁇ .
- This oil suspension can be applied to animal feed and has high bioavailability.
- the high-speed shear stirring is started, and the prepared canthaxanthin solution is atomized by a high-speed rotating nozzle to perform a high-speed stirring of the vegetable oil solution.
- the organic solvent acetone in the canthaxanthin solution is sprayed to a vacuum environment.
- Immediately volatilize after cooling E01 and E02, cooled to storage tanks V01, V02, can be recycled.
- the acetone is also recovered.
- the mixture in the reaction vessel was further heated to 80 ° C, and the ethyl acetate was recovered in vacuo.
- the mixture of R1 in the reaction vessel was filled to obtain 100 kg of the canthaxanthin oil suspension, wherein the canthaxanthin content was 40.0%.
- the average particle size of the canthaxanthin crystal in the final product oil suspension is about 4.2 ⁇ m, which is very beneficial to the improvement of bioavailability in the human body.
- the organic solvent in the carotenoid solution is atomized. After encountering the vacuum environment, it will immediately evaporate. After passing through the heat exchangers E01 and E02, it will be cooled to the storage tanks V01 and V02 and can be recycled. After the carotenoid solution is atomized, the methylene chloride is recovered. Then, the mixture in the reaction kettle was heated to 80 ° C, and the ethanol was recovered by vacuum. The R1 mixture in the reaction vessel was filled to obtain 200 kg of lutein and zeaxanthin oil suspension, wherein the zeaxanthin content was 8.5%, and the lutein content was 19.1. %. The average particle size of lutein and zeaxanthin crystals in the final product oil suspension is about 3.2 ⁇ , which is very beneficial to the improvement of bioavailability in human body.
- the high-speed shear stirring is started, and the prepared lycopene and the natural ⁇ -carotene solution are atomized by a high-speed rotating nozzle to a high-speed stirring vegetable oil solution.
- the organic solvent tetrahydrofuran mist in the carotenoid solution After being exposed to a vacuum environment, it is immediately volatilized. After passing through heat exchangers E01 and ⁇ 02, it is cooled to storage tanks V01 and V02 and can be recycled. After the carotenoid solution is atomized, the tetrahydrofuran is also recovered. Then, the mixture in the reaction kettle was heated to 80 ° C, and the ethyl acetate was recovered in a vacuum.
- the R1 mixture in the reaction vessel was filled to obtain 300 kg of a suspension of lycopene and a natural ⁇ -carotene oil, wherein the lycopene content was 10.5%.
- the natural beta-carotene content is 30.1%.
- the average particle size of lycopene and natural ⁇ -carotene crystals in the final product oil suspension is about 2.7 ⁇ , and no harmful organic solvent residue is detected, which is very advantageous for the improvement of bioavailability in human body.
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Description
一种高生物利用度的类胡萝卜素油悬浮液及其制备方法 技术领域
本发明涉及通过直接雾说化类胡萝卜素溶液使其中的类胡萝卜素 晶体以极细小颗粒悬浮于植物油中, 从而得到一种流动性好, 生物利 用率高的油悬浮液剂型。 属于生物化工领域。
书 背景技术
类胡萝卜素在自然界中广泛存在, 1831年, Wachenroder从胡萝 卜根中首次结晶分离出碳水化合物类的色素, 并以"胡萝卜素"命名; 之后, Berzelius从秋天的叶片中分离提取出黄色的极性色素, 并命名. 为"叶黄素"; 随着生物物理技术的发展, 人们通过色谱方法分离出一 系列的天然色素, 并命名为"类胡萝卜素"。 它们具有共同的化学结构 特征, 分子中心都是多烯键的聚异戊二烯长链, 通过末端的环化、 氧 的加入或键的旋转及异构化等方式产生出许多衍生物。 目前, 己知的 类胡萝卜素成员大概有 600多种。 类胡萝卜素 (Carotenoids)属于类萜化合物, 是胡萝卜素 (Carotene) 和叶黄素 (Xanthophylls)两大类色素的总称。分子中不含有氧原子的碳 氢族类胡萝卜素称为胡萝卜素族; 分子中含有氧功能团 (如羟基、 环 氧基、 甲氧基、 酮基、 羟基等)的衍生物及其酯类则称为叶黄素族。 自然界存在的类胡萝卜素有数百种之多, 但比较常见且数量相对
较大的主要有六种, 它们分别是 β-胡萝卜素、 虾青素、 斑蝥黄素、 叶 黄素、 玉米黄质和番茄红素等。 随着生物技术和合成技术的发展, 这 六大类胡萝卜素中许多种类又存在着多种来源, 如 beta-胡萝卜素可 以是全合成, 又可通过发酵法或养殖盐藻得到, 还可从天然物如棕榈 油中提取; 番茄红素可以是天然来源如从番茄中提取或发酵得到, 也 可是全合成的; 在这些类胡萝卜素中叶黄素是个例外, 由于结构上的 不对称性, 目前只有通过从植物中提取, 而不会高成本地合成。 这六种类胡萝卜素在分子结构上都较为相似, 是一类碳氢化合物 及其氧化衍生物, 它们由 8个类异戊二烯单位组成, 只是在两个末端 六元环上存在细微的差别。类胡萝卜素分子结构中存在的多个共轭双 键发色基团不仅赋予了其在紫外一可见光区有着独特的吸收区 (蓝光 区), 因而其结晶或溶液在可见光下具有十分绚丽的红、 橙或黄色, 因浓度的不同, 显示出的颜色有一定的变化。类胡萝卜素长期被认为 是一类色素, 自然界中秋天的落叶和各种斑谰色彩的动物给人类以无 与伦比的美感。同时这些共轭双键还使得类胡萝卜素成为良好的自由 基猝灭剂, 具有很强的抗氧化活性, 能有效地阻断细胞内的链式自由 基反应, 从而具有多种独特而又重要的生理功能。 类胡萝卜素中最广泛而要重要的是 beta-胡萝卜素, 它是良好的 维生素 A原根据体内维生素 A量的多少, beta-胡萝卜素可自动分解 而补充维生素 A 的不足。 叶黄素和玉米黄质是同分异构体, 其唯一 的区别在于其中一个六元环端链上一个双键的位置不同,它们是唯一 存在于人类眼视网膜上的一种类胡萝卜素,它们选择性地沉积在黄斑 区和整个视网膜, 以黄斑的中心凹周围密度为最高, 视网膜周边部分 逐渐减少。 这些黄斑色素能有效地防止视网膜上面氧化反应的发生,
对视网膜有重要的保护作用。番茄红素对***疾病的预防和治疗有 很好的作用。虾青素也有重要的抗肿瘤和预防癌症的作用等。这就是 为什么许多流行病学研究证实,经常和有规律地消费含类胡萝卜素的 水果和蔬菜可减少慢性疾病, 包括心血管疾病的危险, 同时具有预防 癌症的有益效果。
因此, 营养学家极力推荐添加、 预防性地摄取抗氧化剂维生素和 类胡萝卜素, 食物和药物市场因而为消费者提供大量此类"细胞保护 剂"。 目前市场上出现了各种各样的添加单一或多种类胡萝卜素的健 康食品,但人们补充类胡萝卜素更有效的方式是通过膳食补充剂的形 式摄入, 如各种片剂、 硬胶囊、 软胶囊等, 往往一粒片剂或胶囊就能 满足个人当天全部的类胡萝卜素需求量。 针对这些摄入方式的要求, 市场上也出现了多种类胡萝卜素剂型,如适于直接压片或套硬胶囊的 富含 beta-胡萝卜素的微粒 CarolBeta®, CaroCare®, 富含叶黄素的微 粒 CarolGold®, FloraGlo®, 富含玉米黄质的微粒 CarolZea®, 富含 番茄红素的 Redivivo®等; 也有一些适于装填软胶囊的类胡萝卜素的 油悬液。通过软胶囊方式摄食类胡萝卜素是一种较为方便也是较为流 行的方法。制备软胶囊时用到的类胡萝卜素往往是以油悬浮液的形式 存在, 也就是将类胡萝卜素粉碎到一定的细度然后悬浮于植物油中, 这样类胡萝卜素油悬浮液的流动性就决定了生产过程操作的难易程 度, 我们已经有相关专利公开了降低类胡萝卜素油悬液粘度的方法。
另一方面很重要的一点就是类胡萝卜素油悬液中有效成分颗粒粒 径的大小直接决定了以此油悬液为原料的软胶囊在人体中生物利用
度的高低,类胡萝卜素颗粒粒径越小意味着其被人体摄入后越容易被 吸收利用, 也就是拥有更高的生物利用度, 所以人们总是努力降低油 悬液中类胡萝卜素颗粒径, 让其达到微米级甚至纳米级, 以利于其被 装填入软胶囊后有较高的生物利用度。
而且, 通过软胶囊形式摄食类胡萝卜素时一个重要的因素就是不 能带入过多有害的有机溶剂,这就要求在类胡萝卜素被装填成软胶囊 前有尽量少的步骤接触到有机溶剂,并且有一定的步骤去除在加工过 程中带入的有机溶剂, 从而使其满足人类食用时安全方面的要求。
在先前文献中存在着多种制备类胡萝卜素油悬液的方法。 一般的 方法是将类胡萝卜素晶体进行充分地研磨,再将此研磨后的类胡萝卜 素微粉与植物油充分混合得到油悬浮液,但用此方法时一方面不可能 将类胡萝卜素晶体研磨得很细, 其粒径一般在 15μιη左右, 最终会影 响到用此油悬浮液制成的软胶囊在人体中的吸收利用,生物利用度较 差,另一方面在研磨地过程中不可避免地导致类胡萝卜素晶体温度升 高, 尤其是要将类胡萝卜素颗粒粒径研磨得很细时, 这种升温现象就 更明显,温度的升高必然会引起类胡萝卜素这种很容易被氧化的物质 降解损失, 所以通过研磨方法制备类胡萝卜素油悬浮液并不可取。
而 US6,936,279 Β2中揭示了一种方法制备类胡萝卜素油悬浮液, 其中先将类胡萝卜素与某种非水溶性溶剂混合,再与植物油混合后在 氮气流作用下雾化, 收集雾化后的溶液, 回收其中溶剂, 便得到类胡 萝卜素油悬液。在此过程中, 为了保证雾化后的类胡萝卜素颗粒不再 重新聚集, 要额外加入许多量的乳化剂和水, 而且为了去除大量的有
机溶剂,在收集一定量雾化后的"浓缩液"后要停下雾化操作而进行溶 剂回收, 这在工业化生产上是不利的, 此方法产量不大, 只适于实验 室规模。而且, 防止雾滴中类胡萝卜素晶体重新聚集的措施并不十分 有效, 终产品油悬浮中类胡萝卜素晶体颗粒粒径较大, 更重要的是, 雾化时大量乳化剂的存在对有机溶剂的完全去除是十分不利的,这必 然会给最终产品软胶囊的使用安全性带来隐患。同时没有有效的后续 操作去除这些对油悬浮液制备无任何价值的乳化剂,造成浪费和增加 了安全风险。
本发明中力图找到一种方法制备有较高生物利用度的类胡萝卜素 油悬浮液。此工艺路线中得到的油悬浮液中类胡萝卜素颗粒很细, 平 均颗粒粒径一般小于 5μηι, 易于被人体吸收利用,得到的产品中有机 溶剂几乎没有残留, 有很好的安全性, 而且此工艺有较高的工业化生 产效率, 适于连续化操作。
发明内容
本发明的目的是利用一种高效的方法方便地得到一种类胡萝卜 素油悬浮液,在此工艺中不需要额外的过程来超微粉碎类胡萝卜素晶 体, 而是直接将类胡萝卜素溶解于有机溶剂后喷雾于植物油中, 在此 过程中同时将类胡萝卜素溶液中有机溶剂在真空状态下去除,有机溶 剂的挥发使类胡萝卜素以无定型形式析出, 在高速搅拌的情况下, 析 出的类胡萝卜素晶体不会重新聚集而使其粒径变大,这样就能保证在 最终油悬浮液中类胡萝卜素颗粒足够细, 有利于人体吸收利用, 从而
具有较高的生物利用度。
根据本发明的一方面,本发明提供了一种制备类胡萝卜素油悬浮 液的方法, 所述方法包括如下步骤:
a) 将类胡萝卜素与有机溶剂混合, 加热使其完全溶解, 得到类 胡萝卜素溶液; 最好, 步骤 a)中加热温度为 40°C〜6(TC ;
b) 将步骤 a)中所述类胡萝卜素溶液以雾化方式进入高速搅拌的 植物油溶液中, 并同时在真空环境中回收雾化时产生的有机溶剂, 雾 化完成后有机溶剂同时回收完成, 得到类胡萝卜素油悬浮液;
其中, 所述类胡萝卜素油悬浮液含有颗粒平均粒径小于 5μιη的 类胡萝卜素晶体。
最好, 所述类胡萝卜素选自 β-胡萝卜素、 叶黄素、 玉米黄质、 番 茄红素、 角黄素和虾青素中的至少一种。
最好, 所述有机溶剂为水溶性有机溶剂或非水溶性有机溶剂, 水 溶性有机溶剂为丙酮、 四氢呋喃或异丙醇, 非水溶性有机溶剂为二氯 甲垸、 甲苯或乙酸乙酯。
最好, 所述植物油溶液为大豆油、 玉米油、 葵花籽油、 菜籽油、 花生油、 红花油的可食性植物油中的一种或多种的混合物。
最好, 所述植物油溶液还包括抗氧化剂, 所述抗氧化剂为混合生 育酚、 合成生育酚、 ΒΗΤ、 乙氧喹啉、 抗坏血酸棕榈酸酯或其它可供 食用的抗氧化剂中一种或多种的混合物。
最好, 所述植物油溶液还包括毒性小或无毒的有机溶剂, 所述有
最好,在所述类胡萝卜素溶液以雾化方式进入高速搅拌的植物油 溶液前, 加温并保温到 30°C〜70°C, 并抽真空以保持负压状态。
根据本发明的另一方面, 本发明提供了一种类胡萝卜素油悬浮 液, 所述类胡萝卜素油悬浮液包括所述方法制备的、颗粒平均粒径小 于 5μηι的、 可食用的类胡萝卜素晶体和植物油溶液。 其中, 所述类 胡萝卜素选自 β-胡萝卜素、 叶黄素、 玉米黄质、 番茄红素、 角黄素和 虾青素中的至少一种。 最好, 还包括植物油溶液, 所述植物油溶液为 大豆油、 玉米油、 葵花籽油、 菜籽油、 花生油、 红花油的可食性植物 油中的一种或多种的混合物。其中,所述植物油溶液还包括抗氧化剂, 所述抗氧化剂为混合生育酚、 合成生育酚、 ΒΗΤ、 乙氧喹啉、 抗坏血 酸棕榈酸酯或其它可供食用的抗氧化剂中一种或多种的混合物。
本发明中揭示的工艺适于工业化规模连续操作, 生产效率高, 没 有额外的研磨类胡萝卜素晶体的过程,降低了制备油悬浮液过程中类 胡萝卜素的降解。在雾化类胡萝卜素晶体过程中同时真空回收可重复 使用的有机溶剂, 而不需要专门的步骤去除有机溶剂残留。在雾化类 胡萝卜素晶体溶液过程中保持油 /类胡萝卜素 /有机溶剂混合液高速搅 拌状态, 可防止析出的类胡萝卜无定型晶体重新聚集, 从而能保证终 产品油悬浮液中类胡萝卜素颗粒粒径很小, 平均粒径一般小于 5μπι。 附图说明
图 1表示类胡萝卜素油悬浮液的制备过程简图。
具体实施方式
本发明的优点可以通过以下实施例来体现,但本发明的优点并不 仅限于这些实施例。
如图 1所示, 本发明的具体工艺说明如下:
先将类胡萝卜素晶体与一定比例的有机溶剂混合,加热使其完全 溶解, 再将此类胡萝卜素溶液从反应釜 R1底部通过高速旋转的喷头 雾化后进入植物油中,此植物油中可以包含了一定的抗氧化剂如生育 酚、 天然混合生育酚、 BHT、 抗坏血酸棕榈酸酯等, 重要的是, 在雾 化过程中,高速搅拌能有效地防止析出的无定型类胡萝卜素晶体重新 聚集而使其粒径***。 在此过程中, R1 反应釜处于真空状态, 一方 面能使喷雾后的有机溶剂及时挥发回收,另一方面有利于类胡萝卜素 晶体能以无定型形式及时析出。 有机溶剂通过两级冷凝器 E1 和 E2 后回收于贮罐 V01和 V02中, 可以循环使用。
工艺中用到的有机溶剂可以是水溶性的, 如丙酮、 四氢呋喃、 乙 醇、 异丙醇等, 也可以是非水溶性的, 如二氯甲垸、 甲苯、 乙酸乙酯 等。根据类胡萝卜素晶体在有机溶剂中溶解度的大小, 有机溶剂与晶 体的比例可以调节, 只要求类胡萝卜素能完全溶解于所述的溶剂中。
工艺中的植物油根据生产要求的不同可以是葵花籽油、 大豆油、 菜籽油、 玉米油、 花生油、 红花油等其它任何一种可供食用的植物油 类或它们的混合物。 根据最终油悬浮液中要求达到的类胡萝卜素浓 度, 反应釜中植物油与类胡萝卜素晶体的质量比例可以进行调节。而 且根据需要, 可以将部分植物油放置于反应釜 R1中, 另一部分与有
机溶剂和类胡萝卜素晶体混合溶解。在某些情况下, 特别是要求终产 品油悬液中类胡萝卜素含量较高时, 为了减少反应釜 R1中溶液的粘 度, 可以在植物油中混合一定量的其它有机溶剂, 对这些有机溶剂, 要求其毒性低,而且沸点比用来溶解类胡萝卜素晶体的有机溶剂的沸 点高, 这样在雾化过程中, 通过控制反应釜 R1夹套温度, 就可以让 用来溶解类胡萝卜素晶体的有机溶剂在真空状态下连续地去除,但用 于降低溶液粘度的有机溶剂还不会或很少被带走, 雾化完成后, 再升 高反应釜 R1夹套温度, 真空状态下回收这些有机溶剂。 适合于此类 的有机溶剂有乙醇、 异丙醇、 乙酸异丁酯等。最终产品中油悬浮液中 类胡萝卜素有效浓度依生产需要可进行调节, 可在 5%至 50%之间。
本发明中提到的类胡萝卜素包括所有工业化生产适于人类食 用、包括天然和合成来源的各种类胡萝卜素,如 β-胡萝卜素、叶黄素、 番茄红素、 角黄素、 玉米黄质、 虾青素等或者它们的混合物。 实施例 1
称取叶黄素晶体 18.3kg (含量 82.5%)与 370 kg二氯甲垸充分混 合, 升温到 40°C搅拌溶解得到叶黄素溶液。 同时在反应釜 R1中投入 273 kg大豆油, 9kg混合生育酚, 升温到 30°C时保温, 并抽真空以保 持负压状态。开动高速剪切搅拌, 将制备好的叶黄素溶液通过高速旋 转的喷头雾化进行高速搅泮的大豆油溶液中,叶黄素溶液中的有机溶 剂二氯甲垸雾化遇到真空环境后, 立即挥发, 经过热交换器 E01 和 E02后冷却到贮罐 V01、 V02中, 可以循环使用。 叶黄素溶液雾化完
成后, 二氯甲烷也就回收完成, 灌装反应釜中 R1混合物就得叶黄素 油悬浮液 100kg,其中叶黄素含量 5.0%。叶黄素溶液中有机溶剂在真 空环境中挥发, 叶黄素晶体能及时以无定型方式析出, 但由于高速搅 拌的存在,使得析出的叶黄素无定型晶体不会重新聚集而使颗粒粒径 ***, 所以终产品油悬浮液中叶黄素晶体的平均粒径在 2μη 左右, 而且检测不到溶剂残留, 非常有利于人体的吸收利用。
实施例 2
称取 β-胡萝卜素晶体 103kg (含量 98.5%)与 1000 kg四氢呋喃、 10kg抗坏血酸棕榈酸酯, 充分混合, 升温到 40°C搅拌溶解得到 β-胡 萝卜素溶液。 同时在反应釜 R1中投入 90 kg葵花籽油和玉米油的混 合物 (w/w=l :l), 为减少溶液的粘度同时在反应釜中投入 300kg无水 乙醇, 升温到 40°C时保温, 并抽真空以保持负压状态。 开动高速剪 切搅拌,将制备好的 β-胡萝卜素溶液通过高速旋转的喷头雾化进行高 速搅拌的植物油溶液中, 在此温度下, β-胡萝卜素溶液中的有机溶剂 四氢呋喃雾化遇到真空环境后, 立即挥发, 经过热交换器 E01和 Ε02 后冷却到贮罐 V01、 V02中, 可以循环使用。 β-胡萝卜素溶液雾化完 成后, 四氢呋喃也就回收完成。 再将反应釜中混合物升温到 70°C, 真空回收其中的无水乙醇, 灌装反应釜中 R1混合物就得 β-胡萝卜素 油悬浮液 200kg, 其中 β-胡萝卜素含量 50.0%。 β-胡萝卜素溶液中有 机溶剂在真空环境中挥发, β-胡萝卜素晶体能及时以无定型方式析 出,但由于高速搅拌的存在,使得析出的 β-胡萝卜素无定型晶体不会
重新聚集而使颗粒粒径***,所以终产品油悬浮液中 β-胡萝卜素晶体 的平均粒径在 3μπι左右, 非常有利于在人体中生物利用度的提高。 产品中检测不到溶剂残留。
实施例 3
称取玉米黄质晶体 74kg (含量 81.5%)与 1200 kg二氯甲烷充分混 合, 升温到 40°C搅拌溶解得到玉米黄质溶液。 同时在反应釜 R1中投 入 21 l kg菜籽油和花生油的混合物 (w/w=l :2), 15kg混合生育酚, 为 减少溶液的粘度同时在反应釜中投入 300kg异丙醇, 升温到 30°C时 保温, 并抽真空以保持负压状态。 开动高速剪切搅拌, 将制备好的玉 米黄质溶液通过高速旋转的喷头雾化进行高速搅拌的植物油溶液中, 在此温度下,玉米黄质溶液中的有机溶剂二氯甲烷雾化遇到真空环境 后, 立即挥发, 经过热交换器 E01和 E02后冷却到贮罐 V01、 V02 中, 可以循环使用。 玉米黄质溶液雾化完成后, 二氯甲垸也就回收完 成。 再将反应釜中混合物升温到 80°C, 真空回收其中的异丙醇, 灌 装反应釜中 R1混合物就得玉米黄质油悬浮液 300kg, 其中玉米黄质 含量 20.0%。终产品油悬浮液中玉米黄质晶体的平均粒径在 2.5μη左 右, 非常有利于在人体中生物利用度的提高。
实施例 4
称取番茄红素晶体 26.0kg (含量 96.5%)与 600 kg乙酸乙酯充分混
合, 升温到 60Ό搅拌溶解得到番茄红素溶液。 同时在反应釜 R1中投 入 165 kg红花油, 9kg抗氧化剂 BHT, 升温到 60°C时保温, 并抽真 空以保持负压状态。开动高速剪切搅拌, 将制备好的番茄红素溶液通 过高速旋转的喷头雾化进行高速搅拌的红花油溶液中,番茄红素溶液 中的有机溶剂乙酸乙酯在真空环境中雾化后, 立即挥发, 经过热交换 器 E01和 E02后冷却到贮罐 V01、 V02中, 可以循环使用。 番茄红 素溶液雾化完成后, 乙酸乙酯同时回收完成, 灌装反应釜中 R1混合 物就得番茄红素油悬浮液 200kg, 其中番茄红素含量 12.5%。 番茄红 素溶液中有机溶剂在真空环境中挥发,番茄红素晶体能及时以无定型 方式析出, 但由于高速搅拌的存在, 使得析出的番茄红素无定型晶体 不会重新聚集而使颗粒粒径***,所以终产品油悬浮液中番茄红素晶 体的平均粒径在 5μπι左右, 有利于人体的吸收利用。
称取虾青素晶体 42.0kg (含量 95.2%)与 1000 kg甲苯、 9kg抗氧化 剂乙氧基喹啉, 充分混合, 升温到 60°C搅拌溶解得到虾青素溶液。 同时在反应釜 R1中投入 159 kg葵花籽油, 升温到 70°C时保温, 并 抽真空以保持负压状态。开动高速剪切搅拌, 将制备好的虾青素溶液 通过高速旋转的喷头雾化进行高速搅拌的植物油溶液中,虾青素溶液 中的有机溶剂甲苯在真空环境中雾化后, 立即挥发, 经过热交换器 E01和 E02后冷却到贮罐 V01、 V02中, 可以循环使用。 虾青素溶液 雾化完成后, 甲苯同时回收完成, 灌装反应釜中 R1混合物就得虾青
素油悬浮液 200kg, 其中虾青素含量 20.0%。 虾青素溶液中有机溶剂 在真空环境中挥发, 虾青素晶体能及时以无定型方式析出, 但由于高 速搅拌的存在,使得析出的虾青素无定型晶体不会重新聚集而使颗粒 粒径***, 所以终产品油悬浮液中虾青素晶体的平均粒径在 4μηι左 右, 此油悬浮液可以应用于动物饲料中, 有较高的生物利用率。
实施例 6 称取角黄素晶体 41kg (含量 97.2%)与 1800 kg丙酮充分混合, 升 温到 56°C搅拌溶解得到角黄素溶液。 同时在反应釜 R1中投入 56 kg 玉米油和红花油的混合物 (w/w=3:2), 3kg合成生育酚, 为减少溶液的 粘度同时在反应釜中投入 230kg乙酸乙酯, 升温到 50°C时保温, 并 抽真空以保持负压状态。开动高速剪切搅拌, 将制备好的角黄素溶液 通过高速旋转的喷头雾化进行高速搅拌的植物油溶液中, 在此温度 下, 角黄素溶液中的有机溶剂丙酮雾化遇到真空环境后, 立即挥发, 经过热交换器 E01和 E02后冷却到贮罐 V01、 V02中, 可以循环使 用。 角黄素溶液雾化完成后, 丙酮也就回收完成。 再将反应釜中混合 物升温到 80°C, 真空回收其中的乙酸乙酯, 灌装反应釜中 R1混合物 就得角黄素油悬浮液 100kg, 其中角黄素含量 40.0%。 终产品油悬浮 液中角黄素晶体的平均粒径在 4.2μηι左右,非常有利于在人体中生物 利用度的提高。
实施例 7
称取玉米黄质晶体 10kg、 叶黄素晶体 45kg与 1800 kg二氯甲垸 充分混合, 升温到 40°C搅拌溶解得到玉米黄质和叶黄素溶液。 同时 在反应釜 R1中投入 142 kg菜籽油, 3kg混合生育酚, 为减少溶液的 粘度同时在反应釜中投入 300kg乙醇, 升温到 30°C时保温, 并抽真 空以保持负压状态。开动高速剪切搅拌, 将制备好的叶黄素和玉米黄 质溶液通过高速旋转的喷头雾化进行高速搅拌的植物油溶液中,在此 温度下, 类胡萝卜素溶液中的有机溶剂二氯甲垸雾化遇到真空环境 后, 立即挥发, 经过热交换器 E01和 E02后冷却到贮罐 V01、 V02 中, 可以循环使用。 类胡萝卜素溶液雾化完成后, 二氯甲垸也就回收 完成。 再将反应釜中混合物升温到 80°C, 真空回收其中的乙醇, 灌 装反应釜中 R1混合物就得叶黄素和玉米黄质油悬浮液 200kg, 其中 玉米黄质含量 8.5%, 叶黄素含量 19.1%。 终产品油悬浮液中叶黄素 和玉米黄质晶体的平均粒径在 3.2μιη左右,非常有利于在人体中生物 利用度的提高。
实施例 8
称取天然番茄红素晶体 32kg、天然 β-胡萝卜素晶体 92kg与 2600 kg四氢呋喃充分混合, 升温到 4(TC搅拌溶解得到番茄红素和天然 β- 胡萝卜素溶液。 同时在反应釜 R1中投入 166 kg菜籽油、大豆油和红 花油的混合物 (w/w/w=l :l :l), 5kg合成生育酚和 5kg混合生育酚, 为 减少溶液的粘度同时在反应釜中投入 400kg乙酸乙酯, 升温到 40°C
时保温, 并抽真空以保持负压状态。 开动高速剪切搅拌, 将制备好的 番茄红素和天然 β-胡萝卜素溶液通过高速旋转的喷头雾化进行高速 搅拌的植物油溶液中, 在此温度下, 类胡萝卜素溶液中的有机溶剂四 氢呋喃雾化遇到真空环境后, 立即挥发, 经过热交换器 E01 和 Ε02 后冷却到贮罐 V01、 V02中, 可以循环使用。 类胡萝卜素溶液雾化完 成后, 四氢呋喃也就回收完成。 再将反应釜中混合物升温到 80°C, 真空回收其中的乙酸乙酯, 灌装反应釜中 R1混合物就得番茄红素和 天然 β-胡萝卜素油悬浮液 300kg, 其中番茄红素含量 10.5%, 天然 β- 胡萝卜素含量 30.1%。终产品油悬浮液中番茄红素和天然 β-胡萝卜素 晶体的平均粒径在 2.7μηι左右,且检测不出有害的有机溶剂残留,非 常有利于在人体中生物利用度的提高。
本发明通过上面的实施例进行举例说明, 但是, 应当理解, 本发 明并不限于这里所描述的特殊实例和实施方案。在这里包含这些特殊 实例和实施方案的目的在于帮助本领域中的技术人员实践本发明。任 何本领域中的技术人员很容易在不脱离本发明精神和范围的情况下 进行进一步的改进和完善,因此本发明只受到本发明权利要求的内容 和范围的限制,其意图涵盖所有包括在由附录权利要求所限定的本发 明精神和范围内的备选方案和等同方案。
Claims
1、 一种制备类胡萝卜素油悬浮液的方法, 所述方法包括如下步 骤:
a) 将类胡萝卜素与有机溶剂混合, 加热使其完全溶解, 得到类 胡萝卜素溶液;
b)将步骤 a)中所述类胡萝卜素溶液以雾化方式进入高速搅拌的 植物油溶液中, 并同时在真空环境中回收雾化时产生的有机溶剂, 雾 化完成后有机溶剂同时回收完成, 得到类胡萝卜素油悬浮液;
其中, 所述类胡萝卜素油悬浮液含有颗粒平均粒径小于 5μηι的 类胡萝卜素晶体;所述有机溶剂为水溶性有机溶剂或非水溶性有机溶 剂。
2、 如权利要求 1所述的方法, 其中, 所述类胡萝卜素选自 β-胡 萝卜素、 叶黄素、 玉米黄质、 番茄红素、 角黄素和虾青素中的至少一 种; 所述植物油溶液为大豆油、玉米油、葵花籽油、菜籽油、花生油、 红花油的可食性植物油中的一种或多种的混合物。
3、 如权利要求 1所述的方法, 其中, 所述水溶性有机溶剂为丙 酮、 四氢呋喃或异丙醇, 所述非水溶性有机溶剂为二氯甲垸、 甲苯或 乙酸乙酯。
4、 如权利要求 1所述的方法, 其中, 步骤 a)中加热温度为 40°C 〜60°C。
5、 如权利要求 1或 2所述的方法, 其中, 所述植物油溶液还包 括抗氧化剂, 所述抗氧化剂为混合生育酚、 合成生育酚、 BHT、 乙氧 喹啉、抗坏血酸棕榈酸酯的可供食用的抗氧化剂中一种或多种的混合
6、 如权利要求 5所述的方法, 其中, 所述植物油溶液还包括毒 性小或无毒的乙醇、 异丙醇或乙酸乙酯。
7、 如权利要求 1所述的方法, 其中, 在所述类胡萝卜素溶液以 雾化方式进入高速搅拌的植物油溶液前, 加温并保温到 30°C〜7(TC, 并抽真空以保持负压状态。
8、 一种类胡萝卜素油悬浮液, 所述类胡萝卜素油悬浮液包括由 权利要求 1〜7任一所述的方法制备的、 颗粒平均粒径小于 5μιη的、 可食用的类胡萝卜素晶体和植物油溶液。
9、 如权利要求 8所述的类胡萝卜素油悬浮液, 其中, 所述类胡 萝卜素选自 β-胡萝卜素、 叶黄素、 玉米黄质、 番茄红素、 角黄素和虾 青素中的至少一种; 所述植物油溶液为大豆油、 玉米油、 葵花籽油、 菜籽油、 花生油、 红花油的可食性植物油中的一种或多种的混合物。
10、 如权利要求 8或 9所述的方法, 其中, 所述植物油溶液还包 括抗氧化剂, 所述抗氧化剂为混合生育酚、 合成生育酚、 ΒΗΤ、 乙氧 喹啉、抗坏血酸棕榈酸酯或其它可供食用的抗氧化剂中一种或多种的 混合物。
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CN114469900A (zh) * | 2022-02-21 | 2022-05-13 | 北京元莱健康管理有限公司 | 一种改善眼部症状的药物组合物、制备方法和使用方法 |
CN114469900B (zh) * | 2022-02-21 | 2023-10-03 | 北京元莱健康管理有限公司 | 一种改善眼部症状的药物组合物、制备方法和使用方法 |
Also Published As
Publication number | Publication date |
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US20140030419A1 (en) | 2014-01-30 |
US9622497B2 (en) | 2017-04-18 |
CN102552173A (zh) | 2012-07-11 |
EP2656834B1 (en) | 2016-01-06 |
EP2656834A1 (en) | 2013-10-30 |
EP2656834A4 (en) | 2014-06-11 |
CN102552173B (zh) | 2014-01-29 |
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