直接溶解方法 Direct dissolution method

[0001] 本发明涉及将类胡萝卜素（carotenoid)溶解于食用油和脂肪中的连续方法。 [0001] The present invention relates to a continuous process for the carotenoids (carotenoid) is dissolved in edible oils and fats. 更具体地，涉及在油中直接溶解类胡萝卜素，包括加热油性介质中的悬浮体，随后优选使用在线（in-line)方法在较低温度用油来冷却。 More particularly, it relates directly dissolved in oil carotenoids, including heating oil suspension medium, then preferably used online (in-line) method at a lower temperature to cool the oil. 所得的油溶液可以本身被利用或用作包含类胡萝卜素的营养组合物的在线或分批（batch-wise)的生产。 The resulting oil solution may be used per se or used as nutritional compositions comprising carotenoids online or batch (batch-wise) production.

[0002] 类胡萝卜素广泛用于药物、营养保健品（neutriceutical)、化妆品、食品和饲料工业中。 [0002] Carotenoids are widely used in pharmaceutical, nutraceuticals (neutriceutical), cosmetics, food and feed industries. 这些组合物在本说明书中总称为营养组合物。 These compositions are referred to in this specification nutritional composition. 在饲料工业中，类胡萝卜素用作色素添加剂和精华营养素。 In the feed industry, carotenoid pigments used as additives and extracts nutrients. 传递具有良好吸收和生物利用率的类胡萝卜素是一个主要的问题，因为这些化合物在室温下实际上是不溶于水的。 Transfer of carotenoids with good absorption and bioavailability is a major problem, because these compounds at room temperature is actually insoluble in water. 具体的实例是用于水产养殖的虾青素(astaxanthin)和斑螯黄（canthaxanthin)以及用于禽类业的¢-胡萝卜素（carotene)和玉米黄质（zeaxanthin)。 Specific examples are used for aquaculture astaxanthin (astaxanthin) and cantharidin yellow (canthaxanthin) and for ¢ poultry industry - carotene (carotene) and zeaxanthin (zeaxanthin). 差的溶解性是实现良好的生物利用率的主要阻碍。 Poor solubility is to achieve good bioavailability of the main obstacles. 由于差的溶解特性，这些类胡萝卜素的晶体形式本身未被使用，因而必须首先被配制成有用的饲料和营养添加剂。 Because of poor solubility characteristics, crystalline forms of these carotenoids are not used per se, and therefore must be formulated into useful feed and nutrient additives. 通过如美国专利2，756，177所记载的喷雾干燥或微胶囊截留（catch beadlet)技术制备的在聚合物基质中包含虾青素或斑螯黄的微粒组合物被广泛用于饲料生产中。 Such as by spray drying or entrapped microcapsules (catch beadlet) described in U.S. Patent No. 2,756,177 particulate composition comprising astaxanthin or yellow spots chelating prepared in the polymer matrix are widely used in feed production. 在加工成饲料组合物之前或之后，将可分散的微胶囊或粒料以干燥粉末形式添加或它们可被溶解/分散于水中。 Prior to processing into feed compositions or after dispersible microcapsules or pellets added in the form of a dry powder or they may be dissolved / dispersed in water.

[0003] 本发明用于制备油性类胡萝卜素溶液，包括将可以是晶体、非晶体颗粒或聚集体及其组合的类胡萝卜素分散于油中，并在受热的油相中溶解类胡萝卜素，随后优选使用连续在线方法使用油相来冷却。 [0003] The present invention is for preparing oily carotenoid solution comprising a crystal can be, amorphous carotenoid particles or aggregates and combinations thereof dispersed in oil, and heated oil phase was dissolved in carotenoids, then preferably a continuous line process using an oil phase to cool. 所得的油性类胡萝卜素组合物可以本身直接用于制备饲料或其它组合物。 The resulting oily carotenoid composition may be used directly for preparing feed itself or other compositions. 此方法不需要将类胡萝卜素配制成胶体分散的干燥粉末或含水胶体的微粒组合物，由此避免了溶剂以及与溶剂回收和粉末生产有关的能量的高成本。 This method does not require the carotenoid to be formulated as a dry powder or a colloidal dispersion of colloidal particles an aqueous composition, thus avoiding the solvent and with solvent recovery and powder production related to the high cost of energy. 此外，本方法不需要用过量的水相和乳化剂乳化受热的类胡萝卜素溶液以便同时形成水包油型乳状液。 Carotenoid solution addition, the present method does not require an excess of an aqueous phase and an emulsifier emulsifying heated to simultaneously form an oil-in-water emulsion. 从而，本发明在用于特别是饲料产品的生产和供应链中提供了显著的成本降低。 Thus, the present invention provides a significant cost reduction in feed especially for the production and supply chain.

[0004] US 5，364，563记载了一种制备胶体分散的、可分散于水中的粉末状类胡萝卜素制剂的方法。 [0004] US 5,364,563 describes a process for preparing a colloidal dispersion, dispersible powdered carotenoid preparation in water method. 在高沸点油中含10-50重量％的类胡萝卜素的类胡萝卜素悬浮体被直接拿来与过热蒸汽在增高的压力和温度下接触，并立即冷却，在水胶体的水溶液中乳化，随后将比水包油型（o/w)乳状液喷雾并干燥成粉末。 Containing 10-50% by weight of the carotenoid in a high boiling oil carotenoid suspension was directly brought into contact with the superheated steam at elevated pressure and temperature and cooled immediately, emulsified in an aqueous solution of hydrocolloid, followed by than oil-in-water (o / w) emulsion and spray-dried to a powder.

[0005] US 6，296，877记载了一种制备可分散于水中的颗粒或微胶囊的方法，包括在增高的压力和温度下使用水溶性溶剂溶解至少两种水胶体和类胡萝卜素。 [0005] US 6,296,877 describes a method for preparing water dispersible granules or microcapsules comprising a water-soluble solvent dissolves at least two hydrocolloid and carotenoid at elevated pressure and temperature. 通过用可膨胀胶体的水溶液迅速混合和冷却有机溶剂溶液，类胡萝卜素以胶体分散形式从分子分散溶液中立即沉淀，所得的分散体从溶剂和分散介质中以常规方式分离出来。 By rapid mixing and cooling the organic solvent solution, in the form of dispersed colloidal carotenoid precipitates immediately from the molecular dispersed solution, the resulting dispersion from the solvent and the dispersion medium is separated in a conventional manner with an aqueous swellable colloid. 与US 5，364，563相同，此方法需要溶剂和/或回收步骤，以获得胶体分散的微粒类胡萝卜素组合物。 US 5,364,563 with the same, this method requires a solvent and / or recovery steps to obtain colloid-dispersed particulate carotenoid compositions.

[0006] US 6，664，300涉及一种在高沸点有机液体中制备类胡萝卜素溶液以生产类胡萝卜素乳状液的方法，包括在高沸点有机液体中加热类胡萝卜素悬浮体，以溶解类胡萝卜素，随后立即将所得的溶液添加到乳化剂如水胶体的水溶液中以乳化此溶液。 [0006] US 6,664,300 relates to a high-boiling organic liquid solution was prepared in a process for producing a carotenoid emulsion carotenoids, carotenoid suspension comprises heating in a high boiling organic liquid to dissolve the class carotene, then immediately add the resulting solution to an aqueous solution of colloidal water emulsifier to emulsify the solution. 将乳状液喷雾干燥从而回收胶体分散的类胡萝卜素粉末。 The emulsion is spray dried to recover the colloid-dispersed carotenoid powder.

[0007] 所有上述方法的特征在于在过量的水中用水胶体和/或乳化剂来乳化受热的类胡萝卜素溶液的必需步骤。 [0007] All of the above method is characterized in that the excess of water and the necessary steps colloidal water / emulsifier or emulsifying the heated carotenoid solution in.

[0008] 相比之下，WO 03/102116记载了一种包含溶解于油中的亲脂性聚合物/分散剂的油可分散的类胡萝卜素组合物，不使用在线和规定的短加热程序，并且在制备鱼饲料和其它组合物之前用油冷却。 [0008] In contrast, WO 03/102116 describes an oil containing dissolved in oil lipophilic polymer / dispersant dispersible carotenoid composition without the use of online and prescribed short heating program, and prior to the preparation of fish feed and other compositions oil cooling.

发明内容 DISCLOSURE

[0009] 本发明记载了一种用于类胡萝卜素溶解的在线方法以及相关设备，其可以被在线结合到连续或分批的食品和饲料组合物的生产方法中。 [0009] The present invention describes a method for carotenoid line dissolution and related equipment, which may be incorporated into the production line continuous or batch method for food and feed compositions. 所述方法不需要制备和购买添加到饲料和食品组合物中的单独的干燥粉末类胡萝卜素制剂。 The method does not require the preparation and later added to the feed and food composition of individual carotenoid dry powder formulations. 从而，对于加工成鱼饲料，从优选地非配制的类胡萝卜素开始，在冷却后连续制备具有所期望的类胡萝卜素浓度的油性类胡萝卜素溶液是可能的。 Thus, for processing into fish feed, preferably from unformulated carotenoids began, after cooling the continuous preparation of an oily solution of a carotenoid carotenoid having a desired concentration is possible. 所公开的溶解和冷却设备也可以被设置在独立的模块或相连的模块单元中以便制备大量的油性类胡萝卜素溶液。 The disclosed dissolution and cooling devices can be provided in separate modules or module units are connected in order to prepare a large amount of oily carotenoid solution. 模块特别适合于在线连接到（存在的）饲料生产线上。 Module is particularly suited to online connection to the (present) feed production line. 此方法优选在常压下进行。 This method is preferably carried out at atmospheric pressure. 然而，如果加压的（例如超临界的）流体和装置被单独使用或与加热油结合使用时，该方法也可以在压力下进行。 However, if pressurized (e.g. supercritical) fluids and equipment are used alone or in combination with heating oil, the method can also be carried out under pressure.

[0010] 根据优选的实施方案，本发明记载了一种在线方法：在包括例如混合室的加热区域中在高沸点油相中在最多可为油相沸点的温度下溶解类胡萝卜素组合物达预定时间，随后立即优选在第二混合室中迅速冷却，从而制备油性类胡萝卜素溶液。 [0010] According to a preferred embodiment, the present invention describes an on-line method: for example, comprising a heating zone in the mixing chamber of a high-boiling oil phase in the oil phase up to the boiling point of dissolution of the carotenoid composition predetermined time, preferably immediately thereafter rapidly cooled in the second mixing chamber to prepare an oily carotenoid solution. 溶解类胡萝卜素所需的温度介于所述的类胡萝卜素悬浮体的温度和油相沸点之间。 Between temperature and the boiling point of the oil phase dissolve carotenoids required temperature between the carotenoid suspension. 术语混合包括将受热的油性溶液向冷却介质的添加或反之亦然的冷却介质向受热的油性溶液的添加。 The term mixing includes adding the oily solution of oily solution heated to add a cooling medium or vice versa, the heated cooling medium.

[0011] 因此，本发明记载了如下实施方案： [0011] Accordingly, the present invention is described in the following embodiments:

[0012] 一种制备油性类胡萝卜素组合物的方法，包括： Method [0012] An oily carotenoid compositions comprising:

[0013] i)通过将至少一种类胡萝卜素分散于生理可接受的油相中制备出悬浮体； [0013] i) by at least one carotenoid dispersed in a physiologically acceptable oil phase to prepare a suspension;

[0014] ii)在最大高达油相的沸点的温度下在线加热所述悬浮体达最多30秒，以溶解在所述油相中悬浮的类胡萝卜素，获得受热的油性类胡萝卜素溶液；并且 [0014] ii) at a maximum temperature up to the boiling point of the oil phase of the suspension of the line is heated up to 30 seconds, to dissolve in the oil phase of the carotenoid suspension to obtain a heated oily carotenoid solution; and

[0015] iii)通过选自与生理可接受的油相混合以及使用热交换器的方法，来冷却受热的油性类胡萝卜素溶液，其中油相的温度低于受热的油性溶液。 [0015] iii) through selected with a physiologically acceptable oil phase and mixing methods using a heat exchanger to cool the heated oily carotenoid solution, wherein the oil temperature is lower than the heated oily phase solution.

[0016] 本发明涉及下述优选的实施方案： [0016] The present invention relates to a preferred embodiment:

[0017] • 一种方法，其中通过与比所述悬浮体温度更高的油相混合，而将油性类胡萝卜素悬浮体在100-230°C或100-300°C加热小于5秒，其中所述油相的加热是通过使用选自于用过热蒸汽加热的热交换器、用超临界气体加热的热交换器、用电加热的热交换器、由转子-定子混合器产生的热量以及由超声波混合器产生的热量而进行的。 [0017] • a method, by which the suspension is higher than the temperature of the oil are mixed, and the oily carotenoid suspension at 100-230 ° C or 100-300 ° C heating is less than 5 seconds, wherein The heated oil phase is selected for use by the use of superheated steam heated heat exchanger with a heat exchanger for heating the supercritical gas, electrically heated heat exchanger, the rotor - and the heat generated by the stator mixer Ultrasonic heat mixers carried out.

[0018] • 一种方法，其中类胡萝卜素是晶体类胡萝卜素化合物。 [0018] • a method, wherein the carotenoid is a crystalline carotenoid compound.

[0019] • 一种方法，其中受热的油性类胡萝卜素溶液是通过应用选自于在线添加生理可接受的温度低于受热的油性类胡萝卜素溶液的油相、分批添加到生理可接受的温度低于受热的油性类胡萝卜素溶液的油相、以及使用在线热交换器的方法而冷却的。 [0019] • a method, wherein the heated oily carotenoid solution is added on-line selected by applying physiologically acceptable oil temperature is lower than the heated oily carotenoid solution phase is added portionwise to a physiologically acceptable the oil temperature is lower than the heated oily carotenoid solution phase, and the method of using a heat exchanger and the cooling line of.

[0020] • 一种方法，其中受热的和冷却的油性类胡萝卜素溶液包含最多20，OOOppm的类胡萝卜素，其中受热的油性类胡萝卜素溶液的冷却是通过添加鱼油而在线进行的。 [0020] • a method in which the heated and cooled oily carotenoid solution contains up to 20, OOOppm carotenoid, wherein cooling the heated oily carotenoid solution is carried out by the addition of fish oil and online.

[0021] • 一种方法，其中油性类胡萝卜素的温度在冷却后低于60°C，冷却步骤是在小于30秒的时间内进行的。 [0021] • a method, wherein the oily carotenoid temperature after cooling below 60 ° C, the cooling step is in less than 30 seconds are carried out. [0022] • 一种方法，其中油性类胡萝卜素悬浮体包括基本上纯的类胡萝卜素颗粒，其中类胡萝卜素选自合成或天然的虾青素、斑螯黄、¢-胡萝卜素和玉米黄质，且其中90%的所述颗粒的直径小于15 V- m。 [0022] • A method in which the oily carotenoid suspension comprises a substantially pure carotenoid particles wherein the carotenoid selected from synthetic or natural astaxanthin, cantharidin yellow, ¢ - carotene and zeaxanthin quality, and wherein the diameter of the particles of less than 90% 15 V- m.

[0023] 本发明的另外的实施方案涉及制备营养组合物的方法，包括： [0023] The method further embodiment of the present invention relates to the preparation of nutritional composition, comprising:

[0024] i)通过将至少一种类胡萝卜素分散于生理可接受的油中制备出悬浮体； [0024] i) by dispersing at least one carotenoid in a physiologically acceptable oil suspension was prepared;

[0025] ii)在最大高达油相的沸点的温度下在线加热所述悬浮体达最多30秒，以溶解在所述油相中悬浮的类胡萝卜素，获得受热的油性类胡萝卜素溶液； [0025] ii) at the maximum line heated up to the boiling point of the oil phase of the suspension reaches a maximum of 30 seconds, to dissolve in the oil phase of the carotenoid suspension to obtain a heated oily carotenoid solution;

[0026] iii)通过选自与生理可接受的油相混合以及使用热交换器的方法，来冷却受热的油性类胡萝卜素溶液，其中油相的温度低于受热的油性溶液。 [0026] iii) through selected with a physiologically acceptable oil phase and mixing methods using a heat exchanger to cool the heated oily carotenoid solution, wherein the oil temperature is lower than the heated oily phase solution.

[0027] iv)将冷却的油性类胡萝卜素溶液添加到营养组合物中。 [0027] iv) adding the cooled oily carotenoid solution to nutritional compositions.

[0028] 本发明的进一步的实施方案涉及制备营养组合物的方法，包括： [0028] A further embodiment of the method of the present invention relates to the preparation of nutritional composition, comprising:

[0029] i)通过将至少一种类胡萝卜素分散于生理可接受的油中制备出悬浮体； [0029] i) by dispersing at least one carotenoid in a physiologically acceptable oil suspension was prepared;

[0030] ii)在最大高达油相沸点的温度下在线加热所述悬浮体达最多30秒，以溶解在所述油相中悬浮的类胡萝卜素，获得受热的油性类胡萝卜素溶液； [0030] ii) at the maximum temperature up to the boiling point of the oil phase Live heating the suspension of up to 30 seconds, to dissolve in the oil phase of the carotenoid suspension to obtain a heated oily carotenoid solution;

[0031] iii)通过选自与生理可接受的油相混合以及使用热交换器的方法，来冷却受热的油性类胡萝卜素溶液，其中油相的温度低于受热的油性溶液； [0031] iii) through selected with a physiologically acceptable oil phase and mixing methods using a heat exchanger to cool the heated oily carotenoid solution, wherein the oil temperature is lower than the heated oily phase solution;

[0032] iv)将冷却的油性类胡萝卜素溶液添加到高孔隙度的无机载体中；并且 [0032] iv) to add the oily carotenoid solution was cooled to an inorganic carrier in a high porosity; and

[0033] V)将此载体添加到营养组合物中。 [0033] V) this carrier added to the nutritional composition.

[0034] 本发明进一步记载了虾青素颗粒的油性类胡萝卜素悬浮体，其中虾青素符合下述质量标准和规格： [0034] The present invention is further described in the oily carotenoid astaxanthin suspension of particles in which astaxanthin meet the following quality standards and specifications:

[0035] [0035]

[0036] 本发明进一步记载了斑螯黄颗粒的油性类胡萝卜素悬浮体，其中斑螯黄符合下述质量标准和规格： [0036] The present invention is further described in the oily carotenoid suspension cantharidin yellow particles in which cantharidin yellow comply with the following quality standards and specifications:

[0037] [0037]

[0038] 在本发明进一步的实施方案中，为冷却油性类胡萝卜素溶液而添加的油相可以包括最多30%的乳化水。 [0038] In a further embodiment of the invention, the cooled oily carotenoid solution is added an oil phase may comprise up to 30% of emulsified water.

[0039] 上述虾青素和斑螯黄油性悬浮体满足美国FDA的要求，也特别适合于制备如US5，364，563和US 6，664，300中所记载的可分散于水中的制剂。 [0039] said astaxanthin and cantharidin butter of suspension to meet the FDA's requirements, but also particularly suitable for the preparation US5,364,563 and US 6,664,300 as described in the formulation can be dispersed in water.

[0040] 根据优选的实施方案，在冷却后在线或分批地将油性类胡萝卜素溶液添加到营养组合物中，营养组合物选自饲料丸剂（pellet)、团粒（granulate)、片剂和胶囊等。 [0040] According to a preferred embodiment, after cooling line or batchwise adding the oily carotenoid solution to nutritional composition, a nutritional composition is selected from feed pellets (pellet), pellets (granulate), tablets and capsules and so on. 这样获得的油性溶液在饲料丸剂和其他营养组合物中提供了分子分散的类胡萝卜素在油中更一致的分布。 The thus obtained oily solutions provide molecularly dispersed carotenoid in the oil in a more uniform distribution of feed pellets and other nutritional compositions.

[0041] 进一步地，油性类胡萝卜素溶液可以被添加到具有大内表面的高孔隙度粉末中，其被进一步用营养组合物、优选用饲料组合物进行加工，或者它们自身可被使用并且被加工成用于口腔、药物或营养保健品给药的片剂、胶囊等。 [0041] Further, the oily carotenoid solution may be added to the powder of high porosity with a large inner surface, which is further used nutritional composition, feed composition is preferably used for processing, or they may be used and are themselves processed into the oral cavity, drugs or nutritional supplements administered tablets, capsules and the like.

[0042] 在下述发明详述中，定义和术语具有下述优选的含义： [0042] In the following Detailed Description, definitions and terms have the following preferred meanings:

[0043] “赋形剂”是以所用的数量来说没有药理学活性的材料，并且可以被包含在组合物中以改善技术处理（technical handling)例如类胡萝卜素的溶解性和稳定性并且有助于活体（living organism)的给药。 [0043] "excipient" is used for the number of no pharmacologically active material, and may be included in the composition to improve processing technology (technical handling) such as solubility and stability of carotenoids and has help in vivo administration (living organism) of.

[0044] “溶解（dissolving)”或“溶解（dissolution) ”意思是获得类胡萝卜素（其可以是单体、二聚体、三聚体等）的分子分散体或分子聚集体和/或类胡萝卜素的胶态分散体。 [0044] "dissolution (dissolving)" or "dissolve (dissolution)" means to obtain carotenoids (which may be monomers, dimers, trimers, etc.) of molecular dispersion or molecular aggregates and / or class carotene colloidal dispersion. 评价类胡萝卜素在油相中的溶解程度是通过使油相通过0. 45 ym孔径大小的过滤器过滤，随后HPLC测定滤液中的类胡萝卜素含量并且与未过滤的油相中总类胡萝卜素浓度相比较而进行的。 Evaluation level of carotenoids dissolved in the oil phase by the oil phase by 0. 45 ym pore size filter, the filtrate is then determined by HPLC carotenoid content and unfiltered oil phase and total carotenoids comparing the concentration performed.

[0045] “基本上”意味着至少40wt %。 [0045] "substantially" means that at least 40wt%.

[0046] “配制的类胡萝卜素”指的是具有赋形剂如保护性水胶体或聚合分散剂以及稳定剂的含类胡萝卜素的胶体分散的组合物，并且包括粉末化的细胞以及细胞碎片（细胞碎片），例如微藻类（microalgae)诸如雨生红球藻（H. pluvialis)、绿球藻（Chlorococcum)和红发夫酵母（Phaffia rhodozyma)。 [0046] "formulated carotenoid" refers to a composition having an excipient such as protective hydrocolloids or polymeric dispersants and stabilizers carotenoid-containing colloidal dispersions, and includes powdered cells and cell fragments (cell debris), such as microalgae (microalgae), such as rain pluvialis (H. pluvialis), Prochlorococcus (Chlorococcum) and Phaffia yeast (Phaffia rhodozyma).

[0047] “饲料”包括所有类型的给予活体物种（living species)的食物。 [0047] "feed" includes all types of giving live species (living species) food.

[0048] “鱼饲料”描述了所有包括蛋白质、碳水化合物、油脂（oils)、矿物质、维生素和营养物的在水产业中用于喂鱼特别是鲑科鱼（salmonids)和甲壳纲动物（crustaceans)的饲料组合物。 [0048] "fish feed" describes all include proteins, carbohydrates, fats (oils), minerals, vitamins and nutrients to feed the fish in particular salmonid (salmonids) in aquaculture and crustaceans ( crustaceans) feed composition.

[0049] “晶体类胡萝卜素”描述了包括所限定的多晶型物和伪多晶型物的化合物的晶体结构。 [0049] "Crystal carotenoid" describes the crystal structure of the compound include defined polymorphs and pseudo-polymorphs thereof.

[0050] “在线”涉及了构成连续序列的操作或步骤的整体部分的方法（method)或过程(process)。 [0050] "online" refers to a method constituting an integral part of a continuous sequence of operations or steps (method) or process (process).

[0051] 发明详述 [0051] DETAILED DESCRIPTION

[0052] 类胡萝卜素是一类由八个类异戊二烯单元组成的烃。 [0052] Carotenoids are a class of eight isoprenoid units of hydrocarbons. 类胡萝卜素类的化合物被分为主要两组：胡萝卜素和叶黄素。 Carotenoid compounds are mainly divided into two groups: carotene and lutein. 与胡萝卜素相比，胡萝卜素是纯的多烯烃如¢-胡萝卜素或番茄红素，叶黄素另外包含官能基团部分例如羟基、环氧基和/或氧基。 Compared with carotene, beta-carotene is a pure multi-olefins such as ¢ - carotene or lycopene, xanthophylls additionally contain functional moieties such as hydroxyl, epoxy and / or groups. 这组的典型代表是虾青素、斑螯黄和玉米黄质。 A typical representative of this group is astaxanthin, cantharidin yellow and zeaxanthin.

[0053] 叶黄素（xanthophyll)在自然界是很普遍的,存在于玉米（玉米黄质）、青豆（黄体素（lutein))、红辣椒（辣椒红素（capsanthin))、蛋黄（黄体素）中，也存在于甲壳纲动物和鲑科鱼（虾青素）中。 [0053] lutein (xanthophyll) is very common in nature, found in corn (zeaxanthin), green beans (lutein (lutein)), red pepper (paprika oleoresin (capsanthin)), egg yolk (lutein) also exists in crustaceans, and salmonids (astaxanthin) in. 它们给这些食物赋予特征颜色。 They impart characteristic color to these foods.

[0054] 一些类胡萝卜素可以工业合成，也可从自然界中分离。 [0054] The industrial synthesis of some carotenoids can also be isolated from nature. 它们是重要的天然抗氧化齐U，也是用于食品和饲料工业中的着色剂，以及用于药物工业作为合成染料的替代物。 They are important natural antioxidant Qi U, it is also used in the food and feed industry coloring agents, as well as for the pharmaceutical industry as a substitute for synthetic dyes.

[0055] 叶黄素，在室温环境下几乎不溶于水，在脂肪和油脂中显示出非常低的溶解性。 [0055] lutein, at room temperature practically insoluble in water, show very low solubility in fats and oils. 现有技术中声称有限的溶解性和对氧化的高灵敏性阻碍了获自合成的晶体材料在食品和饲料着色中的直接使用。 Art claims limited solubility and the high sensitivity to oxidation impede a synthetic crystalline materials obtained from the direct use in food and feed in coloring.

[0056] 优选的类胡萝卜素是用于鱼饲料工业中的虾青素和斑螯黄及其混合物。 [0056] Preferred carotenoids for the fish feed industry astaxanthin and cantharidin yellow and mixtures thereof. 对于在其它食品和饲料工业的应用来说，可考虑备选的类胡萝卜素，例如¢-胡萝卜素、番爺红素、胭脂树橙（bixin)、玉米黄质（zeaxanthin)、隐黄素（cryptoxanthin)、黄体素、e-apo-12'胡萝卜素醛以及酯类和衍生物。 For applications other food and feed industry, it may consider alternative carotenoids, such as ¢ - carotene, Fan Ye red pigment, annatto (bixin), zeaxanthin (zeaxanthin), cryptoxanthin ( cryptoxanthin), lutein, e-apo-12 'carotenal and esters and derivatives. 虾青素和斑螯黄的脂肪酸酯和二酯，其更具油溶性，可以用于代替游离类胡萝卜素基质（base)。 Astaxanthin and cantharidin yellow and diesters of fatty acid esters, which more oil soluble, can be used in place of the free carotenoid substrate (base). 优选的实例是用《_3脂肪酸和/或短链羧酸制备的虾青素的二酯，其描述于US 6709688，其引入本文作为参考。 Preferred examples with "_3 fatty acids and / or short chain carboxylic acids produced astaxanthin diester, which is described in US 6709688, which is incorporated herein by reference.

[0057] 类胡萝卜素可以是非晶体的，以H-或J-聚集体的形式或存在于稳定的或亚稳定的多晶型物中。 [0057] The carotenoid may be amorphous, or present in the form of a stable or metastable polymorph in H- or J- aggregates. 适合用于本发明的虾青素和斑螯黄的品质描述于US-FDA数据库(21CFR73. 35以及21CFR73. 75)中，引入本文作为参考。 Suitable for use in the present invention astaxanthin and quality of cantharidin yellow are described in US-FDA database (21CFR73. 35 and 21CFR73. 75), and incorporated herein by reference. 同时，也可以使用基本上纯的类胡萝卜素，前提是副产物被识别，或者属于适于消费的食品和饲料组合物中存在的类胡萝卜素的种类并且已知是无害的。 Also, you can use a substantially pure carotenoids, provided that the by-products to be identified, or of the kind of carotenoids in food and feed suitable for consumption present in the composition and is known to be harmless.

[0058] 可使用虾青素和斑螯黄的纯化合物或混合物以及其多晶型物，非晶体和聚集体形式，其包含最多40wt%的官能的（functional)所有反式类胡萝卜素。 [0058] may use cantharidin astaxanthin and yellow as well as pure compounds or mixtures thereof polymorphs, amorphous forms and aggregates, which include all-trans carotenoids up to 40wt% of the functional (functional). 虾青素可以包含60% -98%，优选80% -96%的反式虾青素，以及2% -40%重量份、优选2% -35%重量份，最优选2%-4%重量份的至少一种类胡萝卜素衍生物在混合物（combination)中作为较少量组分(minor component)。 Astaxanthin may contain 60% -98%, preferably 80% -96% of trans-astaxanthin, and 2% to 40% by weight, preferably from 2% to 35% by weight, most preferably from 2% to 4% by weight parts of at least one carotenoid derivative mixture (combination) as a small amount of component (minor component).

[0059] 应当理解的是配制的类胡萝卜素组合物和天然来源的虾青素，其包含粉末化细胞和细胞碎片例如微藻类诸如雨生红球藻和绿球藻、酵母如红发夫酵母和甲壳纲动物副产物，可以在本发明的鱼饲料的生产中作为虾青素的来源。 [0059] It should be understood that the preparation of the carotenoid composition and a natural source of astaxanthin, which comprises powdered cells and cell debris such as microalgae as pluvialis algae and green ball algae, yeasts such as Phaffia yeast and crustaceans byproduct, can be used as the source of astaxanthin in fish feed production in the present invention. 所描述的方法能够更高的、更一致且均匀的溶解来自（冷冻或喷雾）干燥的细胞组分的类胡萝卜素，从而引入鱼饲料中，由此得到更均一的产品。 The described method can be higher, more consistent and uniform dissolution from a (frozen or spray) dried cells carotenoid components, thereby introducing fish feed, to thereby obtain a more uniform product. 此外，使用用于将虾青素溶解于油相中以及用于生产鱼丸剂的在线方法是一种成本更加有效且工业可行的用于制备具有改进性能的高品质饲料的方法。 In addition, using for astaxanthin dissolved in the oil phase and a line for the production of fish pellet is a method more cost-effective and commercially viable for the method of preparing high quality feed with improved properties.

[0060] 对于根据本发明中所描述的方法的在线溶解，油组合物包含0. Iwt % _4(^七％的悬浮虾青素。90%所述颗粒应当具有小于15 的直径。为在较低温度下迅速溶解，油相中悬浮的类胡萝卜素粉末的平均颗粒大小应当小于15pm，优选在Iym和之间。颗粒大小小于Ium可能更适合于在油中的迅速溶解。假如使用更多类胡萝卜素的可溶多晶型物或非晶体变体，颗粒大小可能更大。颗粒大小的降低可以在胶体球磨机（colloid ballmill)中进行，优选通过在油相中研磨悬浮体。次优选地，但尽管如此也是获得微粉化的类胡萝卜素的可行选择，是例如使用胶体磨（colloid mill)来研磨含有适合的浸润剂（例如磷脂）的类胡萝卜素的水悬浮体。任选地，根据本发明，在去除水之后，干燥粉末可进一、步通过添加赋形剂而加工以改善粉末流动性能并减少起尘性,并且直接添加到油相中并加工。其它选择例如借助空气喷射磨机（air jet mill)的低温研磨和干燥研磨在某些情况下也可以考虑。可选择地，亚微米（submicron)的非晶体类胡萝卜素颗粒可以使用超临界流体通过熔体分散方法而单独制备。如果希望，不计成本（costnot-withstanding),所述方法可以被在线结合到本发明的方法中。类胡萝卜素也可以被分散到高沸点非含水液体，例如多元醇诸如甘油或丙二醇中，并在被添加到油相之前研磨（微粒化）。 [0060] For the dissolution method according to the line described in the present invention, the oil composition comprises 0. Iwt% _4 (^ seven percent of the suspension of astaxanthin particles should have a diameter of less than .90% 15. is in a relatively The average particle size at low temperatures rapidly dissolved in the oil phase of the suspension of the carotenoid powder should be less than 15pm, and preferably between Iym. particle size of less than Ium may be more suitable for rapid dissolution in oil. If you use more classes carotene soluble polymorph or amorphous variant, the particle size may be larger. particle size can be reduced in a colloid mill (colloid ballmill) preferably by milling a suspension in the oil phase. Preferably times, Nevertheless also a viable option to obtain micronized carotenoids, for example using a colloid mill (colloid mill) to grind carotenoid aqueous suspension containing a suitable wetting agent (such as phospholipids) Optionally, according to the invention, after removal of water, can be dried into a powder, and further processed by adding excipients to improve powder flow properties and reduce dusting resistance, and added directly to the oil phase and processed. Other options, for example by means of an air jet mill (air jet mill) of cryogenic grinding and dry grinding in some cases also be considered. Alternatively, submicron (submicron) amorphous carotenoid particles can be prepared separately by melt dispersing method using a supercritical fluid. If you want to, regardless of the cost (costnot-withstanding), the method may be incorporated into the online method of the present invention. carotenoids may also be distributed to high-boiling non-aqueous liquid, such as polyols such as glycerol or propylene glycol, and It is added to the oil phase before grinding (fine particles).

[0061] 在加热过程期间，其中溶解类胡萝卜素的油相是生理可接受的食用油，优选包含抗氧化剂，如a -生育酚和抗坏血酸棕榈酸酯。 [0061] During the heating process, in which the oil phase is dissolved carotenoid class is physiologically acceptable oil, preferably containing antioxidants, such as a - tocopherol and ascorbyl palmitate. 生育酚例如a-生育酚也可以用作油相，以溶解类胡萝卜素。 A- tocopherol e.g. tocopherol may be used as the oil phase to dissolve the carotenoid. 油相可达到高达180°C-230°C的温度。 The oil phase can reach up to 180 ° C-230 ° C temperature. 高沸点油，例如植物油或玉米油、作为MIGLY0L™出售的合成或部分合成甘油三酯是优选的。 High boiling oil, such as vegetable oil or corn oil, MIGLY0L ™ sold as synthetic or partially synthetic triglycerides are preferred. 用于加热过程的油相可以是植物油或鱼油或两种类型的油的混合物。 Oil for heating process phase may be a vegetable oil or fish oil or a mixture of both types of oils. 适合的植物油的实例包括：棉籽油、芝麻油、椰子油或花生油、扁桃油（almondoil)、玉米油、菜籽油(canola oil)/菜籽油(rapeseed oil)、橄榄油、花生油（落花生油）、向日葵油、红花油、植物豆油、扁桃仁油（almond oil)、杏仁油（apricot oil)、鳄梨油、希蒙德木油（jojoba oil)、橙油、朽1檬油、棕榈仁油、南瓜子油、蓖麻油、椰子油（76和110度）、芝麻油、炒芝麻油、亚麻油（flax seed oil)(有机的、传统的和高木酹素）、GLA油（玻璃苣（Borage)、红醋栗（Black Currant)、月见草（EveningPrimrose))、葡萄籽油、榛子油、夏威夷核油（kukui nut oil)、澳洲坚果油(macademianut oil)、mamaku 油、胡桃油(pecan oil)、紫苏子油(perilla oil)、阿月浑子油（pistachiooil)、米糠油、茶树油、核桃油、麦胚芽油、玉米油或者菜籽油（canola oil)/菜籽油（rapeseed oil)。 Examples of suitable vegetable oils include: cottonseed oil, sesame oil, coconut oil or peanut oil, almond oil (almondoil), corn oil, rapeseed oil (canola oil) / canola (rapeseed oil), olive oil, peanut (groundnut) , sunflower oil, safflower oil, vegetable oil, flat peach kernel oil (almond oil), almond oil (apricot oil), avocado oil, jojoba oil (jojoba oil), orange oil, rotten 1 lemon oil, palm kernel oil, pumpkin seed oil, castor oil, coconut oil (76 and 110 degrees), sesame oil, fried sesame, linseed (flax seed oil) (organic, conventional and Takagi sprinkle hormone), GLA oil (borage (Borage) Red currant (Black Currant), evening primrose (EveningPrimrose)), grape seed oil, hazelnut oil, Kukui oil (kukui nut oil), macadamia nut oil (macademianut oil), mamaku oil, walnut oil (pecan oil) , perilla oil (perilla oil), pistachio oil (pistachiooil), rice bran oil, tea tree oil, walnut oil, wheat germ oil, corn oil or rapeseed oil (canola oil) / canola (rapeseed oil) . 优选的植物油是：豆油（无GMO)和亚麻籽油。 Preferred vegetable oils are: soybean oil (non GMO) and flaxseed oil.

[0062] 只要可能，此过程不需要施加外界压力而进行。 [0062] Wherever possible, the process is performed without the application of external pressure. 典型地，使用管道系统的泵作用而产生的水力和流体压力可以在内部产生最多50巴的压力。 Hydraulic and fluid pressure pump action typically used to generate piping system can generate pressure up to 50 bar inside. 但如果需要，可以将压力提高到约300巴，以加速类胡萝卜素的溶解。 But if necessary, the pressure can be increased to about 300 bar, in order to accelerate the dissolution of the class of carotenoids.

[0063] 优选地油相不含水。 [0063] Preferably the oil phase does not contain water. 然而有时用来加热类胡萝卜素溶液的油相和/或将类胡萝卜素分散于其中的油相可以包含少量的，最多大约10-30%的乳化水（油包水型乳状液）。 Sometimes, however, it used to heat the carotenoid solution of the oil phase and / or the carotenoid dispersed therein oil phase may contain small amounts, up to about 10-30% of emulsified water (water-in-oil emulsion). 与油相相比，具有较低沸点的不混溶相的存在能够在压力下产生足够的过热蒸汽，以加速类胡萝卜素在加热区域中的溶解，从而能够使用较高的类胡萝卜素浓度。 Compared with the oil phase, with the presence of lower boiling immiscible phase can generate sufficient superheated steam under pressure to accelerate the carotenoid is dissolved in the heating zone, thereby enabling the use of higher carotenoid concentrations. 同样地，其中溶解类胡萝卜素的油相可以和加压（超临界）流体如CO2混合，后者可以与油相部分混合或溶解于油相中，并通过降低悬浮类胡萝卜素的熔点而能够实现较高的溶解能力。 Likewise, wherein the carotenoid is dissolved and an oil phase can be pressurized (supercritical) fluids such as CO2 mixing, which can be mixed with the oil phase or dissolved in the oil phase, and by lowering the melting point of the carotenoid suspension and can achieve high solubility. 在高压装置和元件的安装和使用中，成本和经济因素是和安全问题一起被考虑的主要因素。 During the installation and use of high-pressure devices and components, the cost and economic factors are the main factors and safety issues to be considered together. 用于加热和溶解的受热油相的量（80°C -230°C )为0. 1-25重量份、优选5_10重量份的类胡萝卜素油悬浮体。 The amount of (80 ° C -230 ° C) for heating and dissolution heated oil phase is 0.5 to 25 parts by weight, preferably 5_10 parts by weight of the carotenoid oil suspension.

[0064] 此方法或在线方法的一部分可以在惰性气体下进行或在加热区域中于加压下进行，以进一步最小化氧化分解。 [0064] This method or process line or in part may be carried out under pressure in the heating zone to further minimize oxidative decomposition in an inert gas. 超临界流体例如CO2的使用引起类胡萝卜素的熔点的显著降低。 Supercritical fluids such as CO2 caused by the use of carotenoids significantly lower melting point. 惰性气体可以是过热气体或加压（超临界）流体，其也可使用以增大加热区域的压力从而使类胡萝卜素在较低温度下溶解更迅速，并增大其在较高浓度下的溶解。 Inert gas may be a gas or superheated pressurized (supercritical) fluids, which may also be used to increase the pressure of the heating zone so that the carotenoid to dissolve more rapidly at lower temperatures and increases at higher concentrations of its dissolved. 气相也可以是过热蒸汽，其由较少量的在通过加热区域时保持在增高的压力下的受热油相中乳化的水产生。 Gas may also be superheated steam, which is maintained by a relatively small amount of pressure at elevated heated oil phase emulsified in water produced through the heating zone.

[0065] 用来将热溶液冷却和/或稀释到低于60°C的油的本体被保持在30°C -60°C或更低。 [0065] The hot solution for cooling and / or dilution of the oil to 60 ° C below the body is kept at 30 ° C -60 ° C or lower. 优选其是不含水的。 Which is preferably non-aqueous. 然而，它可以包含较少比例的水或天然存在于例如粗制天然（鱼）油中的水。 However, it may contain a minor proportion of water, for example, naturally occurring or crude natural (fish) oil in water. 油中水的数量可以是高达10-30wt%*更多。 Oil in the amount of water can be as high as 10-30wt% * more. 与所使用的较大量的油相比，它是较少量的，基本上其是油包水（w/o)体系，不是乳化剂的水溶液。 Compared with the larger amount of oil is used, it is of a relatively small amount, which is substantially water-in-oil (w / o) system, an aqueous solution of the emulsifier is not. 优选地，所使用的油是天然油或部分水解的天然植物或鱼甘油三酯（包括甘油单酯、甘油二酯和甘油三酯或其组合），其是更易于吸收的。 Preferably, the oil used is natural oils or natural vegetable or fish triglyceride partially hydrolyzed (including monoglycerides, diglycerides and triglycerides or a combination thereof), which is more readily absorbed. 其也可以是合成的或半合成的油。 It may also be synthetic or semi-synthetic oils. 适合的鱼油的实例是：特产海洋鱼油(specialty marine oils)，例如具有w-3 酸-30% (18% EPA/12% DHA) ,50%(30% EPA/20% DHA)- 、不含胆固醇、高效DHA 的挪威鳕鱼肝油（3000A/100D、2500A/250D)、金枪鱼或鲣鱼（bonito)的鱼油、鱼肝油、比目鱼（halibut)肝油、绿鳕（pollack)肝油、S鱼肝油、角S烯（squalene)、角藍烧（squalane)、鲑鱼（salmon)油、飞鱼（skipjack)肝油、青鱼(herring)油、鱗鱼(capelin)油、鲱鱼(menhaden fish)油。 Examples of suitable fish oils are: specialty marine oils (specialty marine oils), for example, a w-3 acids -30% (18% EPA / 12% DHA), 50% (30% EPA / 20% DHA) -, excluding cholesterol, high DHA Norwegian cod liver oil (3000A / 100D, 2500A / 250D), tuna or skipjack (bonito) of fish oil, cod liver oil, halibut (halibut) liver oil, pollack (pollack) liver oil, S cod liver oil, angle S ene ( squalene), angle blue burn (squalane), salmon (salmon) oil, flying fish (skipjack) liver oil, herring (herring) oil, capelin (capelin) oil, herring (menhaden fish) oil.

[0066]优选地，其为鱼油，例如可从 Egersund Sildoljefabrikk 以NorseECOil 和NORSlamOil的商品名获得的那些，或来自其它鱼油生产者的鱼油与植物油的混合物。 [0066] Preferably, those of fish oil or mixtures thereof, for example, and may NorseECOil NORSlamOil tradename available from Egersund Sildoljefabrikk from other fish oil producers of fish oil and vegetable oil.

[0067] 在冷却或在低温下添加油相后，在所得的离开热交换器的油溶液中，类胡萝卜素的量为约50ppm_20，OOOppm,优选约100ppm-5，OOOppm,更优选约200_1000ppm。 [0067] After cooling or addition of oil phase at low temperatures, oil exiting the heat exchanger in the resultant solution, the amount of carotenoid class is about 50ppm_20, OOOppm, preferably from about 100ppm-5, OOOppm, more preferably about 200_1000ppm. 相应地,用于冷却受热类胡萝卜素溶液的油相的量，取决的因素为诸如类胡萝卜素、油相和用来溶解的温度、所期望的冷却溶液中类胡萝卜素的最终浓度。 Accordingly, the amount of carotenoid solution for cooling the heated oil phase, depending on the factors such as carotenoids, the final concentration of the oil phase and to dissolve the temperature, the desired cooling solution carotenoids.

[0068] 油性溶液，如根据本发明的方法所获得的，可以被收集到贮存容器中以制备饲料或食品组合物。 [0068] oily solution, according to the method of the present invention as obtained, can be collected into the storage container to prepare a feed or food composition. 在一个优选的实施方案中，所记载的溶解装置，其形成本发明的另一个方面，被整合到鱼饲料生产线中。 In a preferred embodiment, the dissolution apparatus described which forms another aspect of the present invention, it is integrated into fish feed production lines. 当类胡萝卜素是虾青素时，调整温度和加热条件，从而优选地，溶液中反式到顺式虾青素异构体的转化低于总异构体的50%，优选低于30%。 When the carotenoid is astaxanthin, adjust the temperature and heating conditions, thus preferred that the solution to the conversion of cis-trans astaxanthin isomer is less than 50% of the total isomers, preferably less than 30% . 基于虾青素的总重量，可能形成的额外副产物如虾红素、半虾红素和C-25醛应当是低于10%，优选低于5%。 Based on the total weight of astaxanthin, additional byproducts that may be formed as astaxanthin, semi astaxanthin and C-25 aldehyde should be less than 10%, preferably less than 5%.

[0069] 添加到饲料组合物中的含虾青素的油性类胡萝卜素溶液的量可以是l_50wt%。 [0069] adding to the amount of feed composition containing astaxanthin oily carotenoid solution may be l_50wt%. 优选添加的油性溶液的量为10-30wt%。 The amount of the oily solution is preferably added to 10-30wt%. 溶解在这种油性溶液中的类胡萝卜素的量可以为10ppm-300ppm,优选30ppm-100ppm。 The amount of carotenoid dissolved in this oily solution may 10ppm-300ppm, preferably 30ppm-100ppm.

[0070] 本发明的方法不需要在营养组合物和饲料生产中使用冷水可分散的制剂。 [0070] The method of the present invention does not require the use of cold water dispersible formulation of the nutritional composition and feed production. 生产是流水线式的，便于对溶解于油相中的虾青素的量进行在线控制。 Production is streamlined, easy on the amount of astaxanthin dissolved in the oil phase of online control. 此外，本方法能够在添加到饲料丸剂之前化学和物理地监控虾青素。 In addition, this method can feed pellets before adding it to the chemical and physical monitoring of astaxanthin. 其避免了为从根据EP0839004的制剂中释放出虾青素而发生的冷水可分散的制剂的复杂酶预处理。 It avoids the complex enzymatic pretreatment of cold water from the release of astaxanthin formulations according to EP0839004 occurred dispersible formulation.

[0071] 包含类胡萝卜素的油溶液可以被直接添加到彩色脂肪基食物（例如，与¢-胡萝卜素结合的人造黄油），或被添加到家禽或鱼饲料组合物。 [0071] oils contain carotene solution can be added directly to the color of fat-based foods (for example, ¢ - carotene combine margarine), or added to poultry or fish feed composition. 最终冷却的油溶液可以在添加到 Oil solution of the final cooling can be added to the

饲料之前用水乳化，以便于造粒、挤出或造丸。 Before feed water emulsion in order to granulation, extrusion or making pills. 可以在鱼饲料的进一步的加工或干燥过程中去除水分。 Water can be removed in further processing or drying of fish feed. 可以使用减压、常压或加压，在固体饲料组合物的挤出之前、之后或在其过程中向鱼饲料中添加油性溶液。 Decompression may be used, atmospheric pressure or elevated pressure, prior to extrusion of solid feed composition, or added after the oily solution to fish feed in the course. 油性组合物也可以任选地在添加到饲料丸剂之前被过滤，以去除未溶解的材料。 Oily composition may also optionally be added to the feed before the pill was filtered to remove undissolved material. 或者，油性类胡萝卜素溶液可以通过添加到高孔隙度基质和载体中而被加工成固体组合物，利用某些载体的特性来吸收最多其本身重量五倍的油而不失去粉末特性。 Alternatively, the oily carotenoid solution may be added to the high porosity and the carrier matrix is ​​processed into a solid composition, the use of certain characteristics of the carrier to absorb up to five times its own weight without loss of powder properties of the oil. 高孔隙度（100-500m2/g)的无机载体的实例为Zeopharm ®和Neusilin ®。 Examples of high porosity (100-500m2 / g) of the inorganic carrier is Zeopharm ® and Neusilin ®. 所得的微粒固体组合物可以被添加到饲料或食品组分中，并被加工成适合的给料形式。 The resulting particulate solid compositions may be added to feed or food components and is processed into a form suitable for feed. 它们也可以本身作为口腔药物和营养制品组合物而使用。 They can also be itself as an oral medication and nutraceutical compositions and use. 本发明中所采用的优选的高孔隙度的无机载体包括无机化合物，例如磷酸氢钙和硅酸铝镁，已知商标名分别为Fujicalin ® SG和S型以及Neusilin™。 Preferred high porosity inorganic carrier used in the present invention include inorganic compounds such as calcium hydrogen phosphate, and magnesium aluminum silicate, known under the trade name was Fujicalin ® SG and S type and Neusilin ™. Fujicalin ® SG和S型的典型参数包括平均孔径7nm,平均颗粒大小约110 ii m,约2ml/g的比容、BET比表面积为30m2/g_40m2/g，油和水的吸收容量为约0. 8ml/go Neusilin™ 以SI、SGI、UFL2、US2、FH2、FLU FL2、S2、SG2、NFL2N 和NS2N 等级而销售。 Typical parameters Fujicalin ® SG and S type comprising an average pore diameter of 7nm, the average particle size of about 110 ii m, about 2ml / g specific volume, BET surface area of ​​30m2 / g_40m2 / g, oil and water absorption capacity of about 0. 8ml / go Neusilin ™ to SI, SGI, UFL2, US2, FH2, FLU FL2, S2, SG2, NFL2N and NS2N rank and sales. 特别优选的等级是S1、SG1、US2和UFL2。 A particularly preferred level is S1, SG1, US2 and UFL2. 对于许多应用来说最优选的载体材料是US2等级的。 For many applications, the most preferred support material is grade US2. 其它适合的载体材料是具有300m2/g、油吸收容量至少为450ml/100g的Zeopharm ®600(沉淀的非晶体硅酸钙)，油吸收容量为250-300ml/100g的Huber_sorb ® 250NF(沉淀的非晶体硅酸钙）以及140n2/g、油吸收容量为185-215ml/100g的Zeopharm ® 80 (沉淀 Other suitable support materials having 300m2 / g, an oil absorption capacity of at least 450ml / 100g of Zeopharm ®600 (precipitated amorphous calcium silicate), an oil absorption capacity of 250-300ml / 100g of Huber_sorb ® 250NF (precipitated non- crystalline calcium silicate) and 140n2 / g, an oil absorption capacity of 185-215ml / 100g of Zeopharm ® 80 (precipitation

的非晶体二氧化硅)。 Amorphous silica). 那些材料，其是非晶体的，典型地比表面积为约IOOmVg-约300m2/g、油吸收容量为约I. 3ml/g-约4. 5ml/g、平均颗粒大小为约I y m_约14 ym、比容为约2. Iml/g-约12ml/g。 Those materials, which are amorphous, typically from about IOOmVg- specific surface area of ​​about 300m2 / g, an oil absorption capacity of from about I. 3ml / g- about 4. 5ml / g, an average particle size of from about 14 to about I y m_ ym, specific volume of about 2. Iml / g- about 12ml / g. 然而，也可以使用备选的有机或无机多孔材料，只要它们对于类胡萝卜素没有有害影响并且呈现相当大的内表面积。 However, it may also be used alternative organic or inorganic porous material, so long as they have no deleterious effect on the carotenoid and present a large internal surface area. 所使用的载体材料的量取决于有效用于隔绝通道内的类胡萝卜素溶液或分散体的比表面积以及所用的溶液的性质如粘度。 The support material used depends on the nature of the effective channel for the isolation of carotenoid solution or dispersion of the specific surface area, and used as the viscosity of the solution.

[0072] 本发明不排除任选地使用胶体分散的配制的类胡萝卜素，例如粒料和微胶囊，而不是优选的非配制的微粒晶体或非晶体类胡萝卜素化合物，来制备油性类胡萝卜素组合物。 [0072] The present invention does not preclude optionally using colloid-dispersed carotenoid formulation, e.g., pellets and microcapsules, rather than the preferred non-crystalline or amorphous particles formulated carotenoid compounds, prepared oily carotenoid composition. 尽管描述了用于加工类胡萝卜素（特别是虾青素、斑螯黄、玉米黄质和¢-胡萝卜素）的方法，本领域技术人员应当能够将所公开的方法应用于其它可以和类胡萝卜素同时使用、具有类似物理和化学性质、仅仅在加工条件方面有常规变化的化合物，以便添加到营养组合物中。 Although the description of the process for carotenoids (especially astaxanthin, cantharidin yellow, zeaxanthin and ¢ - carotene) method, the skilled person should be able to the disclosed method can be applied to other carotenoids hormone use, having similar physical and chemical properties, the compound has only regular changes in the processing conditions, to add to the nutritional composition. 实例是官能化亲脂化合物，例如谷留醇（sitosterol)、谷留烧(sitostanol)及其衍生物，辅酶QlO以及化合物如脂溶性维生素，特别是维生素A和其衍生物。 Examples of functionalized lipophilic compounds, such as the Valley remain alcohol (sitosterol), Gu left burning (sitostanol) and its derivatives, coenzyme QlO and compounds such as fat-soluble vitamins, especially vitamin A and its derivatives.

[0073] 本方法允许类胡萝卜素以单独或联合的方式进行常规加工。 [0073] This method allows the carotenoid alone or in combination with conventional processing manner. 例如，虾青素和斑螯黄可以一起加工。 For example, astaxanthin and cantharidin yellow can be processed together. 任选地，可以添加用于促进加工的组分或赋形剂中的一种或其结合，所述任选组分和赋形剂包括稳定剂、高沸点油和腊、分散助剂、聚合物、保护性胶体、防腐剂、流动助剂、膜脂质、阳离子、阴离子或非离子表面活性剂。 Optionally, it may be added to facilitate processing of the component or one excipient or a combination thereof, said optional components and excipients comprising stabilizers, high boiling point oil and wax, dispersing aids, polymerization material, protective colloids, preservatives, flow aids, membrane lipids, cationic, anionic or non-ionic surfactants.

[0074] 为改善粉末流动性，类胡萝卜素可以在被添加到油中之前和赋形剂物理混合。 [0074] In order to improve the powder flowability, carotenoid can be added to the oil prior to physical mixing and excipients.

[0075] 应当理解的是本发明的方法是一种通过在线或分批过程制备至少一种类胡萝卜素的油相溶液的新颖的连续方法。 [0075] It should be understood that the method of the present invention is a novel method for continuous on-line or batch process by preparing at least one carotenoid in an oil phase solution. 所述方法不限于使用未配制的、基本上纯的晶体化合物。 The method is not limited to the use of non-formulated, substantially pure crystalline compounds. 也可以使用根据例如US 5, 364, 563,US 6，296，877和WO 03/102116 (其被引入本文作为参考）制备的胶体分散的制剂。 May also be used according to e.g. US 5, 364, 563, US 6,296,877 and WO 03/102116 (which is incorporated herein by reference) Preparation of the colloidal dispersion formulation.

附图说明 Brief Description

[0076] 图I是一种流程示意图，阐述了在线加热和混合，随后用油相在较低温度下冷却以获得类胡萝卜素的油性溶液的设备。 [0076] Figure I is a schematic flow diagram to explain the line heating and mixing, the oil phase followed by cooling at a lower temperature to obtain a solution of the oily carotenoid device.

[0077] 方法 [0077] Method

[0078] 通过参考在图I中所示的适于实施本发明方法的示意性流程图来对本发明进行描述。 [0078] The method of the present invention is adapted to a schematic flow diagram shown in FIG. I refer to the description of the invention. 此方法正常情况下不需要在加压条件下进行，但假如加压（超临界）流体例如CO2和油相一起使用，或者在油相中存在较少量的水，就可产生较高压力。 Under normal circumstances, this method is not required under pressurized conditions, but if pressurized (supercritical) fluid e.g., CO2 and used in conjunction with an oil phase, the oil phase or in the presence of a relatively small amount of water, can produce higher pressure. 适当地座落于加热区域的进出口处的在线加热和冷却室、热交换器、管道、容器、高压元件、压力释放阀和温度传感器等的布置和结构可以被设计以提供最适合的对已有的或新饲料生产线的集成。 Online appropriately heating and cooling chamber is located in the region of the inlet and outlet of heating, heat exchangers, pipes, containers, high-voltage components, pressure relief valve and temperature sensor arrangement and structure can be designed to provide the most appropriate to have Some integrated production line or a new feed.

[0079] 至少一种平均颗粒大小直径介于l-5i!m之间的类胡萝卜素悬浮体，在所选择的油相或适合的流体介质中，基于混合物浓度为约0. Iwt % _40wt%，添加或不添加稳定剂，最初被引入到容器4中。 [0079] at least one of an average particle size diameter of between l-5i! Carotenoid suspension between m, in the selected oil phase or suitable fluid medium, based on the mixture at a concentration of from about 0. Iwt% _40wt% , with or without stabilizers, it is initially introduced into the container 4. 容器I包含不含悬浮的类胡萝卜素的高沸点的油。 High boiling oil without the suspended container I contains carotenoids. 可以通过使微粒类胡萝卜素或类胡萝卜素组合物悬浮并在线研磨来制备类胡萝卜素悬浮体，以便保留(containment)在容器4中或直接注入混合室6。 Through the particulate carotenoid or carotenoid composition is suspended and online grinding to prepare carotenoid suspension in order to preserve (containment) in the container 4 or directly into the mixing chamber 6. 类胡萝卜素悬浮体也可以是预先大规模单独制备的，并在随后的根据本发明的方法的溶解之前存储数月。 Carotenoid suspension may be prepared separately in advance of large-scale, and subsequent storage for several months prior to dissolution according to the method of the present invention.

[0080] 在一个实施方案中，来自容器I的油相通过泵2在将该物流进料到热交换器3之后进料到混合室6，在热交换器3中，所述物流被加热到其沸点或低于其沸点的温度。 [0080] In one embodiment, the oil phase from the container I by the pump 2 in the stream fed to heat exchanger 3 is fed after the mixing chamber 6, in the heat exchanger 3, the stream is heated to a below its boiling point or boiling point. 体系中的油物流可以通过用循环油吹扫（purge)和平衡而达到期待的温度、压力和其它操作条件如流速。 System oil stream can be purged by circulating oil (purge) and balance to achieve anticipated temperature, pressure and other operating conditions such as flow rate. 在容器4中保持在低于100°C的类胡萝卜素悬浮体和混合室6中的受热油物流通过泵5或以直角或成切线进行混合。 Kept in containers of less than 4 to 100 ° C carotenoid suspension and the mixing chamber 6 heat oil stream through the pump 5 or at right angles or tangentially mixed. 也可以使用压缩气体来抽吸悬浮体。 You can also use a compressed gas to suction suspension. 通过调节泵2的传递速率，注意到油、目标温度，加热区域中的混合比率是可预先确定的，以在所期望的停留时间内在通过混合室6后而实现。 By adjusting the delivery rate of the pump 2, noted that the oil, target temperature, the mixing ratio of the heated region is determined in advance, to a desired residence time in the inner chamber 6 is achieved by mixing the rear. 在受热油相中类胡萝卜素的溶解在油的沸点（可以是50°C-30(TC)或其以下进行。溶解的接触时间可以通过提高在加热区域中的停留时间而被延长。这是通过降低混合泵5的流速或延长加热管道7的长度（任选地恒温控制或绝热）而实现的，从而在经加热区域的通过中维持了所期望的温度。图I所示的加热区域由混合室6和绝热管道7组成。其间维持了期望的温度的在加热区域中的停留时间可以最多30秒。 Heating the oil phase were dissolved carotenoid in an oil the boiling point (which may be 50 ° C-30 (TC) or less. The contact time may be dissolved in the heating zone by increasing the residence time is prolonged, which is heating region by reducing the flow rate of the mixing pump 5 or extending the length of the heating conduit 7 (optionally thermostatically controlled or adiabatic) achieved, thereby maintaining the desired temperature in the heating zone passed. I shown by FIG. the mixing chamber 6 and the heat insulating pipe 7 composition. while maintaining the desired temperature in the heating zone residence time may be up to 30 seconds.

[0081] 或者，混合室6的尺寸是这样的，使得有效地形成整个加热区域，且在所选择的泵2的传递速率下，在混合室或室内的悬浮体的停留时间可以最多30秒，优选小于5秒。 [0081] Alternatively, the size of the mixing chamber 6 is such that effective to form the entire heating zone and at the chosen delivery rate of pump 2, the residence time in the mixing chamber or chamber can be up to suspension for 30 seconds, preferably less than 5 seconds.

[0082] 当油相的温度介于50°C -230°C时，其间进行混合和溶解的沿加热区域的通过时间（transit time)优选为0. 1_30秒，优选地当温度介于100°C -230°C时，通过时间为0. 1-10秒。 [0082] When the temperature of the oil phase is between 50 ° C -230 ° C when, during mixing and through time (transit time) dissolved along the heating zone is preferably 0. 1_30 seconds, preferably when the temperature is between 100 ° C -230 ° C, the by 1-10 time of 0.5 seconds. 根据优选的实施方案，在温度介于120°C到180°C，时间介于1-5秒下，任选地在压力下，类胡萝卜素尽可能迅速地溶解于油相中，由此使得降解和异构化最小化以获得目标类胡萝卜素浓度。 According to a preferred embodiment, at a temperature between 120 ° C to 180 ° C, time is between 1-5 sec, optionally under pressure, to dissolve the carotenoid in the oil phase as quickly as possible, thereby making minimize degradation and isomerization to obtain the target carotenoid concentrations. 基本上溶解类胡萝卜素颗粒是可以接受的，使得当油溶液加工后在低于60°C的温度下排出时，溶液中类胡萝卜素的量为至少5(^七％的油中总类胡萝卜素内容物。 Basically dissolve the carotenoid particles is acceptable, so that when the oil solution processed at a temperature lower than the discharge of 60 ° C, the amount of solution in the carotenoid is at least 5 (^ seven percent of the total oil carotenoids Prime contents.

[0083] 为使异构最小化，加热步骤可以是渐进或梯级进行的。 [0083] In order to minimize the isomerization, the heating step may be gradual or steps performed. 当类胡萝卜素的稳定性未被兼顾时，类胡萝卜素悬浮体可以在通过加热区域之前在容器中预加热。 When stability when carotenoids are not taken into account, the carotenoid suspension may be performed before the heating zone by pre-heating in a vessel. 优选地，通过在80°c -120°C之间与受热油相混合，在加热区域中将悬浮体加热到低于类胡萝卜素沸点的温度最多10秒，优选最多5秒。 Preferably, by between 80 ° c -120 ° C is mixed with the heated oil in the heating zone in the suspension is heated to a temperature below the boiling point of the carotenoid for up to 10 seconds, preferably at most 5 seconds. 悬浮体然后沿着其中温度可以高于类胡萝卜素熔点，甚至高于油相的沸点的另外的工段中在120°C -300°C被短暂加热小于5秒。 Suspension then along which the temperature can be higher than the melting point of carotenoids, even higher than the boiling point of the oil phase of the additional section in the 120 ° C -300 ° C is briefly heated less than five seconds. 优选地将悬浮体在120°C _180°C短暂加热0. 1-2秒。 Preferably the suspension at 120 ° C _180 ° C briefly heated 0. 1-2 seconds. 瞬时加热可被描述为“闪蒸-加热”。 Instantaneous heating can be described as "flash - heating."

[0084] 可以在较低温度下通过过热（超临界）临界气体和/或选自诸如以下类型的混合器的高能均化器的集成或并行使用而更有效地进行油相中的溶解：在线转子-定子分散搅拌机、超声粉碎机和高压均化器（包括但不限于微型流化床）。 [0084] by overheating (supercritical) supercritical gas and / or from the following types of mixers such as high energy homogenizer at lower temperatures and more efficiently integrated or dissolved in the oil phase used in parallel: Online Rotor - Stator dispersion mixers, ultrasonic grinder and a high pressure homogenizer (including but not limited to micro-fluidized bed). 目的在于在接近或高于其熔点的温度下以最小的降解和异构程度，尽可能迅速和短暂地崩解和溶解悬浮的类胡萝卜素。 Aimed at near or above its melting temperature with minimal degradation and isomerization degree, as rapidly and briefly disintegration and dissolution of carotenoid suspension. 类胡萝卜素悬浮体也可以被加热，而没有稀释或者在混合室内通过将油悬浮体抽吸通过热交换器而添加受热的油相，其中其在可以甚至高于油相沸点的温度下迅速且短暂地加热。 Under carotenoid suspension it may also be heated, without dilution or mixing chamber by pumping the oil suspension through a heat exchanger and adding heat of an oil phase, where it can be even higher than the boiling point of the oil phase and rapidly briefly heated. 使用能量溶解类胡萝卜素可以直接利用电力加热的热交换器进行或者借助包括但不限于过热蒸汽或受热的超临界气体的介质在压力下间接加热的热交换器进行。 Using an energy dissolving carotenoid directly heated using power or by means of a heat exchanger including but not limited to the superheated steam or the heated supercritical gas at a pressure medium indirectly heated heat exchanger.

[0085] 在通过加热区域之后，热的油溶液在被称为冷却室10的混合室内在小于30秒内，通过经泵9从温度保持在低于受热类胡萝卜素溶液温度的油相容器8中添加冷却的油相或室温的油相，立即在线冷却到低于约60°C，或更低的温度。 [0085] After passing through the heating zone the hot oil solution in the mixing chamber is called the cooling chamber 10 is less than 30 seconds, by a pump 9 via the temperature was kept below the temperature of the heated carotenoid solution, an oil phase vessel 8 add the cooled oil phase or oil phase at room temperature, immediately online cooled to less than about 60 ° C, or lower. 优选冷却进行小于30秒。 Preferably be less than 30 seconds to cool. 特别是如果加入的用以冷却的油相的量不足以将稀释的油相溶液的温度降低到低于60°C，离开冷却室10的管道另外可以使用外部介质例如水、液氮或压缩气体，用热交换器冷却或冷藏。 Especially the temperature if the amount added to the oil phase is insufficient cooling of the diluted oil phase solution is reduced to less than 60 ° C, leaving the duct 10 of the cooling chamber can additionally use an external medium such as water, liquid nitrogen or compressed gas with a heat exchanger to cool or refrigerated. 加入用以冷却的油相的量是受热类胡萝卜素溶液的1-500重量份，优选2-50重量份，这取决于冷却方法和最终溶液中的类胡萝卜素的目标浓度。 Amount of oil phase for cooling is 1-500 parts by weight of the heated carotenoid solution, preferably 2 to 50 parts by weight, depending on the cooling method and the final target concentration of carotenoid in solution. 冷却后的类胡萝卜素油溶液的温度低于60°C，优选30°C -500C，更优选低于30°C。 After the temperature of the cooling carotenoid oil solution below 60 ° C, preferably 30 ° C -500C, more preferably less than 30 ° C.

[0086] 从加热区域排出的热油溶液也可以通过在剧烈搅拌下将其加入到包含已测量的保持在低于60°C或更低温度的油相的容器中而在用于分批制备的存料容器（containmentvessel)中立即冷却。 [0086] hot oil solution from the heating zone can be discharged under vigorous stirring by adding it to contain a measured and maintained in preparation for the batch in the vessel of less than 60 ° C or lower the temperature of the oil phase The deposit container (containmentvessel) cooled immediately. 容器可以进一步低温恒温（cryostatically)冷却。 The container may further cryostat (cryostatically) cooling. 在任何情况下冷却都应当在短时间内进行，优选小于30秒。 Cooling should be carried out in a short time, in any case, preferably less than 30 seconds.

[0087] 适宜的在线监控设施例如量表和控制温度、压力、流速和方向的门阀可以被安装在线路（circuit)中以控制加热和冷却顺序。 [0087] Suitable scale online monitoring facilities such as gate valves and control temperature, pressure, flow rate and direction can be installed in the line (circuit) in order to control heating and cooling. 图I的结构是图解本发明的典型实例。 Figure I is a schematic structure of a typical example of the present invention. 在本发明的范围内，元件的不同结构和排列及其设计是可能的。 Within the scope of the present invention, the different structure and arrangement and design elements it is possible.

[0088] 包括用于加热和冷却的混合室和热交换器的溶解模块可以适应于制备所期望数量的浓度介于50ppm-20, OOOppm之间的类胡萝卜素油溶液。 [0088] comprising dissolving module for heating and cooling the mixing chamber and the heat exchanger can be adapted for preparing a desired number of concentrations between 50ppm-20, carotenoid oil solution OOOppm between. 通量（throughput)可以通过选择混合室的合适设计和尺寸、管口直径、以及与类胡萝卜素油悬浮体所要求的流速有关的压力，和热交换器的容量而按比例提高或降低。 Throughput (throughput) by selecting the appropriate design and dimensions of the mixing chamber, nozzle diameter, flow rate and pressure associated with the carotenoid oil suspension required, and the capacity of the heat exchanger and proportionally increased or decreased. 可以使用利用静态混合器或混合喷嘴（例如管口喷嘴）的混合室。 It can be used with a static mixer or mixing nozzle (eg nozzle orifice) of the mixing chamber. 用于在混合室中将油相加热到50°C-300°C的热交换器的设计考虑了空隙体积和加热表面的表面积、悬浮体通量、温度和压力以及所采用的热交换介质的类型。 Used in the oil phase is heated to the mixing chamber in the design of the heat exchanger 50 ° C-300 ° C in consideration of the void volume and surface area of ​​the heating surface, the suspension throughput, temperature and pressure as well as the heat exchange medium used in the type. 可以采用由能耗为IkW的热交换器供能的溶解模块来制备至少60-1801/h的含250ppm的虾青素的类胡萝卜素油溶液，用于或从容器中分批添加到鱼饲料中或与饲料制造过程在线集成。 Can be used by the energy consumption IkW heat exchanger module for dissolution can be prepared at least 60-1801 / h carotenoid oil solution containing 250ppm of astaxanthin for the divided parts from the container to the fish feed or online integration and feed manufacturing process. 此模块规模可变，从而视情况获得较大量的含较高或较低浓度的类胡萝卜素的溶液。 This module is a variable scale, whereby optionally containing larger amounts of higher or lower concentrations of the carotenoid solution.

[0089] 下述实施例，通过举例并非限制性地证明本发明。 Example [0089] The following, the present invention is not limited to, by way of proof. 本领域技术人员可以容易地对其进行改变，从而在本发明的范围内通过改变类胡萝卜素浓度、能量来源和/或加工温度和条件而实施备选的实施方案。 Those skilled in the art can readily be changed, thereby implemented in alternative embodiments within the scope of the present invention by varying carotenoid concentration, energy source and / or processing temperature and conditions.

[0090] 实施例I [0090] Example I

[0091] 通过使用在获得3000ppm的虾青素浓度的条件下操作的精密加工的SiIverson在线转子/定子混合器，将IOOg的包含80% (+/-2% )合成的、全反式虾青素和大约20%含顺式奸青素、C-25醒奸青素、奸红素（astacine)和半奸红素（semi_astacine)的副产物的晶体加入到大豆油中。 [0091] The use of precision machining under conditions obtain astaxanthin concentration of 3000ppm of operation of SiIverson line rotor / stator mixer, IOOg containing 80% (+/- 2%), synthetic, all-trans astaxanthin vegetarian and contains about 20% cis rape astaxanthin, C-25 wake rape astaxanthin, crystal evil red pigment (astacine) and semi-rape TRs (semi_astacine) by-product was added to soybean oil. 在线混合器和热交换器相连以加热油。 Line mixer and a heat exchanger connected to heating oil. 与转子定子所产生的热相结合，油可以被加热到180°C _230°C的温度达10秒。 Heat generated by the stator and rotor combined oil may be heated to a temperature of 180 ° C _230 ° C for up to 10 seconds. 所得的虾青素油性溶液立即用静态混合器（Sulzer AG, Winterthur, CH)和大于10倍的在40°C加热的Manhedan鱼油混合。 Oily astaxanthin solution was immediately with a static mixer (Sulzer AG, Winterthur, CH) and heated at 40 ° C Manhedan fish oil mixed than 10 times. 所得的油性溶液，分析虾青素的溶解程度，并用于鱼饲料生产。 The resulting oily solution, to analyze the degree of astaxanthin dissolved and for fish feed production. [0092] 实施例2 [0092] Example 2

[0093] 参考图I。 [0093] with reference to Figure I.

[0094] 在室温下，将用量为4% (w/w)的晶体（98%纯）合成虾青素分散在含4% (w/w)a -生育酚的大豆油中，并在70°C进行胶体球磨程序，以获得下述颗粒大小特征的分散体(用激光衍射光谱法测量）：dl0 ：1.Oum, d50 ：2. 5 um, d90 :6 um。 [0094] At room temperature, the amount of 4% (w / w) of the crystal (98% pure) synthetic astaxanthin dispersion containing 4% (w / w) a - tocopherol in soybean oil and 70 ° C were colloid milling process to obtain the following particle size characteristics of dispersion (measured by laser diffraction spectroscopy): dl0: 1.Oum, d50:. 2 5 um, d90: 6 um. 该悬浮体可以单独制备并在容器中贮存，用于根据本发明方法制备虾青素油溶液。 The suspension can be prepared separately and stored in a tank for vegetable oil astaxanthin solution prepared according to the method of the present invention.

[0095] 悬浮体在室温下用大豆油稀释以获得I. 5% (w/w, 15000ppm)奸青素和I. 5 %a -生育酚。 [0095] suspension at room temperature diluted with soybean oil to obtain I. 5% (w / w, 15000ppm) rape astaxanthin and I. 5% a - tocopherol. 将I升的悬浮体于23°C转移到容器4中，轻轻搅拌，并通过混合泵5以lkg/h泵送通过混合室6，其中虾青素悬浮体和从容器I通过泵2在9kg/h下操作而投放的大豆油混合并加热，所述大豆油通过热交换器3已预加热到172°C，从而I : 9(w/w)虾青素悬浮体/预加热油混合物的温度为150°C,包含1500ppm的奸青素。 I lift the suspension were transferred to 23 ° C to vessel 4 and gently stirred and mixed by the pump 5 to lkg / h pumped through the mixing chamber 6, wherein astaxanthin suspensions and I from the container by a pump 2 soybean oil mixed 9kg / h under heating and put in operation, the heat exchanger 3 through the soybean oil was preheated to 172 ° C, whereby I: 9 (w / w) astaxanthin suspension / pre heated oil mixture The temperature of 150 ° C, containing 1500ppm of rape astaxanthin. 通过应用由泵2和混合泵5的联合作用而产生的流速以及绝热管道的体积，该混合物以I秒的通过时间（在150°C )流过绝热管道7，从而溶解虾青素。 By application of the volumetric flow rate and an insulated pipeline by the pump 2 and the mixing pump 5 the combined action of the generated, the mixture I by means of second time (at 150 ° C) flows through the heat insulating pipe 7, thereby dissolving astaxanthin. 溶液立即在冷却室10中与通过泵9来自油容器8的保持在23°C的50kg/h鱼油混合并冷却，从而获得包含250ppm虾青素的收集于容器中的虾青素油性组合物。 Now the solution was cooled in chamber 10 by a pump 9 from the oil vessel 8 is maintained at 50kg / h fish oil were mixed and cooled to obtain the collection contains 250ppm astaxanthin in container oily composition of astaxanthin of 23 ° C.

[0096] 或者，通过热交换器在没有稀释的情况下将150°C的I : 9 (w/w)的虾青素悬浮体/预加热油混合物（包含1500ppm的虾青素）冷却，用液氮或水来冷却，从而获得温度为20°C且收集于容器中的1500ppm的虾青素组合物。 [0096] Alternatively, the heat exchanger in the absence of dilution to 150 ° C to I: 9 (w / w) astaxanthin suspension / pre heated oil mixture (containing 1500ppm astaxanthin) cooled, liquid nitrogen or cooled water to obtain a temperature of 20 ° C and collected in a container astaxanthin 1500ppm of the composition.

[0097] 在通过0. 45 ii m孔径的过滤器过滤1500或250ppm的虾青素组合物后，虾青素含量的HPLC-分析显示，虾青素是完全溶解的，包含75%的所有反式-虾青素和25%的顺式异构体，不含进一步的降解产物。 [0097] by 0. 45 ii m pore size filter 1500 or astaxanthin composition after 250ppm, HPLC- astaxanthin content analysis showed that astaxanthin is completely dissolved, comprising 75 percent of all anti- type - astaxanthin and 25% of the cis isomer, without further degradation products. 油性虾青素溶液可以通过与鱼饲料丸剂混合而被进一步加工。 Oily astaxanthin solution can be mixed with fish feed pellets are further processed.

[0098] 实施例3 [0098] Example 3

[0099] 以与实施例2类似的方式，在室温下将用量为10% (w/w)的实施例I的基本上纯的晶体合成虾青素分散在含10% (w/w) a-生育酚的大豆油中。 [0099] In a similar manner to Example 2, at room temperature in an amount of 10% (w / w) of Example I is substantially pure synthetic astaxanthin crystal dispersion containing 10% (w / w) a - tocopherol soybean oil. 悬浮体在胶体球磨机中在70°C进行研磨，从而获得具有下述颗粒大小特征的分散体：4. 9%> 5um,95. 1%介于 In a colloidal suspension in a ball mill for grinding 70 ° C, thereby obtaining a dispersion having the following particle size characteristics:. 4 9%> 5um, 95 1% between.

2. 7-1 um之间（通过分级过滤测量，随后对虾青素含量进行HPLC分析)。 Between 2. 7-1 um (measured by fractional filtration, followed by astaxanthin content by HPLC analysis). 悬浮体被冷却到室温，用大豆油稀释以获得I. 5% (w/w) (15，OOOppm)的虾青素和I. 5%的a -生育酚。 Suspension was cooled to room temperature, diluted with soybean oil to obtain I. 5% (w / w) (15, OOOppm) astaxanthin and I. 5% of a - tocopherol. 将I升该悬浮体在23°C转移到容器4中，轻轻搅拌，并通过混合泵5以lkg/h的速率泵送通过混合室6，其中将虾青素悬浮体和从容器I进料的大豆油（使用泵2，以9kg/h操作）混合并加热，所述大豆油通过热交换器3预加热到148°C，从而I : 9 (w/w)虾青素悬浮体/预加热油混合物（包含1500ppm的虾青素）的温度为126°C，以溶解虾青素。 The I liter of the suspension at 23 ° C is transferred to vessel 4 and gently stirred and mixed by the pump 5 to lkg / h rate pumped through the mixing chamber 6, wherein the astaxanthin and suspension from the container into the I soybean material (using a pump 2 to 9kg / h operation) were mixed and heated, the soybean oil was heated to 148 ° C by the pre-heat exchanger 3, so I: 9 (w / w) astaxanthin suspension / Pre-heating oil mixture (containing 1500ppm astaxanthin) at a temperature of 126 ° C, to dissolve the astaxanthin. 此混合物泵送通过绝热管道达I秒，并在冷却室10中和经泵9而来自油容器8的50kg/h的23°C的鱼油混合并冷却，以获得含250ppm虾青素且收集于容器中的虾青素的油性组合物。 This mixture is pumped through an insulated pipeline of I sec, and the cooling chamber 10 and via the pump 9 and the fish oil mixture from containers 50kg / h of 23 ° C for 8 and cooled to obtain 250ppm containing astaxanthin and collected in container astaxanthin oily composition.

[0100] 在通过0. 45 ilm孔径的过滤器过滤250ppm的虾青素组合物后，虾青素含量的HPLC-分析显示虾青素是完全溶解的，且包含12%的顺式异构体。 [0100] After passing through 0. 45 ilm pore size filter astaxanthin composition of 250ppm, HPLC- analysis astaxanthin content display astaxanthin is completely dissolved, and contains 12% of the cis isomer .

[0101] 在与鱼饲料丸剂以30wt%的油含量混合时，油性虾青素溶液通过用鱼油稀释到250ppm而进一步加工,从而在丸剂中获得83ppm的奸青素含量。 [0101] In a 30wt% oil content mixed with fish feed pellets, the oily astaxanthin solution was diluted to 250ppm by fish oil is further processed to obtain a rape astaxanthin content of 83ppm in bolus.

[0102] 实施例4[0103] 以和实施例3类似的方式，所得的油性虾青素溶液物流被在线进料到挤出机以制备饲料丸剂。 [0102] Example 4 [0103] Example 3 In a similar manner, the oily astaxanthin solution stream obtained are fed to the extruder line to produce feed pellets.

[0104] 实施例5 [0104] Example 5

[0105] 以和实施例2类似的方式，晶体斑螯黄，其基本上是纯的（92. 5% )，用于代替虾青素。 [0105] In Example 2 in a similar manner, cantharidin yellow crystals, which is substantially pure (92.5%), used in place of astaxanthin.

[0106] 实施例6 [0106] Example 6

[0107] 以和实施例2类似的方式，由天然来源提纯的晶体虾青素用于代替合成虾青素。 [0107] In a similar manner, and 2 embodiment, purified from natural sources of astaxanthin crystal used in place of the synthetic astaxanthin.

[0108] 实施例7 [0108] Example 7

[0109] 以和实施例I类似的方式，用大豆油稀释10%的含I %虾青素的雨生红球藻的悬浮体，从而获得3000ppm的虾青素悬浮体，进而用实施例I的条件加工以获得油性类胡萝卜 [0109] In a similar manner, and I embodiment, diluted 10% soybean oil containing I% astaxanthin pluvialis algae suspension to obtain 3000ppm astaxanthin suspension, and then Example I Conditions processed to obtain an oily carotenoid

素溶液。 Su added.

[0110] 实施例8 [0110] Example 8

[0111] 可以使用包含虾青素的红发夫酵母细胞或细胞碎片代替雨生红球藻悬浮体，如实施例7中所示。 Phaffia yeast cells or cell debris [0111] can be used instead of containing astaxanthin pluvialis algae suspension, as shown in Example 7.

[0112] 实施例9 [0112] Example 9

[0113] 将实施例3的含250ppm的虾青素的油性溶液（Ikg)在搅拌下添加到200g的硅酸铝镁（Neusilin)中。 [0113] 250ppm astaxanthin-containing oily solution (Ikg) will be implemented in Example 3 was added with stirring to 200g of magnesium aluminum silicate (Neusilin) ​​in. 使用干混技术，将所得的干燥粉末（1.2kg)添加到2. 8kg鱼饲料丸剂材料中。 Use dry mixing techniques, and the resulting dry powder (1.2kg) Add to 2. 8kg fish feed pellet material. 鱼丸剂经干燥压缩或挤出而制备，包含25% w/wt的油和63ppm的虾青素。 Fish dried compressed or extruded pellets prepared containing 25% w / wt of oil and 63ppm of astaxanthin.