CN102949307A - LTBP-4 generation accelerant - Google Patents
LTBP-4 generation accelerant Download PDFInfo
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- CN102949307A CN102949307A CN201210280020XA CN201210280020A CN102949307A CN 102949307 A CN102949307 A CN 102949307A CN 201210280020X A CN201210280020X A CN 201210280020XA CN 201210280020 A CN201210280020 A CN 201210280020A CN 102949307 A CN102949307 A CN 102949307A
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Abstract
The invention discovers the physiological activity of algae or plant extracts and applies it to new uses. The invention relates to an LTBP-4 generation accelerant for preparing algae or plant extracts as active ingredients. Described algae or plant extracts belong to red algae, such as Acrochaetiales, Porphyridiales Kylin, Bangiales, Nemalionales, Erythropeltidales Garbary Hansen et Scagel, Composopogonaceae, Cryptonemiales, Corallinales Silva et Johansen, Palmaria palmata, Gelidiales, Rhodogorgonales, Hildenbrandiales Pueschel&Cole, Batrachospermales, Gigartinales, Asparagus, Rhodymeniales, and Ceramiale of red algae, and belong to green algae, such as Volvocales, Sphaeropleales, Oedogoniales, Chaetophorales, Chlorella, Microthamniales, Trebouxiales, Prasiolales, Monomastigales, Dolichomastigales, Trentepohliales, Oltmannsiellopsidales, Chlorodendrales, Dolichomastigales, Nephroselmidales, Ulotrichales, Ulvales, Cladophorales, Acrosiphoniales, Siphonocladales, Caulerpales, Codiales, Bryopsidales, Dasycladales of green algae, and belong to brown algae, such as Dictyotales, Chordariales, Scytosiphonales, Cutleriales, Sporochnales, Desmarestiale, Laminariale and Fucales, and belong to the plant extracts of labiatae, leguminosae, rhamnaceae, actinidiaceae, polygonaceae, grapes, compositae, gentianaceae, comfrey, tremella, lotus, mallow, rutaceae, zingiberaceae and rubiaceae.
Description
Technical field
This relates to the LTBP-4 (Latent TGF β-binding protein-4) that contains algae extract or plant extract and produces promoter.
Background technology
LTBP (Latent TGF β-binding protein; Proliferation factor-beta conjugated protein) section (family) is the protein of the identical Superfamily of fibrin of the fibrous proteins that belong to relevant with solidifying of blood, have by the latent TGF β in conjunction with inertia, TGF β is stored in the matrix with inert condition, and can makes when needed it from the effect of hiding-place activation.
In this proteinoid, known LTBP-4 is relevant with some disease and the function in the living body.That is, except the expression of LTBP-4 and related (non-patent literature 1) between cancer is sent out, also reported calm wait (patent documentation 1) of elastin laminin when LTBP-4 can promote that the inside and outside elastic fiber of organism forms.And then, also have report to claim: in variation LTBP-4 (LTBP4-/-) mice, to find emphysema, possessed the relevant and emophysematous feature of Delayed onset (non-patent literature 2 and patent documentation 2) of falling ill of COPD with the people.
Patent documentation
Patent documentation 1: TOHKEMY 2011-26236 communique
Patent documentation 2: the international WO03/015505 communique that discloses
Non-patent literature
Non-patent literature 1:Bertucci F., et al.Oncogene.23:1377-91,2004
Non-patent literature 2:Sterner-Kock A., et al.Genes Dev.16:2264-2273,2002
Summary of the invention
In the present invention, to be to provide the useful protein with such physiologically active be the generation promoter of LTBP-4 to its purpose.
The inventor conducts in-depth research repeatedly in order to solve above-mentioned problem, found that algae extract or plant extract have LTBP-4 and produce the promotion ability, thereby has finished the present invention.
That is, the present invention relates to contain the LTBP-4 generation promoter of algae extract or plant extract.
Above-mentioned LTBP-4 produces promoter and contains the extract of red algae, green algae or Brown algae as effective ingredient.
Above-mentioned red algae can belong to jackscrew Cutleriales (Acrochaetiales) for being selected from, Porphyridium cruentum order (Porphyridiales), Bangiales (Bangiales), Nemalionales (Nemaliales), red shield Cutleriales (Erythropeltidales), curved branch Cutleriales (Compsopogonales), Cryptonemiales (Cryptonemiales), Corallium Japonicum Kishinouye Cutleriales (Corallinales), ZHANGZAO order (Palmariales), Gelidiales (Gelidiales), the Rhodogorgonales order, kermes Cutleriales (Hildenbrandiales), Bai'an Cutleriales (Bonnemaisoniales), beading Cutleriales (Batrachospermales), Gigartinales (Gigartinales), Thallus Gracilariae order (Gracilariales), Phodymeniales (Rhodymeniales), at least a red algae in the algae of Yi Gu Cutleriales (Ahnfeltiales) and Ceramiale (Ceramiales).
Above-mentioned green algae can be to be selected to belong to volvocales (Volvocales), ring Cutleriales (Sphaeropleales), Oedogoniales (Oedogoniales), Chaetophorales (Chaetophorales), Chaetophorales (Chaetopeltidales,), bead Cutleriales (Chlorellales), the Microthamniales order, the Trebouxiales order, the Prasiolales order, small stream Cutleriales (Mamiellales), the Monomastigales order, the Dolichomastigales order, Trentepohliales (Trentepohliales), the Oltmannsiellopsidales order, the Chlorodendrales order, the Dolichomastigales order, the Nephroselmidales order, Ulotrichales (Ulotrichales), Ulvales (Ulvales), Cladophorales (Cladophorales), push pipe Cutleriales (Acrosiphoniales), Siphonocladales (Siphonocladales), Caulerpa order (Caulerpales), pine Cutleriales (Codiales), at least a green algae in the algae of plumage Cutleriales (Bryopsidales) and Dasycladales (Dasycladales).
Above-mentioned Brown algae can be to be selected to belong to brown shell Cutleriales (Ralfsiales), Dictyotales (Dictyotales), Chordariales (Chordariales), Scytosiphon lomentarius (Lyngh.)J. Ag. order (Scytosiphonales), Cutleriales (Cutleriales), burr Cutleriales (Sporochnales), Desmarestiale (Desmarestiales), Laminariales (Laminariales), at least a Brown algae in the algae of stable dish order (Ishigeales) and Fucales (Fucales).
Above-mentioned plant extract can be to be selected from least a extract that belongs in Labiatae, pulse family, Rhamnaceae, Actinidiaceae, Polygonaceae, Vitaceae, Compositae, Gentianaceae, Boraginaceae, Tremellaceae, Nelumbonaceae, Radix Malvae sylvestris material, Rutaceae, Zingiberaceae and the rubiaceous plant.
The invention still further relates to contain above-mentioned any LTBP-4 produce promoter, LTBP-4 produces composition for promoting.At this, the content of the extract of algae or plant is converted into dry weight, is preferably 0.000001～99 % by weight, more preferably 0.00001～30 % by weight, more preferably 0.0001～10 % by weight, be particularly preferably 0.001～5 % by weight.
It can be cosmetics that above-mentioned LTBP-4 produces composition for promoting.
It can be food that above-mentioned LTBP-4 produces composition for promoting.
The invention still further relates to the application of extract in making LTBP-4 generation promoter of algae or plant.
The invention still further relates to the using method of extract in LTBP-4 generation promoter of algae or plant.
In the such use, preferred red algae, green algae or the Brown algae of using in the application in LTBP-4 generation promoter.
Above-mentioned red algae is preferably to be selected from and belongs to jackscrew Cutleriales (Acrochaetiales), Porphyridium cruentum order (Porphyridiales), Bangiales (Bangiales), Nemalionales (Nemaliales), red shield Cutleriales (Erythropeltidales), curved branch Cutleriales (Compsopogonales), Cryptonemiales (Cryptonemiales), Corallium Japonicum Kishinouye Cutleriales (Corallinales), ZHANGZAO order (Palmariales), Gelidiales (Gelidiales), the Rhodogorgonales order, kermes Cutleriales (Hildenbrandiales), Bai'an Cutleriales (Bonnemaisoniales), beading Cutleriales (Batrachospermales), Gigartinales (Gigartinales), Thallus Gracilariae order (Gracilariales), Phodymeniales (Rhodymeniales), at least a red algae in the algae of Yi Gu Cutleriales (Ahnfeltiales) and Ceramiale (Ceramiales).
Above-mentioned green algae is preferably to be selected from and belongs to volvocales (Volvocales), ring Cutleriales (Sphaeropleales), Oedogoniales (Oedogoniales), Chaetophorales (Chaetophorales), Chaetophorales (Chaetopeltidales,), bead Cutleriales (Chlorellales), the Microthamniales order, the Trebouxiales order, the Prasiolales order, small stream Cutleriales (Mamiellales), the Monomastigales order, the Dolichomastigales order, Trentepohliales (Trentepohliales), the Oltmannsiellopsidales order, the Chlorodendrales order, the Dolichomastigales order, the Nephroselmidales order, Ulotrichales (Ulotrichales), Ulvales (Ulvales), Cladophorales (Cladophorales), push pipe Cutleriales (Acrosiphoniales), Siphonocladales (Siphonocladales), Caulerpa order (Caulerpales), pine Cutleriales (Codiales), at least a green algae in the algae of plumage Cutleriales (Bryopsidales) and Dasycladales (Dasycladales).
Above-mentioned Brown algae is preferably to be selected from and belongs to brown shell Cutleriales (Ralfsiales), Dictyotales (Dictyotales), Chordariales (Chordariales), Scytosiphon lomentarius (Lyngh.)J. Ag. order (Scytosiphonales), Cutleriales (Cutleriales), burr Cutleriales (Sporochnales), Desmarestiale (Desmarestiales), Laminariales (Laminariales), at least a Brown algae in the algae of stable dish order (Ishigeales) and Fucales (Fucales).
Above-mentioned plant extract is preferably and is selected from least a extract that belongs in Labiatae, pulse family, Rhamnaceae, Actinidiaceae, Polygonaceae, Vitaceae, Compositae, Gentianaceae, Boraginaceae, Tremellaceae, Nelumbonaceae, Radix Malvae sylvestris material, Rutaceae, Zingiberaceae and the rubiaceous plant.
Utilize the present invention, can provide the extract of algae or plant is produced promoter as the LTBP-4 of effective ingredient.
Description of drawings
Fig. 1 is that the LTBP-4 that expression will contain the extract of different algae or plant produces the effect of promoter (corresponding to table 1) and the curve chart that contrast (left side) compares.
Fig. 2 is that the LTBP-4 that expression will contain the extract of different types of algae or plant produces the effect of promoter (corresponding to table 2) and the curve chart of contrast (left side) comparison.
Fig. 3 is that the LTBP-4 that expression will contain the extract of different types of algae or plant produces the effect of promoter (corresponding to table 3) and the curve chart of contrast (left side) comparison.
The specific embodiment
Be used for LTBP-4 of the present invention and refer to polypeptide from serial number 1 described base sequence (GenBank AccessionAF051344) or its straight homologues or their variant (comprising SNP, haplocype).The straight homologues of LTBP-4 is not particularly limited, for example can be from arbitrarily animal or mammal.As mammal, such as enumerating cattle, sheep, pig, goat, monkey, rabbit, rat, hamster, Cavia porcellus, mice etc.LTBP-4 is secretory protein, can signal sequence be removed by processing.In the method for the invention, as LTBP-4, can use and remove signal sequence, also can use the number of the writing to sequence that do not eliminate, remove signal sequence but be preferably.In addition, the LTBP-4 variant is not particularly limited, for example can enumerate to 1 in the polypeptide～several aminoacid lack, replacement or addition and sequence, described polypeptide be from the peptide of DNA and with the base sequence numeralization shown in the serial number 1 and peptide, described DNA has the DNA of complementary series and hybridizes under strict condition and with the DNA of LTBP-4 numeralization in the base sequence shown in the serial number 1.
For LTBP-4, except reported its express with related between cancer is sent out, also reported elastin laminin calmness when LTBP-4 can promote the inside and outside elastic fiber formation of organism etc.And then, provided the enlightenment of the slow property emphysema etc. that can treat emphysema, and morbidity related with people's COPD.
Even elastic fiber performance stretching in tissue also can be restored the extracellular fiber of the effect of " elasticity " character.Elasticity be visible in most tissue of organism, in such retractility tissue such as pulmonary artery skin the necessary character of function that be rich in, tissue.For elastic fiber, can think that elastin laminin can be calm crosslinked around the fiber that is called microfibre.Elastin laminin be hydrophobicity strong by the about protein of 750 Amino acid profiles, the calm protein such as LTBP-4 with this behavior of promotion of known elasticity albumen are relevant.
Elastic fiber the age increase or effect by the external essential factors such as protease of inflammatory cell secretion under deteriorated, fracture occurs, therefore, have state or the disease of various elasticity of demand regenerations.The state of elasticity of demand regeneration or disease have emphysema, blood vessel injury, cutis laxa, wound, elastic fiber deteriorated (such as being increased by the age or UV-induced deteriorated, skin lax), pachylosis, arteriosclerosis, large aneurysm, add degeneration of macula disease in age, perineum hernia, anus hernia, berry aneurysm, the digestive tube dyskinesia, decubital ulcer etc.
The present invention relates to promote that this class elastic fiber forms the material of the generation of relevant LTBP-4, found that in algae or plant extract such LTBP-4 produces facilitation, thereby provide algae or plant extract have been produced promoter as the LTBP-4 of effective ingredient.
Algae extract of the present invention mainly refer to from Brown algae, red algae or green algae, to utilize usual way to extract and extract.At this, red algae refers to for example belong to Bangiales (Bangiales) (Bangia Fuscopurpurea wherein, Bangia gloiopeltidicola), Nemalionales (Nemaliales) (Dermonema pulvnatum wherein, Dichotomaria falcata, Scinaia japonica, Scinaia Cottonii, Gloiophloea okamurae, Galaxaura Fastigiata, Helminthocladia australis, Namalion vermiculare), Cryptonemiales (Cryptonemiales) (Grateloupia filicina wherein), Corallium Japonicum Kishinouye Cutleriales (Corallinales) (Calliarthron yessoensis wherein, Fosliella zostericola, Serraticardia Maxima), Gelidiales (Gelidiales) (Acanthopeltis japonica wherein, Gelidiella acerosa, Geridium amansii, Geridium japonicum, Gelidium pacificum, Pterocladia capillacea, Beckerella subcostata), kermes Cutleriales (Hildenbrandiales) (Hildenbrandia rubra wherein), Bai'an Cutleriales (Bonnemaisoniales) (Asparagopsis taxiformis wherein, Delisea japonica), Gigartinales order (Caulacanthus Okamurai wherein, Tylotus lichenoides, Neodilsea yendoana, Pikea californica, Gloiopeltis complanata, Gloiopeltis furcata, Gigartina intermedia, Gigartina teedii, Gigartina tenella, Chondrus elatus, Chondrus giganteus, Chondrus ocellatus, Chondrus verrucosus, Rhodoglossum Pulcherum, Gloiosiphonia capillaris, Cryptohemia luxurians, Gratepoupia angusta, Grateloupia articulata, Carpopeltis asiatica, Carpopeltis carnosa, Grateloupia catenata, Carpopeltis divaricata, Grateloupia divaricata, Grateloupia elata, Grateloupia elliptica, Grateloupia lanceolata, Grateloupia livida, Prionitis patens, Grateloupia ramosissima, Cryptonemia schmitziana, Cyrtymenia sparsa, Grateloupia turuturu, Carpopeltis affinis, Grateloupia okumurai, Polyopes polyideoides, Carpopeltis flabellata, Carpopeltis cornea, Carpopeltis crispata, Hypnea charoides, Hypnea chordacea, Hypnea cornuta, Hypnea flagelliformis, Hypnea flexicaulis, Hypnea japonica, Hypnea saidana, Hypnea variabilis, Callophyllis crispata, Chondrococcus hornemannii, Nemastoma lancifolia, Gigartina ochotensis, Peyssonnelia caulifera, Phacelocarpus japonicus, Ahnfeltia concinna, Gymnogongrus flabelliformis, Ahnfeltia paradoxa, Stenogramma interrupta, Plocamium recurvatum, Plocamium telfairiae, Chondrococcus hornemannii, Chondrococcus japoicus, Sarcodia ceylanica, Schizymenia dubyi, Meristotheca papulosa, Solieria robusta, Thallus Gracilariae order (Gracilariales) (Gracilaria compress wherein, Gracilaria incurvata, Gracilaria rhodocaudata, Corallopsis opuntia, Gracilaria textorii, Gracilaria verrucosa, Phodymeniales (Rhodymeniales) (Champia parvula wherein, Coeloseira pacifica, Ceratodictyon spongiosum, Chrysymenia wrightii, Lomentaria catenata, Lomentaria hakodatensis, Coelarthrum muelleri, Coelothrix irregularis, Rhodymenia intricata, Ceramiale (Ceramiales) (Campylaephora crassa wherein, Campylaephora hypnaeoides, Centroceras clavulatum, Ceramium japonicum, Ceramium kondoi, Ceramium paniculatum, Ceramiu tenerrimum, Griffighsia japonica, Griffithsia subcylindrica, Herpochondria corallinae, Microcladia elegans, Psilothallia dentata, Spyridia elongata, Wrangelia argus, Acrosorium flabellatum, Acrosorium polyneurum, Acrosorium uncinatum, Erythroglossum pinnatum, Nienburagia japonica, Acanthophora orientalis, Acrocystis nana, Benzaitenia yenoshimensis, Chondria crassicaulis, Chondria dasyphylla, Digenea simplex, pterosiphoia fibrillosa, Laurencia intermedia, Laurencia japonensis, Laurencia nipponica, Laurencia okamurae, Laurencia papillosa, Laurencia pinnata, Laurencia saitoi, Laurencia undulate, Leveillea jungermannioides, Rhodomela larix, Polysiphonia senticulosa, Symphyocladia ratiuscula, Symphyocladia marchantioides), jackscrew Cutleriales (Acrochaetiales), Porphyridium cruentum order (Porphyridiales), red shield Cutleriales (Erythropeltidales), curved branch Cutleriales (Compsopogonales), ZHANGZAO order (Palmariales), the Rhodogorgonales order, Bai'an Cutleriales (Bonnemaisoniales), beading Cutleriales (Batrachospermales), the algae of Yi Gu Cutleriales (Ahnfeltiales), represent formal name used at school in the above bracket, as follows.
Green algae refers to belong to Ulotrichales (Ulotrichales) (Collinsiella cava wherein, Collinsilella tuberculata), Ulvales (Ulvales) (Ulva arasakii Chihara wherein, Ulva conglobata, Ulva fasciata, Enteromorpha intestinalis, Enteromorpha linza, Ulva pertusa, Ulva reticulata, Letterstedtia japonica), Cladophorales (Cladophorales) (Anadyomene wrightii wherein, Chaetomorpha aerea, Chaetomorpha crassa, Chaetomorpha linum, Chaetomorpha spiralis, Cladophora conchopheria, Cladophora japonica, Cladophora ohkuboana, Cladophora sakaii, Cladophora wrightiana), push pipe Cutleriales (Acrosiphoniales) (Urospora penicilliformis wherein), Siphonocladales (Siphonocladales) (Boodlea coacta wherein, Boergesenia forbesii, Dictyosphaeria cavernosa, Valonia aegagropila, Valonia aegagropila, Valonia ventricosa), Caulerpa order (Caulerpales) (Caulerpa brachypus wherein, Caulerpa fergusoni, Caulerpa okamurai, Avrainvillea lacerata, Chlorodesmis formosana, Chlorodesmis comosa, Udotea javensis), pine Cutleriales (Codiales) (Codium arabicum wherein, Codium barbatum, Codium coarctatum, Codium contractum, Codium cylindricum, Codium fragile, Codium intricatum, Codium latum Suringar, Codium mamillosum, Codium pugniformis, Codium divaricatum, plumage Cutleriales (Bryopsidales) (Bryopsis harveyana wherein, Bryopsis maxima, Bryopsis triploramosa), Dasycladales (Dasycladales) (Bornetella ovalis wherein, Neomeris annulata, Acetaburaria dentate, Acetabularia ryukyuensis, Halicoryne wrightii), volvocales (Volvocales), ring Cutleriales (Sphaeropleales), Oedogoniales (Oedogoniales), Chaetophorales (Chaetophorales), Chaetophorales (Chaetopeltidales,), bead Cutleriales (Chlorellales), the Microthamniales order, the Trebouxiales order, the Prasiolales order, small stream Cutleriales (Mamiellales), the Monomastigales order, the Dolichomastigales order, Trentepohliales (Trentepohliales), the Oltmannsiellopsidales order, the Chlorodendrales order, the Dolichomastigales order, the algae of Nephroselmidales order etc.
Brown algae refers to belong to brown shell Cutleriales (Ralfsiales) (Heterochordaria abietina, Endoplura aurea), Dictyotales (Dictyotales) (Dictyopteris divaricata, Dictyopteris latiuscula, Dictyopteris prolifera, Dictyopteris undulate, Dictyota dichotoma, Dictyota linearis, Dilophus okamurai, Chlanidophora repens, Pachydictyon coriaceum, Padina arborescens, Padina crassa, Spatoglossum crassum, Spatoglossum pacificum, Zonaria diesingiana), Chordariales (Chordariales) (Papenfussiella kuromo, Tinocladia crassa, Leathesia difformis, Petrospongium rugosum, Chordaria flagelliformis (Na ガ マ Star モ), Nemacystus decipiens (モ ズ Network), Scytosiphon lomentarius (Lyngh.)J. Ag. order (Scytosiphonales) (Colpomenia bullosa, Colpomenia phaeodactyla, Colpomenia sinuosa, Hydroclathrus clathratus, MyelopHycus caespitosus, Endarachne binghamiae, Petalonia fascia, Scytosiphon canaliculatus, Scytosiphon lomentaria), Cutleriales (Cutleriales) (Culeria cylindrica), burr Cutleriales (Sporochnales) (Carpomiltra cabrerae), Desmarestiale (Desmarestiales) (Desmarestia ligulata, Desmarestia tabacoides), Laminariales (Laminariales) (Undaria pinnatifida, Chorda filum, Costaria costata, Ecklonia cava, Ecklonia kurome, Eisenia bicyclis, Laminaria Japonica, Laminaria religiosa, Alaria crassifolia), stable dish order (Ishigeales) (Ishige okamurai Yendo, Ishige foliacea), Fucales (Fucales) (Cystophyllum hakodatensis, Cystoseira prolifera, Cystophyllum sisymbrioides, Sargassum ammophilum, Sargassum confusum, Sargassum fulvellum, Cystophyllum fusiforme, Sargassum giganteifoium, Sargassum hemiphyllum, Sargassum horneri, Sargassum serratifolium, Sargassum muticum, Sargassum nigrifolium, Sargassum okamurae, Sargassum patens, Sargassum piluliferum, Sargassum ringgoldianum, Sargassum thunbergii, Sargassum yamadae, Sargassum yamamotoi, Sargassum yendoi, Turbinaria ornata) etc.
In the present invention, found that the extract of algae or plant has the effect of the generation that promotes this class LTBP-4.Can use separately a kind or be used in combination more than 2 kinds from the extract of algae or plant.As such algae or plant, do not limit, in addition, extract only otherwise the generation facilitation of infringement LTBP-4 refers to water dissolvable composition, acid-solubility composition, alkali-soluble composition, organic solvent soluble component etc. from algae or plant.
Among the present invention, as the composition of the effect with the generation that promotes LTBP-4, as long as for the extract from algae and plant extract, just be not particularly limited.For example, Brown algae can comprise fucoidan, and red algae can comprise carrageenin and/or silicon, and green algae can comprise chlorophyll α and/or β etc.
LTBP-4 among the present invention produces facilitation and is found in plant extract." plant extract " in this description also comprises the plant extract composition fermentation liquid that lactobacillus is got with the composition coexistence of extracting from plant except comprise the composition that extracts from plant.As plant, for example can enumerate and belong to Malvaceae; Rubiaceae; Lardizabalaceae; Cruciferae; Iridaceae; grass family; Urticaceae; Diapensiaceae; Woodsiaceae; five Solanaceaes; Aristolochiaceae; Cucurbitaceae; Plantaginaceae; Guttiferae; Compositae; campanulaceae; Ranunculaceae; Lauraceae; Rhamnaceae; Moraceae; Papaveraceae; Scrophulariaceae; Hypolepis punctata (Thunb) Mett. section; Araeceae; Primulaceae; Labiatae; the Bletilla striata (Thunb.ex A.Murray)Rchb.f. kurrajong; Tremellaceae; Zingiberaceae; thymelaeceae; Caprifoliaceae; Nymphaeceae; Violaceae; Umbelliferae; Osmundaceae; Polygonaceae; Buxaceae; Ericaceae; Commelinaceae; Saururaceae; Hippocastanaceae; Solanaceae; Caryophyllaceae; Nelumbonaceae; Rosaceae; Amaryllidaceae; Convolvulaceae; Mang cattle department of pediatrics; Vitaceae; Fagaceae; Crassulaceae; Paeoniaceae; Actinidiaceae; Pinaceae; pulse family; Hamamelidaceae; Rutaceae; Cornaceae; Menyanthaceae; Boraginaceae; Berberidaceae; Dioscoreaceae; Saxifragaceae; Liliaceae; the orchid family; Gentianaceae; Adoxaceae; the plant of Bignoniaceae etc.
Such plant extract is not particularly limited, can be for being selected from the Radix Scutellariae extract of Labiatae, Bignoniaceae variegated leaf roble, the licorice extract of pulse family, rhamnaceous date fruit extract, Actinidiaceae Fructus actinidiae chinensis seed extract, the polygonum tinctorium ait. of Polygonaceae (formal name used at school: Polygonum tinctorium) leaf, the Cynara scolymus L (Cyhara cardunculus.) leaf extract of Compositae, the Gentiana lutea extract of Gentianaceae, the Radix Arnebiae (Radix Lithospermi) of Boraginaceae (Lithospermum erythrorhizon) extract, the Radix Arnebiae (Radix Lithospermi) extract of Boraginaceae, the Tremella extract of Tremellaceae or contain the Tremella extract of polysaccharide body, the monkey-bread tree leaf extract of Malvaceae or hydrolysis monkey-bread tree leaf extract, the PiceameyeriRehd. Et Wils. extract of Rutaceae or sour orange peel extract, the PiceameyeriRehd. Et Wils. extract of Rutaceae/sour orange peel extract, one kind or two or more in the Alpinia nutaus leaf extract of Zingiberaceae and rubiaceous GAMBIER (the Uncaria gambir Roxb) extract.Need to prove, in the situation that the extract of above-mentioned plant can commercially obtain, also can use simply this commercially available plant extract.
Below content of the present invention is at length described.
Algae or plant extract can directly use the crude product from the extracting solution of natural goods, can also use the crude product separation and purification and product.
Method as the extract that obtains algae or plant is not particularly limited, and can adopt common extraction method.Crude extract such as can by utilize cutting device microtome cutting machine skiving machine etc. with whole algae or all the specific part of plants (root, stem, do, the parts of the plants such as bark, plumelet, leaf, flower, fruit and seed) chop up, to therefrom object be used singly or in combination water, hot water or organic solvent and solvent extract.As organic solvent, can enumerate the pure algae such as methanol, ethanol, 1-propanol, 2-propanol, n-butyl alcohol, 2-butanols, the ester algae such as methyl acetate, ethyl acetate, the ketone algae such as acetone, formaldehyde, dimethyl sulfoxide etc.
In addition, solvent can use the solvent of room temperature or room temperature, can also use heated solvent, hot solvent (solvent is heated near the boiling point).
And then, can under the condition of acid, alkali, extract.As acid, can enumerate the mineral acids such as hydrochloric acid, sulphuric acid, nitric acid, phosphoric acid, perhaps the organic acid such as acetic acid, citric acid, oxalic acid, succinic acid, formic acid, propanoic acid.As alkali, preferably use alkaline, inorganic salts, can potassium hydroxide, sodium hydroxide etc. be shown example.
In addition, can also utilize lyophilization powder method, high-pressure process, superelevation platen press.In high-pressure process, process by 120 ℃, 4 hours hyperbaric heatings, the cell in this algae or the plant is pressurizeed and fragmentation.
Enumerate an example of the extraction conditions of crude extract.Be organic solvent in the situation that extract solvent, extract temperature and be not particularly limited, preferably 1～100 ℃, more preferably in 20～100 ℃ scope, stir 1～24 hour, preferably stirred 1 hour～10 hours.In addition, be water in the situation that extract solvent, the temperature during extraction in the method for extracting based on pressurized hot water, is preferably approximately 0～200 ℃ as long as for below the boiling point of solvent, just be not particularly limited, more preferably approximately 20～130 ℃.In addition, the response time is not particularly limited, and preferably is made as several seconds～a couple of days to get final product, and more preferably is made as 30 minutes～got final product in 6 hours.
Reaction temperature and response time can suitably be selected according to kind and the concentration of solvent.
As long as extract the extract that gets for aforesaid way, just can extract fully the composition with LTBP-4 generation promotion ability.
The extract that obtains is carried out centrifugalize, obtain its supernatant as extracting solution.The polysaccharide part that in described extracting solution, can contain water dissolvable, acid solubility, alkali-soluble or organic solvent solubility.
Method as algae or plant extract being carried out separation and purification from the crude product of extract is not particularly limited, such as following method is arranged: add the quaternary ammonium salts such as cetylpyridinium chloride, make algae or plant extract precipitation, the method for utilizing alcoholic solution to clean; The chromatographic method of the anion exchange resin such as utilization use DEAE cellulose etc.
The algae or the plant extract solution that so extract, make with extra care and get can directly use, in addition, can use with diluted or concentrate and extract, and then, also can be by formation dried powder things such as lyophilizations and used, or be prepared into pasty state and used.
Algae of the present invention or plant extract are produced the treatment of the disease that expression that promoter can be used for resulting from LTBP-4 reduces as the LTBP-4 of effective ingredient.Treatment such as the Delayed onset emphysema that can carry out cancer, emophysematous treatment, and morbidity related with people's COPD etc.In addition, also useful in the treatment of the disease that relates to elastic fiber formation that LTBP-4 produces, relevant.The disease that relevant elastic fiber forms refers to state or the disease of the regeneration of elasticity of demand fiber, such as referring to emphysema, blood vessel injury, cutis laxa, wound, elastic fiber deteriorated (such as the disease that causes because of age increase or ultraviolet), pachylosis, arteriosclerosis, large aneurysm, adding degeneration of macula disease in age, perineum hernia, anus hernia, berry aneurysm, the digestive tube dyskinesia, decubital ulcer etc.And then, in prevention, to improve in lax, the cosmetic purpose that wrinkle is such of skin also be useful.In addition, to produce promoter also be useful as the cultivation of the cell of the regeneration capacity with elastic fiber with reagent etc. for LTBP-4 of the present invention.And then, in the making of the artificial organs such as artificial skin, skin model, artificial blood vessel, play a role.And then, also can consider the application in the research of the LTBP-4 of the unknown itself, can think useful in very wide scope.
LTBP-4 of the present invention produces promoter and can be made into pharmaceuticals, non-drug, food, cosmetics etc., can be in scope widely with the form of any available preparation or compositions in, being preferably can functional food or the form of the cosmetics preparation or the compositions that are used.
Adopt in the situation of any form in pharmaceuticals, non-drug, food, the cosmetics in the compositions that contains LTBP-4 generation promoter of the present invention, content for the extract of algae or plant, be converted into dry weight, for example be made as approximately that 0.000001～99 % by weight gets final product, more preferably approximately 0.00001～30 % by weight, more preferably approximately 0.0001～10 % by weight, be particularly preferably 0.001～5 % by weight.If in above-mentioned scope, then in the use of pharmaceuticals, non-drug, food, cosmetics, can bring into play sufficient LTBP-4 and produce facilitation.
The dose of the algae when the present invention is used for the purposes of pharmaceuticals or health food or the extract of plant can be made as per day for adults 0.0001～5000mg/kg in dry weight.If in above-mentioned scope, then can improve, prevent with being produced as of LTBP-4 necessary disease or state.
The skin preparations for extenal use form
Can adopt known form as the external preparation form of cosmetics or non-drug as the LTBP-4 generation promoter of effective ingredient the extract (crude extract or refining thing) of algae of the present invention or plant.As this class form such as enumerating liquid agent, suspension, Emulsion, unguentum, ointment, gel, varnish, lotion, aerosol, powder agent, poultice, making the such stick of medicinal liquid infiltration sheet material agent, the lip rod in the sheet materials such as non-woven fabrics etc.Wherein, preferably use with the form of liquid agent, suspension, Emulsion, unguentum, ointment, gel, lotion, gel.By forming above-mentioned form, can bring into play fully elastic fiber and form effect.In the skin preparations for extenal use, except the extract that adds algae or plant, in the scope of not damaging effect of the present invention, can cooperate and be added on crust agent (cosmetics, non-drug, pharmaceuticals) known additive in, but matching surface activating agent for example, oil content, alcohols, wetting agent, thickening agent, preservative agent (antiseptic), antioxidant, chelating agen, the pH adjusting agent, stabilizing agent, dispersant, spice, coloring agent, pigment, the pearly luster imparting agent, blood promotes composition, the moisturizing composition, the ultra-violet absorption composition, ultraviolet scattering composition, clean composition, antimicrobial component, astringent component, vitamins, amino acids, the aging resistance composition, the anti-inflammatory composition, whitening composition, the cutin softening composition, the cell-activating composition, water etc.Additive can use separately a kind, perhaps is used in combination more than 2 kinds.
In addition, the concrete purposes of cosmetic composition is not particularly limited, and can enumerate astringent, emulsion, cream, beautifying liquid, Sun block cosmetics, facial film, hand cream, body lotion, the such basic cosmetics of health cream; Cleansing milk, makeup removing product, health shampoo, shampoo, the such cleaning of hair conditioner apply some make up; Foundation cream, sun screen, lip frost, lipstick, the such cosmetic cosmetics of rouge; Bath oil etc.
＜base or carrier 〉
As base or carrier, can enumerate Liquid Paraffin, squalane, Ultralube W 389 (Plastibase etc.), ceresine, alpha-olefin low polymers, the such hydrocarbon of lightweight Liquid Paraffin; Methyl polysiloxane, the cross-linking type methyl polysiloxane, high polymerization methyl polysiloxane, the ring-type silicone, alkyl-modified silicone, the alkyl-modified silicone of cross-linking type, amino modified silicone, polyether modified silicone, polyglycerol-modified silicone, the crosslinked polyether modified silicone, cross-linking type alkyl, polyether modified silicone, the silicone alkyl chain is the modified polyether modified silicone altogether, the silicone alkyl chain is the polyglycerol-modified silicone of modification altogether, polyether-modified side chain silicone, polyglycerol-modified side chain silicone, silicon Acrylote, phenyl modified silicone, the silicone oil that silicone resin is such; Ethyl cellulose, hydroxypropyl cellulose, the such cellulose derivative of hypromellose; Polyvinylpyrrolidone; Carrageenin; The polyethylene butyrate; Polyethylene Glycol; Diox; The butanediol adipate polyester; Isopropyl myristate, octyl dodecanol myristinate, isopropyl palmitate, Palmic acid Petiolus Trachycarpi ester, isononyl isononanoate, the such esters of four 2 ethyl hexanoic acid pentaerythritol esters; Dextrin, the such polysaccharide of maltodextrin; Ethanol, the such lower alcohol of isopropyl alcohol; Glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, Diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, dihydroxypropane single-ether, propylene glycol monopropyl ether, diethylene glycol monoethyl ether, the such glycol ethers of diglycol monotertiary propyl ether; The polyhydric alcohol such as Polyethylene Glycol, propylene glycol, 1,3 butylene glycol, glycerol, Isopropanediol; The water system bases such as water etc.
Base or carrier can use separately a kind or be used in combination more than 2 kinds.
＜additive 〉
As the antioxidant that can contain in the topical composition of the present invention, can enumerate dibenzylatiooluene, butylated hydroxyanisole (BHA), sorbic acid, sodium sulfite, ascorbic acid, arabo-ascorbic acid, Cys hydrochlorate etc.
As surfactant, for example can enumerate anhydrosorbitol list isostearate, sorbitan monolaurate, sorbitan-monopalmityl ester, anhydrosorbitol monostearate, diglycerol anhydrosorbitol five-(2 ethyl hexanoic acid) ester, the diglycerol anhydrosorbitol four-such sorbitan fatty ester class of (2 ethyl hexanoic acid) ester; The methyl glycol fatty acid ester class that propylene glycolmonostearate is such; Polyoxyethylene solidifies Oleum Ricini 40 (HCO-40), polyoxyethylene solidifies Oleum Ricini 50 (HCO-50), polyoxyethylene curing Oleum Ricini 60 (HCO-60), polyoxyethylene curing Oleum Ricini 80 etc. and solidifies castor oil derivative; Polyoxyethylene (20) sorbitan monolaurate (Polysorbate20), polyoxyethylene (20) anhydrosorbitol monostearate (Polysorbate60), polyoxyethylene (20) dehydrating sorbitol monooleate (Polysorbate80), the such polyoxyethylene sorbitan fatty acid ester of polyoxyethylene (20) sorbitan isostearate; Polyoxyethylene list coconut oil fat acid glyceride; The glycerol alkyl ether; Alkyl androstanediol; The polyoxyalkylene alkyl that Polyoxyethylene cetyl ether is such; Stearmide, the such amine of oleyl amine; Silicone-based surfactant that polyoxyethylene methyl polysiloxane copolymer, lauryl PEG-9 poly dimethyl silica ethyl dimethyl siloxane, PEG-9 poly dimethyl silica ethyl dimethyl siloxane are such etc.
As thickening agent, such as enumerating guar gum, locust bean gum, carrageenin, xanthan gum, carboxymethyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, CVP Carbopol ETD2050, acrylic acid alkyl methacrylate copolymer, Polyethylene Glycol, bentonite, (2-(Acryloyloxy)ethanol/acryloyldimethyl taurine Na) copolymer, (ammonium acryloyldime-thyltaurate// vinyl pyrrolidone) copolymer etc.
As preservative agent, can enumerate benzoic acid, sodium benzoate, deoxidation acetic acid, deoxidation sodium acetate, p-Hydroxybenzoic acid isobutyl ester, p-Hydroxybenzoic acid isopropyl ester, butyl p-hydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, methyl parahydroxybenzoate, phenyl phenol etc.
As pH adjusting agent, can enumerate mineral acid (hydrochloric acid, sulphuric acid etc.), organic acid (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate etc.), inorganic alkali (potassium hydroxide, sodium hydroxide etc.), organic alkali (triethanolamine, diisopropanolamine (DIPA), triisopropanolamine etc.) etc.
As chelating agen, can enumerate EDTA2 sodium salt, EDTA calcium 2 sodium salts etc.
As stabilizing agent, can enumerate sodium polyacrylate, dibenzylatiooluene, butylated hydroxyanisole (BHA) etc.
Additive can use separately a kind or be used in combination more than 2 kinds.
＜other effective ingredient 〉
Topical composition of the present invention can contain other effective ingredient in the scope of not damaging effect of the present invention.As the concrete example of effective ingredient, for example can enumerate moisturizing composition, anti-inflammatory composition, antimicrobial component, vitamins, peptide or derivatives thereof, aminoacid or derivatives thereof, cell-activating composition, aging resistance composition, blood and promote into and grade.
In take form
Also can cooperate with pharmaceutically licensed carrier as the algae of effective ingredient of the present invention or the extract of plant, make the solid preparations such as tablet, capsule, granule, powder, the perhaps aqueous preparation such as syrup, injection, thereby per os or the ground administration of non-per os.Above-mentioned preparation can contain conventional additive.As pharmaceutically licensed carrier, can use habitual various organic or inorganic carrier mass as preparation raw material, can cooperate excipient, lubricant, bonding agent, disintegrating agent in the solid preparation; Solvent in the liquid preparation, dissolution aids, suspension, isotonic agent, buffer agent, painlessization agent etc.In addition, also can use the preparation additives such as antiseptic, antioxidant, coloring agent, sweeting agent as required.
Preferred example as excipient, such as enumerating the sugar alcohols such as D-glucitol, mannitol, xylitol, the saccharides such as glucose, white sugar, lactose, fructose, crystalline cellulose, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, calcium hydrogen phosphate, wheaten starch, rice fecula, corn starch, potato starch, dextrin, beta-schardinger dextrin-, light silicon anhydride, titanium oxide, silicic acid magnesium aluminate, Talcum, Kaolin etc.
Preference as bonding agent, such as enumerating the cellulose derivatives such as methylcellulose, ethyl cellulose, hydroxypropyl cellulose, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid series macromolecule, gelatin, arabic gum, amylopectin, alphalysed starch, agar, traganth, sodium alginate, propylene glycol alginate etc.
As the preference of disintegrating agent, such as enumerating starch, low degree of substitution hydroxypropyl cellulose, carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose, hydroxypropyl starch, part alphalysed starch etc.As the preference of solvent, for example can enumerate water for injection, alcohol, propylene glycol, Polyethylene Glycol, Oleum sesami, Semen Maydis wet goods.
As the preference of lubricant, can enumerate stearic acid, magnesium stearate, calcium stearate, KIKKOL MYS-40, palmityl alcohol, Talcum, solidified oil, sucrose fatty acid ester, dimethyl polysiloxane, Apis cerana Fabricius, cera alba etc.
As the preference of dissolution aids, such as enumerating Polyethylene Glycol, propylene glycol, PEARLITOL 25C, benzyl benzoate, ethanol, Trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate etc.As the preference of suspension, such as enumerating hard ester acyl triethanolamine, sodium lauryl sulfate, lauryl alanine, lecithin, killing the surfactants such as algae ammonium, benzethonium chloride, glyceryl monostearate; Such as enumerating the hydrophilic macromolecules such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose etc.
As the preference of isotonic agent, such as enumerating sodium chloride, glycerol, PEARLITOL 25C etc.As the preference of buffer agent, such as enumerating the buffer such as phosphate, acetate, carbonate, citrate etc.As the preference of painlessization agent, such as enumerating benzylalcohol etc.As the preference of antiseptic, such as enumerating parabens, methaform, benzylalcohol, phenethanol, dehydroactic acid, sorbic acid etc.As the preference of antioxidant, such as enumerating sulphite, ascorbic acid etc.
Method as making liquid preparation of the present invention or solid preparation as long as be to comprise that the extract with algae or plant mixes the operation of making liquid preparation or solid preparation with preparation raw material, is not particularly limited, and can use known method.
Solid preparation modulation example:
For example, but the following method of illustration: the preparation compositions that will contain the extract of algae or plant and preparation raw material carries out mixing, makes it pass through mesh screen, thus with the extruding pelletization thing of molding pulverize, the method for granulate; In above-mentioned preparation compositions, add mixing water, utilize vertical comminutor to carry out molding, behind stirring-granulating, utilize the COMIL grinder to carry out the method for crushing screening; After utilizing the roll-type pressuring machine with above-mentioned preparation compositions compression, utilize roll pelletizer to carry out the method for crushing screening; And the dry method that flows behind the stirring-granulating.
In addition, for example in the situation that by directly beating sheet manufacturing, after the preparation compositions mixing of the extract that will contain algae or plant and preparation raw material, directly put into and beat sheet in the tablet machine and get final product.
Food
The LTBP-4 that contains the extract of algae of the present invention or plant produce promoter can by be included in food or the functional food in.
As such food or functional food, can rice be shown example; The various Noodles of Fagopyrum esculentum Moench, Japanese noodle, vermicelli, Chinese face, instant noodles, cup face; The beverages such as refreshment drink, soda pop, nutritious drink, fruit nectar, lactic acid beverage, sports drink; Curry powder, stew, various soup class; The frozen desserts such as ice cream, water ice, shaved ice; Baked Fruit) sugar, cooky are done, confection, chewing gum, chocolate, caked sugar, snacks, cookies, fruit jelly, fruit jam, butter, other burn fruit (Japanese: the snack categories such as; The Aquatic product livestock products processed foods such as breaded fish stick, flesh of fish Rhizoma Dioscoreae cake, Petaso, sausage; The milk product such as modified milk, fermentation milk; Oils and fats and the Oil products such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipping cream, salad dressing; The flavouring agents such as sauce, salad dressing, salty sauce, soy sauce, sauce; Soup, stew, salad, home cooking, fish flour, curing food; The health-nutrition accesary foods of other forms etc.
And then, can prepare and contain the dietary supplement (powder, granule, soft capsule, hard capsule, tablet, chewable tablet, fast disintegrating tablet, syrup, liquid agent etc.) that LTBP-4 of the present invention produces promoter.
In addition, also can contain LTBP-4 of the present invention in bait animals such as house pets and produce promoter.
In food, can add additive as required.As such additive, for example can enumerate glucose, fructose, sucrose, mannose, sorbose, stevioside, Rubusoside, corn syrup, lactose, mannitol, dextrin, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, lactic acid, L-AA, the dl-alpha-tocopherol, sodium erythorbate, glycerol, propylene glycol, fatty acid glyceride, polyglyceryl fatty acid ester, sucrose fatty acid ester, sorbitan fatty ester, arabic gum, carrageenin, casein, gelatin, pectin, agar, vitamin C, vitamin(e) B group, vitamin E, nicotiamide, calcium pantothenate, amino acids, the calcium salt class, surfactant, pigment, spice, preservative agent etc.
Utilization contains the LTBP-4 that the present invention starves algae or plant extract and produces promoter, can be at the external LTBP-4 that makes, and in the research that also can apply the present invention to carry out for LTBP-4 self or elastic fiber.Can also use LTBP-4 of the present invention to produce promoter, at external generations LTBP-4, thereby be used for the making of the artificial organs such as cultivation usefulness reagent, artificial skin, skin model, artificial blood vessel of artificial elastic fiber.In the situation that is applied to the external research of this class, enforcement, also preferably directly use the extract of algae or plant.
For at external generation LTBP-4, and make to extract algae or plant extract and material or make in dry weight contain about 1%～70% to algae or plant extract and the material of extract, make its with can be in the cell coexistence of external making LTBP-4.Such compositions directly can be produced promoter use as LTBP-4 of the present invention.As the concrete method that produces LTBP-4, comprise the method that the cell that produces LTBP-4 is contacted with LTBP-4 generation promoter of the present invention and cultivate.Through cultured cells typically to cell exocrine LTBP-4.Perhaps, can also promote in vivo the generation of LTBP-4.Employed cell can for from the cell of animal arbitrarily, be preferably from mammiferous cell.This class cell can example illustrate the tissue that comes from LTBP-4 and exist, such as from cells such as the cell of skin heart, lung, uterus, heart, kidney, pancreas, spermary, ovary, small intestinal, colon, cartilaginous tissue, fibrous bud cell, smooth muscle cell, epithelial cell, endotheliocytes.Preferred skin fiber sprout cell or the vascular smooth muscle cell used.For the generation of external LTBP-4, also can use the initial culture cell from organism, the cell that the cultivation by undifferentiated cells such as the cell strain through establishing, stem cell gets.
As the cell that can produce LTBP-4, originally refer to not have LTBP-4 and produce cell ability, that be beyond expression q.s, the present invention comprises that also importing the mode that produces LTBP-4 by gene operates the cell that gets.Import in the cell by the carrier that can express the LTBP-4 gene, obtained LTBP-4 and produce the cell of ability or improved the cell that LTBP-4 produces ability thereby can make.
Elastic fiber formation promoter of the present invention can further be contained DANCE, and (developmental arteries and neural crest epidermal growth factor (EGF)-like) expresses enhancer (DANCE inducible factor).Can use DANCE to express enhancer, express enhancer such as enumerating Nan Tian rattan (Caesalpinia crista) extract, four jiaos of upper licensed salt of bean extract, phytic acid and physiology thereof and L-hydroxyproline and the upper licensed DANCE such as salt of physiology thereof; DANCE expression vector or DANCE inducible factor expression vector etc.
[embodiment]
Next, utilize test example, embodiment etc. that the present invention is described particularly, the present invention is not limited to following embodiment.
The extract of (embodiment 1～23, comparative example 1～6) Ge Seed algae of (and plant)
Directly use the commercially available various algae shown in table 1～3 and the extract of plant, be used for LTBP-4 and produce the evaluation test that promotes.
(test example 1) (LTBP-4 produces the evaluation test that promotes)
Test example 1:
Utilize direct absorption method (Direct ELISA method) to implement test.
At first, in 96 orifice plates, sow 3500 in people's fibrous bud cell in each hole, utilize culture medium (DMEM (and Dulbecco ' s Modified Eagle Medium, buy from Invitrogen), 10% N of embryo's serum (FBS, buy from JRH Bioscience), the glutamic acid of 2mM, the penicillin of 100units/mL, the streptomycin of 100g/mL), at 37 ℃, 5%CO
2Under cultivated 48 hours.And then, use the elastic fiber that does not contain serum to form culture medium, namely, use the glutamic acid of DMEM/F 12,2mM, the penicillin of 100units/mL, the streptomycin of 100g/mL, in this serum-free medium, add (record in table 1～3) extract 0.001 % by weight that obtains in embodiment 1～23 and the comparative example 1～6 or do not add, at 37 ℃, 5%CO
2Lower cultivation 3 days.The supernatant (or cytolysis thing) of the fibrous bud cell through cultivating is added in 96 holes, under 4 ℃, leave standstill an evening, form immobile phase.Then, utilize PBS that the hole is cleaned, with PBS with Block Ace (from DS Pharma Biomedical Co., Ltd buys) be diluted to 4 times, the solution that gets is therefrom added in the hole, seal, then will resist LTBP-4 antibody-solutions (buying SC-30360 from Santa Cruz) to add to each hole, at room temperature reacted 1 hour.And then, use PBS that the hole is cleaned, add the secondary antibodies solution (buying ZyMax81-1620 from Zymed Laboratories.Inc.) through the HRP labelling, at room temperature reacted 1 hour, then make chromogenic substrate reaction 10 minutes.Use extinction photometer (colored intensity after the OD450nm assaying reaction stops), the numeral that record gets with comparing in table 1～3, and then at the curve chart of drawing shown in Fig. 1～3.
[table 1]
Table 2
Table 3
The extract of algae or plant demonstrates has excellent LTBP-4 generation facilitation.Especially in the extract or plant that are obtained by red algae or green algae, take Flos Camelliae Japonicae dry extract, monkey-bread tree (Adansonia) etc. as representative, found to have very excellent effect.
(compositions modulation example 1)
Cosmetic composition
The unit of the numerical value among the embodiment of following cosmetic composition is " % by weight ".
Table 4
Emulsion
Table 5
Emulsion
[compositions modulation example 2]
Interior oral compositions
In the prescription example of following food compositions, the weight of the extract of algae or plant is dry weight.
In whole prescriptions of food compositions, the preferred alcohol extract is as the extract of algae or plant.
Table 6
Beverage
Each picked-up is 1 bottle in these beverage three meals in a day.
Table 7
Tablet
Each picked-up is 3 in these tablet three meals in a day.
Claims (15)
1. a LTBP-4 produces promoter, and its extract that contains algae or plant is as effective ingredient.
2. LTBP-4 according to claim 1 produces promoter, and its extract that contains red algae, green algae or Brown algae is as effective ingredient.
3. LTBP-4 according to claim 2 produces promoter, wherein,
Described red algae is to be selected to belong to jackscrew Cutleriales (Acrochaetiales), Porphyridium cruentum order (Porphyridiales), Bangiales (Bangiales), Nemalionales (Nemaliales), red shield Cutleriales (Erythropeltidales), curved branch Cutleriales (Compsopogonales), Cryptonemiales (Cryptonemiales), Corallium Japonicum Kishinouye Cutleriales (Corallinales), ZHANGZAO order (Palmariales), Gelidiales (Gelidiales), the Rhodogorgonales order, kermes Cutleriales (Hildenbrandiales), Bai'an Cutleriales (Bonnemaisoniales), beading Cutleriales (Batrachospermales), Gigartinales (Gigartinales), Thallus Gracilariae order (Gracilariales), Phodymeniales (Rhodymeniales), at least a red algae in the algae of Yi Gu Cutleriales (Ahnfeltiales) and Ceramiale (Ceramiales).
4. LTBP-4 according to claim 2 produces promoter, wherein,
Described green algae is to be selected to belong to volvocales (Volvocales), ring Cutleriales (Sphaeropleales), Oedogoniales (Oedogoniales), Chaetophorales (Chaetophorales), Chaetophorales (Chaetopeltidales,), bead Cutleriales (Chlorellales), the Microthamniales order, the Trebouxiales order, the Prasiolales order, small stream Cutleriales (Mamiellales), the Monomastigales order, the Dolichomastigales order, Trentepohliales (Trentepohliales), the Oltmannsiellopsidales order, the Chlorodendrales order, the Dolichomastigales order, the Nephroselmidales order, Ulotrichales (Ulotrichales), Ulvales (Ulvales), Cladophorales (Cladophorales), push pipe Cutleriales (Acrosiphoniales), Siphonocladales (Siphonocladales), Caulerpa order (Caulerpales), pine Cutleriales (Codiales), at least a green algae in the algae of plumage Cutleriales (Bryopsidales) and Dasycladales (Dasycladales).
5. LTBP-4 according to claim 2 produces promoter, wherein,
Described Brown algae is to be selected to belong to brown shell Cutleriales (Ralfsiales), Dictyotales (Dictyotales), Chordariales (Chordariales), Scytosiphon lomentarius (Lyngh.)J. Ag. order (Scytosiphonales), Cutleriales (Cutleriales), burr Cutleriales (Sporochnales), Desmarestiale (Desmarestiales), Laminariales (Laminariales), at least a Brown algae in the algae of stable dish order (Ishigeales) and Fucales (Fucales).
6. LTBP-4 according to claim 1 produces promoter, wherein,
Described plant extract is to be selected from least a extract that belongs in Labiatae, pulse family, Rhamnaceae, Actinidiaceae, Polygonaceae, Vitaceae, Compositae, Gentianaceae, Boraginaceae, Tremellaceae, Nelumbonaceae, Radix Malvae sylvestris material, Rutaceae, Zingiberaceae and the rubiaceous plant.
7. a LTBP-4 produces composition for promoting, and it contains, and each described LTBP-4 produces promoter in the claim 1～6.
8. LTBP-4 according to claim 7 produces composition for promoting, and it is cosmetics.
9. LTBP-4 according to claim 7 produces composition for promoting, and it is food.
10. the extract of an algae or plant produces application in the promoter making LTBP-4.
11. red algae, green algae or Brown algae application in LTBP-4 generation promoter.
12. application according to claim 11, wherein,
Described red algae belongs to jackscrew Cutleriales (Acrochaetiales) for being selected from, Porphyridium cruentum order (Porphyridiales), Bangiales (Bangiales), Nemalionales (Nemaliales), red shield Cutleriales (Erythropeltidales), curved branch Cutleriales (Compsopogonales), Cryptonemiales (Cryptonemiales), Corallium Japonicum Kishinouye Cutleriales (Corallinales), ZHANGZAO order (Palmariales), Gelidiales (Gelidiales), the Rhodogorgonales order, kermes Cutleriales (Hildenbrandiales), Bai'an Cutleriales (Bonnemaisoniales), Bai'an Cutleriales (Bonnemaisoniales), beading Cutleriales (Batrachospermales), Gigartinales (Gigartinales), Thallus Gracilariae order (Gracilariales), Phodymeniales (Rhodymeniales), at least a red algae in the algae of Yi Gu Cutleriales (Ahnfeltiales) and Ceramiale (Ceramiales).
13. application according to claim 11, wherein,
Described green algae is to be selected to belong to volvocales (Volvocales), ring Cutleriales (Sphaeropleales), Oedogoniales (Oedogoniales), Chaetophorales (Chaetophorales), Chaetophorales (Chaetopeltidales,), bead Cutleriales (Chlorellales), the Microthamniales order, the Trebouxiales order, the Prasiolales order, small stream Cutleriales (Mamiellales), the Monomastigales order, the Dolichomastigales order, Trentepohliales (Trentepohliales), the Oltmannsiellopsidales order, the Chlorodendrales order, the Dolichomastigales order, the Nephroselmidales order, Ulotrichales (Ulotrichales), Ulvales (Ulvales), Cladophorales (Cladophorales), push pipe Cutleriales (Acrosiphoniales), Siphonocladales (Siphonocladales), Caulerpa order (Caulerpales), pine Cutleriales (Codiales), at least a green algae in the algae of plumage Cutleriales (Bryopsidales) and Dasycladales (Dasycladales).
14. application according to claim 11, wherein,
Described Brown algae is to be selected to belong to brown shell Cutleriales (Ralfsiales), Dictyotales (Dictyotales), Chordariales (Chordariales), Scytosiphon lomentarius (Lyngh.)J. Ag. order (Scytosiphonales), Cutleriales (Cutleriales), burr Cutleriales (Sporochnales), Desmarestiale (Desmarestiales), Laminariales (Laminariales), at least a Brown algae in the algae of stable dish order (Ishigeales) and Fucales (Fucales).
15. application according to claim 10, wherein,
Described plant extract is to be selected from least a extract that belongs in Labiatae, pulse family, Rhamnaceae, Actinidiaceae, Polygonaceae, Vitaceae, Compositae, Gentianaceae, Boraginaceae, Tremellaceae, Nelumbonaceae, Radix Malvae sylvestris material, Rutaceae, Zingiberaceae and the rubiaceous plant.
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| JP2011175137A JP6050573B2 (en) | 2011-08-10 | 2011-08-10 | LTBP-4 production promoter |
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| JP6050573B2 (en) | 2016-12-21 |
| JP2013035808A (en) | 2013-02-21 |
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