CN103347531A - 皮肤胶原产生促进剂 - Google Patents
皮肤胶原产生促进剂 Download PDFInfo
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- CN103347531A CN103347531A CN201280008178XA CN201280008178A CN103347531A CN 103347531 A CN103347531 A CN 103347531A CN 201280008178X A CN201280008178X A CN 201280008178XA CN 201280008178 A CN201280008178 A CN 201280008178A CN 103347531 A CN103347531 A CN 103347531A
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- tgf
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- skin collagen
- skin
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Classifications
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Abstract
本发明的目的是提供没有安全性问题的皮肤胶原产生促进剂。本发明的另外一个目的是提供含有上述物质的皮肤胶原产生促进用饮食品和皮肤胶原产生促进用化妆品。将TGF-β和/或通过用胃蛋白酶、胰酶等蛋白酶分解TGF-β获得的TGF-β分解物用作皮肤胶原产生促进剂,或皮肤胶原产生促进用饮食品以及皮肤胶原产生促进用化妆品的有效成分。前述的TGF-β和/或TGF-β分解物具有增加皮肤胶原含量的效果。
Description
技术领域
本发明涉及对防止皮肤粗糙、皱纹和弹性降低等皮肤劣化有用的皮肤胶原产生促进剂、皮肤胶原产生促进用饮食品和皮肤胶原产生促进用化妆品。具体地,本发明涉及包含转化生长因子β(TGF-β)和/或通过用蛋白酶分解TGF-β而得到的TGF-β分解物作为有效成分的皮肤胶原产生促进剂。
背景技术
由在皮肤劣化机理研究中所取得的近期成果已经证实,广泛地说,皮肤的干燥感和皮肤粗糙不仅是由于老龄化新陈代谢减慢而引起,而且还复杂地涉及到阳光(紫外线)、干燥和氧化等因素的作用。显示由于这些因素的影响会使得作为真皮最主要基质组分的胶原纤维显著减少。如果保持由胶原纤维支持的诸如回弹性(resilience)和弹性(elasticity)等皮肤张力的机制由于紫外线等因素的作用而遭到破坏,则皮肤的皱纹和下垂将会增加。由于胶原可以以其分子保留水从而有助于保持皮肤潮湿,因此如果胶原被外部因素破坏,则皮肤会干燥和粗糙。综上所述,期望通过促进作为真皮层主要成分之一的胶原的生物合成来预防皮肤皱纹和下垂而无安全问题的皮肤胶原产生促进剂。
转化生长因子β(TGF-β)是一种存在于哺乳动物乳里的生长因子。TGF-β家族包括五个亚型,该五个亚型为通过二硫键形成大约25kDa的二聚体的蛋白质。TGF-β家族具有调节细胞增生、生物合成、分化和凋亡的促进/抑制的功能。已经证实诱导动物细胞分化的作用是TGF-β的有效作用(专利文献1)。TGF-β作为皮肤成纤维细胞的生长因子也有报道(非专利文献1)。
引用列表
专利文献
专利文献1:日本特开专利公开2004-254674
非专利文献
非专利文献1:J.Dermatol.Sci.,Vol.24(Supple),p.70,2000
发明内容
发明要解决的问题
本发明要解决的问题是提供了一种没有安全问题的皮肤胶原产生促进剂。本发明的另一个要解决的问题是提供含有此类物质的皮肤胶原产生促进用饮食品和皮肤胶原产生促进用化妆品。
用于解决问题的方案
作为为了解决这些问题的对食品素材中包含的产生皮肤胶原产生促进作用的物质的锐意研究的结果,发明者发现TGF-β或者通过分解TGF-β而得到的TGF-β分解物增加了皮肤中的胶原含量,因此完成了本发明。
本发明包括以下实施方案。
(1)一种皮肤胶原产生促进剂,其包含TGF-β和/或TGF-β分解物作为有效成分。
(2)根据(1)所述的皮肤胶原产生促进剂,其中通过蛋白酶分解TGF-β获得所述TGF-β分解物。
(3)根据(2)所述的皮肤胶原产生促进剂,其中所述蛋白酶为选自胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶的一种或多种。
(4)根据(1)至(3)任一项所述的皮肤胶原产生促进剂,其中TGF-β分解物的平均分子量在500以上且8000以下。
(5)一种皮肤胶原产生促进用饮食品,其包含根据(1)至(4)任一项所述的TGF-β和/或TGF-β分解物。
(6)一种皮肤胶原产生促进用化妆品,其包含(1)至(4)任一项所述的TGF-β和/或TGF-β分解物。
(7)一种改善肌质的方法,其通过口服或涂布TGF-β和/或TGF-β分解物来改善肌质。
(8)一种改善肌质的方法,其通过口服10μg/天以上的TGF-β和/或TGF-β分解物,或者涂布0.001至2重量%的TGF-β和/或TGF-β分解物来改善肌质。
(9)一种皮肤胶原产生促进方法,其包含投与TGF-β和/或TGF-β分解物来促进皮肤中胶原产生。
(10)根据(9)所述的皮肤胶原产生促进方法,其中TGF-β分解物通过用蛋白酶分解TGF-β而获得。
(11)根据(10)所述的皮肤胶原产生促进方法,其中蛋白酶为选自胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶的一种或多种。
(12)根据(9)至(11)任一项所述的皮肤胶原产生促进方法,其中TGF-β分解物的平均分子量在500以上且8000以下。
(13)一种皮肤劣化防止或改善方法,其包含投与TGF-β和/或TGF-β分解物。
(14)根据(13)所述的皮肤劣化防止或改善方法,其中TGF-β分解物通过用蛋白酶分解TGF-β而获得。
(15)根据(14)所述的皮肤劣化防止或改善方法,其中蛋白酶为选自胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶的一种或多种。
(16)根据(13)至(15)任一项所述的皮肤劣化防止或改善方法,其中TGF-β分解物的平均分子量为500以上且8000以下
(17)一种皮肤劣化防止或改善剂,其包含TGF-β和/或TGF-β分解物作为有效成分。
(18)根据(17)所述的皮肤劣化防止或改善剂,其中TGF-β分解物通过用蛋白酶分解TGF-β而得到。
(19)根据(18)所述的皮肤劣化防止或改善剂,其中蛋白酶为选自胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶的一种或多种。
(20)根据(17)至(19)任一项所述的皮肤劣化防止或改善剂,其中TGF-β分解物的平均分子量在500以上且8000以下。
(21)一种皮肤劣化防止或改善用饮食品,其包含根据(17)至(20)任一项所述的TGF-β和/或TGF-β分解物。
(22)一种皮肤劣化防止或改善用化妆品,其包含根据(17)至(20)任一项所述的TGF-β和/或TGF-β分解物。
(23)一种纯粹以美容为目的的改善肌质的方法,其通过口服或者涂布TGF-β和/或TGF-β分解物来改善肌质。
(24)一种纯粹以美容为目的的改善肌质的方法,其通过口服10μg/天以上的TGF-β和/或TGF-β分解物,或者涂布0.001至2重量%的TGF-β和/或TGF-β分解物来改善肌质。
发明的效果
本发明提供了包含TGF-β和/或TGF-β分解物作为有效成分的皮肤胶原产生促进剂、皮肤胶原产生促进用饮食品和皮肤胶原产生促进用化妆品。皮肤胶原产生促进剂、皮肤胶原产生促进用饮食品和皮肤胶原产生促进用化妆品具有皮肤胶原产生促进的作用,并用于预防和治疗皮肤皱纹、下垂、干燥感和粗糙。
具体实施方式
本发明的皮肤胶原产生促进剂的特征在于含有TGF-β和/或通过用蛋白酶分解TGF-β而获得的TGF-β分解物作为有效成分。任何来源的TGF-β在本发明中均可使用。例如,人源TGF-β和牛源TGF-β的基因序列已明确并可通过基因重组技术而获得,用基因工程技术生产的TGF-β可以用于本发明中。TGF-β相当大量地存在于牛初乳中,也可从乳中收集。TGF-β也可从细胞培养介质中收集,该细胞来源的TGF-β也可使用。例如,乳来源的TGF-β可以根据已知方法生产(参见,例如,J.Protein Chem.,Vol.10,第565-575页,1991),并且TGF-β可由原料乳,奶粉,脱脂乳,复原乳或通过以下处理的其它加工乳:加热处理、加盐处理、乙醇处理、各种层析处理诸如离子交换层析和凝胶过滤层析,以及根据需要而组合使用的超滤处理。
对于TGF-β分解物,通过用蛋白酶如胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶对TGF-β限制性蛋白水解得到的平均分子量8000以下的肽混合物是可用的。同时,平均分子量的下限以500以上为宜。例如,TGF-β分解物的平均分子量为500以上且8000以下,1500以上且8000以下,2500以上且8000以下,3500以上且8000以下,4500以上且8000以下,5500以上且8000以下,6500以上且8000以下,7500以上且8000以下,500以上且7500以下,1500以上且7500以下,2500以上且7500以下,3500以上且7500以下,4500以上且7500以下,5500以上且7500以下,6500以上且7500以下,500以上且6500以下,1500以上且6500以下,2500以上且6500以下,3500以上且6500以下,4500以上且6500以下,5500以上且6500以下,500以上且5500以下,1500以上且5500以下,2500以上且5500以下,3500以上且5500以下,4500以上且5500以下,500以上且4500以下,1500以上且4500以下,2500以上且4500以下,3500以上且4500以下,500以上且3500以下,1500以上且3500以下,2500以上且3500以下,500以上且2500以下,1500以上且2500以下,500以上且1500以下。
本发明的皮肤胶原产生促进剂是通过口服或涂布从而发挥皮肤胶原产生促进的效果。当口服本发明的皮肤胶原产生促进剂时,有效成分即TGF-β或TGF-β分解物可被直接使用,或者以常规方式制剂化并用作口服剂如粉剂,颗粒剂,片剂,胶囊和饮用剂使用。例如,在本发明中,使用淀粉、乳糖、蔗糖、甘露糖醇、羧甲基纤维素、玉米淀粉和无机盐等赋型剂以常规方式制剂化为粉剂,颗粒剂,片剂和胶囊等口服剂。这种剂型可以通过使用赋型剂和根据需要的药物添加剂如粘结剂、崩解剂、表面活性剂、润滑剂、流动性促进剂、着色剂以及香料等而获得。更具体的说,粘结剂包括例如淀粉、糊精、***树胶、明胶、羟丙基淀粉、羧甲基纤维素钠、甲基纤维素、结晶纤维素、乙基纤维素和聚乙烯吡咯烷酮。崩解剂包括例如淀粉、羟丙基淀粉、羧甲基纤维素、羧甲基纤维素钠、交联羧甲基纤维素钠和结晶纤维素。表面活性剂包括大豆卵磷脂、蔗糖脂肪酸酯等;润滑剂包括滑石、蜡、蔗糖脂肪酸酯、氢化植物油等;流动性促进剂包括无水硅酸、干燥的氢氧化铝、硅酸镁等。
TGF-β或TGF-β分解物可能会与营养素,饮食品等直接或制成制剂后相结合。如果包含TGF-β或TGF-β分解物配着诸如维生素C的通常被认为对胶原产生有效的组分,可以期望进一步的皮肤胶原产生促进作用。由于TGF-β或TGF-β分解物对热相对稳定,因此含有TGF-β或TGF-β分解物的原料可以在通常使用条件下加热杀菌。
当使用本发明的皮肤胶原产生促进剂时,根据使用目的,皮肤胶原产生促进剂可以结合通常使用的已知成分,并制备例如液剂、固形剂或半固形剂等各种剂型,优选的组合物的实例包括软膏(ointment)、凝胶(gel)、面霜(cream)、喷雾剂(spray)、贴剂(patch)、化妆水(lotion)和粉末(powder)等。例如,本发明中的皮肤胶原产生促进剂可以与碳氢化合物如凡士林,十八烷醇,高级脂肪酸低级烷基酯如肉豆蔻酸异丙酯,动物油脂如羊毛脂,多元醇如甘油,甘油脂肪酸酯,单硬脂酸,表面活性剂如聚乙二醇,无机盐,蜡,树脂,水,以及根据需要添加的防腐剂如对羟苯甲酸甲酯和对羟苯甲酸丁酯混合,从而生产出皮肤胶原产生促进用化妆品和药物制剂。
尽管本发明的皮肤胶原产生促进剂的口服有效剂量并不是恒定的,而是根据剂型、投与方式、使用目的和适用所述促进剂的病人的年龄,体重以及病情而适当确定,但是使用大鼠的动物实验的结果发现,皮肤胶原产生促进作用可期望通过以每1kg的大鼠体重摄取10μg以上的TGF-β和/或TGF-β分解物而产生。因此,根据外推法,通过每个成人以10μg/天以上摄入TGF-β和/或TGF-β分解物而期望该效果,并且因此,TGF-β和/或TGF-β分解物可能要结合饮食品或者作为药物投与才能确保该必要量。可以根据需要采用每天数次的分开形式进行投与。
虽然本发明的皮肤胶原产生促进剂的涂布有效量依据剂型而各异,但是基于适用的组合物的总剂量,TGF-β和/或TGF-β分解物可能较好的控制在0.001至2重量%。但是,如果该组合物在用作沐浴添加剂时稀释,则含量可进一步增加。
实施例
在下文中参考实施例和试验例将详细描述本发明;但是,这些实施例仅示例性地示出本发明的实施方案,本发明不受限于这些实施例。
实施例1
使用去离子水充分地洗涤填充有3,000g S-琼脂糖凝胶的柱,在使10,000升脱脂乳通过柱后,使用去离子水充分地洗涤该柱,然后用0.1至1.0M氯化钠的线性梯度来洗脱该柱。用苯基-S琼脂糖凝胶疏水柱层析对含有TGF-β的洗脱级分再进行分级。这个级分在HPLC体系中用C4和C8反相层析和凝胶过滤层析中更进一步的连续处理得到412mg的TGF-β(级分A),用这种方法获得的TGF-β可以直接用作皮肤胶原产生促进剂。
实施例2
将25mg实施例1中得到的级分A悬浮于100ml水中后,加入胰酶至终浓度为1%从而在37℃下进行酶处理5分钟至6小时。在90℃下进行热处理5分钟从而失活此酶后,通过冻干得到24mg的TGF-β分解物(级分B、C和D)。以这种方法得到的TGF-β分解物B、C和D的平均分子量分别是约8000、约500和约300。级分B和C可以直接用作皮肤胶原产生促进剂。
[试验例1]
通过使用大鼠的动物实验检测了实施例1中得到的级分A和实施例2中得到的级分B到D的胶原产生促进作用。将7周龄的维斯塔(Wistar)雄性大鼠分成九个试验组(n=6),该九个试验组由投与生理盐水组(对照组),以大鼠每公斤体重投与10μg实施例1中得到的级分A的组(A-1组),以大鼠每公斤体重投与100μg实施例1中得到的级分A的组(A-2组),以大鼠每公斤体重投与10μg实施例2中得到的级分B到D的组(B-1到D-1组),和以大鼠每公斤体重投与100μg实施例2中得到的级分B到D的组(B-2到D-2组)组成,每天使用探针为每只大鼠口服一次,饲养十天。关于皮肤中胶原的量,按照Nimni等人的方法(参见Arch.Biochem.Biophys.,第292页,1967)处理大鼠的真皮后,可以测定可溶级分中羟脯氨酸的量。因为羟脯氨酸为仅包含于胶原中的特殊氨基酸,并占构成胶原全部氨基酸的约10%,所以可估算胶原的量(参见Ryuji Asano等人,BioIndustry,第12页,2001)。结果示于表1中。
[表1]
每个数值表示平均值±标准偏差(n=6)。
*表示与对照组相比存在显著性差异(p<0.05)。
结果显示,十周后可溶级分中羟脯氨酸的量与对照组相比,所有试验组中都明显更高。因此可以证明平均分子量在500以上且8000以下的TGF-β和TGF-β分解物具有皮肤胶原产生促进作用,可作为皮肤胶原产生促进剂使用。当TGF-β和TGF-β分解物以每公斤体重至少10μg的量投与于大鼠时,可观察到皮肤胶原产生促进作用。
[试验例2]
通过使用人成纤维细胞株(CCD45SK(ATCCRL1506)取自白人女性皮肤)来测定实施例1中获得的级分A和实施例2中获得的级分B的胶原产生促进作用。使用含有10体积%胎牛血清(以下缩写为FBS)的改良Eagle培养基(MEM)(由Dainippon Pharmaceutical Co.,Ltd.制造的“10-101”)将正常人成纤维细胞株以4×104个细胞/孔/0.4ml接种至24孔板,并在37℃、饱和水蒸气下用5%CO2培养24小时,并更换为含有0.6体积%FBS的MEM培养基。将实施例1获得的级分A和实施例2获得的级分B添加至各孔(以0.1体积%终浓度)(n=6)并培养24小时,然后添加β-氨基丙腈和氚代L-脯氨酸(终浓度分别为50μg/ml和1μCi/ml),并培养细胞另外的24小时后以获得培养液。按照Webster等人的方法(参见Analytical Biochemistry,第220页,1979)将胶原级分从以此方式获得的该培养液中分级,并测定在胶原级分中已被吸收的放射能。进行了未添加TGF-β和TGF-β分解物的相同试验作为对照。结果示于表2。
表2
每个数值表示平均值±标准偏差(n=6)。
*表示与对照组相比存在显著性差异(p<0.05)。
结果显示,所有添加TGF-β及TGF-β分解物的组表现出的胶原产生促进能力是未加TGF-β及TGF-β分解物组(对照)的两倍或以上。因此,表明TGF-β及TGF-β分解物对皮肤成纤维细胞的胶原产生有促进作用,并且可以用作皮肤胶原产生促进剂。
实施例3
用常规方法制成组成如表3所示的皮肤胶原产生促进用饮料。制造的饮料的风味良好,即使在室温下保存1年后所述风味也不劣化,并且没有例如沉淀等问题。
表3
实施例4
根据常规方法制备、成形和烘焙具有表4所示组成的生面团(dough)从而生产皮肤胶原产生促进用饼干。
表4
实施例5
根据常规方法制备具有表5组成的皮肤胶原产生促进剂。
表5
实施例6
根据常规方法制备含有表6组分的化妆水。
表6
实施例7
根据常规方法制备具有表7所示组成的面霜。
表7
[试验例3]
使用实施例6中获得的化妆水和实施例7中获得的面霜来进行实际使用试验。使用除了不添加TGF-β及TGF-β分解物以外具有与实施例6或7的相同组成的比较品。将面部皮肤下垂、具有细微皱纹并且皮肤干燥的20个成年女性以每组10人随机分成2组(组E和F)并将具有粗糙手部皮肤的20名女性以每组10人随机分成2组(组G和H),将2g本发明的化妆水涂布于E组的面部,2g比较品化妆水涂布于F组的面部,2g本发明的面霜涂布于G组的手指,2g比较品面霜涂布于H组的手指,在正常用量的情况下用相似的方式每天两次,持续10天。结果如表8所示。
表8
++:涂布10天后观察到显著的改善效果。
+:涂布10天后观察到改善效果。
±:涂布10天后没有观察到改善效果(与十天前比较无变化)。
从表8中看出,与使用比较品的化妆水和面霜的F组和H组相比,特别是在使用实施例6的化妆水和实施例7中面霜的E组和G组的干燥感和皮肤粗糙上,呈现出了显著的改善效果。
Claims (8)
1.一种皮肤胶原产生促进剂,其包含TGF-β和/或TGF-β分解物作为有效成分。
2.根据权利要求1所述的皮肤胶原产生促进剂,其中所述TGF-β分解物通过用蛋白酶分解TGF-β而得到。
3.根据权利要求2所述的皮肤胶原产生促进剂,其中所述蛋白酶为选自胰蛋白酶、胰酶、胰凝乳蛋白酶、胃蛋白酶、木瓜蛋白酶、激肽释放酶、组织蛋白酶、嗜热菌蛋白酶和V8蛋白酶的一种或多种。
4.根据权利要求1至3任一项所述的皮肤胶原产生促进剂,其中所述TGF-β分解物的平均分子量在500以上且8000以下。
5.一种皮肤胶原产生促进用饮食品,其包含根据权利要求1至4任一项所述的TGF-β和/或TGF-β分解物。
6.一种皮肤胶原产生促进用化妆品,其包含根据权利要求1至4任一项所述的TGF-β和/或TGF-β分解物。
7.一种改善肌质的方法,其通过口服或涂布TGF-β和/或TGF-β分解物来改善肌质。
8.一种改善肌质的方法,其通过口服10μg/天以上的TGF-β和/或TGF-β分解物,或者涂布0.001至2重量%的TGF-β和/或TGF-β分解物来改善肌质。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1952192A (en) * | 1991-08-12 | 1993-02-18 | Societe Des Produits Nestle S.A. | Milk derived polypeptide for suppressing major histocompatability complex class-II |
CN1771051A (zh) * | 2003-05-07 | 2006-05-10 | 雪印乳业株式会社 | 皮肤胶原产生促进剂 |
US20090048145A1 (en) * | 2004-06-09 | 2009-02-19 | Scil Technology Gmbh | In situ hardening paste, its manufacturing and use |
WO2010006412A1 (en) * | 2008-06-23 | 2010-01-21 | Innovactiv Inc. | Cosmetic compositions comprising asteroidea body fluid and methods of use thereof |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES360433A1 (es) * | 1968-11-20 | 1970-11-16 | Rocador Sa | Procedimiento para la fabricacion de un compuesto de hierrotrivalente apropiado para administracion por via oral. |
KR920002163B1 (ko) * | 1988-08-05 | 1992-03-19 | 온코겐, 어 리미티드 파트너쉽 | TGF-β를 이용한 건선 치료방법 |
JPH0625288A (ja) * | 1992-07-10 | 1994-02-01 | Kuraray Co Ltd | ペプチドまたはその塩 |
US5420243A (en) | 1993-01-26 | 1995-05-30 | Celtrix Pharmaceuticals, Inc. | Biologically active TGF-β2 peptides |
US6974796B1 (en) * | 1999-08-17 | 2005-12-13 | Girsh Leonard S | Therapeutic compositions for treatment of a damaged tissue |
CA2296311A1 (en) * | 1999-01-28 | 2000-07-28 | Universite Laval | Enzymatic hydrolysate of milk proteins |
JP4291967B2 (ja) * | 2001-11-08 | 2009-07-08 | 雪印乳業株式会社 | 皮膚コラーゲン産生促進剤 |
JP2004254674A (ja) | 2003-02-25 | 2004-09-16 | Mutsumi Takagi | 動物細胞の分化誘導培養方法 |
US7744895B2 (en) * | 2005-08-31 | 2010-06-29 | Yamanashi University | Methods of treating allergies using TGF-β1 and allergens |
JP2009524425A (ja) * | 2006-01-27 | 2009-07-02 | プロスティミクス カンパニー リミテッド | 脂肪由来幹細胞を利用した成長因子の大量生産方法 |
SG10202109176RA (en) | 2006-02-23 | 2021-09-29 | Viacyte Inc | Compositions and methods useful for culturing differentiable cells |
JP5274814B2 (ja) * | 2007-03-13 | 2013-08-28 | 雪印メグミルク株式会社 | 美白剤 |
US8247435B2 (en) * | 2009-02-19 | 2012-08-21 | Thornthwaite Jerry T | Formulations for treating human and animal diseases |
JP5955499B2 (ja) | 2010-09-30 | 2016-07-20 | 雪印メグミルク株式会社 | 皮膚コラーゲン産生促進剤 |
JP2012077018A (ja) | 2010-09-30 | 2012-04-19 | Snow Brand Milk Products Co Ltd | 皮膚コラーゲン産生促進剤 |
JP5890100B2 (ja) | 2011-02-09 | 2016-03-22 | 雪印メグミルク株式会社 | 皮膚コラーゲン産生促進剤 |
JP2012188384A (ja) | 2011-03-10 | 2012-10-04 | Snow Brand Milk Products Co Ltd | 美肌剤 |
-
2011
- 2011-02-09 JP JP2011026446A patent/JP5890100B2/ja active Active
-
2012
- 2012-02-07 US US13/982,012 patent/US20130310318A1/en not_active Abandoned
- 2012-02-07 KR KR1020137023003A patent/KR101705938B1/ko active IP Right Grant
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1952192A (en) * | 1991-08-12 | 1993-02-18 | Societe Des Produits Nestle S.A. | Milk derived polypeptide for suppressing major histocompatability complex class-II |
CN1771051A (zh) * | 2003-05-07 | 2006-05-10 | 雪印乳业株式会社 | 皮肤胶原产生促进剂 |
US20090048145A1 (en) * | 2004-06-09 | 2009-02-19 | Scil Technology Gmbh | In situ hardening paste, its manufacturing and use |
WO2010006412A1 (en) * | 2008-06-23 | 2010-01-21 | Innovactiv Inc. | Cosmetic compositions comprising asteroidea body fluid and methods of use thereof |
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