CN101222856B - Novel use of organic compounds - Google Patents

Novel use of organic compounds Download PDF

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CN101222856B
CN101222856B CN2006800258799A CN200680025879A CN101222856B CN 101222856 B CN101222856 B CN 101222856B CN 2006800258799 A CN2006800258799 A CN 2006800258799A CN 200680025879 A CN200680025879 A CN 200680025879A CN 101222856 B CN101222856 B CN 101222856B
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skin
lutein
composition
people
animal
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CN101222856A (en
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瑞吉纳·古拉尔奇克
卡林·威兹
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DSM IP Assets BV
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DSM IP Assets BV
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Priority claimed from PCT/EP2006/006851 external-priority patent/WO2007009657A1/en
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Abstract

The present invention is directed to the use of a compound selected from the group consisting of ss-carotene, lutein, lycopene and ss-cryptoxanthin, and mixtures thereof and combinations thereof with CoQ-I O for maintaining the energy metabolism, the energy flow and/or the energy production in skin or of skin of animals including humans, for maintaining the respiratory function of the skin of animals including humans, for energizing the skin, maintaining and supporting the radiance and natural glow of the skin of animals including humans and for promoting a healthy appearance of the skin of animals including humans for preventing UV-A radiation-induced mtDNA mutagenesis in skin of animals including humans, as well as for the manufacture of a composition, preferably an orally applicable composition, for these uses and the corresponding methods. The present invention is further directed to the use of a compound selected from the group consisting of ss- carotene, lutein, lycopene and ss-cryptoxanthin, and mixtures thereof and combinations thereof with CoQ-10 in sunscreens as well as daily care products to improve their photoprotective potential, as well as to their use as effective micronutrients for skin maintenance. Furthermore the present invention is directed to compositions, preferably orally applicable compositions, comprising a certain amount of at least one compound selected from the group consisting of ss-carotene, lutein, lycopene and ss-cryptoxanthin and mixtures thereof and combinations thereof with CoQ-10 as active ingredient, characterized in that the amount is effective for such uses as mentioned above.

Description

The novel use of organic compound
The present invention relates to be selected from beta carotene, lutein, the combination (comprising all their E-and Z-stereoisomer) of compound of lycopene and β-kryptoxanthin and composition thereof and itself and Co-Q10 (CoQ-10) is used for following purposes: keep animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production, keep the respiratory function of animal (comprising the people) skin, be the skin energy supply, keep and support brightness and the natural gloss of animal (comprising the people) skin, and the healthy appearance that promotes animal (comprising the people) skin, with the radiation-induced mtDNA mutagenesis of UV-A in prevention animal (the comprising the people) skin, also relate to composition (but composition of preferred oral application) and corresponding method that this class carotenoid manufacturing is used for these purposes.The combination that the invention still further relates to compound of being selected from beta carotene, lutein, lycopene and β-kryptoxanthin and composition thereof and itself and CoQ-10 is used for opacifier and daily nursing product improving the purposes of their photoprotection abilities, and they are as the purposes of effective micronutrient of safeguarding skin.In addition, the invention still further relates to following composition (but preferred oral application composition), described composition comprises combination and the steric isomer thereof of a certain amount of at least a compound that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin and composition thereof and itself and CoQ-10.In the present specification and claims, title " lutein " and " β-kryptoxanthin " comprise its mono fatty acid ester and double acid ester (preferably, be and saturated chain alkanoic acid (as acetic acid, propionic acid, laurate, myristic acid, palmitic acid, stearic acid and butanedioic acid) monounsaturated fatty acids (PUFA) (as the ester of oleic acid and polyunsaturated fatty acid (as leukotrienes, linoleic acid, DHA and arachidonic acid)).
UV-A radiation (namely with 320 light radiation to the 400nm wavelength) is to directly effect of SF performance.Particularly, the prolonged and repeated UV-A of being exposed to radiation causes the generation of mitochondria in these cells (mt) dna mutation, and this is than not exposing skin high by 40% (Berneburg al., Journal ofInvestigative Dermatology, 2004).This class sudden change is the common deletion of specific 4977-bp fragment in the mitochondrial DNA (mtDNA).The gene of 7 polypeptide compositions of the special influence coding of 4977-bp deletion mitochondrial respiratory chain.This mt deletes even stops the back at irradiation also is detectable in skin, and can be detected after the several months, and further accumulation is the level up to 32 times.Therefore the UV-A radiation causes permanent chronic risk to skin, even when non-exposure (also is afterwards).Mitochondrial DNA damage causes the deterioration of mitochondrial respiration-chain function, therefore then such situation can occur: compare with the energetic supersession of the skin that never is exposed to UV, the energetic supersession of the violent skin that exposes and before exposed is impaired.Bio-energy shortage and the breathing that reduces cause cell dysfunction.Therefore, people need be the continuous accumulation of permanent basis prevention mt DNA deletion when namely individuality is not exposed to UV (even), to avoid the harmful result to the Skin Cell energetic supersession.
Have been found that now, be selected from beta carotene, lutein, the combination of compound of lycopene and β-kryptoxanthin and composition thereof and itself and CoQ-10, particularly be selected from lutein, carotenoid of lycopene and β-kryptoxanthin and composition thereof can prevent this class damage of sudden change/delete form among the mtDNA, thereby be maintained the energetic supersession of animal (comprising the people) skin, be maintained the respiratory function of animal (comprising the people) skin, be maintained and support animal (comprising the people) skin brightness and natural gloss and the healthy appearance that promotes animal (comprising the people) skin.The respiratory function of skin mainly comprises the oxidative phosphorylation that occurs in the Skin Cell, and this is the prerequisite of producing atriphos (ATP) from nutrients.
Therefore, the combination of the compound and composition thereof that an object of the present invention is to be selected from beta carotene, lutein, lycopene and β-kryptoxanthin and itself and CoQ-10 is used for following purposes: keep animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production.
To be the compound and composition thereof that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin be used for following purposes with the combination of itself and CoQ-10 to another object of the present invention: the respiratory function of keeping animal (comprising the people) skin.
To be the compound and composition thereof that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin be used for following purposes with the combination of itself and CoQ-10 to another object of the present invention: for the skin energy supply, keep and support brightness and the natural gloss of animal (comprising the people) skin and the healthy appearance that promotes animal (comprising the people) skin.
To be the compound and composition thereof that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin be used for following purposes with the combination of itself and CoQ-10 to another object of the present invention: the mtDNA mutagenesis that prevention animal (comprising the people) skin UV-A is radiation-induced.
In some specific embodiments, the present invention relates to be selected from the purposes of definition as mentioned of the carotenoid and composition thereof of lutein, lycopene, β-kryptoxanthin.
Special embodiments more of the present invention are:
The ◇ beta carotene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
◇ β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
◇ lutein is used for keeping the purposes of energetic supersession, energy stream and/or the energy production of animal (comprising the people) skin or skin;
The ◇ lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lutein and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lutein and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lutein and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lycopene and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lycopene and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ CoQ-10 and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lycopene, lutein and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ lycopene, CoQ-10 and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ CoQ-10, lutein and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ CoQ-10, lutein and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ β-kryptoxanthin, lutein and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ β-kryptoxanthin, lutein, CoQ-10 and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ β-kryptoxanthin and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ β-kryptoxanthin and lutein is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ β-kryptoxanthin and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene and β-kryptoxanthin is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin and lutein is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, lutein and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, lutein and lycopene is used for keeping the purposes of energetic supersession, energy stream and/or the energy production of animal (comprising the people) skin or skin;
The combination of ◇ beta carotene, CoQ-10 and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, CoQ-10 and lutein is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, lutein, CoQ-10 and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin, CoQ-10 and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and CoQ-10 is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein, CoQ-10 and lycopene is used for keeping the purposes of animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production;
The ◇ beta carotene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
◇ β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
◇ lutein is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The ◇ lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lutein and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lutein and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lutein and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lycopene and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lycopene and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ CoQ-10 and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lycopene, lutein and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ lycopene, CoQ-10 and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ CoQ-10, lutein and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ CoQ-10, lutein and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ β-kryptoxanthin, lutein and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ β-kryptoxanthin, lutein, CoQ-10 and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin and lutein is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, lutein and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, lutein and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, CoQ-10 and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, CoQ-10 and lutein is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ β-kryptoxanthin and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ β-kryptoxanthin and lutein is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ β-kryptoxanthin and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene and β-kryptoxanthin is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, lutein, CoQ-10 and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin, CoQ-10 and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and CoQ-10 is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein, CoQ-10 and lycopene is for the purposes of the respiratory function of keeping animal (comprising the people) skin;
The ◇ beta carotene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
◇ β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
◇ lutein is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The ◇ lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lutein and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lutein and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lutein and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lycopene and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lycopene and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ CoQ-10 and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lycopene, lutein and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ lycopene, CoQ-10 and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ CoQ-10, lutein and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
◇ CoQ 10, the combination of lutein and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ β-kryptoxanthin, lutein and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ β-kryptoxanthin, lutein, CoQ-10 and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ β-kryptoxanthin and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ β-kryptoxanthin and lutein is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene and β-kryptoxanthin is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin and lutein is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, lutein and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, lutein and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, CoQ-10 and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, CoQ-10 and lutein is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, lutein, CoQ-10 and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin, CoQ-10 and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein and CoQ-10 is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
The combination of ◇ beta carotene, β-kryptoxanthin, lutein, CoQ-10 and lycopene is used for the purposes of the radiation-induced mtDNA mutagenesis of prevention animal (comprising the people) skin UV-A;
Wherein in these particular that relate to such use of the present invention, listed compound/combination preferably is used for the only active component of composition of following purpose, described purpose is: keep energetic supersession in animal (the comprising the people) skin or skin, energy stream and/or energy production, keep the respiratory function of animal (comprising the people) skin, be the skin energy supply, keep and support brightness and the natural gloss of animal (comprising the people) skin, and promote the healthy appearance of animal (comprising the people) skin and/or prevent the radiation-induced mtDNA mutagenesis of UV-A in animal (the comprising the people) skin.
In the present invention relates to other embodiment of such use, described compound/combination preferably also makes up with at least a compound that is selected from beta carotene, vitamin C, vitamin E, resveratrol and (-)-Epigallo-catechin gallate (EGCG), more preferably, with at least a compound combination that is selected from vitamin C, vitamin E, resveratrol and/or (-)-Epigallo-catechin gallate (EGCG), most preferably, with resveratrol and/or the combination of (-)-Epigallo-catechin gallate (EGCG).
For people (people according to heavy 70kg determines usually), lutein every day dosage should be greater than 0.1mg, be preferably more than 0.5mg, dosage every day of lycopene is preferably more than 0.1mg, and dosage every day of β-kryptoxanthin is preferably more than 0.1mg, is preferably more than 0.5mg, beta carotene every day dosage greater than 0.1mg, be preferably more than 0.3mg, and/or CoQ-10 every day dosage greater than 1mg, be preferably more than 10mg (most preferably 30-60mg).
For the general application of people's (people according to heavy 70kg determines usually), dosage every day of lutein should not surpass 40mg, preferably be no more than 25mg, dosage every day of lycopene is no more than 60mg, preferably is no more than 30mg, dosage every day of β-kryptoxanthin is no more than 20mg, preferably be no more than 15mg, dosage every day of beta carotene is no more than 20mg, preferably is no more than 10mg, and/or dosage every day of CoQ-10 is no more than 200mg, preferably is no more than 60mg.
In some embodiments of the present invention, for people's (people according to heavy 70kg determines usually), lutein every day dosage can be between 0.1 to 40mg, more preferably between 0.5 to 25mg, lycopene every day dosage between 0.1 to 60mg, more preferably between 1.0 to 30mg, β-kryptoxanthin every day dosage between 0.1 to 20mg, more preferably between 0.5 to 15mg, beta carotene every day dosage between 0.1 to 20mg, more preferably between 0.3 to 10mg, and/or CoQ-10 every day dosage between 1 to 500mg, preferably between 1 to 200mg, more preferably between 10 to 60mg.
For people (people of heavy 70kg), ascorbic every day, dosage can be between 100mg mg and 5g, more preferably between 200mg and 1.5g, change, vitamin E every day dosage can be between 15mg and 2g, more preferably 15 and 500mg between change, resveratrol every day dosage can 1 and 100mg between, more preferably 5 and 50mg between change, and/or (-)-Epigallo-catechin gallate (EGCG) every day dosage can be between 10mg and 1.5g, more preferably 50 and 300mg between change.
A further object of the invention is the compound and composition thereof that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin and itself and the combination of CoQ-10 and their stereoisomer, and/or under the situation of lutein and β-kryptoxanthin their monoesters and the purposes of dibasic acid esters and composition thereof; Particularly be selected from lutein, lycopene, the carotenoid of β-kryptoxanthin (comprising all their stereoisomers), and/or under the situation of lutein and β-kryptoxanthin they mono fatty acid ester and double acid ester and composition thereof for the manufacture of the purposes of following composition (but composition of preferred oral application), described composition is used for keeping animal (comprising the people) energetic supersession skin or skin, energy stream and/or energy production, keep the respiratory function of animal (comprising the people) skin, and the radiation-induced mtDNA mutagenesis of UV-A in prevention animal (the comprising the people) skin.
Another object of the present invention is composition, but the composition of preferred oral application, it comprises a certain amount of at least a beta carotene that is selected from, lutein, the combination of compound of lycopene and β-kryptoxanthin and composition thereof and itself and CoQ-10 is as active component, preferably be selected from lutein, lycopene and β-kryptoxanthin (comprising all their stereoisomers), it is characterized in that described amount can keep in animal (the comprising the people) skin or the energetic supersession of skin effectively, energy stream, energy production, keep the respiratory function of animal (comprising the people) skin, keep and support brightness and the natural gloss of animal (comprising the people) skin, promote the healthy appearance of animal (comprising the people) skin, and the radiation-induced mtDNA mutagenesis of UV-A in prevention animal (the comprising the people) skin.
Of the present invention another be composition to purpose, but the composition of preferred oral application, it comprises at least a lutein that is selected from of a certain amount, lycopene, the carotenoid of β-kryptoxanthin and stereoisomer thereof, and/or under the situation of lutein and β-kryptoxanthin its monoesters and dibasic acid esters as active component, it is characterized in that described amount keeps in animal (the comprising the people) skin or the energetic supersession of skin effectively, energy stream, energy production, keep the respiratory function of animal (comprising the people) skin, keep and support brightness and the natural gloss of animal (comprising the people) skin, promote the healthy appearance of animal (comprising the people) skin, the radiation-induced mtDNA mutagenesis of UV-A in prevention animal (the comprising the people) skin.
But but composition according to the present invention comprises the composition of topical application and oral application.But the composition of preferred oral application.
Yet scope of the present invention is got rid of following part or Orally administered composition, and described composition contains and is lower than 1, the beta carotene mixing lycopene of 0.95: 1 to 1: 50 weight ratio particularly, and additionally contain lutein and/or kryptoxanthin alternatively.
Term " but composition of topical application " comprises " cosmetic formulations " or " cosmetic composition " that is applicable to any kind that is applied on the animal skin, as oil in water emulsion, water-in-oil emulsion, multiple emulsion, microemulsion, PET-emulsion, bikering emulsion, hydrogel, alcogel, fat gel, single-phase or multi-phase solution, foam, ointment, emplastrum, suspension, powder, breast frost, cleaning agent, soap and other common combinations thing of liquid or solid, it also can be by pen, as facial mask or as spray applications.
The term that uses in this application " cosmetic formulations " or " cosmetic composition " refer to RomppLexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, among the New York at the undefined cosmetic composition of title " Kosmetika ".Composition of the present invention also can contain cosmetics commonly used or medicine adjuvant and additive, as anticorrisive agent/antioxidant, and fatty material/oil; water, organic solvent, silicone; thickening agent; softening agent, emulsifying agent, opacifier; defoamer; wetting agent, aromatic, surfactant; filler; screening agent, anion; cation; nonionic or basic poly body and composition thereof, propellant; acidifying or basifier; dyestuff; colouring agent; pigment or nanometer pigment, for example being applicable to by physics blocking-up ultra-violet radiation provides those of light protective effect, or is formulated any other composition of cosmetics into or medicine usually.
Antioxidant/the anticorrisive agent of unnecessary amount is normally preferred.According to the present invention, can use all known antioxidants that are formulated usually in cosmetics into or the medicine.Particularly preferably be and be selected from following antioxidant: amino acid (glycine for example, histidine, tyrosine, tryptophan) and derivative, imidazoles (for example urocanic acid (urocanic acid)) and derivative thereof, peptide is D for example, the L-carnosine, the D-carnosine, L-carnosine and derivative (for example anserine), carotenoid, except beta carotene, gamma carotene, carotenoid beyond lycopene and the β-kryptoxanthin, chlorogenic acid and derivative, liponic acid and derivative (for example dihydro liponic acid), aurothioglucose (aurothioglucose), propyl group deracil and other sulfhydryl compound (thioredoxin (thioredoxine) for example, glutathione, cysteine, cystine, cystamine (cystamine) and glycosyl thereof, the N-acetyl group, methyl, ethyl, propyl group, amyl group, butyl and lauryl, palmityl, oleoyl, γ-flax acyl group (γ-linoleyl-), cholesteryl (cholesteryl-) and glyceride) and salt, thiodipropionic acid two lauryls (dilaurylthiodipropionate), thiodipropionic acid two (octadecane ester), thiodipropionic acid and derivative (ester thereof, ether, peptide, fat, nucleotides, nucleosides and salt) and sulphoxide imine (sulfoximine) compound of low-down compatible dosage (for example pmol is to μ mol/kg) (fourth methyllanthionine sulphoxide imine for example, homocysteine sulfoxide amine, fourth methyllanthionine sulfoxide, penta, oneself, heptan the methyllanthionine sulphoxide imine), extra (metal) chelating agent (α-hydroxy fatty acid for example, palmitic acid, phytic acid, lactoferrin), alpha-hydroxy acid (citric acid for example, lactic acid, malic acid), humic acid (huminic acid), gallic acid, Galla halepensis extract, bilirubin, biliverdin, EDTA (edetate), EGTA and derivative thereof, unrighted acid and derivative thereof (gamma-linoleic acid for example, linoleic acid, oleic acid), folic acid and derivative thereof, vitamin C and derivative (for example ascorbyl palmitate and magnesium ascorbyl phosphate (Mg-ascorbylphosphate), STAY-C 50, the acetic acid sodium ascorbate, tocopherol and derivative (for example Vitwas E), nat. the mixture of vitamin E, vitamin A and derivative (Retinol Palmitate) and benzoic acid coniferyl ester (coniferylbenzoat), rutinic acid (rutinic acid) and derivative, the alpha-glycosyl rutin (α-glycosylrutin), forulic acid, furfurylidene glucitol (furfurylidenglucitol), carnosine, butylated hydroxytolyene, butylated hydroxy anisole, trihydroxybutyrophenone, urea and derivative thereof; Mannose and derivative, zinc and derivative (ZnO for example; ZnS0 4), selenium and derivative (for example selenomethionine), the suitable derivative (salt, ester, ether, sugar, nucleotides, nucleosides, peptide and fat) of stilbene and derivative (for example oxidation stilbene, trans oxidation stilbene) and described active component.One or more anticorrisive agent/antioxidants can exist to the amount of about 10wt.% with about 0.01wt.% of accounting for present composition gross weight.Preferred one or more anticorrisive agent/antioxidants exist to the amount of about 1wt.% with about 0.1wt.%.
Typically, topical composition also can contain surface active ingredient such as emulsifying agent, solubilizer etc.Emulsifying agent makes two or more immiscible liquid homogeneous phase make up.In addition, emulsifying agent plays the effect of stable composition.Can use emulsifying agent to form O/W among the present invention, W/O, O/W/O emulsion/microemulsion, described emulsifying agent comprises the sorbitan oleate, NOFABLE SO-992, sorbitan isostearate, sorbitan trioleate, polyglycereol-3-diisopstearate (polyglyceryl-3-diisostearate), the polyglycerol ester of oleic acid/isostearic acid, the own ricinoleate ester of polyglycereol-6 (polyglyceryl-6 hexaricinolate), polyglycereol-4-oleate, polyglycereol-4-oleate/PEG-8 propane diols cocoa acid esters, oleamide DEA, TEA myristinate (TEAmyristate), the TEA stearate, dolomol, odium stearate, potassium laurate, ricinoleic acid potassium, theobromic acid sodium, tallow fatty acid sodium, potassium ricinoleate (potassium castorate), enuatrol and composition thereof.Other suitable emulsifying agent is phosphate and salt thereof, for example phosphoric acid cetyl ester (Amphisol A), p diethylaminobenzoic acid hydramine cetyl ester (Amphisol ), potassium cetyl phosphate (potassium cetyl phosphate) (Amphisol
Figure 2006800258799_2
K), plant glycerophosphate (hydrogenatedvegetable glyceride phosphates) of glycerine oleic acid sodium phosphate (sodiumglyceryl oleate phosphate), hydrogenation and composition thereof.In addition, one or more synthetic polymer can be used as emulsifying agent.For example, PVP eicosylene copolymer, acrylate/acrylic acid C10-C30 Arrcostab intersection polymer, acrylate/stearyl alcohol polyethers-20 methacrylate copolymer (acrylates/steareth methacrylate copolymer), PEG-22/ dodecyl diol copolymer, PEG-45/ dodecyl diol copolymer and composition thereof.Preferred solvent is phosphoric acid cetyl ester (Amphisol
Figure 2006800258799_3
A), p diethylaminobenzoic acid hydramine cetyl ester (Amphisol
Figure 2006800258799_4
), potassium cetyl phosphate (potassium cetyl phosphate) (Amphisol
Figure 2006800258799_5
K), PVP eicosylene copolymer, acrylate acrylic acid C10-C30 Arrcostab intersection polymer, PEG-20 sorbitan isostearate, sorbitan isostearate and composition thereof.Described one or more emulsifying agents exist to the total amount of about 20wt.% with about 0.01wt.% of accounting for present composition gross weight.Preferred about 0.1wt.% of use arrives the emulsifying agent of about 10wt.%.
The fat of topical composition advantageously is selected from mutually:
◇ mineral oil and mineral wax;
◇ oil, for example tricaprin or tricaprylin and castor oil;
◇ oil or wax and other natural or artificial oil are the ester of aliphatic acid and alcohol (for example isopropyl alcohol, propane diols or glycerine) in preferred embodiments, or the ester of fatty alcohol and carboxylic acid or aliphatic acid;
◇ benzoic acid alkyl ester and/or
◇ silicone oil, for example dimethyl polysiloxane, diethyl polysiloxanes, diphenyl polysiloxanes, cyclomethicone and composition thereof.
The exemplary fatty material that can be impregnated in the oil phase of emulsion of the present invention, microemulsion, oleogel, water dispersant or fat dispersant advantageously is selected from: the ester of the alkyl carboxylic acid that has 3 to 30 carbon atom, saturated and/or undersaturated, linearities or a branch and the alcohol that has 3 to 30 carbon atom, saturated and/or undersaturated, linearities and/or branch; Aromatic carboxylic acid and have saturated and/or unsaturated, the linearity of 3 to 30 carbon atoms or the ester of the alcohol of branch.This class ester can be favourable be selected from octyl palmitate, the theobromic acid monooctyl ester, the isostearic acid monooctyl ester, myristic acid octyl group dodecane ester, different n-nonanoic acid cetyl ester, isopropyl myristate, isopropyl palmitate, isopropyl stearate, acid isopropyl, BS, the just own ester of laurate, oleic acid ester in the positive last of the ten Heavenly stems, the different monooctyl ester of stearic acid, stearic acid ester in the different ninth of the ten Heavenly Stems, isononyl isononanoate, palmitic acid 2-Octyl Nitrite, laurate 2-Octyl Nitrite, stearic acid 2-hexyl ester in the last of the ten Heavenly stems, palmitic acid 2-octyl group dodecyl ester, the enanthic acid stearyl, oleic acid oil base ester (oleyloleate), erucic acid oil base ester (oleylerucate), oleic acid savoy ester (erucyloleate), savoy acid erucyl ester, oleic acid tridecyl ester, trimellitic acid tridecyl ester, and synthetic from these esters, semisynthetic or natural mixture, for example jojoba oil (jojoba oil).
Other fat constituent that is applicable to topical composition of the present invention comprises polar oil, for example lecithin and fatty acid triglyceride, namely have the saturated and/or undersaturated of 8 to 24 carbon atoms (preferred 12 to 18 carbon atoms), carboxylic acid triglycerides straight chain or branch, wherein said fatty acid triglyceride preferably is selected from synthetic, semisynthetic or natural oil (cocoa glyceride (cocoglyceride) for example, olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, Sweet Almond Oil, palm oil, coconut oil, castor oil, the castor oil of hydrogenation, little wheat oil, grape-kernel oil, Queensland nut wet goods etc.); Nonpolar oil is hydrocarbon and wax linear and/or branch for example, for example mineral oil, vaseline (vaseline); Polyisobutene and the isohexadecane of paraffin oil, saualane (squalan) and squalene (squalen), polyolefin, hydrogenation, preferred polyolefin is poly decene; Dialkyl ether, for example dioctyl ether (dicaprylylether); The silicone oil of linearity or ring-type, for example preferred cyclohexyl methyl siloxanes (cyclomethicone); Octamethylcy-clotetrasiloxane, hexadecyldimethyl benzyl ammonium siloxanes (cetyldimethicone), hexamethyl cyclotrisiloxane, dimethyl silicone polymer, poly-(tolyl siloxanes) and composition thereof.
Other fat constituent that can advantageously mix topical composition of the present invention is Isoeicosane; Neopentyl glycol two heptanoates; Propane diols dicaprylate/dicaprate; Sad-/capric acid-/two glycerol succinic acid ester (caprylic-/capric-/diglycerylsuccinate); Butanediol caprylate/decylate; Lactic acid C12-13 Arrcostab; Tartaric acid two (C12-13 alkyl) ester; Three different stearins (triisostearin); Dipentaerythritol six caprylates/six decylates; Emerest 2384; Tricaprylin; Dimethyl isosorbide (dimethylisosorbid).The particularly preferred mixture that is to use benzoic acid C12-15 Arrcostab and isostearic acid 2-ethylhexyl, the mixture of the mixture of benzoic acid C12-15 Arrcostab and different n-nonanoic acid tridecyl ester and benzoic acid C12-15 Arrcostab, isostearic acid 2-ethylhexyl and different n-nonanoic acid tridecyl ester.The particularly advantageous mixture that is to use benzoic acid C12-15 Arrcostab and 2-ethylhexyl, the mixture of the mixture of benzoic acid C12-15 Arrcostab and different n-nonanoic acid tridecyl ester and benzoic acid C12-15 Arrcostab, isostearic acid 2-ethylhexyl and different n-nonanoic acid tridecyl ester.
The oil phase of the present composition also can contain natural vegetable wax or animal wax, for example beeswax, Chinese wax, bumblebee wax (bumblebee wax) and other insect wax and sher butter and cocoa butter.
Can in topical composition of the present invention, mix wetting agent (moisturizing agent) to keep moisture of skin or to give the skin moisturizing.By providing protective layer to stop moisture to be called lubricant from the wetting agent of skin evaporation.Lubricant also provides softening or the effect of releiving at skin surface, and it is considered to the part is used usually is safe.Preferred lubricant comprises mineral oil, lanolin, vaseline, glycerine capric acid/trioctanoate, cholesterol, silicone is dimeticone for example, cyclomethicone, apricot kernel oil, jojoba oil, avocado oil, castor oil, sunflower oil, coconut oil, grape-kernel oil, cocoa butter, olive oil, aloe extract, aliphatic acid such as oleic acid and stearic acid, fatty alcohol such as cetanol and hexadecanol (ENJAY), the adipic acid diisopropyl ester, the benzoic ether of C9-C15 alcohol and hydroxybenzoate, the different pelargonate of different nonyl, ether is polyoxypropylene butyl ether and polyoxypropylene cetyl ether and benzoic acid C2-C15 Arrcostab for example, and composition thereof.Most preferred lubricant is hydroxybenzoate, aloe vera (aloe vera), benzoic acid C12-15 Arrcostab and composition thereof.Lubricant exists to the dosage of about 20wt.% with about 1wt.% of accounting for composition total weight.Preferred amounts of lubrication be from about 2wt.% to about 15wt.%, most preferably from about 4wt.% to about 10wt.%.
Thereby be combined with water its wetting agent of staying skin surface is called wetting agent (humectant).Suitable wetting agent can be impregnated in the topical composition of the present invention, and described wetting agent for example glycerine, polypropylene glycol, polyethylene glycol, lactic acid, pyrrolidones contains carbonic acid, urea, phosphatide, collagen, elastin laminin, ceramide, lecithin D-sorbite, PEG-4 and composition thereof.Other suitable wetting agent is water-soluble and/or the polymer wetting agent of polysaccharide family that can expand and/or the water-setting colloidality, for example hyaluronic acid, shitosan and/or the Fucogel that can obtain from SOLABIA S
Figure 2006800258799_6
The polysaccharide that is rich in fucose of 1000 (CAS-Nr.178463-23-5).One or more wetting agents alternatively with account for the present composition from about 0.5wt.% to about 8wt.%, preferably the dosage from about 1wt.% to about 5wt.% exists.
The water of the preferred topical composition of the present invention can contain cosmetics commonly used or the medicine additive is for example pure, lower alcohol (preferred alcohol and/or isopropyl alcohol) particularly, lower glycol or polyalcohol and ether thereof, preferred propane diols, glycerine, ethylene glycol, glycol monomethyl ethyl or single-butyl ether, propylene glycol monomethyl or single ethyl or single-butyl ether, diglycol monotertiary methyl or single ethylether and similar products; Polymer; Foam stabiliser; Electrolyte and one or more thickeners especially.Can be used for that the suitable thickener with the assist in generating homogeneity of product comprises in the present invention prescription: carbomer, silica, magnesium silicate and/or alumina silicate, beeswax, stearic acid, stearyl alcohol polysaccharide and derivative thereof (for example xanthans, hydroxypropyl cellulose, polyacrylamide), acrylate copolymer, preferred carbomer (independent 980,981,1382,2984,5984 type carbopole for example
Figure 2006800258799_7
Or its mixture).Can be included in the present composition the suitable nertralizer in order to the composition of neutralize emulsifying agent for example or foam dose/stabilizing agent, include but not limited to alkaline hydrated oxide, for example NaOH and potassium hydroxide; Organic base such as diethanol amine (DEA), triethanolamine (TEA), aminomethyl propanol and composition thereof; Amino acid, for example arginine and lysine and any combination of aforementioned substances arbitrarily.Nertralizer can be with about 0.01wt.% to about 8wt.%, and preferably 1wt.% is present in the composition of the present invention to the dosage of about 5wt.%.
Adding electrolyte in the present composition can be essential with the performance that changes hydrophobic emulsifying agent.Therefore, emulsion/microemulsion of the present invention can preferably contain a kind of or the some kinds of electrolyte that comprise the salt of anion, comprises chloride, sulfate, carbonate, borate or aluminate, but is not limited only to this.Other suitable electrolyte can be based on organic anion, for example (but being not limited to) lactate, acetate, benzoate, propionate, tartrate and citrate.For cation, preferably select ammonium, alkylammonium, alkali metal or alkaline-earth metal, magnesium ion, iron ion or zinc ion.Particularly preferred salt is potassium chloride and sodium chloride, magnesium sulfate, zinc sulfate and composition thereof.Electrolyte can be present in the composition of the present invention to the dosage of about 8wt.% with about 0.01wt.%.
Topical composition of the present invention can be preferably provides with the form of emulsion, gel, creme, breast, ointment, powder or the solid tube glue rod of emulsion, thickening, optionally is packaged as aerosol, can provide with the form of mousse, foam or spraying.Also can be suspension in solvent or the fatty material or the form of dispersion liquid according to topical composition of the present invention, or the form of emulsion or microemulsion (particularly O/W or w/o type, O/W/O or w/o type), for example creme or breast, vesicle dispersant (vesicular dispersion) is perhaps with ointment, gel, solid tube glue rod or aerosol mouse form.Emulsion also can comprise the surfactant of anion, non-ionic, cationic or both sexes.
Term " but composition of oral application " comprises (reinforcement) food, (reinforcement) (animal) feed and the beverage of any kind, also comprises clinical nutrition product and food additives and corresponding additive: food additive, beverage additive, feed addictive.Also comprise functional food/functional feed, i.e. food/the feed of the health benefits that strengthens to provide how special with vitamin or pharmaceutical preparation, and nutrient drug namely has pill or the other medicines product of nutritive value.
But the composition according to oral application of the present invention can also contain the hydrocolloid of protectiveness (as colloid; protein; the starch of modifying); adhesive; become membrane agent; encapsulation agent (encapsulatingagent)/material; wall/shell material; matrix compounds; dressing; emulsifying agent; surfactant; solubilizer (oil; fat; wax; lecithin etc.); adsorbent; carrier; filler; auxilliary compound; dispersant; wetting agent; processing aid (solvent); flowable; mask agent; weighting agent; jelly; gel former; antioxidant and antimicrobial.
Can also contain according to composition of the present invention and to be selected from following compound: vitamin C and derivative thereof (as ascorbic acid acetate, ascorbic acid four different palmitates, magnesium ascorbyl phosphate, STAY-C 50, ascorbic acid sodium acetate), vitamin E and derivative (for example alpha-tocopherol acetate) thereof, resveratrol, (-)-Epigallo-catechin gallate (EGCG) and composition thereof are preferably selected from compound of resveratrol and (-)-Epigallo-catechin gallate (EGCG) and composition thereof.
But the composition according to oral application of the present invention can be the form (galenic form) that is applicable to the Orally administered any galenica of animal body (comprising human body), for example solid form such as food or feed, food or feed are pre-mixed the food of thing, reinforcement or feed (additive/additive), tablet, pill, granule, lozenge, capsule and effervesce prescription such as powder and tablet, or liquid form, as solution, emulsion or suspension, for example beverage, paste and oil suspension.Paste can be packed in duricrust or the soft shell capsule, and wherein said capsule has the matrix of gelatin (from separate sources such as pig, ox or poultry), starch or starch derivatives or other polymer (for example cellulose derivative).But the composition of oral application can be the form of controlled (delay) release formulation.
The example of enriched food comprises cereal bars, cures thing such as cake and cookies.
Beverage comprises soft and alcoholic drink, and will add the liquid preparation in the into drinking water and liquid food.Soft drink is for example soft drink, sports drink, fruit juice, lemonade, tea and milk beverage.Liquid food is for example soup and dairy products.
In certain preferred embodiments of the present invention, but the composition of oral application is beverage, contain 0.1 to 40mg amount, preferred 0.5 to the 25mg lutein of measuring in the described beverage every liter [L], and/or 0.1 lycopene to 60mg amount, preferred 1 to 30mg amount, and/or 0.1 to 20mg amount, β-the kryptoxanthin of preferred 0.5 to 15mg amount, and/or 1 to 500mg amount, preferred 5 arrives the CoQ-10 of 60mg amount.In another preferred embodiment, contain the lutein of 0.2 to 50mg amount in the described beverage every liter [L], and/or the lycopenes of 2 to 50mg amounts, and/or the β-kryptoxanthin of 0.1 to 30mg amount, and/or the CoQ-10 of 1 to 200mg amount.
In preferred embodiments more of the present invention, but the composition of oral application is beverage, the beta carotenes that also contain 1 to 50mg amount, preferred 2 to 10mg amounts in every liter of the described beverage, and/or 100 vitamin Cs to 5000mg amount, preferred 200 to 1000mg amounts, and/or 15 vitamin Es to 2000mg amount, preferred 100 to 500mg amounts, and/or 5 to 100mg, the resveratrol of preferred 10-50mg amount, and/or (-)-Epigallo-catechin gallate (EGCG) of 10 to 1500mg amounts, preferred 15-500mg amount.
Be used for purposes of the present invention, particularly preferred beverage contains the vitamin C of 120mg, the vitamin E of 21mg, the beta carotene of 2.4mg, the lutein of 1mg, β-kryptoxanthin of 0.2mg, the lycopene of 4.8mg, the resveratrol of 20mg and (-)-nutgall catechin gallic acid ester of 300mg for every part, wherein every part of size is 240mL.
Animal in the context of the invention can be mammal (comprising the people), fish and bird.
Preferred mammiferous example comprises dog, cat, guinea pig, screech owl rabbit (jackrabbit), hare, ferret, horse and ruminant (ox, sheep and goat) except the people.Preferred fish is for example canary of pet fish (aquarium fish) (goldfish, bright and beautiful carp (koi)), cage bird.
Of the present invention other to as if following method:
-keep the method for energetic supersession in animal (the comprising the people) skin or skin, it comprises step: the combination at least a compound that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin (preferably being selected from lutein, lycopene and β-kryptoxanthin) of described (using to the preferred oral) effective dose that has the animal of needs to use and composition thereof and itself and CoQ-10 comprises all their stereoisomers.
-keep the method for the respiratory function of animal (comprising the people) skin, it comprises step: the combination at least a compound that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin (preferably being selected from lutein, lycopene and β-kryptoxanthin) of described (using to the preferred oral) effective dose that has the animal of needs to use and composition thereof and itself and CoQ-10 comprises all their stereoisomers.
The method of the radiation-induced mtDNA mutagenesis of UV-A in-prevention animal (the comprising the people) skin, it comprises step: the combination at least a compound that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin (preferably being selected from lutein, lycopene and β-kryptoxanthin) of described (using to the preferred oral) effective dose that has the animal of needs to use and composition thereof and itself and CoQ-10 comprises all their stereoisomers.
The effective dose of lutein is the concentration amount in the scope between 0.25 and 3 μ M of using lutein in the blood plasma of back that makes in these three kinds of methods.
The effective dose of lycopene is to make the concentration use lycopene in the blood plasma of back between 0.25 and 3.0 μ M in these three kinds of methods, from 0.5 to 1.0 μ M preferably, preferred between 0.5 and 2.0 μ M the amount in the scope.
The effective dose of β-kryptoxanthin is to make the concentration of using β-kryptoxanthin in the blood plasma of back between 0.1 and 2 μ M in these three kinds of methods, preferably the amount in from 0.25 to the 5 μ M scope.
The effective dose of CoQ-10 is to make the concentration of using CoQ-10 in the blood plasma of back at 5 to 10 μ M in these three kinds of methods, the amount between the preferred 5 and 8 μ M in the scope.
In the certain preferred embodiments of these methods, described compound/carotenoid and at least a compound combination that is selected from vitamin C, vitamin E, resveratrol and (-)-nutgall catechin gallic acid ester are preferably with the compound combination that is selected from resveratrol and (-)-nutgall catechin gallic acid ester.
According to the present invention; the combination of at least a compound and composition thereof that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin and itself and CoQ-10 also can be used in opacifier and the daily nursing product; to improve their light protective capability; and as effective micronutrient of safeguarding skin, especially for energetic supersession/energy stream and/or energy production and the respiratory function of (the comprising the people) skin that watches for animals.
Therefore; a further object of the invention is for the method that improves opacifier and daily nursing product light protective capability; described method comprises step: the combination of at least a compound that is selected from beta carotene, lutein, lycopene and β-kryptoxanthin and composition thereof that adds effective dose and itself and CoQ-10 comprises all their stereoisomers.Herein the concentration of lutein can 0.01 and 1000ppm between, more preferably 0.1 and 50ppm, most preferably 0.5 and 5ppm between change, this is the gross weight according to opacifier or daily nursing product.The concentration of lycopene can 0.01 and 1000ppm between, more preferably 0.1 and 50ppm between, most preferably 0.5 and 10ppm between change, this is the gross weight according to opacifier or daily nursing product.The concentration of CoQ-10 can be between the 0.001 and 1.0 weight %, more preferably change between the 0.01 and 0.3 weight %, and this is the gross weight according to opacifier or daily nursing product.The concentration of β-kryptoxanthin can 0.01 and 1000ppm between, more preferably 0.1 and 10ppm between, most preferably 0.2 and 5ppm between change, this is the gross weight according to opacifier or daily nursing product.
In addition according to the present invention; the combination of at least a compound and composition thereof that is selected from lutein, lycopene and β-kryptoxanthin and itself and CoQ-10 also can be used in opacifier and the daily nursing product; to improve their photoprotection ability; as effective micronutrient of safeguarding skin, especially for energetic supersession/energy stream and/or energy production and the respiratory function of (the comprising the people) skin that watches for animals.
Therefore; it is for the method that improves opacifier and daily nursing product light protective capability that the present invention also has a kind of purpose, and described method comprises the steps: to add the combination of at least a compound that is selected from lutein, lycopene and β-kryptoxanthin of effective dose and composition thereof and itself and CoQ-10.Herein the concentration of lutein can 0.01 and 1000ppm between, more preferably 0.1 and 50ppm, most preferably 0.5 and 5ppm between change, this is the gross weight according to opacifier or daily nursing product.The concentration of lycopene can 0.01 and 1000ppm between, more preferably 0.1 and 50ppm between, most preferably 0.5 and 10ppm between change, this is the gross weight according to opacifier or daily nursing product.The concentration of β-kryptoxanthin can 0.01 and 1000ppm between, more preferably 0.1 and 10ppm between, most preferably 0.2 and 5ppm between change, this is the gross weight according to opacifier or daily nursing product.
All active components, particularly beta carotene, lutein, lycopene, β-kryptoxanthin and the CoQ-10 of use related to the present invention can be that maybe can be chemical synthesis (comprising biotechnology/genetic engineering method) (namely the separating from natural origin) of natural origin.
Particularly preferably being can be from DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland) lycopene that obtains with trade name redivivo 10%FS, redivivo (lycopene) 10%WS commerce.
Particularly preferably being can be from DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland) commercial beta carotene, lycopene, lutein, CoQ-10 and the β-kryptoxanthin that obtains.The product form of lycopene, lutein and CoQ-10 is for example from the known trade name redivivo of DSMNutritional Products TM(lycopene) 10%FS, redivivo TM(lycopene) 10%WS, redivivo TM(lycopene) 5%TG or TG/P, lutein CWS/S-TG, TG or TG/P and All-Q TM(Co-Q10) 10%TG/P or CWS/S.
Other is suitable can the commercial product that obtains to be LycoVit (Lycopene) TG 10%, Lycovit 20% Dispersion, Lutein 5% DC or Coenzyme Q10 10%DC from BASF, and from Lycobeads 5%, LycoPen 2% SG Dispersion and the Lyc-O-Mato 15% of Lycored, from the FloraGlo (lutein) of Kemin, from the Xangold of Cognis
Figure 2006800258799_8
10%Natural Lutein Esters Beadlet is from the following lutein form of PIVEG: as Beadlets-25%; Beadlets CWD 25% (can be scattered in cold water); Oil-20%; The lutein of Powder-70% and from the CoQ10 of Kaneka.
By following examples the present invention is further set forth.
Embodiment
General
Chemicals
Carotenoid, lutein, lycopene, β-kryptoxanthin and luteole are from DSMNutritional Products AG (Kaiseraugst, chemical laboratory Switzerland).Ammonium acetate p.a., butylated hydroxy-methylbenzene (BHT) p.a., oxolane (THF) p.a., triethylamine p.a. from Fluka Chemie AG (Buchs, Switzerland), all other chemicals from Merck (Darmstadt, Germany).
Standard liquid
Be dissolved in the storage solutions for preparing lutein, lycopene, β-kryptoxanthin and luteole in 0.025% BHT (v/w) solution by the compound with 3-5mg.Measure suitable dilution factor concentration according to the Lambert-Beer rule and based on extinction coefficient (1%/lcm) by photometer measurement at once afterwards.
Culture medium
As Free Radicals Biol.Med.2003, described in 34, the 456-464, lutein, lycopene, β-kryptoxanthin and luteole are sent in the cultured cells.In brief, containing THF and 0.025% BHT is used to send complete carotenoid and contrast solution in the normal person fibroblast of cultivating as the above-mentioned storage solutions of anticorrisive agent and carrier.As mentioned above, with photometer measurement employed carotenoid concentration, and use carotenoid THF and the THF solution with the concentration of from 0 to 3 μ M of appointment in the culture medium.
Cell culture
People's foreskin sample from circumcision is set up the SF culture, and Eagle ' s Min. basal medium (PAA Laboratories GmbH, Linz, Austria) the middle cultivation.Containing 5%CO 2Wet air in cell is cultured to fusion.
Embodiment 1: when having lutein, lycopene, β-kryptoxanthin and luteole the fell fibroblast is carried out UV-A-irradiation and analyze
UV-A-irradiation
As J.Biol.Chem.1999, the described UV-A-irradiation that carries out of 274,15345-15349.Cell is by the 8J/cm from Sellas Sunlight (Systems Dr.Sellmeier) irradiation apparatus 2The UV-A radiation.UV-A output is by UV-A-Meter (Waldmann GmbH ﹠amp; Co.KG, Villingen-Schwenningen Germany) measures, and finds that under its pipe at 30cm-target distance approximately be every square centimeter of 70 milliwatt.In order to induce common deletion, in a week or continuous two weeks with cell irradiation every day three times, continuous 4 days.Then by trypsase digestion collecting cell.The cell that keeps half is used for the DNA extracting, second half again coated plate be used for continuing to cultivate.
The DNA extracting
Use QIAmp Tissue Kit (Qiagen, Hilden, Germany) extracting cell DNA from normal HF.
Pcr analysis
As J.Invest.Dermatol.1998,110,149-152 and Leukemia 1995,9 carry out nested PCR described in the 1704-1710.In brief, use primer C1 and C2 amplification to obtain the PCR product of long 247 base-pairs, can assessing the total amount of mtDNA in the solution, thereby as with reference to fragment.By the combination of primer to A1/A2 and B1/B2, amplify this fragment of the common deletion of representative.Primer tasteless nucleotide A1/A2 is designed to the regional annealing outside the common deletion in mitochondrial genomes.In addition, polymerase extension event is selected as the amplification fully of wild type PCR product too short, and the mtDNA-fragment with deletion that causes only more lacking is effectively increased.In order to improve sensitivity and specificity, carry out second from elementary PCR product and take turns nested PCR (B1/B2).The linear amplification condition such as the P.Henninger et al.in Biol.Chem.Hoppe-Seyler 1993,374 that are used for 35 circulations at the most of each base-pair, 625-629 is described to be determined.In the 100 μ l reaction volumes that contain 0.1-0.3 μ g genomic DNA and 0.5 Taq of unit polymerase, carry out elementary PCR (A1/A2 and C1/C2).Use primer and nucleotides with the concentration of 1 μ M and 400 μ M respectively.Perkin-Elmer DNAThermal Cycler 480 (Perkin-Elmer Applied Biosystems, Weiterstadt, Germany) in amplification PCR product, primer tasteless nucleotide by Invitrogen (Karlsruhe, Germany) synthetic.
Primer tasteless nucleotide
Following sequence and oligonucleotides position (showing in round parentheses) are according to Anderson et al.in Nature 1981,290,457-465's: A1,5 ' GCA GTA ATA TTA ATA ATT TTCATG 3 ' (7293-7316); A2,5 ' CTA GGG TAG AAT CCG AGT ATG TTG 3 ' (13928-13905); B1,5 ' TGA ACC TAC GAG TAC ACC GA 3 ' (7901-7920); B2,5 ' GGG GAA GCG AGG TTG ACC TG 3 ' (13650-13631); C1,5 ' ATGCTT GTA GGA CAT AAT AA 3 ' (219-238); C2,5 ' AGT GGG AGG GGAAAA TAA TA, 3 ' (466-447).
The dna gel electrophoresis
(Sigma-Aldrich Chemie GmbH, Munich Germany) carry out in 1% of dyeing the Ago-Gel using ethidium bromide (0.20 μ l/ml).
Restriction Enzyme is analyzed
The identity of amplification PCR products in order to identify digests analysis with Restriction Enzyme XbaI (New EnglandBiolabs) to fragment.
The result
The effect of lycopene
3 independently experiments have been made up altogether.In all 3 experiments, the consistent lycopene of finding protects fibroblast to avoid the generation of the radiation-induced common deletion of UV-A.
Representative result of experiment is presented in the table 1: after 1 week, the UV-A radiation can induce " half deletion " as the mark sudden change of extensive DNA deletion in the fell fibroblast, and factor is 18.In the dosage (0.25-3 μ M) of all tests, add the formation that lycopene has suppressed the radiation-induced common deletion of UV-A.Observe protection fully at 0.5,1 μ M and 2 μ M places.
Table 1: the effect of lycopene
Given lycopene concentration in UV-A radiation+cell With respect to untreated cell, the popularization degree of mtDNA deletion
0 18.13
0.25μM 2.90
0.5μM 1.22
1.0μM 1.53
2.0μM 1.53
3.0μM 2.52
The effect of lutein
3 independently experiments have been made up altogether.In all 3 experiments, find that lutein protection fibroblast avoids the generation of the radiation-induced common deletion of UV-A.
Representative result of experiment is presented in the table 2: after 1 week of UV-A radiation, can be observed factor and be 6 common deletion and induce.Under the concentration (0.25-3 μ M) of all tests, lutein can prevent to induce fully.
Table 2: the effect of lutein
Given lutein concentration in UV-A radiation+cell With respect to untreated cell, the popularization degree of mtDNA deletion
0 8.39
0.25μM 0.98
0.5μM 0.27
1.0μM 0.71
2.0μM 0.37
3.0μM 0.59
The effect of kryptoxanthin
Made up 3 independently experiments altogether, representational experiment is shown among Fig. 3.After 2 weeks, the UV-A radiation factor is 6 common deletion.Under the concentration of all tests, induce by β-kryptoxanthin and abolish fully.
Table 3: the effect of β-kryptoxanthin
Given β-kryptoxanthin concentration in UV-A radiation+cell With respect to untreated cell, the popularization degree of mtDNA deletion
0 3.93
0.1μM 0.80
0.25μM 0.64
0.5μM 0.25
1.0μM 0.62
2.0μM 0.25
3.0μM 1.03
The effect of luteole
3 experiments have been made up altogether.Luteole all shows in any experiment does not have effect.
Embodiment 2: the preparation beverage
(C) WS=(cold) water soluble, S=starch, TG=tablet grade, CC=transparent crystal
The fruit juice basic recipe [g]
The orange juice concentrate, low 65 ° of Brix Scales of pulp 594.0
70 ° of Brix Scales of carrot fruit juice concentrates 84.0
65 ° of Brix Scales of clarification lemon juice 39.0
The orange flavor oil 0.5
Ethanol p.a. 0.5
Deionized water 265.72
Ascorbic acid 7.14
Beta carotene 10%CWS/S 1.43
Lutein 5%CWS/S-TG 1.14
β-kryptoxanthin 5%CWS 0.2
Lycopene 10%CWS/S-TG 2.86
Vitamin E 15%CC 8.57
[0208]
Amount to 1000.0
Dissolving carotenoid and vitamin E product form in the part deionized water.
The blended fruit juice concentrate adds remaining water, gentle agitation predissolve carotenoid and vitamin E product form.
In mixture, add ascorbic acid, be stirred to dissolving.
Orange oil and ethanol premix are combined into the oil component of homogeneous phase, it is added in fruit juice concentrates.
With the rotor-stator homogenizer with its pre-emulsification.
With high pressure homogenizer P 1200bar, P 2The 50bar homogenize.
Emulsion is carried out pasteurizing (72 ℃, 15 seconds).
Should leave standstill before emulsion uses at least one day, and be stored in shady and cool place.
Drink formula [g]
64 ° of Brix Scales of syrup 156.2
Sodium Benzoate 0.2
Deionized water 43.6
Teavigo TM 0.1
Beverage matrix 70.0
Running water extremely 1000.0
Teavigo is DSM Nutritional Products Ltd., Kaiseraugst, and Switzerland is used for the trade mark of (-)-nutgall catechin gallic acid ester (EGCG).
Sodium Benzoate is dissolved in the deionized water, stirs adding syrup and (-)-nutgall catechin gallic acid ester down.
Stir and add beverage matrix down.
With running water mixture is adjusted to one liter of beverage.
Pack in the vial and carry out pasteurizing (72 ℃, 15 minutes).
Embodiment 3: the preparation beverage
Prepare fruit juice matrix in the mode similar to embodiment 2:
Fruit juice matrix [g]
The orange juice concentrate, low 65 ° of Brix Scales of pulp 594.0
[0226]
70 ° of Brix Scales of carrot fruit juice concentrates 84.0
65 ° of Brix Scales of clarification lemon juice 39.0
The orange flavor oil 0.5
Ethanol p.a. 0.5
Deionized water 265.72
Ascorbic acid 7.14
Lutein 5%CWS/S-TG 1.14
Vitamin E 15%CC 8.57
Amount to 1000.0
According to the step of mentioning among the embodiment 2 fruit juice matrix is processed into final beverage.
Drink formula [g]
64 ° of Brix Scales of syrup 156.2
Sodium Benzoate 0.2
Deionized water 43.6
Teavigo TM 0.1
Beverage matrix 70.0
Running water extremely 1000.0
Embodiment 4: the preparation beverage
Prepare fruit juice matrix in the mode similar to embodiment 2:
Fruit juice matrix [g]
The orange juice concentrate, low 65 ° of Brix Scales of pulp 594.0
70 ° of Brix Scales of carrot fruit juice concentrates 84.0
65 ° of Brix Scales of clarification lemon juice 39.0
The orange flavor oil 0.5
Ethanol p.a. 0.5
[0232]
Deionized water 265.72
Ascorbic acid 7.14
β-kryptoxanthin 5%CWS/S-TG 0.2
Vitamin E 15%CC 8.57
Amount to 1000.0
According to the step of mentioning among the embodiment 2 fruit juice matrix is processed into final beverage.
Drink formula [g]
64 ° of Brix Scales of syrup 156.2
Sodium Benzoate 0.2
Deionized water 43.6
Teavigo TM 0.1
Beverage matrix 70.0
Running water extremely 1000.0
Embodiment 5: the preparation beverage
Prepare fruit juice matrix in the mode similar to embodiment 2:
Fruit juice matrix [g]
The orange juice concentrate, low 65 ° of Brix Scales of pulp 594.0
70 ° of Brix Scales of carrot fruit juice concentrates 84.0
65 ° of Brix Scales of clarification lemon juice 39.0
The orange flavor oil 0.5
Ethanol p.a. 0.5
Deionized water 265.72
Ascorbic acid 7.14
Lycopene 10%CWS/S-TG 2.86
Vitamin E 15%CC 8.57
Amount to 1000.0
[0238]According to the step of mentioning among the embodiment 2 fruit juice matrix is processed into final beverage.
Drink formula [g]
64 ° of Brix Scales of syrup 156.2
Sodium Benzoate 0.2
Deionized water 43.6
Teavigo TM 0.1
Beverage matrix 70.0
Running water extremely 1000.0
Embodiment 6: the preparation cereal bars
Redivivo is DSM Nutritional Products Ltd., Kaiseraugst, and Switzerland is used for the trade mark of lycopene.
The composition that is used for the 1kg prescription [g]
The fructose that pulverizes 120.0
Honey 150.0
Frangible cereal 145.0
Cornflakes 100.0
Raisins 110.0
Almond 85.0
Shredded coconut stuffing 90.0
Vegetable oil 60.0
Emulsifying agent 5.0
Glucose syrup 58.0
Maltodextrin powder DE 10 71.0
The mixed tocopherol of doing 30% 0.1
Water 9.0
Redivivo
Figure 2006800258799_9
(lycopene) 10% WS or lutein 5%CWS/S
0.5 1.0
[0243]-(can commerce derive from DSMNutritional Products Ltd., Kaiseraugst is Switzerland) with other dry ingredient (for example maltodextrin powder, the fructose that pulverizes) premixed with lycopene 10% WS or lutein 5% CWS/S.
-in stirring bowl, mix all the components up to the mixture that forms homogeneous phase.
-mixture is coated with about 1cm being coated with oily baking tray.
-cured 20 minutes at 180 ℃.
-make the cereal bars plate be cooled to room temperature and be cut into the piece of rod size.
-packing and sealing in the aluminium bag.
Embodiment 7: the plain sheet (straight tablet) of preparation CoQ-10
Composition Label Excessive Amount
Mg The Mg/ sheet
1 Co-Q10, the form that can directly compress 30 20
As ALL-Q 10%TG/P 360.00
2 Lactose list hyrate, the one-tenth piece
As Tablettose 80 (1) 416.00
3 Glyceryl behenate, atomizing
As Compritol 888ATO (2) 16.00
4 Crospovidone (crospovidone)
As Polyplasdone XL-10 (3) 8.00
Total tablet is heavy 800.00
Auxiliary material supplier:
(1)Tablettose 80:Fa.Meggle,Megglestr.6-12,83512 Wasserburg,Germany
(2)Compritol 888 ATO:Fa.Gattefosse AG,Haldenstr.11,6006 Luzern,Switzerland
(3)Polyplasdone XL 10,ISP Technologies Inc.,Wayne,New Jersey,USA
Step
I mixed 5 minutes in rotary drum mixer 1,2 and 4
II adds among the I with 3 and mixed 20 minutes
III presses and is tablet
Embodiment 8: preparation contains the tablet of lycopene, lutein, CoQ-10 and β-kryptoxanthin
Composition The trade mark claim Excessive Amount
Mg The Mg/ sheet
1 Co-Q10, the form that can directly press 30 20
As ALL-Q 10% TG/P 360.00
2 Lycopene, the form that can directly press
As redivivo 5% TG/P 240.0
3 Lutein, the form that can directly press
As lutein 5% CWS/S-TG 120.00
4 β-kryptoxanthin, the form that can directly press
As β-kryptoxanthin 5% beadlets 72.00
5 Lactose list hyrate, the one-tenth piece
As Tablettose 80 (1) 784.00
6 Crospovidone
As Polyplasdone XL-10 (2) 16.00
7 Dolomol 8.00
Total tablet is heavy 800.0
Auxiliary material supplier
(1)Tablettose 80:Fa.Meggle,Megglestr.6-12,83512 Wasserburg,Germany
(2)Polyplasdone XL 10,ISP Technologies Inc.,Wayne,New Jersey,USA
Step
I is with 1-6 mixture 15 minutes in rotary drum mixer
II adds I with 7 and mixed 2 minutes
III presses and is tablet

Claims (10)

1. the combination that only is made of lutein and CoQ-10 is for the manufacture of the purposes of composition, described composition is used for keeping energetic supersession, energy stream and/or the energy production of animal skin or skin, keep zoodermic respiratory function, for the skin energy supply, keep and support zoodermic brightness and natural gloss, with the zoodermic healthy appearance of promotion, with the radiation-induced mtDNA mutagenesis of UV-A in the prevention animal skin, described animal comprises the people.
2. purposes according to claim 1, but wherein said composition is the composition of oral application.
3. the combination that only is made of lutein and CoQ-10 is used for improving the purposes of opacifier and daily nursing product photoprotection ability.
4. composition, its active component is made up of lutein and the CoQ-10 of effective dose, it is characterized in that described amount is for keeping in the animal skin or the energetic supersession of skin, energy stream and/or energy production, keep zoodermic respiratory function, for the skin energy supply, keep and support zoodermic brightness and natural gloss, with promote that the radiation-induced mtDNA mutagenesis of UV-A is that effectively described animal comprises the people in zoodermic healthy appearance and the prevention animal skin.
5. composition according to claim 4, but wherein said composition is the composition of oral application.
6. according to each described composition in the claim 4 to 5, it is characterized in that it is enriched food, beverage, fortified feed or corresponding additive, functional food, functional feed, nutrient drug, clinical nutrition product or food additives.
7. according to the composition of claim 4, it is characterized in that it is the form of tablet, pill, granule, lozenge, capsule or effervescent agent prescription.
8. according to the composition of claim 4, it is characterized in that the people of counterweight 70kg, lutein every day dosage from 0.1 to 40mg, and/or CoQ-10 every day dosage from 1 to 500mg.
9. according to the composition of claim 4 or claim 5, it is characterized in that it is beverage, contain the lutein of 0.2 to 50mg amount in every liter of the described beverage, and/or the CoQ-10 of 1 to 200mg amount.
10. improve the method for the light protective capability of opacifier and daily nursing product, described method only comprises the steps: to add the combination that lutein and CoQ-10 by effective dose constitute.
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US5290605A (en) * 1989-06-29 1994-03-01 Niva Shapira Sun-exposure nutritional supporting composition
EP0712630A3 (en) * 1994-11-17 1996-05-29 Jcb Cosmetiques Oral composition for the prevention of sun allergies containing a carotenoid, a tocopherol, ascorbic acid and selenium
US6110478A (en) * 1996-06-12 2000-08-29 Laboratoire Oenobiol Composition having tanning and photoprotective activity, and its cosmetic applications

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US5290605A (en) * 1989-06-29 1994-03-01 Niva Shapira Sun-exposure nutritional supporting composition
EP0712630A3 (en) * 1994-11-17 1996-05-29 Jcb Cosmetiques Oral composition for the prevention of sun allergies containing a carotenoid, a tocopherol, ascorbic acid and selenium
US6110478A (en) * 1996-06-12 2000-08-29 Laboratoire Oenobiol Composition having tanning and photoprotective activity, and its cosmetic applications

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