CN114404577B - 一种促进脂肪细胞内甘油三酯降解的外用组合物及其制备方法和用途 - Google Patents
一种促进脂肪细胞内甘油三酯降解的外用组合物及其制备方法和用途 Download PDFInfo
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Abstract
本发明属于医药生物技术领域,具体涉及一种促进脂肪细胞内甘油三酯降解的外用组合物及其制备方法和用途,其特征在于:所述组合物以重量份数计包含:组分A脂肪分解代谢相关酶1‑300份、组分B代谢调控蛋白0.5‑80份、组分C促进代谢化合物0.5‑50份和组分D B族维生素0.5‑50份。本发明可以实现外用涂抹的方式局部靶向降解皮下脂肪细胞内的甘油三酯,不仅不破坏脂肪细胞膜,还可以实现甘油三酯的有效降解。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种促进脂肪细胞内甘油三酯降解的外用组合物及其制备方法和用途。
背景技术
肥胖,是指一定程度的明显超重与脂肪层过厚,是由于摄入的热量高于能量消耗并且长期不平衡,脂肪组织等大量脂肪沉积而导致的一种状态。肥胖可以分为全身性肥胖和局部肥胖两大类。全身性肥胖不仅影响个人的工作、生活和美观,而且对健康也有相当的危害性。肥胖容易导致各种慢性疾病,如2型糖尿病(T2D)、高脂血症、心血管疾病(CVD)、高血压、脑血管病、阻塞性睡眠呼吸暂停等。局部肥胖虽然一般不会造成严重的健康问题,但却是一个更为普遍的社会问题,其指的是身体某一部分脂肪蓄积过多而发生的肥胖,以腹部、手臂、大腿和臀部等部位最为常见。
目前,多种方法可以用于治疗肥胖,如饮食改变、运动、行为改变、手术和药物治疗等等。临床上应用于去除皮下脂肪的方法和药物以介入类为主:药物方式多以单一组分通过注射介入的方式调控整个机体代谢来实现整个机体的脂肪减少,一些减脂类药物是来治疗代谢性疾病,如2型糖尿病,注射会容易引起低血糖和肝肾功能损伤及代谢紊乱的副作用。有效的手术方式是通过负压吸脂的方式将皮下脂肪组织抽吸至体外,易引发栓塞、窒息等副作用风险。以裂解脂肪细胞方式以注射为主的溶脂针,容易诱发炎症和皮下注射不均引发的组织凹凸。冷冻或热熔物理方式使皮下脂肪细胞坏死或者凋亡,无法解决甘油三酯代谢的问题,因此甘油三酯降解有效率不高。
可见,现有的医疗技术和方法多以破坏和减少脂肪组织和细胞为主,旨在减少皮下脂肪细胞,暴力破坏减少脂肪细胞数量,大量脂肪囤积在有限脂肪细胞中,当这些细胞不堪重负,就会选择死亡或者功能失调,会将脂质溢出到本不应该储存脂肪的地方。这些脂质转移到肝脏诱发脂肪肝,如转移到胰腺就会诱发糖尿病,转移至心脏会诱发心血管疾病,腹部脂肪可能会围绕在器官周围并引起炎症发生。
最新的研究成果认为,脂肪储存最健康的地方是皮下脂肪,不破坏细胞只减少甘油三酯成为最健康有效的减脂方式(例如,参见Mengle Shao,Chelsea Hepler,QianbinZhang, et al. Pathologic HIF1α signaling drives adipose progenitordysfunction in obesity. Cell Stem Cell. February 03, 2021 DOI:10.1016/j.stem.2020.12.008)。
但是,目前市场上缺乏安全有效的促进脂肪细胞内甘油三酯降解的外用组合物产品。
发明内容
本发明的目的在于克服上述现有技术的不足之处,提供一种可以实现以外用涂抹方式局部靶向降解皮下脂肪细胞内甘油三酯的促进脂肪细胞内甘油三酯降解的外用组合物,以实现在不破坏脂肪细胞膜前提下的甘油三酯的有效降解。
具体地,通过以下几个方面的技术方案实现了本发明:
在第一个方面中,本发明提供了一种促进脂肪细胞内甘油三酯降解的外用组合物,所述组合物以重量份数计包含组分A至组分D的两种或更多种:组分A脂肪分解代谢相关酶1-300份、组分B代谢调控蛋白0.5-100份、组分C促进代谢化合物0.5-80份和组分D B族维生素0.5-50份,其中在所述外用组合物中,组分A和/或组分B是必需包含的,组分C和组分D是任选包含的。
优选地,所述组合物以重量份数计包含组分A至组分D的两种或更多种:组分A脂肪分解代谢相关酶50-100份、组分B代谢调控蛋白20-100份、组分C促进代谢化合物20-50份和组分D B族维生素10-40份。
或者,在另一个实施方式中,所述组合物以重量份数计包含组分A至组分D的两种或更多种:组分A脂肪分解代谢相关酶200-300份、组分B代谢调控蛋白20-100份、组分C促进代谢化合物20-50份和组分D B族维生素10-40份。
在另一个更进一步的实施方式中,所述组合物以重量份数计还包含:稳定剂和脂质分子20-60份。
更优选地,稳定剂和脂质分子30-50份。
在一个优选实施方式中,所述组分A脂肪分解代谢相关酶选自甘油激酶、甘油-3-磷酸脱氢酶、丙酮酸脱氢酶复合物、脂肪酸α-羟化酶、肝脂酶、脂酰辅酶a合酶、脂酰辅酶A脱氢酶、磷脂酶A1、磷脂酶A2、酯酶、肉碱-脂酰转移酶I、脂酰肉碱移位酶I、脂酰肉碱移位酶II、脂肪酶类、硫解酶、柠檬酸合酶、琥珀酸脱氢酶、乌头酸酶、异柠檬酸脱氢酶、琥珀酰辅酶A合成酶、延胡索酸酶或苹果酸脱氢酶中的一种或多种;和/或
所述组分B代谢调控蛋白选自脂滴包被蛋白(PLIN)、补体因子D、钙调蛋白、腺苷酸环化酶、瘦素合成酶中的一种或多种;和/或
所述组分C促进代谢化合物选自左旋肉碱或含有左旋肉碱成分的物质或者茶叶提取物,所述茶叶提取物包含茶多酚(儿茶素)、生物碱(包括咖啡碱、茶碱、可可碱等)、茶蛋白)等;和/或
所述组分D B族维生素选自维生素B1、维生素B2、维生素B3、维生素B5、维生素B6、维生素B7、维生素B9或维生素B12中的一种或多种;
进一步优选地,所述组分A脂肪分解代谢相关酶选自甘油激酶、丙酮酸脱氢酶复合物、脂酰辅酶a合酶、甘油-3-磷酸脱氢酶、肉碱-脂酰转移酶I、脂酰肉碱移位酶II、脂酰肉碱移位酶II、脂肪酶类、琥珀酸脱氢酶、柠檬酸合酶、硫解酶、琥珀酰辅酶A合成酶、延胡索酸酶、异柠檬酸脱氢酶或苹果酸脱氢酶中的一种或多种;和/或
所述组分B代谢调控蛋白选自PLIN、补体因子D、钙调蛋白、腺苷酸环化酶、瘦素合成酶中的一种或多种;和/或
所述组分C促进代谢化合物选自左旋肉碱或含有左旋肉碱成分的物质或者茶叶提取物包含茶多酚(儿茶素)、生物碱(包括咖啡碱、茶碱、可可碱等)、茶多糖、茶蛋白)等;和/或
所述组分D B族维生素选自维生素B1、维生素B2、维生素B5、维生素B6、维生素B7或维生素B12中的一种或多种。
值的注意的是,本发明人在研究过程中,意外地发现了将上述组分A脂肪分解代谢相关酶、组分B代谢调控蛋白、组分C促进代谢化合物和组分D B族维生素组合在一起使用,在促进甘油三酯有效降解方面即可产生显著的协同增效作用。因此,组分A-组分D并不仅限于上文中所述的具体种类,也可以将其替换为本领域技术人员知晓的其他常规脂肪分解代谢相关酶、代谢调控蛋白、促进代谢化合物和B族维生素。
在第二个方面中,本发明涉及上述第一个方面所述的外用组合物的制备方法,包括以下步骤:
按照重量份数将上述第一个方面所述的各种组分按比例混匀,然后进行冻干制成粉剂。
在第三个方面中,本发明涉及上述第一个方面所述的外用组合物在制备促进脂肪细胞内甘油三酯降解的外用减肥产品中的用途。
其中,所述产品是药物、保健品或化妆品。
在一个优选的实施方式中,所述产品是将上述第一个方面所述的外用组合物与药物、保健品或化妆品领域的适宜辅料混合以制成各种剂型制备的。
在更优选的实施方式中,所述产品的剂型是粉剂、膏剂、糊剂、溶液剂、乳剂、贴剂、霜剂、凝胶剂、搽剂或喷雾剂。
优选地,所述粉剂为冻干粉剂。
可以采用在药物、保健品以及化妆品领域公知的辅料以及制备方法制备本发明上述第三个方面所述的外用减肥产品。
为了增强本发明外用组合物的作用效果,可以将本发明外用组合物与常规脂肪靶向递送系统或经皮导入装置结合使用,这是本领域的常规技术手段。
本发明相对于现有技术,具有以下有益效果:
(1)本发明提供了一种可以实现以外用涂抹方式局部靶向降解皮下脂肪细胞内甘油三酯的促进脂肪细胞内甘油三酯降解的外用组合物,成功实现了在不破坏脂肪细胞膜前提下的甘油三酯的有效降解。
(2)本发明首次发现,本发明外用组合物中的组分A-组分D中的至少三种组分在一起使用在促进甘油三酯有效降解方面具有显著的协同增效作用。
(3)本发明外用组合物使用方便,起效迅速,且长期使用不会产生耐药性,无任何副作用,十分安全可靠。
附图说明
图1:MTT分析本发明组合物(实施例11)对原代脂肪细胞和人皮肤成纤维细胞存活率的影响。细胞经过不同浓度本发明组合物(2.5、5、10、20、40、80、160、320和640 μg/mL)作用48小时后,进行MTT分析(每个样品重复三次)。
图2:分析本发明组合物(实施例11)作用脂肪细胞48小时后,油性红O染色,显微镜观察细胞形态及细胞内脂肪含量的变化。其中图2A表示对照组结果;图2B表示本发明组合物处理组结果。
图3:本发明组合物(实施例11)对人原代脂肪细胞脂肪含量影响。原代脂肪细胞经不同浓度(2.5、5、10、20、30、40、50和60 μg/mL)本品作用48小时后脂肪降解率的变化(每个样品重复三次)。
图4:样品抽检检测对脂肪细胞内脂肪滴的降解效应。检验结果显示,抽检的10个批次本发明组合物(实施例11)的样品,脂肪细胞内脂肪降解率均达到63%左右。
图5:本发明组合物(实施例16)不同组分的去除对脂肪降解率的影响。(-A):产品不含组分A组;(-B):产品不含组分B组;(-C):产品不含组分C组;(-D):产品不含组分D组;(完全):产品。产品浓度为50 μg/mL。图中“a, b, c和d”表示在p<0.05水平的显著性差异。
图6:相同喂养条件及体重的小鼠通过脂肪层注射后体重变化情况。DIO肥胖小鼠体重达到约45g附近时进行处理,处理后分别在第1、2、4、6、9、12、15和18天观察测量和记录小鼠体重变化。图中:对照组为PBS组;本发明组合物(实施例16)不含组分A组(-A);本发明组合物(实施例16)不含组分B组(-B);本发明组合物(实施例16)不含组分C组(-C);本发明组合物(实施例16)D组(-D);本发明组合物(实施例16)(完全)。“*”代表在p<0.05水平差异性显著,“**”代表在p<0.01水平差异性显著。
图7:本发明组合物(实施例21)不同组分的去除对受试者上臂围(A)和大腿围(B)的影响。受试者共120名,随机分六组,每组20名,图中:对照组为PBS组;本发明组合物(实施例21)不含组分A组(-A);本发明组合物(实施例21)不含组分B组(-B);本发明组合物(实施例21)不含组分C组(-C);本发明组合物(实施例19)D组(-D);本发明组合物(实施例21)(完全)。图中“a, b, c, d和e”表示在p<0.05水平的显著性差异。
图8:本发明组合物(实施例22)不同组分的去除对受试者面部紧致效果的影响。受试者共120名,随机分六组,每组20名,图中:对照组为PBS组;本发明组合物(实施例22)不含组分A组(-A);本发明组合物(实施例22)不含组分B组(-B);本发明组合物(实施例22)不含组分C组(-C);本发明组合物(实施例22)D组(-D);本发明组合物(实施例22)(完全)。图中“a, b, c, d和e”表示在p<0.05水平的显著性差异。
图9:在使用本发明组合物(实施例22)后,受试者面部紧致效果的改善情况照片。其中:(A)某个代表性女性受试者;(B)另外一个代表性女性受试者。
具体实施方式
下面参照具体的实施例对本发明做进一步说明。应当理解,此处所描述的具体实施例仅用于解释本发明,并不用于限定本发明的范围。
实施例中未注明具体技术或条件者,按照本领域内的文献所描述的技术或条件,或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者,均为可通过正规渠道购买得到的常规产品。
下面实施例中的实验方法,如无特殊说明,均为常规方法。下述实施例中所用的试验材料,如无特殊说明,均为市售产品。
制备实施例:
以下实施例中使用的原料均以重量份数计。
实施例1:甘油-3-磷酸脱氢酶、(100份)、苹果酸脱氢酶(50份)、PLIN(30份)、咖啡碱(15份)、维生素B6(5份)。
实施例2:甘油-3-磷酸脱氢酶、(200份)、肝脂酶(100份)、补体因子D(100份)、茶多酚(50份)。
实施例3:脂酰肉碱移位酶I(100份)、脂酰辅酶A脱氢酶(100份)、腺苷酸环化酶(30份)、左旋肉碱、维生素B5(10份)。
实施例4:脂酰肉碱移位酶I(100份)、瘦素合成酶(100份)、左旋肉碱(10份)。
实施例5:脂酰肉碱移位酶II(100份)、补体因子D(100份)、咖啡碱(50份)、维生素B5(30份)。
实施例6:甘油激酶(300份)、补体因子D(100份)、左旋肉碱(10份)、维生素B6(10份)。
实施例7:琥珀酸脱氢酶(100份)、瘦素合成酶(50份)、左旋肉碱(30份)维生素B6(35份)。
实施例8:甘油-3-磷酸脱氢酶(50份)、左旋肉碱(50份)、维生素B6(30份)。
实施例9:苹果酸脱氢酶(80份)、柠檬酸合酶、咖啡碱(50份)、左旋肉碱(30份)维生素B12。
实施例10:琥珀酰辅酶A合成酶(100份)、PLIN(100份)、咖啡碱(50份)、维生素B12(10份)。
实施例11:琥珀酸脱氢酶(100份)、补体因子D(100份)、左旋肉碱(50份)、维生素B1(20份)。
实施例12:延胡索酸酶(300份)、补体因子D(100份)左旋肉碱(50份)、茶多酚(10份)、维生素B12。
实施例13:柠檬酸合酶(100份)、苹果酸脱氢酶(50份)、PLIN(100份)、左旋肉碱(50份)、维生素B5(30份)。
实施例14:丙酮酸脱氢酶复合物(100份)、腺苷酸环化酶(100份)、茶叶提取物(30份)、左旋肉碱(30份)。
实施例15:丙酮酸脱氢酶复合物(100份)、瘦素合成酶(100份)、可可碱(50份)。
实施例16:丙酮酸脱氢酶复合物(100份)、琥珀酸脱氢酶(50份)、钙调蛋白(60份)、补体因子D(40份)、茶多酚(30份)、维生素B6(40份)。
实施例17:苹果酸脱氢酶(100份)、补体因子D(100份)左旋肉碱(30份)、维生素B7(10份)。
实施例18:硫解酶(100份)、脂肪酶类(50份)、钙调蛋白(100份)左旋肉碱(50份)、维生素B6(30份)。
实施例19:硫解酶(100份)、苹果酸脱氢酶(50份)、瘦素合成酶(100份)(50份)、维生素B1(10份)。
实施例20:苹果酸脱氢酶(200份)、PLIN(100份)、左旋肉碱(30份)。
实施例21:丙酮酸脱氢酶复合物(100份)、琥珀酸脱氢酶(50份)、瘦素合成酶(50份)、补体因子D(40份)、咖啡碱(50份)、维生素B7(生物素)(10份)。
实施例22:、丙酮酸脱氢酶复合物(100份)、硫解酶(50份)、甘油-3-磷酸脱氢酶(50份)、钙调蛋白(100份)、左旋肉碱(25份)、茶多酚(25份)、维生素B12(40份)。
实施例23:异柠檬酸脱氢酶(100份)、PLIN(50份)、咖啡碱(50份)、维生素B12(40份)。
本发明促进脂肪细胞内甘油三酯降解的外用组合物的制备方法如下所示:
按照重量份数将上述实施例1-23中所述的各种组分按比例混匀,然后进行冻干制成粉剂。
随后,可以采用在药物、保健品以及化妆品领域公知的辅料以及制备方法将上述粉剂制成外用减肥产品。
效果实施例:
1、细胞水平实验
1.1实验方法
1.1.1脂肪细胞分离
(1)取4周龄SD大鼠,处死,取睾丸脂肪垫,PBS清洗干净,清除干净结缔组织。
(2)在PBS液体里将脂肪垫剪碎。
(3)去除PBS,加入0.25%的胰酶,在37℃温度下处理30 min-1 h,并不停的摇动。
(4)加入完全培养液(DMEM+10%胎牛血清),终止胰酶。同时用200目筛网过滤。去除未消化的组织。
(5)用PBS充分洗涤细胞3次。再加入完全培养液,37℃放置40min。
(6)将细胞倒入Matrix胶包被的细胞培养板
(7)24h后细胞贴壁完全,备用。
1.1.2细胞毒性实验
将分离得到的原代脂肪细胞(或者购买的人皮肤成纤维细胞HSF)培养到一定数量后,消化计数,然后铺于96孔板,每孔约10000个细胞,细胞继续培养24小时贴壁,然后加入完全培养基溶解的不同含量的待测样品,随后在培养箱继续培养48小时,结束后每孔加入50μL的1 mg/mL的MTT溶液,放入培养箱继续培养4小时,取出,弃上清,每孔加入150 μLDMSO溶液,振荡30 min,使用多功能酶标仪在540 nm测量吸光度。
1.1.3脂肪降解评估
1.1.3.1 显微镜观察
将分离得到的原代脂肪细胞铺板于12孔板,每孔细胞约20000个,贴壁培养24小时后,加入完全培养基溶解的本品(60 μg/mL),作用48小时后,对细胞进行油红O染色,然后使用显微镜观察细胞形态变化。
1.1.3.2 细胞水平甘油三酯脂肪降解率
将分离得到的原代脂肪细胞铺板于96孔板,每孔细胞约10000个,贴壁培养24小时后,加入完全培养基溶解的不同剂量本品及其他对比组,作用48小时后,对细胞进行油红O染色,然后用异丙醇处理染色后的细胞,使用多功能酶标仪在490 nm波长下测定吸光度值,每组3个复孔,依据以下公式计算脂肪细胞内脂肪降解率。
脂肪降解率=(OD对照组-OD实验组)×100%/OD对照组
其中OD对照组指对照组OD值平均值;OD实验组指各个实验组OD值平均值。
1.2实验结果
1.2.1 细胞毒性分析
如图1所示,通过对皮下两种正常细胞(上述自行制备的原代脂肪细胞或商购的人皮肤成纤维细胞)的MTT实验分析,可以看出,所采用本发明组合物(实施例11)浓度达到640μg/mL时,细胞存活率均在80%以上,可以看出本品对细胞存活率影响比较低。本品在进行细胞水平实验时,当作用浓度小于80 μg/mL时,细胞存活率均在95%以上,后续细胞实验采用产品浓度范围均小于80 μg/mL。
为了节约篇幅,在细胞毒性分析中使用的本发明组合物(实施例11)得到的实验结果仅是代表性的,实质上已对本发明制备实施例1-23中制备得到的所有组合物均进行了上述实验,并且得到了与上述代表性结果一致的结论(具体数据未列出)。
1.2.2 脂肪细胞内脂肪颗粒降解
原代脂肪细胞经样品作用48小时后,加入脂肪颗粒染色剂(油性红O),如图2表明本发明组合物(实施例11)样品作用后脂肪细胞的脂肪颗粒几乎消失,而在此过程中并未出现细胞裂解或细胞碎片现象;作用过程中细胞形态完整;说明有效成分通过细胞膜进入脂肪细胞内并有效降解甘油三酯。
采用不同浓度的本发明组合物(实施例11)作用于原代脂肪细胞后,发现随着产品浓度的升高,脂肪降解率呈现递增趋势(图3)。同时我们以细胞水平脂肪降解率作为指标,评价了本发明组合物(实施例11)不同批次产品脂肪降解效率的稳定性,如图4所示,结果表明不同批次产品脂肪降解效果稳定。
如图5所示,以完全培养基作为对照组,考察了本发明组合物(实施例16)中A、B、C和D组分的分别去除对脂肪降解率的影响。完全的本发明组合物(实施例16)在该浓度下脂肪降解率在63%左右,符合前面的实验结果。
当从产品中去除组分A时,产品脂肪降解率显著下降,达到2%附近。当产品去除成分B时,产品脂肪降解率下降至30%附近。这些结果表明,组分A是产品中脂肪降解的关键活性成分,因此组分A的缺失引起产品脂肪降解率的显著下降,几乎丧失作用。而组分B的去除引起产品脂肪降解率下降约50%,通过数据分析,组分A和组分B在脂肪降解方面不存在叠加作用,而是组分B对组分A的脂肪降解作用具有显著的协同促进作用。当产品去除成分C或者D时,产品脂肪降解率下降约15%,这说明组分C或者D对组分A的减脂作用也具有一定协同促进作用,但是该协同促进作用不如组分B明显。
为了节约篇幅,在脂肪细胞内脂肪颗粒降解分析中使用的本发明组合物(实施例11或实施例16)得到的实验结果仅是代表性的,实质上已对本发明制备实施例1-23中制备得到的所有组合物均进行了上述实验,并且得到了与上述代表性结果一致的结论(具体数据未列出)。
2、动物实验
2.1实验方法
2.1.1动物
DIO肥胖小鼠模型若干只(南京大学模式动物研究所),体重25-35 g。
2.1.2 动物实验分组
待小鼠体重增加至约45 g时,开始分组,每组10只,分组情况如下:
(1)对照组即PBS组;(2)本发明组合物(实施例16)不含组分A组(-A);(3)本发明组合物(实施例16)不含组分B组(-B);(4)本发明组合物(实施例16)不含组分C组(-C);(5)本发明组合物(实施例16)不含组分D组(-D);(6)本发明组合物(实施例16)(完全)。
小鼠作用后,分别在第1、2、4、6、9、12、15和18天观察测量和记录小鼠体重变化。剂量以产品冻干粉质量计算,每只小鼠使用上述(1)-(6)组的样品的剂量25 mg。
2.1.3 作用方式为皮肤涂抹
首先使用脱毛剂,对小鼠腹股沟进行脱毛处理,随后涂抹待测品,最后借助脉冲导入仪作用5 min,观察测量和记录小鼠体重变化。
2.2 实验结果
如图6所示,对照组小鼠随着时间增加,体重呈现递增的趋势,当不含组分A的本发明组合物(实施例16)作用小鼠时,小鼠体重也是呈现递增趋势,增长速度略低于对照组。当不含组分B的本发明组合物(实施例16)作用小鼠时,小鼠体重先下降,并在第4至9天维持稳定,然后呈现递增趋势。不含组分C或者D的本发明组合物(实施例16)作用小鼠时,小鼠体重的变化趋势与(-B)组相似,但是相同时期动物体重显著下降。然而当完全本发明组合物(实施例16)作用于动物时,相同时期动物体重下降速度最快、动物体重最低。
动物实验结果表明,本发明组合物(实施例16)中组分A对小动物脂肪降解起到关键作用,因此组分A去除时,小鼠体重整体呈现递增趋势。当组分B去除时,组分A也能够减去动物脂肪,使得体重在第一周呈现递减趋势,但是与完全组相比,减脂效果显著下降,这说明组分B对组分A的减脂作用具有明显的促进作用。组分C和组分D也能够影响产品效果,说明组分C和组分D对组分A的减脂作用也具有一定促进作用。
为了节约篇幅,在动物实验中使用的本发明组合物(实施例16)得到的实验结果仅是代表性的,实质上已对本发明制备实施例1-23中制备得到的所有组合物均进行了上述实验,并且得到了与上述代表性结果一致的结论(具体数据未列出)。
3、在肥胖志愿者中进行的效果试验
3.1 实验方法
3.1.1 身体四肢脂肪降解
试验时,首先测量受试者大腿围和上臂围,作为体验前数据,然后将本发明组合物(实施例21)受试品涂抹在受试者大腿处和上臂处,借助脉冲导入仪设备导入,每次需时50-80 min,每隔7天一次,每次500 mg,3次为一个疗程,每次单个手臂使用两支、每次单腿使用两支,手臂做1个疗程,大腿做2个疗程,做完之后第7天,分别测量受试者大腿围和上臂围。
手臂围测量时,在手臂上围内测以手臂肘关节和肩关节为两端,取中间位点进行臂围测量。大腿围测量时,在大腿上围内测,以膝关节和髋关节为两端,取中间位点进行大腿围测量。将每组20名受试者在相对应阶段得到的数据进行汇总求平均值,最终得到单支手臂围或者大腿围减少量(单位:cm)。
依据受试品不同,实验分组如下:
(1)对照组PBS组(20人);(2)本发明组合物(实施例21)不含成分A组(-A)(20人);(3)本发明组合物(实施例21)不含成分B组(-B)(20人);(4)本发明组合物(实施例21)不含成分C组(-C)(20人);(5)本发明组合物(实施例21)不含成分D组(-D)(20人);(6)本发明组合物(实施例21)(完全)(20人)。
3.1.2 面部皮肤紧致
在进行上述第3.1.1部分实验的同时进行这部分实验。每次将冻干粉溶于调配液,均匀涂抹本发明组合物(实施例22)受试品于面部,然后采用脉冲导入仪导入,一个疗程3次,一次两支,每隔7天一次,每支250 mg,在一个疗程结束第7天测量面部紧致指标。
依据受试品不同,实验分组如下:
(1)对照组PBS组(20人);(2)本发明组合物(实施例22)不含成分A组(-A)(20人);(3)本发明组合物(实施例22)不含成分B组(-B)(20人);(4)本发明组合物(实施例22)不含成分C组(-C)(20人);(5)本发明组合物(实施例22)不含成分D组(-D)(20人);(6)本发明组合物(实施例22)(完全)(20人)。
面部紧致指标通过拍照观察和参照2000年发表于《中国美容医学》设定的评估方法(例如,参见,杨萍. 谢红. 经络减肥仪瘦脸220例临床观察. 《中国美容医学》第9卷第5期,339),测量面部2条线长度:A线:从右耳廓与面部连结的最高点,经下颌骨边缘过下颌中部最低点,对称到左耳廓最高点的围度;B线:从右耳廓与面部连结的最低点,横过鼻唇沟的中点,对称到左耳廓最低点的围度;以A、B两条线长度总和的变化衡量面部紧致塑形效果变化。
3.2、实验结果
3.2.1 上臂围和大腿围
如图7所示,本发明组合物(实施例21)产品作用后,受试者上臂围和大腿围分别降低约3.7 cm和4.0 cm,当去除组分A时,上臂围和大腿围的减少量与对照组接近,说明当组分A去除时,产品几乎失去效果,组分A是产品关键有效成分。与完全产品比较,当组分B去除时,产品效果明显下降,这说明组分B对组分A在减脂方面具有协同促进效果。组分C和D的去除也能够降低产品效果,但是影响幅度不如组分B,这说明组分C和D对组分A也具有一定的协同促进效果。
3.2.2 面部紧致
如图8所示,本发明组合物(实施例22)产品作用后,受试者面部减脂紧致指标A线与B线总和降低约3.2 cm,产品中去除C或者D,AB线总长分别下降2.7和2.8 m,这说明组分C或者组分D能够促进组分A的作用。当去除组分A时,AB线总长下降约0.64 cm,与对照组非常接近(0.59 cm),当去除组分B时,AB线总长下降约1.4 cm,这说明组分A是产品关键成分,去除组分A产品几乎失去减脂紧致效果。与完全产品比较,当去除组分B时,即使组分A存在,产品的效果也是显著下降,根据数据可以判断,专利产品组分A是关键有效成分,组分B对组分A在面部减脂紧致效果方面具有显著协同促进作用。当然组分C和D也能够在一定程度上促进组分A的效果。图9为在使用本发明组合物(实施例22)后,受试者面部紧致效果的改善情况照片。
为了节约篇幅,在临床实验中使用的本发明组合物(实施例21和22)得到的实验结果仅是代表性的,实质上已对本发明制备实施例1-23中制备得到的所有组合物均进行了上述实验,并且得到了与上述代表性结果一致的结论(具体数据未列出)。
综上所述,上述实验结果表明,本发明可以实现外用涂抹的方式局部靶向降解皮下脂肪细胞内的甘油三酯,不仅不破坏脂肪细胞膜,还可以实现甘油三酯的有效降解。
显然,本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。
Claims (9)
1.一种促进脂肪细胞内甘油三酯降解的外用组合物,其特征在于:所述组合物由以重量份数计的以下组分制成:琥珀酸脱氢酶100份、补体因子D 100份、左旋肉碱50份、维生素B1 20份。
2.一种促进脂肪细胞内甘油三酯降解的外用组合物,其特征在于:所述组合物由以重量份数计的以下组分制成:丙酮酸脱氢酶复合物100份、琥珀酸脱氢酶50份、钙调蛋白60份、补体因子D 40份、茶多酚30份、维生素B6 40份。
3.一种促进脂肪细胞内甘油三酯降解的外用组合物,其特征在于:所述组合物由以重量份数计的以下组分制成:丙酮酸脱氢酶复合物100份、琥珀酸脱氢酶50份、瘦素合成酶50份、补体因子D 40份、咖啡碱50份、维生素B7 10份。
4.一种促进脂肪细胞内甘油三酯降解的外用组合物,其特征在于:所述组合物由以重量份数计的以下组分制成:丙酮酸脱氢酶复合物100份、硫解酶50份、甘油-3-磷酸脱氢酶50份、钙调蛋白100份、左旋肉碱25份、茶多酚25份、维生素B12 40份。
5.权利要求1-4中任一项所述的外用组合物的制备方法,其特征在于:包括以下步骤:
按照重量份数将权利要求1-4中任一项所述的各组分按比例混合后,然后进行冻干制成粉剂。
6.权利要求1-4中任一项所述的外用组合物在制备促进脂肪细胞内甘油三酯降解的外用减肥产品中的用途,其特征在于:所述产品是药物或化妆品。
7.根据权利要求6所述的用途,其特征在于:所述产品是将权利要求1-4中任一项所述的外用组合物与药物或化妆品领域的适宜辅料混合以制成各种剂型制备的。
8.根据权利要求7所述的用途,其特征在于:所述产品的剂型是粉剂、膏剂、糊剂、溶液剂、乳剂、贴剂、霜剂、凝胶剂、搽剂或喷雾剂。
9.根据权利要求8所述的用途,其特征在于:所述粉剂为冻干粉剂。
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