包含类胡萝卜素的遮光组合物 It contains opacifying carotenoid composition

技术领域 Technical Field

本发明涉及包含源自藻类化合物硅曱藻黄素、硅藻黄素、墨角藻黄素和相关化合物的组合物。 The present invention relates to a compound derived from algae algae silicon Yue flavin, flavin diatoms, fucoxanthin and related compounds compositions. 优选地，该组合物为药物或化妆品组合物， 尤其是具有光防护特性的组合物，例如遮光剂，其用于预防由将身体外 Preferably, the composition is a pharmaceutical or cosmetic compositions, particularly having light-shielding properties of a composition, e.g., opacifying agents, for the prevention of the outer body

层或表面例如皮肤和头发暴露于太阳光镨的uv和可见光谱区造成的损害。 Layer or surface damage such as skin and hair exposed to sunlight praseodymium uv and visible region caused.

背景技术 Background

阳光由电磁辐射的连续光谱组成，所述电磁辐射分为三个主要的波 Sunlight by the electromagnetic radiation spectrum consisting of a continuous, said electromagnetic wave radiation is divided into three main

长区：紫外(UV)、可见和红外。 Long District: Ultraviolet (UV), visible and infrared. UV辐射包含200~400nm的波长，而可见光为400~700nm。 UV radiation comprises a wavelength of 200 ~ 400nm, visible light of 400 ~ 700nm. 紫外光镨还进一步分为三个区段，分别具有截然不同的生物效应：UVA(320 ~ 400nm) 、 UVB(280 ~ 320nm)和UVC(200~280nm)。 UV praseodymium further divided into three sections, each having distinct biological effects: UVA (320 ~ 400nm), UVB (280 ~ 320nm) and UVC (200 ~ 280nm).

充分地记载了阳光对皮肤的破坏作用，多方面的有害作用包括皮肤灼伤、过早老化和皱紋(光老化(dermatoheliosis))，恶性前损害（阳光角化病)的发展和各种恶性肿瘤。 Fully documented damaging effects of sunlight on the skin, and many of the harmful effects include skin burns, premature aging and wrinkles (photoaging (dermatoheliosis)), premalignant lesions (sun keratosis) development and a variety of malignancies.

虽然平流层臭氧层有效地阻止UVC射线达到地球表面，但是UVA 和UVB辐射以足以对皮肤和眼睛造成重大生物后果的量到达地球表面。 Although stratospheric ozone layer effectively prevents UVC rays to reach the Earth's surface, but UVA and UVB radiation in an amount sufficient to cause significant skin and eye biological consequences of reaching the earth's surface. 到达地球表面的UV辐射包含卯~ 99%的UVA和1 ~ 10%的UVB。 UV radiation reaching the earth's surface contains sockets to 99% of UVA and from 1 to 10 percent of UVB. 已经广泛地记载了UVB的损害作用。 It has been widely documented damaging effects of UVB. 这些高强度射线的短期作用是红斑和灼伤。 Short-term effects of these high-intensity radiation is erythema and burns. 从较长期来看，皮肤癌的风险是显著的，这是因为245 ~ 2卯nm的UV辐射被DNA最大地吸收，并且能够在二聚体形式的嘧啶附近的DNA中直接导致诱发光化产物或损害。 In the longer term, the risk of skin cancer is significant, because the 245 nm to 2 d UV radiation is absorbed by DNA maximally, and can result in a direct form of pyrimidine dimers induced in the vicinity of DNA photoproducts or damage.

UVA射线不直接被DNA吸收，但是可以通过形成能够与细胞蛋白质和DNA反应的自由基氧物质导致间接的有害影响。 UVA rays do not directly absorbed by the DNA, but can be formed to work with cellular proteins and DNA by free radical oxygen species lead to indirect harmful effects. UVA射线的强度较低；它们透过皮趺表面并导致长期损害，例如过早地形成皱紋和光老化，并认为是致癌的。 Low intensity UVA rays; they instep through skin surface and cause long-term damage, such as premature formation of wrinkles and photoaging, and considered to be carcinogenic. 皮肤癌是最普通的癌症类型，在美国每年大约发生800 000例。 Skin cancer is the most common type of cancer, about 800,000 cases occurred each year in the United States. 大部分皮肤癌或者是基底细胞类型的或者是鳞状类型的， 并倾向于緩慢地生长和扩散。 Most skin cancers are basal cell or squamous type or types, and tend to grow and spread slowly. 恶性黑色素瘤是一种更加严重形态的皮肤 Melanoma is a more serious form of skin

癌形式，现在每年增加约4%。 Cancer forms, now increased by approximately 4% per year.

太阳光镨中诱发黑色素瘤的的辐射的确切波长是未知的，但是可获得的有限数据表明UVR光镨是最重要的，尤其是UVB但也可能是UVA 和可见的蓝光。 Praseodymium sunlight-induced melanoma exact wavelength radiation is unknown, but the limited data available indicate that UVR light praseodymium is most important, especially UVB and UVA, but also may be visible blue light. 随着逐渐意识到UVA损害加剧了黑色素瘤和其它肿瘤的风险，显然需要广泛的光谱保护。 With increasingly aware of UVA damage aggravated risk of melanoma and other tumors, a clear need for broad spectrum protection. 测量遮光剂功效的传统方法是防晒因子(SPF)值，其被定义为：与未处理的皮肤相比，在灼伤前皮肤可以忍受的延长地暴露于UVB射线。 Traditional methods for measuring the efficacy of sunscreens is sun protection factor (SPF) value, which is defined as: compared to untreated skin, skin burns can endure before prolonged exposure to UVB rays. 几项研究提到SPF因子给出的关于由UVA和可见的蓝光引起的伤害的潜在危险的安全假象。 Several studies mention potentially dangerous false sense of security about the damage from the UVA and blue visible due to the SPF factor gives.

鉴于遮光剂使用方便，所以一直认为它们是保护免于太阳光线的主要组分。 Given sunscreens easy to use, it has been that they are protected from the sun's rays are the main component. 遮光剂通过吸收、反射或散射太阳光线而起作用，并由此或者遮敝皮肤免于太阳光线或者将光能转换为无害的能量形式。 Opacifiers by absorbing, scattering or reflecting the sun's rays and act, and thereby masking spacious or skin from the sun's rays or the energy of light is converted to harmless form. 可以将防晒剂粗略地分为化学和物理滤光剂。 Sunscreens can be roughly divided into chemical and physical filters agent. 物理遮光剂为无机微粒，其通过反射或散射太阳光线作为广镨光防护剂。 Physical sunscreens are inorganic particles, which by reflecting or scattering the sun's rays as a wide praseodymium light protectant. 广泛使用的物理阻挡物为氧化锌和二氧化钛。 Physical barriers to the widespread use of zinc oxide and titanium dioxide. 已知它们提供良好的光防护，但是在化妆品中缺少吸引力； 它们不被皮肤吸收并作为白色层留在皮肤表面上。 They are known to provide good light protection, but less attractive in cosmetics; they are not absorbed by the skin and left as a white layer on the skin surface.

化学遮光剂被皮肤吸收，通过吸收由太阳发射的射线并作为振动能(热）重新发射该光能来发挥其遮光活性。 Chemical sunscreens are absorbed by the skin, re-emission by absorbing the light energy emitted by the sun's rays as vibrational energy (heat) to exert its light-blocking activity. 普通的化学遮光剂包括PABA(对氨基苯甲酸)及其衍生物、肉桂酸酯、水杨酸酯、邻氨基苯甲酸酯、樟脑衍生物、苯并咪唑、三溱酮、氰双苯丙烯酸辛酯(octocrylene)、 尿刊酸、双咪唑化物（bisimidazylate)和苯甲醚三噢（anisotriazine )。 Common chemical sunscreen agents include PABA (para-aminobenzoic acid) and its derivatives, cinnamic acid esters, salicylic acid esters, anthranilic acid esters, camphor derivatives, benzimidazole, three Qin ketone, octocrylene octyl ester (octocrylene), urocanic acid, bis-imidazole compound (bisimidazylate) and anisole three oh (anisotriazine).

对于遮光化合物，主要关注的是消费者的安全。 For the Blackout compound, the main concern is the safety of consumers. 所得的调查结果表明某些遮光化合物是潜在地光过敏的，例如PABA，已知其在1~2%的人群中引起光过敏反应（Kimbrough， 1997， J. Chem. Ed" 74 (1)，第51-53页）。虽然物理遮光剂通常认为是良好的光防护剂，但是也讨论了其安全性，这是因为通过人类成纤维细胞的体外研究表明基于太阳暴晒和二氧化钛的结合会形成羟基自由基，其导致DNA中的链断裂(Dunforda等，1997， FEBS Lert" 418，第87-卯页）。 Survey results obtained show some light-shielding compounds are potentially allergic to light, such as PABA, is known to cause allergic reaction in 1 to 2% of the population (Kimbrough, 1997, J. Chem. Ed "74 (1), p. 51-53). Although the physical sunscreens generally considered to be good light repellant, but also to discuss its security, because the in vitro study of human fibroblasts show sun exposure based on a combination of titanium dioxide and the formation of hydroxyl free radicals, which cause DNA strand breaks (Dunforda, etc., 1997, FEBS Lert "418, Article 87- d p). 此外，所有这些化学物质被光分解为未知化合物且尚未研究长期的安全性影响。 In addition, all of these chemicals are unknown compounds and photolysis study long-term safety has not been affected.

尤其需要用于评价UVA保护的好方法，这是因为现在还没有这种标准存在。 In particular, a good way to evaluate the need for UVA protection, it is because there is no such standard exists. 尽管逐渐地意识到广谱保护的重要性，但是研究表明宣称具 Despite increasingly aware of the importance of broad-spectrum protection, but studies show that having declared

有良好UVA防护的市售遮光剂不足以发挥抗UVA射线保护作用(Haywood等，2003， J. Invest. Derm., 121 (4)，第862页）。 There are good commercial sunscreens UVA protection is not enough to play the role of anti-UVA ray protection (Haywood et, 2003, J. Invest. Derm., 121 (4), p. 862). 特别地，在较长波长(370 ~ 400nm)UVA辐射中，可获得的滤光剂的保护性不足，尤其是对400nm以上波长的保护不足或没有保护。 In particular, in the longer wavelength (370 ~ 400nm) UVA radiation, the protective filter agent available is insufficient, especially less than 400nm wavelength for protection or no protection.

大多数市售护肤霜中的UV和太阳光防护化合物是合成的，并且因为消费者更愿意使用天然产品，所以对具有相同或更高功效的天然化合物的研究变得更重要。 Most commercial skin cream in the UV and sun protective compounds are synthesized, and because consumers are more willing to use natural products, so the study with the same or higher efficacy of natural compounds become more important.

在高等植物、珊瑚、蓝藻和浮游植物中研究了各种有机体和天然提取物的UV吸收性能，但是天然遮光化合物的商业化仍然是有限的。 In higher plants, coral, cyanobacteria and phytoplankton in the study of various organisms and natural extracts UV absorption properties, but the commercialization of natural light blocking compounds is still limited. 仍需要作为在太阳光镨的UV和可见光范围中有效滤光的源于天然的吸光剂或遮光剂。 Still required as sunlight praseodymium UV and visible range of effective filtering from the natural light absorbers or sunscreens.

令人惊奇地，证实了叶黄素组中的不连续的类胡萝卜素族为有效的UV和可见光过滤剂（尤其是用在动物皮肤上，特别是人类），为抗氧化剂，为金黄色和为油可溶的和稳定的。 Surprisingly, confirmed the lutein group discrete carotenoid family as an effective UV and visible light filters (especially used in animal skin, especially a human), an antioxidant, is golden yellow and oil soluble and stable. 该族包含类胡萝卜素硅甲藻黄素、 硅藻黄素、墨角藻黄素和它们的衍生物。 The family contains carotenoids silicon peridinin, diatoms Flavin, fucoxanthin and their derivatives.

硅甲藻黄素、硅藻黄素和墨角藻黄素为叶黄素组中的类胡萝卜素， 在IO个世界范围的重要的形成水华的浮游生物类的50%中发现：硅藻类（Diatoms )、 沟鞭藻类（Dinoflagellates )、 定鞭金藻类(Prymnesiophytes )、棵藻类(Euglenophytes )、金藻类(Chrysophytes )。 Silicon peridinin, diatoms flavin and fucoxanthin as carotenoids lutein group, 50% of the IO class plankton world-wide importance of the formation of blooms found: diatoms (Diatoms ), dinoflagellates (Dinoflagellates), fixed whip gold algae (Prymnesiophytes), trees, algae (Euglenophytes), golden algae (Chrysophytes). 墨角藻黄素也大量地存在于其它有机体中，例如海藻、raphidocyte和褐藻类(大藻类)如墨角藻(Fucus vesiculosus )。 Fucoxanthin is also present in a large number of other organisms, such as algae, raphidocyte and brown algae (macroalgae) as Fucus (Fucus vesiculosus).

硅藻类、沟鞭藻类和定鞭金藻类的特征在于具有在春季和夏季的高光照条件下合成大量硅甲藻黄素和硅藻黄素的能力，同时保留在峡湾、 海岸区中和沿着冰边缘的浅的含盐上层中。 Diatoms, dinoflagellates and fixed whip gold algae characterized by a large amount of silicon peridinin synthesis and the ability of diatoms flavin in the spring and summer high-light conditions, while retaining the fjords, coastal areas and along the ice Salt upper edge of the shallow.

这些有机体已经发展了有效的光防护机理，以最小化可能由它们暴 These organisms have developed effective light protection mechanism in order to minimize possible violence by their

露于过量光强度而产生的光抑制。 Photoinhibition exposed to excessive light intensity generated. 在被光强度的突然增加激活的短期防护中，过量吸收的光能量的光防护辐射耗散被认为是重要机理。 A sudden increase in activated light intensity short-term protection in excess absorbed light energy dissipation light radiation protection is considered an important mechanism. 在该机理中，在称为非光化学猝灭(NPQ)的方法中，涉及叶黄素硅甲藻黄素和硅藻黄素。 In this mechanism, the method is called non-photochemical quenching (NPQ), the silicon peridinin involving lutein and diatoms flavin. 硅甲藻黄素位于主要的捕光（light harvesting)色素蛋白复合物(LHC)中，在此其通常接收光能并将能量送到光系统II(PS II)中的 Silicon peridinin located in the main light-harvesting (light harvesting) pigment-protein complex (LHC), where it typically receives light and energy to the photosystem II (PS II) in the

反应中心。 The reaction center. 在NPQ中，珪甲藻黄素被解环氧化（de-epoxydized)为硅藻黄素，所述硅藻黄素在耗散过量光能而不是将其送到反应中心中起到活性作用。 In NPQ, the Gui peridinin be de-epoxidation (de-epoxydized) diatom flavin, flavin in the diatom dissipation of excess energy rather than to play an active role in the reaction center .

发明内容 DISCLOSURE

本发明人发现硅甲藻黄素、硅藻黄素、墨角藻黄素和相关化合物作为遮光剂具有特别有用的性能，尤其是当用于活生物体时。 The present inventors have found that silicon peridinin, diatoms Flavin, fucoxanthin and related compounds as sunscreens have particularly useful properties, especially when used in a living organism time.

这些化合物之前没有被证实具有吸光化合物的任何功用。 Any function has not been confirmed before the light absorbing compounds of these compounds. 硅甲藻黄素和硅藻黄素尤其是罕见的类胡萝卜素，被认为难于分离且稳定性差。 Silicon dinoflagellates and diatoms flavin flavin especially rare carotenoids, is considered difficult to isolate and poor stability. 特别地，当硅甲藻黄素和墨角藻黄素同时出现在生物系统中时，认为同时分离两种化合物是相当困难的。 In particular, when the silicon peridinin and fucoxanthin also appear in biological systems, that the separation of the two compounds at the same time is very difficult. 现在本发明人分离出了稳定形式的化合物并研究了它们的性能。 The present inventors have now isolated a stable form of the compound and study their properties. 惊奇地发现这些类胡萝卜素适用于吸收辐射，尤其是用于之前忽略的蓝光，因此在依赖于阳光吸收性质的应用中具有功效，例如作为遮光剂。 Surprised to find that these carotenoids suitable for absorbing radiation, particularly for ignoring blue before, it has efficacy depends on the sunlight-absorbing properties in applications such as sunscreens.

在第一方面，本发明提供包含类胡萝卜素或者其药物上可接受的衍生物或盐的组合物，所述类胡萝卜素优选为叶黄素、羟基类胡萝卜素(尤其是二羟基类胡萝卜素)或环氧类胡萝卜素，其中所述类胡萝卜素含有任选取代的线性不饱和的含有共轭双键的烷基链，其中在所述链的各端 In a first aspect, the present invention provides a composition comprising a carotenoid or a pharmaceutically acceptable derivative or salt thereof, preferably the carotenoids lutein, hydroxy carotenoids (particularly dihydroxy carotenoids ) or epoxy carotenoids, wherein the carotenoid-containing unsaturated optionally substituted linear conjugated double bond-containing alkyl chain, wherein each end of said chain

被环烷基取代，并且其中所述烷基链含有至少一个-C3l^R2-基团，其中 Is cycloalkyl, and wherein the alkyl chain contains at least one -C3l ^ R2- group, wherein

&和R2可以相同或不同且分别为氢原子、羟基或烷基，或同与其连接的碳原子形成所述环烷基基团之一的部分或全部。 & And R2 may be the same or different and are each a hydrogen atom, a hydroxyl group or an alkyl group, or taken together with the carbon atom forming part or all of the cycloalkyl groups one.

优选地，所述-C3RiRr基团选自下列基团之一： Preferably, the -C3RiRr group is selected from one of the following groups:

CR尸C-CR2画、-OC-CRiRaXm^-OC-,其中，优选地， 或R2为氢，并且其它R基团(或者A和R2两者)和与其连接的碳原子为末端环烷基基团的部分或全部。 CR corpse C-CR2 painting, -OC-CRiRaXm ^ -OC-, wherein, preferably, or R2 is hydrogen and the other R group (or both A and R2) and with the carbon atom attached to the end of the cycloalkyl a group of some or all of them.

作为替代方案，所述的类胡萝卜素包含-CR工^.C工CR2-或-CRfC^CR2-， As an alternative, the carotenoid containing -CR workers ^ .C workers CR2- or -CRfC ^ CR2-,

其中，仅存在任选的键之一，根据存在的键Ri或R2可以不存在或一起存在于末端碳原子上。 Wherein, optionally, there is only one bond may be absent or present on the terminal carbon atom together with the key according to the presence or Ri R2.

在特别优选的方面中，所述类胡萝卜素为下式： In a particularly preferred aspect, the carotenoid to the following formula:

其中 Among them

a和c分别为0~2的整数，其中a+d优选等于1; b为6〜25的整数，尤其优选ll、 13、 14、 16、 17或19; Ri和R2如上定义； a and c are each an integer of 0 to 2, wherein a + d is preferably equal to 1; b is an integer of 6~25, particularly preferred ll, 13, 14, 16, 17 or 19; Ri and R2 are as defined above;

R3和Rs可以相同或不同，分别为环烷基或环烷基的一部分，并且所述环烷基的剩余部分由Ri、R2或R4(或A和R2)和与其连接的碳原子提供； 和 R3 and Rs may be the same or different and are each a part of a cycloalkyl group or a cycloalkyl group, the cycloalkyl group and the remaining portion is provided by Ri, R2 or R4 (or A and R2) and connected with the carbon atoms; and

R4为任选取代的烷基、氢原子、氧原子或羟基基团，或者同与其连接的碳原子一起可以形成所述环烷基基团之一的部分或全部，其中如果R4 为氧原子并由此提供羰基，则邻接的碳原子具有两个R4基团，优选为氢原子。 R4 is an optionally substituted alkyl group, a hydrogen atom, an oxygen atom or a hydroxyl group, or taken together with the carbon atoms are attached may form part or all of one of the cycloalkyl group, wherein if R4 is an oxygen atom, and thereby providing a carbonyl group, the adjacent carbon atoms having two R4 groups, preferably a hydrogen atom.

因此，该化合物可以为下式： Thus, the compound can be of the formula:

<formula>formula see original document page 10</formula> <Formula> formula see original document page 10 </ formula>

其中，相对上式，R4由R"〜R4s表示，（其中任选地可以不存在=CR4r-CR4s-)， a为O, b为17或19， c为l， R3和R4a—起与和它们相连的碳原子形成环状基团，Rs和R2—起与和它们相连的碳原子形成环状基团。（在可替代的实施方案中，在上式中的基团-CRiCCR2Rs可以被基团-CEC-CRiR2Rs替代。） Which, relative to the previous formula, R4 by the R "~R4s said (which optionally can be absent = CR4r-CR4s-), a is O, b is 17 or 19, c is l, R3 and R4a- play with and the carbon atoms to which they are attached form a cyclic group, Rs and R2- play with the carbon atom they are attached form a cyclic group. (In an alternative embodiment, the formula can be based groups -CRiCCR2Rs Mission -CEC-CRiR2Rs instead.)

任选地，-«^4«14-基团可以用上文所述的-0^114(:0-基团代替。在 Optionally, - «^ 4« 14- groups may use the above -0 ^ 114 (: 0-group instead.

优选的方面中，所述-CR4CR4-基团为-CR4bCR4c-。 A preferred aspect, the -CR4CR4- group is -CR4bCR4c-. R4广Ru的一个或多 One or more of R4 wide Ru

个优选为烷基，尤其优选R4d、 FU、 R4m和R4q为烷基，优选曱基。 Preferred is an alkyl group, particularly preferably R4d, FU, R4m and R4q is alkyl, preferably Yue group.

优选的环状基团(在烃链的任一端可以相同或不同）为任选取代的芳烃或非芳烃，优选为己基基团。 Preferred cyclic groups (at either end of the hydrocarbon chain may be the same or different) is an optionally substituted aromatic or non-aromatic hydrocarbon, preferably hexyl group. 所述环状基团优选为取代的环己基、环己烯基基团(例如l-环戊烯-l-基)或环己烷二价基亚环己基，其中这些基 The cyclic group is preferably a substituted cyclohexyl group, cyclohexenyl group (e.g., cyclopentenyl -l- l- yl) cyclohexane or a divalent cyclohexyl sulfoxide group, wherein these groups

团优选在碳环的一处或多处被烷基、环氧基团、羟基或羰基取代，其中这些基团本身也可以被取代。 Group is preferably a carbon ring or multiple alkyl, an epoxy group, a hydroxyl group, or carbonyl, in which these groups themselves can be substituted.

在特别优选的方面中，环状基团为环己基，并且该己基的C2被羟基或烷基(优选曱基)取代(和/或Cl和C2具有环氧基团），C4被烷基(优选甲基)、和/或羟基(其本身可以被羰基取代，即得到乙酰氧基)取代， C6被烷基优选甲基双取代。 In a particularly preferred aspect, cyclic group is cyclohexyl, and the hexyl C2 is hydroxy or alkyl (preferably Yue) substituted (and / or Cl and C2 having an epoxy group), C4 is alkyl ( preferably methyl), and / or hydroxyl (which itself may be substituted with a carbonyl group, i.e., to give acetyloxy) substituent, C6 disubstituted by alkyl preferably methyl.

在此提及的烷基可以为单或多不饱和的并包括烯基和炔基。 In this mentioned alkyl group may be mono- or polyunsaturated and include alkenyl and alkynyl. 所述基团可以含有至多40个碳原子。 The group may contain up to 40 carbon atoms. 烷基链优选为C15~C25,例如C19~ C23。 The alkyl chain preferably C15 ~ C25, for example C19 ~ C23. 取代的烷基优选更短，例如优选烷基含有至多IO个碳原子，例如1~5个碳原子。 Substituted alkyl is preferably shorter, e.g., preferably an alkyl group containing up to IO carbon atoms, e.g., 1 to 5 carbon atoms. 尤其优选例如具有l、 2或3个碳原子的直链饱和烃。 Particularly preferred, for example having a l, 2 or 3 linear carbon atoms saturated hydrocarbons. 取代的烷基可以是单或多取代的，例如它们可以为烷氧基烷基、羟基烷氧基烷基、多羟基烷基、羟基多亚烷氧基烷基、氧杂烷基、多氧杂烷基等。 Substituted alkyl groups may be mono- or polysubstituted, for example they may alkoxyalkyl, hydroxyalkoxy alkyl, polyhydroxy alkyl, hydroxyalkyl, alkoxyalkyl polymethylene, oxa-alkyl, polyoxy heteroalkyl like.

因此，环状基团可以选自： Thus, a cyclic group may be selected from:

其反映通常在类胡萝卜素中发现的环状基团，其中所示的R基团对应于分子的其余部分，并且C16、 C17和/或C18可以被如上所述的烷基或含氧基团替代，并且如果合适的话，转化为环己基环的环己烯基环和/ 或C3可以被如上所述的烷基或含氧基团取代。 Which reflects generally found in carotenoids cyclic group, wherein the group represented by R corresponds to the rest of the molecule, and C16, C17 and / or C18 alkyl groups may be as described above or oxygen-containing groups alternative, and, if appropriate, into alkylcyclohexyl ring cyclohexenyl ring and / or C3 as described above may be substituted or oxygen-containing groups. 根据本发明，优选的环状基团为： <formula>formula see original document page 12</formula>因此，优选的化合物为如此的在烃链上含有一个或多个亚二烯基 According to the present invention, the preferred cyclic groups are: <formula> formula see original document page 12 </ formula> Therefore, it is preferable for such compounds containing one or more sub-groups on the hydrocarbon chain diene

(alkadienylene)或亚炔基(优选一个或多个亚二丙烯基或亚乙炔基）的类胡萝卜素，其中所述亚二烯基或亚炔基可以包含作为末端环状基团一部分的碳。 (Alkadienylene) or alkynylene group (preferably one or more sub-diallyl or ethynylene) a carotenoid, wherein the alkylene diene or alkynylene group may contain carbon as part of a terminal cyclic group.

本发明的类胡萝卜素基于具有任选取代的P、 S、 Y、 K、 （p或X环状 The present invention is based on carotenoids optionally substituted with P, S, Y, K, (p or cyclic X

基团的胡萝卜素结构，如上文所述。 Carotene group structure, as described above. 这样的类胡萝卜素优选在与在胡萝 Such carotenoids preferably with the carrot

卜素结构上的选自a)6、 7; b)6，、 7'; c) 7、 8;和d) 7，、 8'位相对应的一个或多个位置处具有至少一个二脱氢基团。 Bu structural elements selected from a) 6, 7; b) 6 ,, 7 '; c) 7, 8; and d) 7 ,, 8' phase at one or more positions corresponding to at least a two-dehydrogenation group. 特别优选二脱氢基团存在于6'、 7'和/或7'、 8'位处。 Particularly preferred didehydro- group is present in 6 ', 7' and / or 7 ', 8' is located.

优选地，上述组不包含天然存在的类胡萝卜素，除了根据本发明在此描述的特别提到的类胡萝卜素例如墨角藻黄素、硅藻黄素和硅甲藻黄素以及优选的它们天然存在的衍生物例如它们的断、脱或降类胡萝卜素衍生物或降解产物之外。 Preferably, the above group does not contain a naturally occurring carotenoids, except such as fucoxanthin, diatoms and silicon peridinin flavin and they preferred naturally occurring carotenoids according to the present invention specifically mentioned herein described derivatives such as their break, drop off or outside of carotenoid derivatives or degradation products. 在优选方面中，上述组没有扩展到异黄素(alloxanthin)、新黄素、隐藻黄素（crocoxanthin)或无隔藻黄素，尤其优选新黄素。 In a preferred aspect, the above-mentioned group did not extend to genistein (alloxanthin), neoxanthin, Cryptophyta flavin (crocoxanthin) or without partition algae Flavin, particularly preferably neoxanthin.

特别优选地，类胡萝卜素为5，6-环氧-3，3',5'-三羟基-6'，7'-二脱氢陽5,6,7，8，5'，6'-六氢-P，p-胡萝卜素画8-酮3'國乙酸酯(优选3S， 5R， 6S， 3'S， 5'R， 6'R)、 5，6-环氧-7',8'-二脱氢-5，6二氢-p，p-胡萝卜素-3,3，-二醇(优选3S， 5R， 6S)或7'，8'-二脱氢-p,p-胡萝卜素-3，3，-二醇(优选3R, 3'R)。 Particularly preferably, the carotenoid is 5,6-epoxy-3,3 ', 5'-trihydroxy-6', 7'-didehydro male 5,6,7,8,5 ', 6'- hexahydro -P, p- carotene Videos 8- ketone 3 'States acetate (preferably 3S, 5R, 6S, 3'S, 5'R, 6'R), 5,6- epoxy -7', 8 ' - didehydro-5,6-dihydro--p, p- carotene 3,3 - diol (preferably 3S, 5R, 6S) or 7 ', 8'-didehydro -p, p- carotene 3,3 - diol (preferably 3R, 3'R).

特别优选地，所述化合物为具有如图l所示的结构的硅甲藻黄素、 硅藻黄素或墨角藻黄素。 Particularly preferably, the compound having the structure shown in Figure l silicon peridinin, diatoms flavin or fucoxanthin.

在特别优选的方面中，类胡萝卜素为下式： In a particularly preferred aspect, the carotenoid to the following formula:

R3 - CR4a—CR4b - CR4C - CR,d - CR" - CR4f - CR4g - CR4h - CR" - CR,3 - CR4k - CR4l — CR化-CR4n - CR4。 R3 - CR4a-CR4b - CR4C - CR, d - CR "- CR4f - CR4g - CR4h - CR" - CR, 3 - CR4k - CR4l - CR of -CR4n - CR4. - CR4p - C3 - Rs - CR4p - C3 - Rs

其中 Among them

当-C3RiR;r为-CR产C-CR;r时为氢原子，或者当-(:31^112画为-C三C-CRiR;r时&与R2和R5—起形成环状基团的一部分； When -C3RiR; r is -CR producing C-CR; when r is a hydrogen atom, or when - (: 31 ^ 112 paintings is -C three C-CRiR; when r & and R2 and R5- together form a cyclic group part;

R3为选自环状基团I 、 II和m(如上所定义)的环状基团； R3 is selected from cyclic groups I, II and m (as defined above) cyclic groups;

每个R4广R4p为任选地取代的烷基、氢原子、氧原子或羟基，其中 Each R4 is widely R4p is an optionally substituted alkyl group, a hydrogen atom, an oxygen atom or a hydroxyl group, wherein

如果R4为氧原子，则相邻的碳原子具有两个R4基团，优选R吣R4b、 If R4 is an oxygen atom, with the two adjacent carbon atoms R4 groups, preferably R Qin R4b,

R4d、 R4e、 R»f、 R4h、 R«、 R4j、 R*k、 R4m、 Rtn、 R40为氛原子且R4c、 R4d, R4e, R »f, R4h, R«, R4j, R * k, R4m, Rtn, R40 for the atmosphere atom and R4c,

R4g、 R41、 R4p为曱基，或者-CR4a-CR4b-为-CHrCO-基团； R4g, R41, R4p as Yue group, or -CR4a-CR4b- to -CHrCO- group;

Rs为环状基团的一部分，其中所述环状基团可以与R3相同或不同， 并且当-C3lUR2-为-CR尸C-CR2-时所述环状基团的其余部分由R2和其所连接的碳提供、或者当-C3RiR2-为-CEC-CI^R2-时由Ri和R2及其所连接的碳原子提供，或者其药物上可接受的衍生物或盐。 Rs as part of a cyclic group, wherein said cyclic group R3 may be the same or different, and when -C3lUR2- when -CR corpse C-CR2- to the rest of the cyclic group represented by R2 and its provide carbon connected, or when -C3RiR2- is -CEC-CI ^ R2- when provided by a carbon atom and Ri and R2 are attached, or a pharmaceutically acceptable derivative or salt thereof.

特别优选地，R3为环状基团I或III且Rs(与R2或者和R2 —起)为环状基团I或II，优选I且优选-C3R!R2-为-C^C-CI^R2-。 Particularly preferably, R3 is cyclic group I or III and Rs (with or R2 and R2 - starting) cyclic group I or II, preferably I and preferably -C3R R2- is -C ^ C-CI ^! R2-.

在特别优选的方面中，类胡萝卜素为下式： In a particularly preferred aspect, the carotenoid to the following formula:

R3 一CR4a - CR4b - CR4e - CR4a—CR4a—CR"—CR4s匿CR化-CR" - CR4j - CR4k - CR4l — CR4m -CR4n-CR4。 R3 a CR4a - CR4b - CR4e - CR4a-CR4a-CR "-CR4s of hiding CR -CR" - CR4j - CR4k - CR4l - CR4m -CR4n-CR4. -CR4p國CsC-R(:; 其中 -CR4p Country CsC-R (:; wherein

可以相同或不同的R3和R6分别为选自环状基团I和III(如上所定 May be the same or different R3 and R6 are selected from cyclic groups I and III (set out above

义)的环状基团； Yi) is a cyclic group;

每个R4a〜R4p为任选地取代的烷基、氢原子、氧原子或幾基，其中 Each R4a~R4p is an optionally substituted alkyl group, a hydrogen atom, an oxygen atom, or several groups, wherein

如果R4为氧原子，则相邻的碳原子具有两个R4基团，优选R&、 R4b、 If R4 is an oxygen atom, with the two adjacent carbon atoms R4 groups, preferably R &, R4b,

R4d、 ^4e、 R4f、 R4h、 R4i、 &j 、 R4k、 R4m、 R4n、 R40为氛原子且R4c、 R4d, ^ 4e, R4f, R4h, R4i, & j, R4k, R4m, R4n, R40 for the atmosphere atom and R4c,

R4g、 R4p为甲基基团，或者其药物上可接受的衍生物或盐。 R4g, R4p as a methyl group, or a pharmaceutically acceptable derivative or salt thereof.

优选R6为环状基团I。 Preferably R6 is a cyclic group I. （当R3和R6为环状基团I时，所述化合物为硅藻黄素，当R3为环状基团III且R6为环状基团I时，所述化合物为硅甲 (When R3 and R6 is a cyclic group I, the compound is a diatom Flavin, when R3 is a cyclic group III and R6 is a cyclic group I, the compound is silicon A

藻黄素。 Algae flavin. ） )

将在下文中详细描述的药物上可接受的衍生物包括降解产物例如硅甲 The pharmaceutically described in detail below acceptable derivatives include methyl degradation products, such as silicon

藻色素（diadinochrome),其中相对于上式，R3-CR4a-CR4b-为稠合杂环基团，其中环状基团III的环氧基团的氧与包含共轭双键的烷基链形成键，以形成含有氧原子、来自烷基链的CR4a-CR4b和来自环状基团III 的两个碳原子的5元杂环基团。 Algal pigment (diadinochrome), which with respect to the above formula, R3-CR4a-CR4b- fused heterocyclic group, wherein the oxygen cyclic group III of the epoxy group containing an alkyl chain of conjugated double bonds formed bond to form containing an oxygen atom, an alkyl chain from CR4a-CR4b from cyclic groups III and two carbon atoms of 5-membered heterocyclic group.

在可替代的优选方面中，类胡萝卜素为下式： In an alternative preferred aspect, carotenoids by the following formula:

R3 - CR4a - CR4b - CR4C — CR4a - CR4e - CR4f — CR43 — CR4h—CR4i - CR" — CR4k - CR41 — CR4m 一CR4n - CR4o - CR4p - CH-C=R7; R3 - CR4a - CR4b - CR4C - CR4a - CR4e - CR4f - CR43 - CR4h-CR4i - CR "- CR4k - CR41 - CR4m a CR4n - CR4o - CR4p - CH-C = R7;

其中 Among them

可以相同或不同的r3和r7分别为选自环状基团ii和ni(如上所定 R3 may be the same or different and are selected from cyclic r7 groups ii and ni (set out above

义)的环状基团； Yi) is a cyclic group;

誦CR4a-CR4b國为CH2-CO画基团； Chant CR4a-CR4b States CH2-CO painting group;

每个R4c〜R4p为任选地取代的烷基、氢原子、氧原子或羟基，其中如果R4为氧原子，则相邻的碳原子具有两个R4基团，优选R4d、 R^、 Each R4c~R4p is an optionally substituted alkyl group, a hydrogen atom, an oxygen atom or a hydroxyl group, wherein if R4 is an oxygen atom, the adjacent carbon atoms having two R4 groups, preferably R4d, R ^,

R4f、 R<4h、 R4i、 R"、 Rtk、 R4m、 Rtn、 R40为氛原子且R4c、 R《g、 议41、 R4f, R <4h, R4i, R ", Rtk, R4m, Rtn, R40 for the atmosphere atom and R4c, R" g, 41 meeting,

R4p为甲基基团，或者其药物上可接受的衍生物或盐。 R4p as a methyl group, or a pharmaceutically acceptable derivative or salt thereof.

优选R3为环状基团in，优选R7为环状基团n。 R3 is preferably a cyclic group in, preferably R7 is a cyclic group n.

"药物上可接受的"或"生理可接受的，，意思是该组分必须与在组合物中的其它组分相容且对于接受者是生理可接受的。 "Pharmaceutically acceptable" or "physiologically acceptable ,, means that the components must be compatible with the other ingredients in the composition and are physiologically acceptable to the recipient.

药物上可接受的衍生物(其具有与上述化合物相同或相似的功能特性) 包括全反式到顺式-反式混合物到全顺式的异构体并包括光学异构体(例 Pharmaceutically acceptable derivatives (which has the same or similar compounds above features) including the all-trans to cis - trans mixture of cis isomer to and including optical isomers (Example

如，对于珪甲藻黄素为3S， 5S， 6R， 3'R和3S， 5R， 6S， 3'R)。 For example, for Gui peridinin as 3S, 5S, 6R, 3'R and 3S, 5R, 6S, 3'R). 衍生物还包括通过例如烃主链的修饰，例如通过用一个或多个烷基取代，任一个或者两个环状基团（例如如上所述)的修饰而被修饰的分子，前提是这些修饰不改变在此所述的化合物的功能特性。 Derivatives also include for example, by modification of the hydrocarbon backbone, e.g., by substitution with one or more alkyl groups, either one or two cyclic groups (e.g. as described above) of the modified molecule to be modified, provided that these modifications do not change the functional properties of the compounds described herein. 例如，衍生物扩展到酯， 例如可以用脂肪酸酯化类胡萝卜素。 For example, ester derivatives extended to, for example, carotenoids esterified with fatty acids.

衍生物还扩展到可以天然存在的衍生物，例如开环、脱和降类胡萝卜素衍生物。 Derivatives can also be extended to derivatives of naturally occurring, e.g., ring opening, and drop off the carotenoid derivative. 开环类胡萝卜素(seco-carotenoid)是指经历了氧化分裂而没损失任何碳原子的类胡萝卜素衍生物。 Open loop carotenoids (seco-carotenoid) refers to undergo oxidative cleavage of carotenoids and did not lose any derivative carbon atoms. 脱类胡萝卜素(apo-carotenoid) 为在氧化分裂过程中碳骨架变短的衍生物，降类胡萝卜素 Off carotenoids (apo-carotenoid) is in the process of oxidation of the carbon skeleton division shortened derivative drop carotenoids

(nor-carotenoid)为通过除了碳碳键断裂之外的方法除去碳原子的衍生物。 (Nor-carotenoid) by the addition of carbon-carbon bond cleavage of carbon atoms removed derivative. 因此，衍生物扩展到缩短了的类胡萝卜素，例如其中从异戊二烯聚合物链除去一个或多个异戊二烯单元。 Therefore, to shorten the extended derivatives carotenoids, e.g., wherein the removal of one or more of isoprene units from isoprene polymer chain.

衍生物还包括环氧衍生物和它们的5， 8环氧异构体。 Derivatives also include ethylene derivatives and their 5, 8 epoxy isomers. 还包括降解产物，例如其中墨角藻黄素的羰基与例如硼氢化钠在乙醇中反应。 Also include degradation products, such as fucoxanthin which a carbonyl group, such as sodium borohydride in ethanol. 如上所述，化合物产品硅甲藻色素为硅甲藻黄素的典型的降解产物。 As noted above, a typical product of silicon compound degradation products dinoflagellate pigment peridinin of silicon. 还包括例如在之前所述的在氯仿中用氯化氢处理上述化合物之后产生的脱水衍生物。 Further comprising dehydrating derivatives e.g. in chloroform before and after said treatment with hydrogen chloride generated above compounds.

为了它们在化妆品和药物的应用，还可产生衍生物以改变本发明的化合物，例如通过加入乾向基团或官能团，例如以改善亲油性、帮助细胞转运、溶解度和/或稳定性。 In order to use them in cosmetics and drugs can also produce derivative compounds of the present invention to change, for example by adding dried to a group or a functional group, such as to improve lipophilic help cellular transport, solubility and / or stability. 因此，可以将低聚糖、脂肪酸、脂肪醇、 氨基酸、肽或蛋白质缀合到上述化合物上。 Therefore, the oligosaccharides, fatty acids, fatty alcohols, amino acids, peptides or proteins conjugated to said compound. 衍生物可以为"前药"的形式， 使得施用时可以通过分裂来除去附加的组分，例如可以通过由酯化作用附加的取代基的分裂，所述由酯化作用附加的取代基通过酯酶的作用除去。 May be removed by cleavage additional components may be in the form of a derivative "prodrug", so when administered, for example, by the esterification additional substituent by the esterification additional substituents split, the group via an ester The role of the enzyme is removed.

可以测试保持功能活性的衍生物，以通过在此描述的测试确定它们是否保持所希望的特性，例如测定光防护特性。 You can maintain the functional activity of the test derivative, by the test described herein to determine whether they maintain the desired characteristics, e.g., light-shielding properties were measured.

用于施用的活性组分可以被适当地改进，以用于药物组合物中。 The active ingredient for administration may be appropriately modified to be used in pharmaceutical compositions. 例如，根据本发明所用的化合物可以通过使用上述衍生物稳定，而免于降解。 For example, by using the above-described derivatives stable against degradation while the compound according to the present invention is used.

也可以例如通过使用适当的添加剂如盐或非电解质、乙酸盐、SDS、 EDTA、柠檬酸盐或乙酸盐緩冲液、甘露醇、甘氨酸、HSA或聚山梨醇酯，在组合物中稳定活性组分。 It may be, for example, such as a salt or electrolytes, acetate, SDS, EDTA, citrate or acetate buffers, mannitol, glycine, HSA or polysorbate, stabilized by the use of suitable additives in the composition active ingredient.

药物上可接受的盐优选为生理可接受的有机或无机酸的酸加成盐。 Pharmaceutically acceptable salts are preferably physiologically acceptable acid addition salts of organic or inorganic acids. 合适的酸包括例如盐酸、氢溴酸、硫酸、磷酸、乙酸、乳酸、杵檬酸、 酒石酸、丁二酸、马来酸、富马酸和抗坏血酸。 Suitable acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, citric acid pestle, tartaric acid, succinic acid, maleic acid, fumaric acid, and ascorbic acid. 也可以通过例如沉淀方便地得到憎水盐。 It can be easily obtained by hydrophobic salts such as precipitation. 合适的盐包括例如乙酸盐、溴化物的盐、氯化物的盐、 柠檬酸盐、盐酸盐、马来酸盐、甲磺酸盐、硝酸盐、磷酸盐、硫酸盐、 酒石酸盐、油酸盐、硬脂酸盐、曱苯磺酸盐、钙盐、镁盐、钾盐和钠盐。 Suitable salts include for example acetate, bromide salts, chloride, citrate, hydrochloride, maleate, methanesulfonate, nitrate, phosphate, sulfate, tartrate, oil acid, stearate, Yue besylate, calcium, magnesium, potassium and sodium salts. 盐形成的方法在本领域是常规的。 A salt formation are conventional in the art.

优选地，用于组合物的和用于本发明用途的化合物得自或源于天然 Preferably, the compound used in the composition for the use of the invention obtained or derived from natural

存在的源。 Existing source. 但是，它们可以全部或部分合成地生成(例如由市售的类胡 However, they may be wholly or partially synthetically generated (e.g., by a commercially available type Hu

萝卜素如p-胡萝卜素、叶黄素、黄体素或zeaxanthin),或者提纯后衍生。 Carotenoids such as p- carotene, lutein, lutein or zeaxanthin), or after purification derived. 优选地，该化合物由天然源分离得到，优选大藻类或微观藻类类， 特别是属于浮游植物类硅藻类、沟鞭藻类、定鞭金藻类、棵藻类和金藻类的微观藻类类，尤其优选来自硅藻类Phaeodactulym tricornutum或Procentrum minimum或者微观藻类类小三毛金藻。 Preferably, the compound derived from natural source separation, preferably large algae or microscopic algae class, especially those belonging to the class of phytoplankton diatoms, dinoflagellates, will whip gold algae, trees, algae and micro-algae class gold algae, particularly preferably from diatoms Phaeodactulym tricornutum or Procentrum minimum or microscopic algae class small San Mao golden algae.

墨角藻黄素也可以从各种其它源中分离，例如任何海藻(界：原生生物，门：褐藻门)如包括上述的墨角藻(Fucus vesiculosus )、Fucos serratus 和极北海带(Laminaria Hyperborea)。 Fucoxanthin can also be isolated from a variety of other sources, such as any algae (community: protists, doors: Phaeophyta) as including the aforementioned Fucus (Fucus vesiculosus), Fucos serratus and hyperborea (Laminaria Hyperborea ). 其它源包括：Undaria pinnitifida、 马尾藻(Sargassum muticum)、 巨藻(Macrocystis pyrifera)、 Macrocystis angustifolia、 Padina boryana、 Ecklonia maxima、 Laminaria pallida、 Ecklonia biruncinata 、 Pelagophycus porra 、 Turbinaria ornata 、 Bifurcaria brassicaeformis和Splachnidium rugosum。 Other sources include: Undaria pinnitifida, Sargassum (Sargassum muticum), kelp (Macrocystis pyrifera), Macrocystis angustifolia, Padina boryana, Ecklonia maxima, Laminaria pallida, Ecklonia biruncinata, Pelagophycus porra, Turbinaria ornata, Bifurcaria brassicaeformis and Splachnidium rugosum.

本发明的化合物可从天然源中分离出来或者从已被改性的天然源中分离出来，以制造用于本发明的类胡萝卜素，例如通过转化微生物有机体以制造所需的合成酶，并从这些有机体中分离出化合物。 Compounds of the invention may be isolated from natural sources or it has been isolated from natural sources modified in order to manufacture carotenoid present invention, e.g., organisms to produce the desired synthase by transformation of microorganisms, and from These organisms were isolated compound.

这些化合物通过现有技术方便地分离，例如通过拆分和色谱法(见Haugan & Liaaen-Jensen， 1989, Phytochemistry, 28 (10),第2797-2798 页）或者HPLC(Zapata等.，2000， MEPS， 195,朵29-45页）。 These compounds are readily separated by techniques such as chromatography and by resolution (see Haugan & Liaaen-Jensen, 1989, Phytochemistry, 28 (10), p. 2797-2798) or HPLC (Zapata et., 2000, MEPS 195, flowers 29-45 pages). Britten法也可以用于分离例如墨角藻黄素（分别见Britton等和Schiedt & Liaaen-Jensen, 1995, 在"Carotenoids, Volume 1A: Isolation and Analysis"中，Eds . Britton等，Birkhauser Verlag, Basel,第13-16页和第81-108页）。 Britten method can also be used to isolate such as fucoxanthin (see Britton, etc. respectively and Schiedt & Liaaen-Jensen, 1995, in. "Carotenoids, Volume 1A: Isolation and Analysis" in, Eds Britton, etc., Birkhauser Verlag, Basel, p. 13-16 and p. 81-108). 所述化合物还可以通过已用于类胡萝卜素分离的超临界C02 萃取来分离（Mendes等，2003， Inorganica Chimica Acta, Vol. 356，第328-334页;Valderrama等，2003， J. Chem. Eng. Data, 48,第827-830 页)。 The compounds can also be separated by supercritical C02 extraction has been used to separate the carotenoid (Mendes et, 2003, Inorganica Chimica Acta, Vol 356, the first 328-334 pages;. Valderrama, etc., 2003, J. Chem Eng. . Data, 48, p. 827-830).

用于本发明组合物的化合物还可以根据实施例中所述的方案分离。 Compounds used in the compositions of the present invention may also be separated according to the scheme described in the Examples. 这些方法和这些方法的产品形成本发明的另外的方面。 These methods and products of these methods form a further aspect of the present invention. 因此，在另一个方面中，本发明提供从藻类中提纯类胡萝卜素的方法，包括如下步骤： Thus, in another aspect, the present invention provides a purified carotenoids from algae, comprising the steps of:

(i)使藻类与水混合，将pH值调到8〜12(优选pH值为8~10，例如pH值为8.3); (I) algae mixed with water, the pH adjusted to 8~12 (preferably a pH of 8 to 10, such as pH value of 8.3);

(ii) 加入醇，优选乙醇(或可替代的甲醇），使最终水与醇的比为0.2~ 1.5: lO(优选0.3 ~ 1.0: 1，例如0.3: 1); (Ii) adding an alcohol, preferably ethanol (or alternatively methanol), to give a final ratio of water to alcohol is 0.2 ~ 1.5: lO (preferably 0.3 to 1.0: 1, e.g., 0.3: 1);

(iii) 以0.75 ~ 1.5: lO(优选1 ~ 1.4: 1，例如1.3: l)的水-醇与有机溶剂比，用液体有机溶剂（有机相)萃取所述醇-水混合物(水相），所述液 (Iii) to 0.75 ~ 1.5: lO (preferably 1 to 1.4: 1, e.g., 1.3: l) of water - alcohol with an organic solvent ratio, with a liquid organic solvent (organic phase) extraction of the alcohol - water mixture (aqueous phase) the liquid

体有机溶剂优选为庚烷(或可替代的己烷)； Organic solvent is preferably heptane (or alternatively in hexane);

(iv) 例如在低于10。 (Iv) e.g. below 10. C如S5。 C as S5. C、 0°C、 -5。 C, 0 ° C, -5. C、 -10。 C, -10. 。 . 或-20°。 Or -20 °. (如5~10。。） 下任选地冷却所述有机相超过5分钟，例如15~60分钟，或更长，例如12〜26小时，例如24小时；和 (E.g. 5 to 10 ..) optionally cooling down the organic phase over 5 minutes, for example 15 to 60 minutes, or longer, e.g. 12~26 hours, e.g., 24 hours; and

(v) 收集水相和/或有机相，并由此纯化类胡萝卜素。 (V) collecting the water phase and / or organic phase, and thus purified carotenoids.

在上述方法中，加入水、醇和有机溶剂的顺序不重要。 In the above method, water, alcohol and organic solvent is not critical sequence. 因此，醇和水可以先后加入，然后可以加入有机溶剂，或者可以混合醇和有机溶剂， 随后加入水。 Thus, alcohol and water can be added sequentially, may then be added to the organic solvent, alcohol or an organic solvent may be mixed, followed by addition of water.

优选地，所述方法用于分离硅甲藻黄素、硅藻黄素和/或墨角藻黄素， 其中硅甲藻黄素和硅藻黄素从有机相中分离，墨角藻黄素从水相中分离。 Preferably, the method for separating silicon peridinin, diatoms flavin and / or fucoxanthin, wherein the silicon dinoflagellates and diatoms flavin flavin separated from the organic phase, fucoxanthin from the aqueous phase separation. 步骤(iii)优选通过在环境温度例如15 ~ 25。 Step (iii) is preferably at ambient temperature, for example by 15 to 25. C如约20。 C such as about 20. C下混合30 ~ 90 分钟如l小时来实现。 C mixing 30 to 90 minutes as l hour to achieve. 一般方法的具体变化在实施例中描述。 Specific changes in the general procedure described in the Examples.

用于本方法的醇在室温下为液体并可溶于水但不溶于庚烷，且优选为乙醇或曱醇，尽管可以使用其它醇例如丙醇。 This method is used in an alcohol liquid at room temperature and is soluble in water but insoluble in heptane, and preferably ethanol or 曱 alcohol, although other alcohols such as propanol. 有机溶剂基本上不可与水互溶并优选在-20'C下为液体，例如庚烷、己烷或戊烷。 The organic solvent is substantially non-miscible with water and preferably at -20'C to a liquid, such as heptane, hexane or pentane.

如此分离的化合物优选基本上不含源于原料或源于在分离步骤中使用的物质的任何污染成分。 Preferred compounds thus separated from the raw or substantially free from substances used in the separation step any contaminating components. 特别优选地，所述化合物被提纯到纯度高于50%或60%例如大于70%、 80%或90%,优选高于95%或99%， 纯度以w/w(干重)计。 Particularly preferably, the compound is purified to a purity of greater than 50% or 60%, for example greater than 70%, 80% or 90%, preferably greater than 95% or 99%, with a purity w / w (dry weight) count. 这样的纯度级别对应于所需的具体化合物，但是包括其异构体和任选的其降解产物。 Such specific compound desired purity level corresponds to, but including its isomers and optionally its degradation product. 如果合适的话，可以使用具有较低 If appropriate, can be used with lower

纯度的浓缩制品，例如含有高于1%、 2%、 5%或10%的所需化合物， 如高于20%或30%。 Purity concentrated products, such as those containing more than 1%, 2%, 5% or 10% of the desired compound, such as more than 20% or 30%.

可以通过分析方便地评估纯度的级别，例如使用UV/可见分光光度法、HPLC分析法或质镨法。 You can easily assess the level of purity of the analysis, such as the use of UV / visible spectrophotometry, HPLC mass spectrometry or praseodymium law. 合成生成的或改性的化合物应该类似地不含污染成分。 Compound synthetically produced or modified should be similarly free of contaminants.

根据本发明所用的类胡萝卜素可以基于例如合成的碳骨架合成地 According to the present invention, carotenoids may be used, for example based on carbon skeleton synthesized synthetically

生成。 Generation. 该骨架可以使用在本领域已知的技术生成，例如Witting型反应、 Grignard和Nef反应、烯醇-醚缩合、Reformatsky反应、Robinson's Mannic碱合成、还原或氧化二聚反应和Wurtz反应（见例如Haugan, Dr. Ing. thesis, University of Trondheim， NTH， 1994,自155页和Mayer & Isler, 1971,在"Carotenoids"中，Ed. Isler， Birkh3user， Basel,第325 页)。 The skeleton can be used in the generation known in the art, for example Witting type reaction, Grignard reaction and Nef, alcohol - ether condensation, Reformatsky reaction, Robinson's Mannic base synthesis, reduction or oxidation reaction and the Wurtz dimerization reaction (see, for example Haugan , Dr. Ing. thesis, University of Trondheim, NTH, 1994, from 155 and Mayer & Isler, 1971, in "Carotenoids" in, Ed. Isler, Birkh3user, Basel, p. 325).

然后可以使用在本领域中已知的技术来修饰碳骨架，由此生成所需的类胡萝卜素。 You can then use the techniques known in the art to modify the carbon skeleton, thereby generating the desired carotenoids. 例如，可以如（Ito等，1994, Pure & Appl. Chem" 66 (5 )， 第939-946页)所述的合成墨角藻黄素，其中C10碳骨架部分与提供环状端基的分子缩合。在Haugan等，1994， supra,第165-205页中描述了硅藻黄素的合成。可以由硅藻黄素通过在硅藻黄素的5，-6'或5-6双键处引入环氧基团来制备硅甲藻黄素。可以使用在本领域中已知的技术如上所述地制造这些合成制备的类胡萝卜素的衍生物。 For example, as (Ito et, 1994, Pure & Appl. Chem "66 (5), the first 939-946 pages) of the synthetic fucoxanthin, which part of the carbon skeleton of the molecule C10 provides cyclic end groups condensation in Haugan, etc., 1994, supra, p. 165-205 describes the synthesis of flavin diatoms can be made by the diatoms diatom flavin flavin 5, 6 'or 5-6 double bond the introduction of epoxy group to prepare a silicone peridinin may be used in known in the art technology to produce carotenoid synthesis of these derivatives as described above.

所述类胡萝卜素化合物可以作为唯一的活性成分存在于所述组合物中，或者可以与其它成分尤其是其它活性成分组合，例如以增加可以提供的光保护范围和/或改变产品的物理或化学特性或使其吸引消费者。 The carotenoid compounds can be used as the sole active ingredient present in the composition, or may be with the other ingredients, especially other active ingredients, e.g., to increase light range can provide protection and / or physical or chemical change in the product Characteristics or make it attractive to consumers. 因此，例如一种或多种另外的遮光化合物可以包含在组合物中或者与所述组合物共施用。 Thus, for example, one or more additional light blocking compound may be included in the composition or co-administered with the composition. 可以使用化学或物理遮光剂，例如如上文所述的能够吸收/猝灭辐射尤其是太阳辐射、特别是光镨中的UVB和较短UVA 范围或近红外范围的遮光剂。 You can use chemical or physical sunscreens, such as described above is capable of absorbing / radiation, especially solar radiation quenching, especially in light praseodymium shorter UVA and UVB range or near infrared range of opacifiers. 可以使用的化合物包括UVB/UVA2滤光剂（其在2卯〜340nm范围内滤光)例如甲氧基肉桂酸辛酯、氧苯酮、水杨酸辛酯、胡莫柳酯、氰双苯丙烯酸辛酯、帕地马酯O、邻氨基苯甲酸薄荷酯和2-苯基苯并咪唑-5-磺酸。 Compounds may be used include UVB / UVA2 filter agent (which filter within 2 d ~340nm range) such as octyl methoxy, oxybenzone, octyl salicylate, homosalate, octocrylene Sheen ester, Pa Race ester O, menthyl anthranilate and 2-phenyl benzimidazole-5-sulfonic acid. UVA1滤光剂（在340 ~ 400nm范围内滤光)包括阿伏苯宗、氧化锌和二氧化钛。 UVA1 filter agent (within the range of 340 ~ 400nm filter) include avobenzone, zinc oxide and titanium dioxide. 但是，优选使用在自然界中发现的化合物，例如其它类胡萝卜素、（如在此所描述的）、霉胞菌素样氛基酸或scytonemin。 Preferably, however, compounds found in nature, for example other carotenoids, (as described herein), mildew-like atmosphere cytochalasin acid or scytonemin.

在此所描述的类胡萝卜素可以组合使用。 Carotenoids described herein can be used in combination. 因此，例如根据本发明优选的组合物可以包含两种或更多种如本文所描述的类胡萝卜素，例如选自硅甲藻黄素、硅藻黄素、硅甲藻色素和墨角藻黄素的两种或更多种化合物，尤其优选硅甲藻黄素和墨角藻黄素。 Thus, for example in accordance with the preferred compositions of the invention may contain two or more carotenoids, as described herein, for example, selected from silicon peridinin, flavin diatoms, dinoflagellates pigments and silicon Fucus yellow two or more compounds pigment, particularly preferred silicon peridinin and fucoxanthin.

本发明的组合物可以用于各种生物和非生物应用。 The compositions of the invention can be used in a variety of biological and non-biological applications. 因此，组合物可用于任意非生物物质，其中需要光防护(或着色)特性，例如在塑料、涂 Thus, the compositions can be used in any non-biological material, wherein the light-shielding required (or coloring) characteristic, for example in plastics, coating

料、蜡、（建筑物或车辆)的窗户、太阳能电池板、风挡、着色剂或清漆、 玻璃、隐形眼镜、合成透镜中，以避免对使用它们的产品或者被提供太阳光保护的生物实体的光损害或太阳光损害(例如褪色)。 Materials, waxes, (building or vehicle) windows, solar panels, windshield, colorants or varnish, glass, contact lenses, synthetic lens in order to avoid the use of their products or provide sun protection are biological entities light damage or sunlight damage (such as discoloration). 本发明的化合物可以应用到这些物质或浸到这些物质中。 The compounds of the invention may be applied to these substances or dipped in these substances.

因此，本发明还延伸到一种制备光防护或光保护产品的方法，包括将本发明的化合物或组合物应用到所述产品，或者用所述化合物或组合物浸渍所述产品。 Accordingly, the present invention also extends to a process for producing light-shielding or light protection products, comprising the compounds or compositions of the present invention is applied to the product, or use of the compound or composition of the product is impregnated. 本发明的化合物或组合物制备所述产品的用途也被认为是本发明的一个目的。 The preparation of a compound or composition of the products of the present invention is also considered an object of the present invention. 由此形成的光防护或光保护产品构成本发明的另一个方面。 Thereby forming a light-shielding or light protection products constitute another aspect of the present invention.

优选地，本发明的组合物为包含如上文所述的化合物的药物组合物和一种或多种如下文所述的药物上可接受的赋形剂和/或稀释剂。 Preferably, the composition of the present invention is a pharmaceutical composition comprising a compound as described above and as described below, one or more acceptable pharmaceutical excipients and / or diluents.

在此描述的化合物具有光防护、着色和抗氧化特性。 The compounds described herein have light protection, color and antioxidant properties.

因此在此描述的组合物可用于化妆品或医药应用。 Thus the compositions described herein can be used in cosmetic or pharmaceutical applications. 因此，在此描述的药物组合物可以为化妆品组合物、抗氧化组合物或光保护滤光剂或遮光剂。 Accordingly, the pharmaceutical compositions described herein may be a cosmetic composition, antioxidant compositions or light protective filter or opacifiers. 本发明还提供用作药物的该组合物。 The present invention also provides compositions as a medicament.

在此描述的化合物为引人注目的金黄色并因此可以用于利用该色彩的化妆品或将附加特性加到本发明的遮光剂。 Compound as described herein, and thus striking golden color can be used to exploit the additional features added to the cosmetic or sunscreen agents of the present invention. 因此，在此描述的遮光剂和/或化妆品制剂具有选自着色、遮光和抗氧化特性的两种或更多种特性。 Therefore, sunscreen and / or cosmetic formulations described herein have selected coloring, shading and antioxidant properties of two or more features. 作为对该作为着色剂的特性的替代或补充，所述化合物可以利用它们的抗氧化或光防护特性。 As this characteristic as a colorant Alternatively or additionally, the compounds may take advantage of their antioxidant or light-shielding properties.

因此，在另一个方面中，本发明提供作为化妆品、遮光剂(光保护滤光剂）或抗氧化剂的在此描述的组合物。 Thus, in another aspect, the present invention provides a cosmetic sunscreens (light protection filter agent) or antioxidant compositions described herein.

在此提及的"化妆品，，是指以非医学目的用在人或非人动物上的组合物。 In this reference to "cosmetic ,, refers to non-medical purposes is used in the human or non-human animal compositions.

在此使用的"遮光剂，，或"光保护滤光剂"或"光防护组合物"是指适于施用到个体的组合物，其对光辐射提供保护(即，作为吸收光或阳光 As used herein, "sunscreens ,, or" light protection filter agent "or" photoprotective composition "refers to a composition suitable for administration to an individual, which provides optical radiation protection (ie, as the absorption of light or sunlight

的化合物），特别是紫外线和可见光，优选波长为280 ~ 700nm，尤其优选至少350~500nm，例如370 ~ 500nm或400 ~ 500nm。 Compound), particularly ultraviolet and visible light, preferably having a wavelength of 280 ~ 700nm, and particularly preferably at least 350 ~ 500nm, such as 370 ~ 500nm or 400 ~ 500nm. 优选地，在所述組合物中的至少一种化合物能够在这些波长范围中实现保护。 Preferably, at least one compound in the composition to achieve protection in these wavelength ranges. 可以用各种技术评价保护，包括发展光诱发响应所用的时间或该响应的严重程 It can be used to protect a variety of technical evaluation, including the development of light-induced response time used or the severity of the response

度，例如红斑或灼伤，例如使用通常可用的测试来确定SPF的级别。 Degrees, such as erythema or burns, for example using commonly available test to determine the level of SPF. 当进行这样的测试时，优选该组合物实现的SPF至少为2，优选至少10、 20、 30或50。 When such a test, the composition is preferably implemented SPF of at least 2, preferably at least 10, 20, 30 or 50.

但是，为了方便地测试功效例如过滤不明显导致该响应的波长(例如，UVA，尤其是长波长UVA，即340〜400nm)的光，可以进4亍生物体外测试，例如通过包含所需化合物的滤光剂(用来模拟皮肤)过滤光，或确定消光系数，以测定这些化合物吸收辐射的能力。 However, for example, filtration easily test the efficacy of the response wavelength obvious cause (e.g., UVA, especially long wavelength UVA, i.e. 340~400nm) light can enter the right foot 4 vitro test, e.g., by including the desired compound filter agent (used to simulate the skin) filtered light, or the extinction coefficient is determined, to determine the ability of these compounds to absorb radiation. 在使用包含测试化合物的滤光剂的方法中，可以通过评价经过所述滤光剂的辐射(例如特定波长的）的级别、或通过例如在对辐射敏感并对该辐射表现出响应的细胞上评价经过含有或不含所述测试化合物的滤光剂的所述辐射的影响，来直接或间接地测定吸收功效。 Containing the test compound in the method of filtering agent, it can be evaluated through the filter agent by radiation (e.g., a particular wavelength) level, for example, or by the radiation of the radiation-sensitive and exhibits the response of the cells After evaluation of the impact filter containing the test agent or compound does not contain the radiation absorbing effect measured directly or indirectly.

优选地，在这些测试中，（例如，如实施例中所述的），所述化合物在给定波长处阻止超过40%、优选超过50%~60%的透射。 Preferably, in these tests, (e.g., as described in the embodiment), the compound at a given wavelength to prevent more than 40%, preferably more than 50% to 60% transmission. 用于本发明组合物的优选的化合物优选在400 ~ 500nm范围内表现出最大吸收， 例如在400 ~ 500nm范围内的给定波长处的吸收为在350nm处的吸收的1.5~2倍以上。 Preferred compounds are preferably used in the compositions of the present invention is in the range of 400 ~ 500nm exhibits maximum absorption, for example, within the range of 400 ~ 500nm to absorb at a given wavelength is at least 1.5 to 2 times the absorption at 350nm.

用于生物体外分析的合适的技术包括：将测试化合物施加给优选模拟皮肤的基质(例如，具有模拟的皮肤紋理的胶原基质或石英片），然后所述基质被反映全太阳辐射的辐射或优选较窄波长的辐射照射，例如使用氙弧来模拟太阳UV光语，例如290 ~ 400nm。 Suitable techniques for in vitro analysis comprising: a test compound is preferably applied to the skin of the analog substrate (e.g., having a simulated skin texture or quartz sheets of collagen matrix), then the whole matrix is ​​reflected solar radiation, radiation or preferably narrow wavelength radiation, e.g., using a xenon arc solar simulator to UV light language, e.g., 290 ~ 400nm.

例如使用Labsphere UV-1000S UV透射分析仪(Labsphere Inc., North Sutton， NH)可以测定测试化合物的UV吸光度。 For example Labsphere UV-1000S UV transmission analyzer (Labsphere Inc., North Sutton, NH) can be determined UV absorbance of the test compound. 通过例如临界波长测定法（由Diffey等，2000， J. Am. Acad. Dermatol" 43 (6),第1024-1035页所述)评价的测试化合物吸收UVA的能力表明所述测试化合物在光镨的UV范围内的吸收功效。优选地，所述临界波长大于360nm，尤其优选大于370nm或380nm，尤其是与上述的SPF值结合。 For example, by critical wavelength assay (manufactured by Diffey et, 2000, J. Am. Acad. Dermatol "43 (6), said first p 1024-1035) evaluated the ability of the test compound indicates that the UVA absorption of the test compound in the light-Pr UV absorption effect within the range. Preferably, the critical wavelength greater than 360nm, and particularly preferably greater than 370nm or 380nm, in particular in combination with the above-described SPF value.

因此，本发明提供处理或预防对人或非人动物的辐射影响的方法， 其中将如上文所述的药物化合物或组合物施用到所述动物上。 Accordingly, the present invention provides a treatment or prevention of radiation effects on human or non-human animal, wherein the pharmaceutical compound as described above or a composition is administered to the animal on. 另外，本发明提供在此所述的药物化合物或组合物在制备用于处理或预防对人或非人动物体的辐射影响的药物中的用途。 In addition, the present invention provides pharmaceutical compounds described herein or compositions in preparation of a medicament for the treatment or prevention of radiation effects on human or non-human animal body in.

在优选方面中，本发明提供处理或预防对人的太阳辐射影响的方法，其中将如上文所述的药物化合物或组合物局部地施用到所述人的皮肤或头发上。 In a preferred aspect, the present invention provides a method of treatment or prevention of human effects of solar radiation, which as described above, a pharmaceutical compound or composition is applied topically to the human skin or hair. 该方法用来保护皮肤或头发免于所述太阳辐射的有害作用。 This method is used to protect the skin or hair from the deleterious effects of solar radiation.

在此所用的"辐射"是指来自一种或多种自然或合成光源的直接或 As used herein, "radiation" means from one or more natural or synthetic sources of direct or

间接的辐射，特别是来自太阳的，即太阳辐射。 Indirect radiation, especially from the sun, namely solar radiation. 优选地，所述辐射为280 ~ 700nm的光，尤其优选至少350 ~ 500nm，例如400 ~ 480nm或400 ~ 500nm。 Preferably, the radiation is 280 ~ 700nm light, particularly preferably at least 350 ~ 500nm, such as 400 ~ 480nm or 400 ~ 500nm. 所述辐射的"作用"可以为损害作用，包括皮肤的灼伤、红斑、 过早老化和皱紋(光老化)、前恶性损害（阳光角化病)的发展和各种恶性肺瘤或其它例如化妆品原因的不希望的作用，如黑色素沉积。 Said radiation "effect" can be damaging effects, including skin burns, erythema, premature aging and wrinkles (photoaging), before malignant lesions (sun keratosis) the development and malignant lung tumors or other such as cosmetics cause of undesirable effects, such as melanin deposition.

在此使用的"处理，，是指相对于存在于所述个体的身体的未受辐射的不同部位的症状或作用或者未受辐射的相应个体，将所述辐射的一种或多种症状或作用例如灼伤或色素沉积的出现或程度降低、减轻或消除，优选降低、减轻或消除到正常的非辐射水平。"预防"是指完全地防止或降低或减轻所述症状或作用开始的程度或时间（例如延迟)。 "Treatment as used herein refers ,, symptoms or effects relative to unirradiated present in different parts of the body of the individual or the individual respective unirradiated, one or more symptoms of the radiation or effects such as burns or reduce the presence or extent of pigmentation, reduce or eliminate, preferably reduced, to reduce or eliminate non-normal radiation levels. "Prevention" refers to preventing or reducing or completely reduce the extent of the symptoms or onset of action or time (eg delay).

根据本发明的处理或预防方法可以有利地与在处理或预防辐射影响中有效的一种或多种活性成分的施用结合。 It can be advantageously combined with the administration of an effective treatment or prevention of the effects of radiation in one or more active ingredients according to the treatment or prevention method according to the invention. 优选地，所述附加活性成分包括遮光剂（如在此描述的和本领域已知的）、抗氧化剂、维生素和通常在本领域的遮光剂和化妆品配方中使用的其它成分。 Preferably, the additional active ingredients include sunscreen agents (as described herein and known in the art), antioxidants, vitamins and other ingredients normally used in this field of sunscreens and cosmetic formulations.

因此，本发明的药物组合物还可以含有一种或多种所述活性成分。 Accordingly, the pharmaceutical compositions of the present invention may also contain one or more of the active ingredient.

根据本发明的又一方面，我们提供含有在此定义的一种或多种化合物和一种或多种附加的活性成分的作为组合制剂的产品，以同时、单独或连续地用于人或动物的治疗。 According to a further aspect of the present invention, we provide this as a combined preparation containing one or more compounds as defined and one or more additional active ingredients of products, simultaneously, separately or sequentially to human or animal treatment.

用一种或多种生理可接受的载体、赋形剂和/或稀释剂以常规方式配制。 With one or more physiologically acceptable carriers, excipients and / or diluents formulated in conventional manner. 如果合适的话，根据本发明的组合物是已灭菌的，例如如果存在栽体或赋形剂的话，在载体或赋形剂加入之前或之后通过Y-射线辐照、高压灭菌或热灭菌，以提供无菌的制剂。 If appropriate, the composition according to the invention is sterilized, for example, if there is, then plant body or vehicle, carrier or excipient is added before or after the Y- ray irradiation, autoclaving or heat off bacteria, to provide sterile formulations.

因此，所述活性成分可以任选地与其它活性物质一起作为组合制剂与一种或多种常规载体、稀释剂和/或赋形剂结合，以生成常规药物制 Thus, the active ingredient may optionally together with other active substances as a combined preparation with one or more conventional carriers, diluents and / or excipients, to produce conventional pharmaceutical preparations

剂例如片剂、丸剂、粉剂、锭剂、囊袋(sachet)、胶囊、酏剂、混悬剂(作为注射液或输注液)、乳剂、溶液、糖浆、气雾剂(作为固体或在液体介质中）、骨剂、软和硬凝胶胶囊、栓剂、无菌注射液、无菌封装粉末等。 Agents such as tablets, pills, powders, lozenges, capsular bag (sachet), capsules, elixirs, suspensions (as injection or infusion solutions), emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), bone agent, soft and hard gelatin capsules, suppositories, sterile injectable solutions, sterile packaged powders and the like. 可生物降解的聚合物(例如聚酯、聚酸酐、聚乳酸或聚乙醇酸)可以用于固体植入物。 Biodegradable polymers (e.g., polyesters, polyanhydrides, polylactic acid or polyglycolic acid) can be used in a solid implant. 所述组合物可以通过使用冷冻干燥、过冷或帕尔玛酶(Permazyme)来稳定。 The composition can be dried by using a freeze, or cold Parma enzyme (Permazyme) to stabilize.

合适的赋形剂、载体或稀释剂为乳糖、葡萄糖、蔗糖、山梨醇、甘露醇、淀粉、阿拉伯树胶、磷酸钙、碳酸钙、乳糖钙(calcium lactose)、 玉米淀粉、藻酸盐、黄蓍胶、明胶、硅酸钙、微晶纤维素、聚乙烯基吡咯烷酮、纤维素、水糖浆、水、水/乙醇、水/乙二醇、水/聚乙二醇、丙二醇、甲基纤维素、羟基苯甲酸甲酯、羟基苯曱酸丙酯、滑石、硬脂酸镁、矿物油或脂肪物质如硬脂或其合适的混合物。 Suitable excipients, carriers or diluents are lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, calcium carbonate, lactose, calcium (calcium lactose), corn starch, alginates, tragacanth glue, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water syrup, water, water / ethanol, water / glycol, water / polyethylene glycol, propylene glycol, methylcellulose, methyl paraben, propyl gallate hydroxyphenyl 曱, talc, magnesium stearate, mineral oil or fatty substances such as stearic or suitable mixtures thereof. 还可以使用用于获得持续释放的制剂的试剂，例如羧酸聚亚曱基、羧曱基纤维素、醋酸邻苯二甲酸纤维素或聚乙酸乙烯酯。 Reagents may also be used for obtaining sustained release formulations, such as carboxylic acid polyalkylene 曱 group, carboxy group 曱 cellulose, cellulose acetate phthalate or polyvinyl acetate.

组合物可以另外包括润滑剂、润湿剂、乳化剂、增粘剂、造粒剂、 崩解剂、粘合剂、渗透活性剂（osmotic active agent)、悬浮剂、防腐剂、 甜味剂、调味剂、吸收增强剂（例如表面渗透剂，或者用于鼻递送的， 例如胆汁盐、卵磷脂、表面活性剂、脂肪酸、螯合剂）、褐色上色剂、 有机溶剂、抗氧化剂、稳定剂、润肤剂、硅树脂、a-羟基酸、緩和剂、 防沫剂、保湿剂、维生素、香料、离子或非离子增稠剂、表面活性剂、 填料、离子或非离子增稠剂、螯合剂、聚合物、推进剂、碱化剂或酸化剂、乳浊剂、着色剂和脂肪族化合物等。 The compositions may additionally include lubricating agents, wetting agents, emulsifiers, tackifiers, granulating agents, disintegrating agents, binders, osmotic agents (osmotic active agent), suspending agents, preservatives, sweeteners, flavoring agents, absorption enhancers (e.g. surface penetrant, or for nasal delivery, for example bile salts, lecithins, surfactants, fatty acids, chelators), brown toner, an organic solvent, an antioxidant, a stabilizer, emollients, silicones, a- hydroxy acid, demulcent, anti-foaming agents, moisturizing agents, vitamins, fragrances, ionic or non-ionic thickeners, surfactants, filler, ionic or nonionic thickeners, chelating agents , polymers, propellants, basifying agents or acidifying agents, opacifying agents, coloring agents and aliphatic compounds.

可以配制本发明的组合物，以便在通过使用本领域众所周知的技术施用给人体之后，提供活性成分的快速、持续或延迟释放。 The compositions of the invention may be formulated so that after using the techniques known in the art of administering to the human body, to provide quick, sustained or delayed release of the active ingredient.

所述组合物可以为任何合适的剂型以递送或乾向特定细胞或组织， 例如作为乳剂或在脂质体、嚢泡(niosome)、微球、纳米粒子等中，通过它们可以吸收、吸附、引入或结合活性成分。 The composition may be in order to deliver to a particular cell or tissue or dry, such as an emulsion or in liposomes, bubble Nang (niosome), microspheres, nanoparticles, etc., they can be absorbed by adsorption to any suitable dosage form, or a combination of the active ingredient is introduced. 这可以有效地将产品转化为不溶形式。 This product can effectively be converted to insoluble form. 这些粒子形式可以同时克服稳定性(例如降解)和递送问题。 These particles form can overcome stability (such as degradation) and delivery problems.

这些粒子可以携带用来改善循环时间的合适的表面分子(例如，浆液成分、表面活性剂、polyoxamine卯8、 PEG等）、或用于位点特异性耙向部分如特定结合细胞受体(cell borne receptor)的配体。 These particles may carry appropriate surface molecules to improve circulation time (for example, serum components, surfactants, polyoxamine d 8, PEG, etc.), or rake for site-specific binding to a portion such as a specific cell receptor (cell borne receptor) ligands. 用于药物递送 For drug delivery

和耙向的合适技术在本领域是众所周知的并在W099/62315中描述。 And suitable techniques to rake in the art are well known and are described in W099 / 62315 in.

优选使用溶液、混悬剂、凝胶剂和乳剂，例如可以在水、气、水基液体、油、凝胶、乳液、水包油或油包水乳液、分散体或其混合物中载带活性成分。 Preferably use solutions, suspensions, gels and emulsions, for example, water, air, water-based liquids, oils, gels, emulsions, water-in-oil or oil-in-water emulsion, dispersion or a mixture thereof with an active carrier ingredients.

组合物可以用于局部(例如皮肤或头发)、口服或肠胃外施用，例如通过注射。 The composition may be for topical (e.g. skin or hair), oral or parenteral administration, e.g., by injection. 但是，优选局部组合物和施用，并包括凝胶剂、霜剂、骨剂、 喷雾剂、洗剂、油骨、棒、皂、粉末剂、膜、气溶胶、滴、泡沫、溶液、 乳剂、混悬剂、分散体如非离子泡分散体(non-ionic vesicle dispersion)、 乳状液和本领域的任意其它常规药物形式。 Preferably, however, topical compositions and administration, and include gels, creams, bone, sprays, lotions, oils bones, rods, soaps, powders, films, aerosols, drops, foams, solutions, emulsions, suspensions, dispersions such as nonionic bubble dispersion (non-ionic vesicle dispersion), emulsions and any other conventional in the art form of the drug.

骨剂、凝胶剂和霜剂可以例如用水基或油基外加合适的增稠剂和/ 或胶凝化剂配制。 Bone, gels and creams may, for example water-based or oil-based addition of suitable thickening and / or gelling agent formulation. 洗剂可以用用水基或油基配制并通常还包含一种或多种乳化剂、分散剂、悬浮剂、增稠剂或着色剂。 Lotions may be formulated with water-based or oil-based, and generally also contain one or more emulsifying agents, dispersing agents, suspending agents, thickening agents, or coloring agents. 粉末可以借助任何合适的粉末基形成。 Powder can be formed by any suitable powder base. 滴和溶液可以用水基或非水基配制，还包含一种或多种分散剂、增溶剂或悬浮剂。 Dropwise and the solution can be formulated with water-based or non-aqueous base also comprising one or more dispersing agents, solubilizing agents or suspending agents. 气溶胶喷雾通过使用合适的推进剂方便地由加压包装递送。 Conveniently delivered in an aerosol spray from a pressurized package by use of a suitable propellant.

作为替代方案，所述组合物可以以适于口服或肠胃外施用的形式提供。 Alternatively, the composition may be adapted for oral or parenteral administration form. 因此，可替代的药物形式包括含有所述活性成分和任选的一种或多种惰性常规栽体和/或稀释剂的素片（plain tablet)或包衣片、胶嚢、混悬剂和溶液，所述惰性常规载体和/或稀释剂如玉米淀粉、乳糖、蔗糖、 微晶纤维素、硬脂酸镁、聚乙烯吡咯烷酮、柠檬酸、酒石酸、水、水/ 乙醇、水/乙二醇、水/山梨醇、水/聚乙二醇、丙二醇、硬脂醇、羧甲基纤维素或脂肪物质如硬脂或其合适的混合物。 Therefore, alternative pharmaceutical forms include an active ingredient and optionally one or more inert conventional containing the plant and / or diluent tablets (plain tablet) or coated tablets, gum Nang, suspensions and solution, the inert conventional carriers and / or diluents such as corn starch, lactose, sucrose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycol , water / sorbitol, water / polyethylene glycol, propylene glycol, stearyl alcohol, carboxymethylcellulose or fatty substances such as stearin or suitable mixtures thereof.

活性成分在本发明组合物中的浓度取决于所用的化合物的性质、施用的方式、治疗过程、患者的年龄和体重、化妆品或药物指示、待处理的身体或身体部位，并可根据选择变化或调整。 The active ingredient in the compositions of the present invention, the concentration depends on the nature of the compound used, the mode of administration, the course of treatment, the patient's age and weight, the cosmetic or pharmaceutical indication, the body or body part to be treated, and according to the selection or change adjustment. 但是，对于在此描述的化合物的浓度范围通常为0.0005、0.001或0.01 ~ 25%，例如0.01 ~ 10%, 如0.1~5%，如1~5%(对于施用的最终制剂的w/w，尤其是局部施用的）。 However, the compounds described herein are generally 0.0005,0.001 or concentration range of 0.01 to 25%, e.g., 0.01 to 10%, such as 0.1 to 5%, such as 1 to 5% (for administration of the final formulation w / w, especially the topical application). 所述浓度通过参照化合物自身的量测定，因此应适当考虑到组合物的纯度。 The concentration was determined by reference to the measured amount of the compound itself, and therefore should give due consideration to the purity of the composition. 根据所处理的、施用单次剂量的动物，有效的单次剂量可以处于1〜100mg/天的范围，优选2〜10mg/天。 Depending on the process, the administration of a single dose of an animal, an effective single dose may be in the range 1~100mg / day, preferably 2~10mg / day.

可以通过在医药领域已知的任何合适的方法进行施用，包括例如口服、肠胃外(例如肌肉内、皮下、腹膜内或静脉内）、经皮、经颊、直肠或局部施用或通过吸入施用。 It may be administered by any suitable method known in the field of medicine, including e.g., oral, parenteral (intramuscular, subcutaneous, intraperitoneal or intravenous, for example), transdermal, buccal, rectal or topical administration, or by inhalation. 优选的施用形式为口服施用或最优选局部施用。 The preferred form of administration is oral administration or most preferably topical administration. 应该理解，如果活性成分是可消化的，那么口服施用有其局限性。 It should be appreciated, if the active ingredient is digestible, the oral administration has its limitations. 为了克服这些问题，可以如上所述地稳定所述成分。 To overcome these problems, to stabilize the composition as described above.

可以在辐射之前、期间或之后进行施用，以对辐射影响提供预防或处理。 It may be performed before radiation, during or after administration, to provide prevention or treatment of radiation effects. 因此，例如所述组合物可以在辐射前至多例如1天，但是优选少 Thus, for example, the composition can be up to 1 day before irradiation, for example, but preferably less

于1小时，可以在辐射期间和辐射后的任何时间，例如在辐射后的12 个小时内，口服施用或局部^f吏用。 In one hour, at any time during radiation and after radiation, for example within 12 hours after irradiation, oral or topical administration officials with ^ f.

遮光制剂可以作为如上文所述的局部制剂提供，尤其是作为身体、 脸或唇乳、泡沫、喷雾、洗液、凝胶或香脂提供。 Sunscreen formulation can be used as a topical formulation as described above to provide, especially as the body, the face or lip cream, foam, spray, lotion, gel or balm provided. 根据它们的配方和在组合物中所用的化合物，本发明的遮光制剂还可以具有化妆品特性，例如引入附加的组分或者选择本发明的着色化合物。 Depending on their formulation and in the composition of the compound used, sunscreen formulation of the present invention may also have cosmetic properties, such as the introduction of additional components or select a colored compound of the present invention. 类似地，在此描述的化妆品制剂可以具有遮光特性。 Similarly, the cosmetic formulations described herein may have light shielding characteristics.

本发明还扩展到包含上文所描述的组合物的特殊的化妆品组合物或制剂（个人护理产品）。 The present invention also extends to comprise the compositions described above special cosmetic compositions or formulations (Personal care products). 这样的制剂可以釆取化妆品(例如眼部或脸部产品，包括眼影、底粉、唇骨、粉底、睫毛油、腮红、眼线骨、指曱抛光剂、遮瑕霜和遮瑕粉底、防晒化妆品）、霜剂、洗液或着色剂的形式。 Such formulations can be implemented to take cosmetics (such as eye or face products, including eyeshadow, pink bottom lip bone, foundation, mascara, blush, eyeliner bone, finger Yue polish, concealer and foundation concealer, sunscreen cosmetics) , in the form of creams, lotions or coloring agents. 所述制剂优选为无水或含水的固体或糊的形式。 The formulation is preferably anhydrous or aqueous solid or paste form. 本发明的类胡萝卜素可以用来为所述制剂赋予颜色、遮光和/或抗氧化特性。 Carotenoids present invention can be used to impart color to the formulation, sunscreen and / or antioxidant properties. 对于遮光产品， 组合物可以如上文所述的特别地局部施用到皮肤上。 For light-shielding products, the composition may be topically applied as described in particular to the skin. 对于头发的处理或保护，组合物可以为护发素、喷雾、凝胶、摩丝、香波、护理剂、洗液、 乳液或染色产品。 For hair treatment or protection, the composition may be a hair conditioner, spray, gel, mousse, shampoos, care agents, lotions, emulsions or dyed product.

因此，本发明还扩展到制备上述遮光制剂或化妆品制剂的方法，包括将如上文所述的化合物或组合物加到药物上可接受的稀释剂、载体和/或赋形剂或基础遮光剂或化妆品中，其中所述遮光剂或化妆品可以包含赋予光防护和/或化妆(例如，着色)特性的成分。 Accordingly, the present invention also extends to a method for preparing said sunscreen formulation or cosmetic formulation comprising a compound or composition as described above is added to pharmaceutically acceptable diluents, carriers and / or excipients or base or opacifier cosmetics, sunscreens or cosmetics wherein may contain impart light protection and / or make-up (for example, color) properties of ingredients. 本发明的化合物或组合物制备这种化妆品/遮光剂的用途也认为是本发明的目的。 Use of a compound or composition of the present invention is the preparation of such cosmetic / sunscreen is also considered to be an object of the invention.

可以应用或施加所述组合物的动物包括遭受光辐射有害作用的哺乳动物、爬行动物、鸟类、昆虫和鱼类。 You can apply or applying the composition of animals include suffer harmful effects of optical radiation of mammals, reptiles, birds, insects and fish. 本发明组合物所应用的动物优选为哺乳动物，尤其是灵长类、家畜、牲畜和实验室动物。 The composition of the present invention is applied animal preferably a mammal, especially primates, domestic animals, livestock and laboratory animals. 因此，优选 Therefore, preferably

的动物包括小鼠、大鼠、兔、豚鼠、猫、狗、猴、猪、牛、山羊、绵羊和马。 The animals include mice, rats, rabbits, guinea pigs, cats, dogs, monkeys, pigs, cattle, goats, sheep and horses. 特别优选将所述组合物应用或施用给人。 Particularly preferred application of the composition or administered to a human.

所述组合物可以应用的"身体外层，，或"身体表面"包括身体外层如皮肤、身体的生长物如毛发和曱和表面如粘膜，但是也包括其它动物体上的等价物如鳞或羽毛。 The composition can be applied to the "outer body ,, or" body surface "includes the body such as the outer layer of the skin, body hair growths such as mucous membranes and 曱 surface, but also including other equivalents on the animal body, such as scales or Feathers.

附图说明 Brief Description

仅作为说明给出下列实施例，其中参考的附图如下： Only following examples are given by way of illustration, with reference to the accompanying drawings which are as follows:

图l表示硅曱藻黄素(I)、硅藻黄素(II)、墨角藻黄素(III)和硅曱藻色素(IV)的化学结构； Figure l denotes a silicon Yue algae flavin (I), diatoms flavin (II), fucoxanthin (III) and silicon Yue algal pigment (IV) chemical structure;

图2表示硅甲藻黄素(1)、硅藻黄素(II)、墨角藻黄素(III)和硅甲藻色素(IV)在丙酮溶液中的吸收光谱； Figure 2 shows a silicon peridinin (1), diatoms flavin (II), fucoxanthin (III) and silicon dinoflagellate pigment (IV) absorption spectrum in acetone solution;

图3表示使用不同浓度的墨角藻黄素和硅曱藻黄素的积分球分析的透射光谱。 Figure 3 shows the transmission spectra of different concentrations of fucoxanthin and silicon 曱 algae flavin integrating sphere analysis. 使用市售遮光剂SPF60作为对比。 Use a commercially available sunscreens SPF60 comparison. 体外皮肤+饱和的植物脂肪酸三甘油酯用作对照物。 In vitro skin + saturated vegetable fatty acid triglyceride used as a control. 曲线1:体外皮肤+饱和的植物脂肪酸三甘油酯，2: SPF60， 3: 2.76mg/ml的墨角藻黄素，4: 0.55mg/ml的墨角藻黄素，5: 0.25mg/ml的墨角藻黄素，6: 0.64 mg/ml的珪甲藻黄素7: 0.13mg/ml的硅曱藻黄素；和 Curve 1: In vitro skin + saturated vegetable fatty acid triglyceride, 2: SPF60, 3: fucoxanthin 2.76mg / ml in, 4: 0.55mg / ml of fucoxanthin, 5: 0.25mg / ml The fucoxanthin, 6: 0.64 mg / ml of Gui peridinin 7: 0.13mg / ml of silicon Yue algae flavin; and

图4表示作为硅甲藻黄素和墨角藻黄素浓度的函数在454nm处透射率的降低(数据来自积分球分析)。 Figure 4 shows a silicon peridinin and fucoxanthin concentration as a function of the decrease in transmittance at 454nm (data from the integrating sphere analysis). 浓度为给定化合物和它们降解产物(顺式-墨角藻黄素和硅甲藻色素)的总和。 The concentration of a given compound and their degradation products (cis - fucoxanthin and silicon dinoflagellate pigment) combined. 带有方块的实线为硅曱藻黄素。 The solid line with squares of silicon 曱 algae flavin. 带有菱形的实线为墨角藻黄素。 Solid lines with diamond for fucoxanthin. 虚线表示预计的线性关系。 Dashed line represents the expected linear relationship.

具体实施方式实施例l:制剂 DETAILED DESCRIPTION OF EXAMPLE l: Formulation

才艮据本发明的示例性制剂如下： It was Gen exemplary formulations of the present invention are as follows:

遮光剂 Sunscreens

爽身水 Body lotion

制剂1 %w/w Formulation 1% w / w

羊毛脂4.5 Lanolin 4.5

可可脂2.0 Cocoa butter 2.0

硬脂酸甘油酯3.0 Stearin 3.0

硬脂酸2.0 Stearate 2.0

二甲基对氨基苯甲酸辛酯(UVB滤光剂，任选的） 7.0 Dimethyl PABA octyl ester (UVB filter agent, optional) 7.0

2-羟基-4-曱氧基二苯甲酮(UVB滤光剂，任选的） 3.0 Hydroxy-4-yloxy Yue benzophenone (UVB filter agent, optionally) 3.0

对羟基笨曱酸丙酯0.1 Ben Yue of hydroxy propyl gallate 0.1

对羟基苯甲酸甲酯0.3 Methyl paraben 0.3

三乙醇胺1.0 Triethanolamine 1.0

山梨醇5.0 Sorbitol 5.0

本发明的类胡萝卜素1.0 ~ 5.0 Carotenoids present invention is 1.0 to 5.0

水平衡至100 Water Balance to 100

制剂2 Formulation 2

阶段A %w/w Phase A% w / w

豆蔻酸异丙酯4.0 Isopropyl myristate 4.0

矿物油6.5 Mineral oil 6.5

葡萄子油2.5 Grape seed oil 2.5

硬脂醇2.0 Stearyl alcohol 2.0

矿脂2.0 Petrolatum 2.0

甲氧基肉桂酸辛酯(UVB滤光剂，任选的） 5.0 Octyl methoxycinnamate (UVB filter agent, optionally) 5.0

本发明的类胡萝卜素1.0 ~ 5.0 Carotenoids present invention is 1.0 to 5.0

阶段B Phase B

硬脂酸脱水山梨醇酯6.0 Sorbitan monostearate 6.0

荒麻油酰胺MEA-碌基琥珀酸二钠0.2 Sesame oil shortage amide group MEA- busy disodium 0.2

丙三醇4.0 Glycerol 4.0

尿囊素0.2 Allantoin 0.2

d-泛醇0.8 d- panthenol 0.8

二氧化钛和水(任选的） l5.0 Titanium dioxide and water (optional) l5.0

水平衡至100 Water Balance to 100

(阶段A和B) (Phase A and B)

阶段C Phase C

防腐剂适量 Preservative q.s.

通过单独地将阶段A和B加热到別。 By individually heating the phase A and B to the other. C 、然后将阶段A加到阶段B 中并剧烈搅拌来制备。 C, and then added to phase A and phase B prepared with vigorous stirring. 均匀后，在緩慢搅动下将混合物冷却到25°C，随后加入阶段C。 Evenly, slow agitation mixture is cooled to 25 ° C, followed by addition of phase C.

护发产品 Hair Care Products

香波％w/w Shampoo% w / w

阴离子表面活性剂2.5 ~ 1.5活性的 An anionic surfactant activity of 2.5 to 1.5

两性表面活性剂0 ~ 4活性的 Amphoteric surfactants 0-4 Activity

烷醇酰胺0 ~ 5 聚合/締合增稠剂0~5 Alkanolamides 0-5 polymerization / associative thickener 0-5

本发明的类胡萝卜素1~5 Carotenoids present invention is 1 to 5

UVA/B滤光剂(例如，甲氧基肉桂酸辛酯、阿伏苯宗1~10 或氧苯酮）-任选的 UVA / B filter agent (for example, methoxy octyl, avobenzone 1 to 10 or oxybenzone) - optional

防腐剂适量 Preservative q.s.

香料适量 Perfume q.s.

pH调节剂适量 pH adjuster q.s.

电解质适量 Electrolyte right amount

水平衡至100 Water Balance to 100

美发喷剂％w/w Hair Spray% w / w

树脂增塑剂0~2 Resin Plasticizer 0-2

成膜性树脂2 ~ 8 Film-forming resin 2 to 8

乙醇0~70 Ethanol 0 to 70

烷醇胺或可替代的中和剂0~4 Alkanolamine or alternative neutralizer 0-4

本发明的类胡萝卜素1~5 Carotenoids present invention is 1 to 5

UVA/B滤光剂（例如，曱氧基肉桂酸辛酯、阿伏苯宗1~10 或氧苯酮）-任选的 UVA / B filter agent (for example, Yue, octyl group, avobenzone 1 to 10 or oxybenzone) - optional

防腐剂适量 Preservative q.s.

香料适量 Perfume q.s.

烃或可替代的推进剂10~40 Hydrocarbon propellant or alternatively 10 to 40

水平衡至100 Water Balance to 100

实施例2:萃取方案硅甲藻黄素的萃取(从微观藻类中） Example 2: Extraction program silicon peridinin extraction (from microscopic algae)

在覆有铝箔的设备中在氮气氛中进行萃取。 Cover with aluminum foil in the equipment for extraction in a nitrogen atmosphere.

1. 将微观藻类三角褐指藻(P. tricornutum)的水悬浮液(每升水14g 干重)的pH值调节到8.3，并加入乙醇，使水：乙醇的最终比为0.3: 1.0。 1. The microscopic algae Phaeodactylum (P. tricornutum) aqueous suspension (14g dry weight per liter of water) to adjust the pH to 8.3, and the addition of ethanol, water: ethanol final ratio is 0.3: 1.0.

2. 在20。 2. 20. C下通过混合庚烷(水-乙醇溶液：庚烷-1.3: lO)萃取乙醇-水溶液l小时。 C lower by mixing heptane - extraction of ethanol - water l h (anhydrous ethanol solution: lO: heptane -1.3).

3. 通过离心法(在3222 xg下10分钟)将溶液分成三相：富集珪曱藻黄素和墨角藻黄素的上层庚烷相，富集叶绿素和叶绿素降解产物的下层乙醇-水相，和含有沉淀物质的第三中间相。 3. by centrifugation (at 3222 xg for 10 minutes) into a three-phase solution: Gui Yue enriched algae and fucoxanthin flavin upper heptane phase, enriched in chlorophyll and chlorophyll degradation products of lower ethanol - aqueous phase, and third intermediate phase containing the precipitated material. 在乙醇-水相中硅甲藻黄素和墨角藻黄素的浓度比约为1: 6。 In ethanol - aqueous phase silicon peridinin and fucoxanthin concentration ratio of about 1: 6.

4. 将水加到乙醇-水相中，直到达到水：乙醇为0.7: 1.0。 4. Water was added to ethanol - aqueous phase until it reaches the water: ethanol of 0.7: 1.0. 由近似量的庚烷萃取该溶液并通过离心法(同步骤3)分离相。 The approximate amount of heptane and the solution is extracted by centrifugation (with step 3) a separate phase. 硅甲藻黄素富集在庚烷相中(硅甲藻黄素：墨角藻黄素=1: 1)，墨角藻黄素和墨角藻黄素衍生物在乙醇-水相中。 Silicon dinoflagellates Huangsu Fu set in heptane phase (silica peridinin: fucoxanthin = 1: 1), fucoxanthin and Fucus flavin bio ethanol - aqueous phase.

5. 在-20'C下保存庚烷相过夜，以分离通过上述离心法分离的墨角藻黄素。 5. Save heptane phase at -20'C overnight to isolate fucoxanthin separated by the centrifugal method. （作为替代方案，可以用吸液管除去沉淀物质。） (As an alternative, it can be removed with a pipette sediment.)

6. 由上文所述的用庚烷相进行HPLC进一步提纯硅甲藻黄素，以得到60-70%的在初始原料中发现的纯硅甲藻黄素。 6. From the above described phase HPLC with heptane further purified silicon peridinin to obtain 60-70% of the initial raw material found in pure silicon peridinin.

优化 Optimization

改变上述基本方法中的各种参数，以确定水浓度、pH和温度对分离法的影响。 The basic method of varying the various parameters in order to determine the effect of water concentration, pH and temperature on the separation method. 结果如下表所示。 The results are shown below.

1.改变水的浓度 1. Change the water concentration

下表表示使用不同水浓度的类胡萝卜素的相分布(％)。 The table below shows the distribution of different water use relative concentrations of carotenoids (%). 该方法在室温、无pH调节下进行。 The method at room temperature, no pH adjustment is carried out.

<table>table see original document page 30</column></row> <table> <Table> table see original document page 30 </ column> </ row> <table>

2.温度/pH效应 2. Temperature / pH effect

下表表示在用庚烷萃取叶绿素a后，温度和pH对通过用庚烷萃取水：乙醇相(l: l)分离硅曱藻黄素和墨角藻黄素的影响。 The following table shows the after heptane extraction of chlorophyll a, temperature and pH of the aqueous extracted by heptane: ethanol phase (l: l) Separation of silicon 曱 flavin algae and fucoxanthin in. 所示的值为各个化合物在所示相中的量。 Phase amount of each compound is shown in Fig. 括弧中的值表示两相之间的％分布。 The values ​​in parentheses indicate% distributed between the two phases.

<table>table see original document page 30</column></row> <table> <Table> table see original document page 30 </ column> </ row> <table>

回收: Recycling:

<table>table see original document page 31</column></row> <table>因此，硅曱藻黄素在各种温度下是稳定的，而墨角藻黄素对较高 <Table> table see original document page 31 </ column> </ row> <table> Thus, silicon 曱 flavin algae at various temperatures are stable, while for higher fucoxanthin

墨角藻黄素的萃取(从大藻中） Fucoxanthin extraction (from large algae)

该方法为硅甲藻黄素方法(上述)的修改。 This method is silicon peridinin method (described above) changes.

1.将叶和柄(来自藻极北海带(algae Laminaria hyperborea))切成 1. Place the leaves and stem (from hyperborea algae (algae Laminaria hyperborea)) was cut

段。 Section.

2. 将乙醇(5ml)和庚烷(5ml)加到藻原料(lg，湿重）中，在Whirl混合器中混合(3xl5s),并在4。 2. Ethanol (5ml) and heptane (5ml) was added to algal material (lg, wet weight), in the Whirl mixer (3xl5s), and 4. C下放置4小时。 C for 4 hours. （在某些方案中，在这个阶段，离心混合物，并从乙醇或庚烷部分萃取类胡萝卜素。在其它方案中，用甲烷代替乙醇。） (In some scenarios, at this stage, the mixture was centrifuged, and partially from ethanol or heptane extracted carotenoids. In other aspects, methane instead of ethanol.)

3. 加入1.5ml水，在Whirl混合器中混合(3 x 15s)，并在4。 3. 1.5ml of water was added, mixed in a Whirl mixer (3 x 15s), and 4. C下放置1小时。 C for 1 hour. 离心(在3222 xg下io分钟)溶液，乙醇-水相用于进一步提纯墨角藻黄素。 After centrifugation (at 3222 xg at io minutes) solution, ethanol - aqueous phase for further purification fucoxanthin. （如上文所述的通过HPLC进行提纯。） (As by HPLC purification described above.)

4. 得到800ng/g(干重）的产量。 4. get 800ng / g (dry weight) of production.

该方法提供一种用于大规模萃取墨角藻黄素而同时除去其它细胞组分的萃取方法，其它细胞组分被认为难以从样品中从类胡萝卜素(例如叶绿素a)中分离。 The method provides for a large-scale extraction of fucoxanthin while removing other cellular components extraction method, and other cell components are considered difficult from carotenoids (such as chlorophyll a) separated from the sample.

实施例3:使用体外皮肤模型的吸收辐射功效方法 Example 3: In vitro skin model radiation absorbing effect of the method

使用Springsteen体夕卜方法(Springsteen 等，1999， Analytica Chimica Acta, 380，第155-164页）。 Use Springsteen body Xi Bu method (Springsteen, etc., 1999, Analytica Chimica Acta, 380, the first 155-164 pages). 体外皮肤用作皮肤模拟物，饱和的植物脂肪酸三甘油酯(Miglyol)(Miglyol 812F Neutraloel CHG,040卯6)用作溶剂。 In vitro skin as a skin mimics plant saturated fatty acid triglyceride (Miglyol) (Miglyol 812F Neutraloel CHG, 040 d 6) as solvent. 用Varian Cary 300 Cone紫外可见分光光度计（带有积分球) 进行测试。 With Varian Cary 300 Cone UV-visible spectrophotometer (with integrating sphere) for testing. 在所图3所示的浓度下测试墨角藻黄素和硅曱藻黄素(如实施例2中所述的分离）。 Test fucoxanthin and silicon 曱 flavin algae at concentrations shown in Figure 3 (separation in Example 2 in the Examples).

结果 Result

硅甲藻黄素和墨角藻黄素的结果(在不同浓度)如图3所示。 Silicon peridinin and fucoxanthin results (at different concentrations) shown in Figure 3. 结果与常规SPF60防晒乳液比较，证明化合物吸收辐射的能力，尤其是在光镨的蓝光范围，但是也在上UVA范围。 Results Compared with conventional sunscreen lotion SPF60, demonstrate that the compounds ability to absorb radiation, especially in light of the blue range praseodymium, but also in the UVA range. 图4表示相对于光的波长作图的％透射率。 Figure 4 shows the relative% transmittance of light wavelength is plotted. 虚线表示浓度和吸收之间的大致关系，表明为在454nm(蓝光)处提供足够保护，在最终溶液中小于5mg/ml是足够的。 Dashed line indicates the approximate relationship between concentration and absorption, indicating to provide adequate protection at 454nm (blue) at less than in the final solution 5mg / ml is sufficient.