直接溶解方法本发明涉及将类胡萝卜教caroteno】d)溶解于食用油禾n脂肪中的连续方法。 Direct dissolution process of the present invention relates to a carotenoid teach caroteno] d) was dissolved in edible grain n fats in a continuous process. 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-lme)方法在樹氐温度用油来^4卩。 More particularly, it relates directly dissolved in oil carotenoids, including heating oil suspension medium, then preferably used online (in-lme) Di method tree oil to a temperature of 4 ^ Jie. 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. 类胡萝卜素广泛用于药物、营养保健品(neutnceutical)、化妆品、食品和饲料工业中。 Carotenoids are widely used in pharmaceutical, nutraceuticals (neutnceutical), 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P-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 the poultry industry, P- 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. 由于差的溶解怜性，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。 Due to poor solubility of pity, crystalline forms of these carotenoids itself is not used, and thus must first be formulated into useful feed and nutritional additives. 通过如美国专利2,756,177所记载的喷雾干燥或繊囊截留(catch beadlet)技术制备的在聚合物基质中包含虫下青素或斑螯黄的微粒组合物被广泛用于饲料生产中。 U.S. Patent No. 2,756,177 by spray drying or described entrapped 繊 capsule (catch beadlet) under insect astaxanthin or yellow spots chelating microparticle composition comprising a polymer matrix in the prepared feed is widely used in the 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. 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im使用连续在线方法使用油相来冷却。 The present invention for preparing an oily carotenoid solution comprising the carotenoid can be crystals, amorphous particles or aggregates and combinations thereof dispersed in oil, and heated oil phase was dissolved in carotenoids, and then use im Online method uses continuous 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7K胶体的微粒组合物，由lt爐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 7K-containing composition, the solvent and the Free lt furnace 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7K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 use of an excess emulsification 7K heated phase and an emulsifier 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. 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齐啲方法。 US 5,364,563 describes a method of preparing GOD homogeneous colloidal dispersion can be dispersed in a powdered carotenoid system water. 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7K溶液中乳化，随后将it沐包油型(0/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 colloidal solution of 7K, then it Mu-oil type (0 / w) emulsion and spray-dried into a powder. US 6,296,877记载了一种制备可分散于水中的颗粒或鹏囊的方法，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。 US 6,296,877 describes a method Peng capsule particles or the preparation of a water dispersible, including the use of 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M混合和冷去陏机溶剂溶液，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 mixing an aqueous solution of M swellable colloid and the solution cooled to 陏 solvent, carotenoid in colloidal disperse form from the molecule precipitated immediately dispersed solution, the resulting dispersion from the solvent and the dispersion medium is separated in a conventional manner. 与US 5,364,563相同，此方法需要翻诉B/或回收步骤，以获得胶体分散的微粒类胡萝卜素组合物。 And US 5,364,563 the same, this method requires turning v B / or recovery steps to obtain a colloidal dispersion of particles carotenoid composition. 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，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孚L化此溶液。 US 6,664,300 relates to a high-boiling organic liquid solution is prepared carotenoids produced carotenoid emulsion, comprising heating in a high boiling organic liquid carotenoid suspension to dissolve, carotene, then immediately obtained The solution was added to an aqueous solution of an emulsifier such as hydrocolloids to Corfu L of this solution. 将孚L状液喷雾干燥从而回收胶体分散的类胡萝卜^f分末。 The L-shaped Corfu was spray-dried to recover a colloidal dispersion of carotenoids f ^ end points. 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。 All the above methods are characterized by an excess of water in the colloidal and water necessary steps / or emulsifiers to emulsify the heated carotenoid solution. 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。 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 process, and in preparation Before oil cooling fish feed and other compositions. 发明内容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。 The present invention discloses a method and associated equipment online for carotenoid dissolved, which can be incorporated into the production process online continuous or batch of food and feed composition. 所述方法不需要制备和购买添加至糊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 paste and food compositions of the individual carotenoid dry powder formulations. 从而，对于加工成鱼饲料，从jm地非配制的类胡萝卜素开始，在y辨卩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, from jm to unformulated carotenoids began, after resolution Jie y oily carotenoid solution continuously preparing 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. 此方制腿在常压下进行。 This party system leg at atmospheric pressure. 然而，如果加压的(例如超临界的)流体和装置被制虫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 made when insects or in combination with heating oil, the method can also be carried out under pressure. 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,在第二混合室中ffii!冷却，从而制备油性类胡萝卜素溶液。 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 the carotenoid composition is dissolved a predetermined time, Immediately thereafter, ffii in the second mixing chamber! cooled, thereby preparing 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7賴卩介质向受热的油性溶液的添加。 The term mixing includes adding the oily solution is added to the cooling medium heat or vice versa 7 Lai Jie medium to the heat of an oily solution. 因此，本发明记载了如下实施方案： 一种制备油性类胡萝卜素组合物的方法，包括：0 ilil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； 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，以溶角裕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in) ffiii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。 Accordingly, the present invention is described as follows embodiment: A method for preparing an oily carotenoid composition comprising: 0 ilil dispersing at least one carotenoid in a physiologically acceptable oil phase to prepare a suspension; ii) maximum up to the boiling point temperature of the oil phase of the online heating the suspension of up to 30 seconds, to dissolve the oil phase margin carotenoid suspension to obtain a heated oily carotenoid solution; and in) ffiii selected from 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. 本发明涉及下述雌的实»案：• 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條100-230°C加热小于5秒，其中所述油相的加热是il3K顿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。 The present invention relates to a female real »case: • a method in which by a higher temperature than the suspension of oil mixed and oily carotenoid suspension Article 100-230 ° C heat less than five seconds, wherein the oil is heating phase il3K Dayton selected from superheated steam heat exchanger, with a supercritical gas heat exchanger for heating, electric heating of the heat exchanger, the rotor - stator mixer heat generated and the heat generated by the ultrasonic mixer carried out. • 一种方法，其中类胡萝卜素是晶体类胡萝卜素化合物。 • a method, wherein the carotenoid is a crystalline carotenoid compound. • 一种方法，其中受热的油性类胡萝卜素溶液^I31应用选自于在线添加生理可接受的MJ^低于受热的油性类胡萝卜素溶液的油相、分批添加至性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。 • a method in which a heated oily carotenoid solution is selected from the online application ^ I31 adding physiologically acceptable MJ ^ oil below the heated oily carotenoid solution phase is added portionwise to the grounds on acceptable temperature lower than the oil heated oily carotenoid solution phase, and the use of online heat exchanger and cooling method. • 一种方法，其中受热的和冷却的池性类胡萝卜素溶液包含最多20,000ppm 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。 • a method in which heated and cooled pools of carotenoid solution contains up to 20,000ppm carotenoids, wherein cooling the heated oily carotenoid solution is carried out by the addition of fish oil and online. • 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。 • a method, wherein the oily carotenoid temperature after cooling below 60 ° C, the cooling step is in less than 30 seconds conducted. • 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、p-胡萝卜素和玉米黄质，且其中90。 • 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, p- carotene and zeaxanthin, and 90. /。 /. 的所，粒的直径小于15^m。 By, grain diameter of less than 15 ^ m. 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：0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； ii)在最大高达油相的沸点的温度下在线加热所逸悬浮体达最多30秒,以溶角祐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；ill) ilii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。 Further embodiments of the present invention relates to a method for preparing a nutritional composition, comprising: 0 by dispersing at least one carotenoid in a physiologically acceptable oil suspension was prepared; ii) at maximum up to the boiling point of the oil phase Live heating Yat suspension of up to 30 seconds, to dissolve the oil phase angle woo carotenoid suspension to obtain a heated oily carotenoid solution; ill) ilii selected from physiologically acceptable oil phase mixing and use The method of the heat exchanger, to cool the heated oily carotenoid solution, wherein the oil temperature is lower than the heated oily phase solution. iv)将冷却的油性类胡萝卜素溶液添加到营养组合物中。 iv) adding the cooled oily carotenoid solution to nutritional compositions. 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：i) M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；ii) 在最大高达油相沸点的^it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；ill) Mil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；iv) 救钟啲油性类胡萝卜素溶液添加到高孔隙度的无机载体中；并且v) 将此载体添加至措养组合物中。 A further embodiment of the present invention relates to a method for preparing a nutritional composition, comprising: i) M at least one carotenoid is dispersed in physiologically acceptable oil suspension was prepared; ii) a maximum of up to the boiling point of the oil phase ^ it heating said suspension under line of up to 30 seconds, to dissolve in the oil phase of the carotenoid suspension to obtain a heated oily carotenoid solution; ill) Mil selected with a physiologically acceptable oil phase mixing and the use of The method of the heat exchanger, to cool the heated oily carotenoid solution, wherein the oil temperature is lower than the heated oily phase solution; iv) to save the clock GOD oily carotenoid solution is added to an inorganic carrier in a high porosity; and v ) Add to measures to support this carrier composition. 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，其中虫下青素符合下述质量标准和规格:<table>table see original document page 8</column></row> <table>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：质量标准 规格<table>table see original document page 9</column></row> <table>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。 The present invention further discloses oily carotenoid astaxanthin suspended particles, wherein the lower insect astaxanthin quality standards and meet the following specifications: <table> table see original document page 8 </ column> </ row> <table> The present invention further discloses oily carotenoid suspension cantharidin yellow particles in which cantharidin yellow comply with the following quality standards and specifications: quality standard <table> table see original document page 9 </ column> </ row> < table> In a further embodiment of the present invention, the cooled oily carotenoid solution is added an oil phase may comprise up to 30% of emulsified water. 上述虾青素和斑螯黄油性悬浮術薛足美国FTDA的要求，也特别适合于制备如US 5,364,563和US 6,664,300中所记载的可分散于水中的制剂。 He said astaxanthin and cantharidin butter of levitation Xue foot American FTDA requirements, but also particularly suitable for the preparation as US 5,364,563 and US 6,664,300 as described in the formulation of water-dispersible. 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)、片齐诉口胶囊等。 According to a preferred embodiment, after cooling line or batch to add an oily carotenoid solution to nutritional composition, nutritional composition is selected from feed pellets (pellet), pellets (granulate), Qi v mouth piece capsules. 这样获得的油性溶液在词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。 Oily solution thus obtained provide a molecular dispersion of carotenoid in oil more consistent distribution of feed pellets in words and other nutritional composition. 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。 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 themselves may be used and is processed into used in the mouth, drugs or nutritional supplements administered tablets, capsules and the like. 在下述发明详述中，定义和术语具有下述优选的含义："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 handlingM列如类胡萝卜素的溶解性和稳定性并且有助于活^(lrving organism)的给药。"溶贿dissdving)"或'溶贿dissolution)"意思是获f験胡萝卜素（其可以是单体、二聚体、三聚体等）的舒分散体或分子聚集体和/或类胡萝卜素的胶态分散体。评价类胡萝卜素在油相中的溶解程度是M51使油相通过0.45nm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。"基本上"意(^至少40wt%。"配制的类胡萝卜素"指的是具有赋形齐咖保护性7K胶体或聚合分散剂以及稳定齐啲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(//. p/wv/afo)、绿球藻(C7z/oracoccww)禾口红发夫酵母(尸/7q^a Aodk^ma)。"饲料"包括所有，的^?活体物种(Mng spedes)的食物。"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。"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。"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)。发明详述类胡萝卜素是一类由八个类异戊二烯单元组成的烃。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。与胡萝卜素相比，胡萝卜素是纯的多烯烃如p-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。这组的典型l^是奸青素、斑螯黄和玉米黄质。叶黄素(xanthophyll)在自然界是很普遍的，存在于玉辨玉米黄质)、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(奸青萄中。它们给这些食物赋予特征颜色。一些类胡萝卜素可以工业合成，也可从自然界中分离。它们是重要的天然抗氧化剂，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。 In the following detailed description of the invention, the following terms have the definitions and preferred meanings: "excipient" is used for the number of no pharmacologically active material, and may be included in the composition to improve processing technology (technical handlingM administration is as kind carotene solubility and stability and contribute to live ^ (lrving organism) of. "dissolve bribe dissdving)" or "dissolve bribery dissolution)" means eligible f omen carotene (which may be monomers, dimers, trimers, etc.) Shu dispersion or molecular aggregates and / or carotenoids colloidal dispersion. Evaluation extent carotenoids is dissolved in the oil phase of the oil phase through a 0.45 M51 nm pore size filter, the filtrate is then determined by HPLC and carotenoid content in the oil phase and total carotenoid concentration compared to unfiltered carried out. "substantially" means (^ at least 40wt%. "preparation carotenoids "refers to forming homogeneous coffee having a protective colloid 7K or polymeric dispersants and stabilizing GOD homogeneous colloidal dispersion containing carotenoid composition, and includes powdered cells and cell debris (cell debris), For example microalgae (microalgae), such as rain pluvialis (//. p / wv / afo), Prochlorococcus (C7z / oracoccww) Wo lipstick rhodozyma (P / 7q ^ a Aodk ^ ma). "feed" including all, of ^? live species (Mng spedes) food. "fish feed" describes all include proteins, carbohydrates, fats (oils), minerals, vitamins and nutrients to feed the fish used in aquaculture in particular are salmonids (salmonids) and crustaceans (crustaceans) feed composition. "Crystal carotenoid" describes the crystal structure of the compound include defined polymorphs and pseudo-polymorphs thereof. "Online" It relates to a method constituting an integral part of a continuous sequence of actions or steps of (method) or process (process). DETAILED DESCRIPTION Carotenoids invention is a class of eight isoprenoid units hydrocarbons. carotenoids The main compound is divided into two groups: carotene and lutein compared with carotene, carotene pure polyenes, such as p- carotene or lycopene, xanthophylls additionally contain functional moieties such as hydroxyl group,. epoxy and / or group. This group is typically l ^ rape astaxanthin, cantharidin yellow and zeaxanthin. Lutein (xanthophyll) is very common in nature, present in jade identified zeaxanthin), green beans (lutein (lutein)), red pepper (paprika oleoresin (capsanthin)), egg yolk (lutein), but also present in crustaceans, and salmonids (evil green grapes in. They give the characteristic color to these foods Some industrial synthesis of carotenoids can also be isolated from nature. They are an important natural antioxidant, 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. 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。 Lutein, at room temperature is almost insoluble in water, fats and oils exhibit very low solubility. 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. 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。 Preferred carotenoids are used in 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|3-胡萝卜素、番燕红素、胭脂树斷ixin)、玉米黄质(zeaxanthm)、隐黄素(ciyptoxanthin)、 黄体素、卩-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 | 3- carotene, Fan Yanhong factors, annatto off ixin), zeaxanthin (zeaxanthm), cryptoxanthin ( ciyptoxanthin), lutein, Jie -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co-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A^文作为参考。 A preferred example is the co-3 fatty acids and / or short-chain carboxylic acids produced astaxanthin diester, which is described in US 6709688, A ^ which is incorporated herein by reference. 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。 The carotenoid may be amorphous, in the form of H- or J- aggregates or present in a stable or metastable polymorph in. 适合用于本发明的虾青素和斑螯黄的品质描述于US-FDA 翻解21CFR73.35以及21CFR73.75)中，引A^文作为参考。 Suitable for use in the present invention astaxanthin and quality of cantharidin yellow are described in US-FDA turned Solutions 21CFR73.35 and 21CFR73.75) in A ^ cited 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. 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。 You can use astaxanthin and pure compounds or mixtures of cantharidin yellow and its polymorphs, amorphous forms and aggregates, which contain up to 40wt. /。 /. 的官能的(fimctional)所有反式类胡萝卜素。 The functional (fimctional) all-trans carotenoids. 虾青素可以包含60%-98%,优选80%-96%的反式虫下青素，以及2%40%重量份、• 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)中作为较少量组饼minor component)。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。所描述的方法肖的多更高的、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，由此得至哽均一的产品。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髙品质饲料的方法。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0.1wt%40wt% 的悬浮虹青素。9(f/。所^f辦立应当具有小于15,的直径。为在较低;^g下M 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15|Lun，优选在lMin和5mih之间。颗粒大小小于l^m可能更适合于在油中的fflil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 ball mill)中进行，j趟ilil在油相中研磨悬浮体。次«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(coUoui 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細少起尘性，并胆接添加至鹏相中并加工。 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瞎况下也可以考虑。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(cost not-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)。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(x-生育酚和抗坏血酸棕榈酸酯。 Astaxanthin may contain 60% -98%, preferably 80% -96% of trans-astaxanthin insects, and 2% 40% by weight, • 2% "35% parts by weight, most preferably from 2% 4% by weight at least one carotenoid derivative mixture (combination) group as a relatively small amount cake minor component). It should be understood that formulated carotenoid compositions and astaxanthin from natural sources comprising 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. The method described in Shaw The more higher, more consistent and uniform dissolution from the (frozen or spray) carotenoid dry cellular components, thereby introducing fish feed, thereby obtaining a uniform product to choking. In addition, the use for the shrimp astaxanthin dissolved in the oil phase and a line for the production of fish pellet is a more cost effective method for preparing and Gao quality feed with improved properties for commercially viable methods for line according to the method of the present invention are described dissolved oil composition comprises 0.1wt% 40wt% suspension rainbow astaxanthin .9 (f / ^ f run the stand should have a diameter of less than 15, is at a low;.. ^ g under M dissolved in the oil phase suspension The average particle size of the carotenoid powder should be less than 15 | Lun, preferably between lMin and 5mih particle size of less than l ^ m may be more appropriate to dissolve in oil fflil If you use more soluble carotenoids. polymorph or crystal variants, the particle size may be larger. particle size can be reduced in a colloidal mill (colloid ball mill), j is the grinding times ilil suspension in the oil phase. times «ground, but nevertheless also a viable option to obtain micronized carotenoids, for example using a colloid mill (coUoui mill) to grind carotenoid aqueous suspension containing a suitable wetting agent (such as phospholipids) Optionally, according to the present invention, After removal of water, dry powder can be further processed by the addition of excipients to improve powder flow properties and less dusting of fine, and then add the gall to Peng phase and processing. Other options, for example by means of an air jet mill (air jet mill) The cryogenic grinding and dry grinding in some blind conditions can also be considered. Alternatively, submicron (submicron) amorphous carotenoid particles can be prepared separately by melt dispersing method using a supercritical fluid. If you want, do not count cost (cost not-withstanding), the method may be incorporated into the online method of the present invention. carotenoid may also be dispersed in a high boiling non-aqueous liquid, e.g., a polyol such as glycerin or propylene glycol and is added the oil phase before grinding (micronized). During the heating process, the carotenoid dissolved therein a physiologically acceptable oil phase is oil, preferably containing antioxidants, such as (x- 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。 The oil phase can reach up to 180. C-230。 C-230. C的温度。 C temperature. 高沸点油，例如植物油或玉米油、作为MIGLYOLtm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, sold as MIGLYOLtm 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(almond oil)、玉米油、菜籽油(canolaoiiy菜籽油(rapeseedoil)、橄榄油、花生油(落花生油)、 向日葵油、红花油、植物豆油、扁杉M二油(almondoil)、杏仁油(apricotoil)、鍔梨油、希蒙德木油(jopbaoil)、橙油、柠檬油、棕谰仁油、南瓜子油、蓖麻油、椰子油(76和110度)、芝麻油、炒芝麻油、亚麻油(flaxseedoil)(有机的、传统的和高木酚素)、GLA油(玻璃苣(Borage)、红醋栗(Black CuiTant)、月见草(Evening Primrose》、葡萄籽油、榛子油、夏威夷核油(kukm nut oil)、澳洲坚果油(macademia nirt oil)、 mamaku油、胡杉^油(pecan oil)、紫苏子油(perilla oil)、阿月浑子油(pistachio oil)、米康油、茶树油、核桃油、麦胚芽油、玉米油或者菜籽油(canola oil)/菜籽油(rapeseedoil)。优选的植物油是：豆油(无GMO)和亚^l子油。只要可能，此过程不需要施加外界压力而进行。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。但如果需要，可以将压力提高到约300巴，以力fl速类胡萝卜素的溶解。，地油相不含水。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(油包水型乳状銜。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。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CCV混合，后者可以与油相部分混合或溶解于油相中，并fflil斷氐悬纟楼胡萝卜素的熔点而能够实现较高的溶解能力。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。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。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懒军。超临界流体例如C02的使用引起类胡萝卜素的熔点的显著降低。惰性气体可以是过热气体锄口压(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^it下溶解更fflil，并增大其在较高浓度下的溶解。 Examples of suitable vegetable oils include: cottonseed oil, sesame oil, coconut oil or peanut oil, almond oil (almond oil), corn oil, rapeseed oil (canolaoiiy rapeseed (rapeseedoil), olive oil, peanut oil (arachis oil), sunflower oil , safflower oil, soybean oil plant, flat cedar M two oil (almondoil), almond oil (apricotoil), E, ​​avocado oil, jojoba oil (jopbaoil), orange oil, lemon oil, palm kernel oil Lan, pumpkin seed oil , castor oil, coconut oil (76 and 110 degrees), sesame oil, fried sesame oil, linseed oil (flaxseedoil) (organic, conventional and Takagi lignan), GLA oil (borage (Borage), red currant (Black CuiTant ), evening primrose (Evening Primrose ", grape seed oil, hazelnut oil, Kukui oil (kukm nut oil), macadamia nut oil (macademia nirt oil), mamaku oil, Hu Shan ^ oil (pecan oil), perilla Oil (perilla oil), pistachio oil (pistachio oil), Micon oil, tea tree oil, walnut oil, wheat germ oil, corn oil or rapeseed oil (canola oil) / rapeseed oil (rapeseedoil). Preferably Vegetable oils are: Soybean oil (non-GMO) seed oil, and alkylene ^ l Whenever possible, the process is performed without the application of external pressure and the hydraulic fluid pressure pumping Typically, the piping system can be generated internally generated up to 50 pressure bar, but if desired, can be increased to about 300 bar pressure to force fl speed carotenoids dissolve., to the oil phase free of water. Sometimes, however, used to heat the carotenoid solution of the oil phase and / or the immiscible phase in the presence of carotenoid dispersed therein oil phase may contain small amounts, up to about 10-30% of emulsified water (water-in-oil emulsion title. Compared with the oil phase, capable of having a lower boiling point under sufficient pressure to generate superheated steam, in order to accelerate the carotenoid is dissolved in the heating zone, thereby enabling the use of higher carotenoid concentrations. Similarly, where the dissolved carotenoid and oil phase can be pressurized (supercritical) CCV fluids such as mixing, which can be mixed with the oil phase or dissolved in the oil phase and fflil Di hanging off the floor, the melting point of Si-carotene and can achieve a higher solubility in the installation and use of high voltage equipment and components cost and economic factors are the main factors and safety issues to be considered together amount (80.C-230.C) heating oil for heating and dissolved phase is 0.1 to 25 parts by weight, preferably 5 to 10 parts by weight part of the carotenoid oil suspension. This method or online method can be carried out or to be under pressure in the heating zone, to further minimize oxidation lazy army under an inert gas. supercritical fluids such as C02 caused by the use of carotenoids significantly lower the melting point of the inert gas can be superheated gas hoe opening pressure (supercritical) fluids, which may also be used to increase the pressure of the heating zone so that the carotenoid is dissolved in a lower and more fflil ^ it under, and increase its dissolved at higher concentrations. 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. 用来将热溶液冷去口和/^^释到低于60。 It is used to heat the solution was cooled to oral and / ^^ release to less than 60. C的油的本体被保持在30。 Oil body C is maintained at 30. C-60。 C-60. C或更低。 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7JC。 However, it may contain a minor proportion of water, for example, naturally occurring or crude natural (fish) oils 7JC. 油中水的数量可以是高达10-30wt。 Oil in the amount of water can be as high as 10-30wt. /。 /. 或更多。 Or more. 与所{顿的较大量的油相比，它是较少量的，基本上其是油包7Ww/o:)体系，不是乳化剂的水溶液。 Compared with the larger amount of oil {Dayton, it is a relatively small amount of oil which is substantially 7Ww / o :) system is not aqueous emulsifier. imt也，所使用的油是天然油或部分7jc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。 imt also, the oil used is natural oils or natural vegetable or fish triglyceride fraction 7jc Solutions (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co-3酸-30。 Suitable examples of fish oils are: specialty marine fish oil (specialty marine oils), for example, a co-3 acid -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/1 OOD、 2500A/250D)、金枪鱼或鲣鱼(bonito) 的鱼油、鱼肝油、比目鱼(halibut)肝油、绿鳕(poUack)肝油、鲨鱼肝油、角鲨烯(squalene)、角鲨烷(squalane)、鲑鱼(salmon)油、飞鱼(skipjack)肝油、青鱼(herring) 油、鳞鱼(capelin)油、鲱鱼(menhaden fish)油。 (18 ./ EPA / 12 ./ DHA..), 50% (30% EPA / 20% DHA) -, no cholesterol, high DHA Norwegian cod liver oil (3000A / 1 OOD, 2500A / 250D), tuna or skipjack (bonito) of fish oil, cod liver oil, halibut (halibut) liver oil, pollack (poUack) liver oil, shark liver oil, squalene (squalene), squalane (squalane), salmon (salmon) oil, flying fish (skipjack) liver oil, herring (herring) oil, capelin (capelin) oil, herring (menhaden fish) oil. 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，^自其它鱼油生产者的鱼油与植物油的混合物。 Preferably, those ^ from other fish and fish oil producers in a mixture of vegetable oil as fish oil, for example, to NorseECOil and NORSlamOil trade names obtained from Egersund Sildoljefabrikk. 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-20,000ppm，优选约100ppm-5,000ppm,更优选约200-1000ppm。 After cooling or addition of oil phase at low temperatures, oil exiting the heat exchanger in the resulting solution, the amount of carotenoid is from about 50ppm-20,000ppm, preferably from about 100ppm-5,000ppm, more preferably about 200-1000ppm. 相应地，用于7賴卩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, for the amount of heating oil 7 Lai Jie carotenoid solution 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. 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。 Oily solutions, 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. 当类胡萝卜素是虫下青素时， 调整温度和加热条件，从而ite地，溶液中反式至,式虾青素异构体的转化低于总异构体的50%， <腿低于30%。 When the carotenoid astaxanthin is lower when insects, adjust the temperature and heating conditions, thereby ite, a solution to trans conversion astaxanthin isomers of less than 50% of the total isomers <leg below the 30%. 基于虫下青素的总重量，可能形成的额外副产物如虫下红素、半虫下红素和025醛应当是低于10%， ^^低于5%。 Based on the total weight of astaxanthin under worms and additional byproducts that may be formed as follows insect red pigment, red pigment and the lower half insect aldehyde 025 should be less than 10%, less than 5% ^^. 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%。 Add 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%. 溶角裕这种油性溶液中的类胡萝卜素的量可以为10ppm-300ppm，伏选30ppm-100ppm。 This amount of carotenoids in oily solution dissolved margin for 10ppm-300ppm, Volt choose 30ppm-100ppm. 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。 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虫下青素的量进行在线控制。 Production is streamlined, easy to dissolved in the oil phase of insect amount of astaxanthin-line 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奸青素。 In addition, this method can feed pellets before adding it to monitor chemical and physical evil 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. 包含类胡萝卜素的油溶液可以lffi接添加到彩色脂肪基食物(例如，与M月萝卜素结合的人造黄油)，或被添加到家禽或鱼饲料组合物。 Oil solution containing carotenoids can lffi then added to the color of fat-based foods (for example, in conjunction with the M month carotene margarine), or added to poultry or fish feed composition. 最终冷却的油溶液可以在添加到饲料之前用水乳化，以便于造粒、挤出或造丸。 The cooled oil solution may eventually added to the feed water before emulsification, in order to facilitate granulation, extrusion or making pellets. 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至搞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 engage the carrier matrix and the porosity 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(100-500m"g)的无机载体的实例为Zeopharm⑧和Neusilin⑧。所得的微粒固体组合物可以被添加至糊料或食品组分中，并被加工成适合的给料形式。 它们也可以本身作为口腔药物和营养制品组合物而使用。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NeusilinTM。 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,，约2ral/g的比容、BET比表面积为30m2/g40m2/g，油和水的吸收容量为约0.8ml/g。 NeusilkTM以Sl、 SG1、 UFL2、 US2、 FH2、 FL1、 FL2、 S2、 SG2、 NFL2N和NS2N等级而销售。特别优选的等级是Sl、 SG1、 US2和UFL2。对于许多应用来说最tte的载体材料是US2等级的。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Zeopharm⑧600(沉淀的非晶体硅酸钙），油吸收容量为250-300ml/100g的Huber-sorb⑧250NF(沉淀的非晶体硅勝巧以及140m2/g、油吸收容量为185-215ml/100g的Zeopharai® 80(沉淀的非晶体二氧化硅)。那些材料， 其是非晶体的，典型地比表面积为约100m々g-约300m2/g、油吸收容量为约1.3ml/g-约4.5ml/g、平均颗粒大小为约l拜-约14,、比容为约2.1ml/g-约12ml/g。 然而，也可以使用备选的有机或无机多?L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。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。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。尽管描述了用于加工类胡萝卜素銜别是奸青素、斑螯黄、 玉米黄质和(3-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。实例是官能化亲脂化合物，例如谷甾酉孰sitosterol)、谷甾烷(sitostanol)及其衍生物，辅酶QIO以及化合物如S^溶性维生素，特别是维生素A和其衍生物。 Examples of high porosity (100-500m "g) of the inorganic carrier is Zeopharm⑧ and Neusilin⑧. The resulting particulate solid compositions may be added to the paste or food ingredients, and is processed into a form suitable for feeding. They also may itself be used as oral pharmaceutical and nutraceutical compositions used preferably high porosity inorganic carrier used in the present invention include inorganic compounds such as calcium hydrogen phosphate, and magnesium aluminum silicate, are known under the trade name Fujicalin® SG and S-type and NeusilinTM. Fujicalin® SG and S-parameters including the average pore size of typical 7nm, an average particle size of about 110 ,, about 2ral / g specific volume, BET surface area of ​​30m2 / g40m2 / g, oil and water absorption capacity of about 0.8ml / g. NeusilkTM to Sl, SG1, UFL2, US2, FH2, FL1, FL2, S2, SG2, NFL2N and NS2N level and sales. A particularly preferred level is Sl, SG1, US2 and UFL2. For many tte most applications support material is grade US2. Other suitable carrier materials having 300m2 / g, an oil absorption capacity of at least 450ml / 100g of Zeopharm⑧600 (precipitated amorphous calcium silicate), an oil absorption capacity of 250 300ml / 100g of Huber-sorb⑧250NF (amorphous silicon deposited wins clever and 140m2 / g, an oil absorption capacity of 185-215ml / 100g of Zeopharai® 80 (precipitated amorphous silica). Those materials, which are non-crystalline typically about 100m々g- specific surface area of ​​about 300m2 / g, an oil absorption capacity of about 1.3ml / g- about 4.5ml / g, an average particle size of about l worship - about 14 ,, specific volume of about 2.1ml / g- approximately 12ml / g. However, it may also be used organic or inorganic multiple alternative? L material, so long as they are carotenoid and exhibit no deleterious effects of the relatively large surface area. The amount of the carrier material depends on properties useful for isolation of carotenoid solution or passage surface area, and the ratio was used as the viscosity of the dispersion. The present invention does not preclude optionally using colloid-dispersed carotenoid formulation, e.g., pellets and microcapsules, instead preferred non-crystalline or amorphous particles formulated carotenoid compounds to prepare the oily carotenoid composition. Although a title not used in the manufacture of carotenoids astaxanthin is evil, cantharidin yellow, zeaxanthin and (3-carotene) method, the skilled person should be able to be applied to other methods disclosed can be used simultaneously, and carotenoids, having similar physical and chemical properties, the compound has only regular changes in the processing conditions, in order to Add to the nutritional composition. Examples are functional lipophilic compounds, such as sitosterol unitary what sitosterol), sitosterol alkyl (sitostanol) and its derivatives, coenzyme QIO and compounds such as S ^ soluble vitamins, especially vitamin A and its derivatives . 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。 This method allows carotenoids alone or in combination manner conventional processing. 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、高沸点油和蜡、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 oils and waxes, dispersing aids, polymerization material, protective colloids, preservatives, flow aids, membrane lipids, cationic, anionic or non-ionic surfactants. 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。 To improve the powder flowability, carotenoid can be added to the oil prior to physical mixing and excipients. 应当理解的是本发明的方法是一种通过在线或分ft啦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。 It should be understood that the method of the present invention is a novel method for continuous online or sub-ft it at least one class of carotenoids process for preparing 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US5,364,563、 US6,296,877和WO 03/102116 (其被引入本文作为参考)制备的胶体分散的制剂。 It may also be used, for example US5,364,563, US6,296,877 and WO 03/102116 (which is incorporated herein by reference) Preparation of a colloidal dispersion formulation according to. 附图说明图1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。 Figure 1 is a schematic flow diagram to explain the line heating and mixing, and then the oil phase at a lower temperature of the cooling device in order to obtain an oily carotenoid solution. 方法M参考在图l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。 Method M Reference is suitable methods of the invention are schematically shown in the flowchart in Figure l for 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C02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., C02 and an oil phase used in conjunction with, or in the presence of a relatively small amount of the oil phase 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. 至少一种平均颗粒大小直径介于l-5^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0.1wt。 The average particle size diameter of at least one of between l-5 ^ m carotenoid suspension between, in the selected oil phase or suitable fluid medium, based on the mixture at a concentration of about 0.1wt. /o40wtQ/。 / O40wtQ /. ，添加或不添加稳定剂，最初被引入到容器4中。 , With or without stabilizers, it is initially introduced into the container 4. 容器1包含不含悬浮的类胡萝卜素的高沸点的油。 High boiling oil without the container 1 contains a suspension of carotenoid. 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. 在一个实施方案中，来自容器1的油相ffi51泵2在将该物流进料到热交换器3之后进料至嗨合室6，在热交换器3中，所述物流被加热至'谋沸点或低于其沸点的温度。 In one embodiment, the pump from the oil phase ffi51 container 1 2 stream is fed to a heat exchanger in the feed after 3 to 6 Hey combined chamber, the heat exchanger 3, the stream is heated to a 'plan 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«作条件如流速。 System oil stream can be purged by circulating oil (purge) and expect to achieve balance temperature, pressure and other «for conditions such as flow rate. 在容器4中保持在低于100。 Kept in containers of less than 100. 4. C的类胡萝卜素悬浮体和混合室6中的受热油物流M51泵5或以直角或成切线进行混合。 Carotenoid dispersion and mixing chamber C, 6 heating oil stream M51 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. M31调节泵2的传M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Mil混合室6后而实现。 Adjusting the transmission rate of the pump M31 M 2, noting that the oil, target temperature, the mixing ratio of the heated region is determined in advance, to a desired residence time in the internal mixing chamber 6 after Mil achieved. 在受热油相中类胡萝卜素的溶解在油的沸点（可以是50°C-300°C)或其以下进行。 Heating oil phase carotenoids dissolved in boiling oil (which can be 50 ° C-300 ° C) or less performed. 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。 The contact time can be dissolved in the heating region by increasing the residence time is prolonged. 这是S31降低混合泵5的流速或延长加热管道7的长度(任选她恒温控制或绝热)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。 This is the S31 reduce mixing pump flow rate 5 or prolonged heating pipe lengths 7 (Optional thermostatic control her or insulation) and implemented so as to maintain the desired temperature by the heated area. 图1所示的加热区域由混合室6和绝热管道7组成。 Heating zone shown in Figure 1 from the mixing chamber 6 and 7 insulated pipeline components. 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。 While maintaining the desired temperature in the heating zone residence time may be up to 30 seconds. 或者，混合室6的尺寸是这样的，使得有效地形成齡加热区域，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。 Alternatively, the size of the mixing chamber 6 is such that the effective heating area formed age, and at the selected transmission rate of the pump 2, the residence time in the mixing chamber or chamber can be up to suspension for 30 seconds, preferably less than 5 sec. 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 timeM她为0.1-30秒，优选地当温度介于100。C-230°C时， 时间为0.1-10秒。根据te的实施方案，在纟鹏介于120。C到180°C，时间介于l-5秒下，任选地在压力下，类胡萝卜素尽可能fflili也溶解于油相中，由此使得P絲狩卩异构化最小化以获得目标类胡萝卜素浓度。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的纟鹏下排出时，溶液中类胡萝卜素的量为至少50wt。/。的油中总类胡萝卜素内容物。为使异构最小化，加热步骤可以是渐进或梯级进行的。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M加热区域之前在容器中预加热。 «地，M31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。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。伏选地将悬浮体在120°C-180°C短暂加热0.1-2秒。瞬时加热可被描述为"闪霧加热"。可以在较低温度下通过过热弾临界)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itt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戮包括但不限于微型流化床)。 When the temperature of the oil phase is between 50 ° C-230 ° C when, during mixing and dissolution along the heating zone by time (transit timeM she 0.1-30 seconds, preferably when the temperature is between 100.C-230 ° C, the time is 0.1 to 10 seconds. According to an embodiment of te, between the Si Peng 120.C to 180 ° C, the time between l-5 sec, optionally under pressure, as the carotenoid fflili also dissolved in the oil phase, thereby making P wire hunting Jie isomerization minimized to obtain the target carotenoid concentrations substantially dissolve the carotenoid particles is acceptable, so that when the oil solution processed in less than 60 When the Si Peng .C under discharge, the amount of solution in the carotenoid is at least 50wt. /. of oil in total carotenoids contents. In order to minimize the isomerization, the heating step may be gradual or rung When When not taking into account the stability of carotenoids, carotenoid suspension may be performed before the heating zone in the vessel M preheating. «ground, M31 between 80.C-120.C mixed with heating oil, heating area in the suspension was heated to a temperature below the boiling point of the carotenoid for up to 10 seconds, preferably at most 5 seconds. Then the suspension along which the temperature may be higher than the melting point of carotenoids, even higher than the boiling point of the oil phase of a further section中在120°C-300°C被短暂加热小于5秒。伏选地将悬浮体在120°C-180°C短暂加热0.1-2秒。瞬时加热可被描述为"闪霧加热"。可以在较低温度下通过过热弾临界)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itt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戮包括但不限于微型流化床)。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M和短暂地崩解和溶解悬浮的类胡萝卜素。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BM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M且短暂地加热。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趟伤界气体的介质在压力下间接加热的热交换器进行。在M:加热区域之后，热的油溶液在被称为冷却室io的混合室内在小于30 秒内，通过经泵9从纟显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M^口的油相或室温的油相，立即在线冷却至舰于约60。 c，或更低的^JS。 «7賴口进行小于30秒。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?破降低到低于60°C，离开冷却室10的管道另外可以使用外部介质例如水、液氮或压縮气体，用热交换器冷却或冷藏。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。冷却后的类胡萝卜素油溶液的温度低于60。 C，雌30。 C-50。 C-50. C，更«低于30°。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招氐于60。 C顿低M^的油相的容器中而在用于分批制备的存料容器(containment vessel)中立即7賴口。容器可以进一步低温直温(ciyostatically)^4卩。在任何情况下冷却都应当在短时间内进行，优选小于30秒。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斷circmt)中以控制加热和7賴口顺序。图1的结构是图解本发明的典型实例。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。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-20,000ppm之间的类胡萝卜素油溶液。通量(throughput) 可以M3i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。可以使用利用静态混合器或混合喷嘴(例如管口喷B銜的混合室。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、、M和压力以及所采用的热交换介质的类型。可以采用由肯嫩为lkW 的热交换器供能的溶解模i姊制备至少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^1程在线集成。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。下述实施例，通过举例并非限制性地证明本发明。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/鄉卩工纟鹏和劍牛而实施备选的实施方案。实施例1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Silverson在线转子/定子混合器，将100g的包含80%(+/-2%)合成的、全反式虫下青素和大约20%含顺式虾青素、C-25醛奸青素、虾红素(astacine)和半虾红素(semi-astacine)的副产物的晶体加入到大豆油中。在线混合器和热交换器相连以加热油。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?驢达10秒。所得的虾青素油性溶液立即用静态混合教Sulzer AQ Winterthur， CH) 和大于10倍的在40°C加热的Manhedan鱼油混合。所得的油性溶液，分析虫下青素的溶解程度，并用于鱼饲料生产。实施例2参考图l。在室温下，将用量为4y。 (w/w)的晶体(98Q/o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«粒大小特征的分散#(用激光衍射光谱法测量)：dlO: lO,, d50: 2.5拜,d90: 6,。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虫下青素油溶液。悬浮1tt室温下用大豆油稀释以获得1.5% (w/w, 15000ppm)虾青素和1.5% a-生育酚。将1升的悬浮体于23。 C转移到容器4中，轻轻搅拌，并M混合泵5以1 kg/h泵M过混合室6，其中虹青素悬浮体和从容器1通过泵2在9 kg/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1:9 (w/w)虾青素悬浮体/预加热油混合物的温度为150°C，包含1500ppm的虾青素。 M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魏的体积，该混合物以1秒的舰时间(在150。C)流过绝热管道7，从而溶解虾青素。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7賴卩，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。或者，通过热交换皿没有稀释的情况下将150°C的l:9(w/w)的虫下青素悬浮依预加热油混合物(包含1500ppm的虾青素)7转卩，用液氮或7jC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。在通过0.45,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P絲牟产物。油性虫下青素溶液可以ffiil与鱼饲料丸剂混合而被进一步加工。实施例3以与实施例2對以的方式，在室温下将用量为10。 /。 /. (w/w)的实施例1的基本上纯的晶体合成奸青素分散在含10% (w/w) ot-生育酚的大豆油中。悬浮^E胶体球磨机中在70。 C进行研磨，从而获得具有下M粒大小特征的分散体：4.9%> 5,、95.1%介于2.7-1,之间(M31分级过滤测量，随后对虾青素含量进行HPLC 分析)。悬浮体被冷却到室温，用大豆油稀释以获得l，/。 (w/w)(15,000ppm)的虾青素和1.5。 /。 /.的a-生育酚。将1升该悬浮体在23。 C转移到容器4中，轻轻搅拌， 并通31混合泵5以1 kg/h的速率^M31混合室6，其中将虫下青素悬浮体和从容器1进料的大豆油Cf顿泵2，以9 kg/h操作)混合并加热，所述大豆油舰热交换器3预加热到148°C，从而l:9(w/w)虾青素悬浮体/预加热油混合物(包含1500ppm的虫下青素)的温度为126°C，以溶解虫下青素。此混合物泵^lil绝热管道达1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。在舰0.45拜？ L径的过滤器过滤250ppm的虾青素组合物后，虾青素含量的HPLC-分析显示虫下青素是完全溶解的，且包含12%的顺式异构体。在与鱼饲料丸剂以30wt"/。的油含量混合时，油性虫下青素溶液M用鱼油稀释到250ppm而进一步加工，从而在丸剂中获得83ppm的虾青素含量。实施例4以和实施例3對以的方式，所得的油性虫下青素溶液物流被在线进料到挤出机以制备饲料丸剂。 实施例5以禾喊施例2對以的方式，晶体斑螯黄，其基本上是纯的(92.5%)，用于代替虫下青素。 实施例6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M成虫下青素。实施例7以和实施例1类似的方式，用大豆油稀释10%的含1%虹青素的雨生红球藻的悬浮体，从而获得3000ppm的虫下青素悬浮体，进而用实施例1的条件加工以获得油性类胡萝卜素溶液。实施例8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。 实施例9将实施例3的含250ppm的虫下青素的油性溶銜lkg)在搅拌下添加到200g的硅勝哉KNeusilin)中。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。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。