苦瓜提取物系列报道(三):除了帮助调节血糖还能抗发炎:专利定序19肽(Insumate®)

01

发炎是万病的根源
慢性疾病为导致全球死亡的重要原因之一,根据世界卫生组织报导,2020年全球73%的死亡与慢性疾病相关。研究发现,身体的慢性发炎正是导致大部分慢性疾病的主要原因,例如:糖尿病、心血管疾病、过敏、类风湿性关节炎、癌症等疾病[1]。除了遗传因素外,环境、生活作息与饮食对身体发炎反应的影响亦是息息相关,根据美国哈佛医学院的报导,精制的谷物、加工肉类以及红肉、反式脂肪、油炸食物容易造成体内氧化压力不平衡造成的发炎反应;而绿色蔬菜、莓果类水果、坚果、橄榄油、脂肪酸含量高的鱼类,则可以提供给我们抗氧化及抗发炎的效果[2]
 

02

关注抗氧化
很多现代人生活繁忙,三餐饮食不正常,因此食用方便的抗氧化的补充品越来越普遍。根据机构预测,全球抗氧化补充剂的市场在2022年会有45亿美元的市场,而我国,抗氧化的美容美颜保健产品市场规模在2017年已突破百亿元规模。其中,天然虾青素、西红柿红素、白藜芦醇、维他命皆为我国常见的抗氧化补充剂。而蛋白类可以帮助消除发炎反应,目前消费者比较容易联想到的是胶原蛋白肽。胶原蛋白不仅可以提供抗老、美肌的功效,动物实验更发现可与身体的发炎反应部位作用,增加抗发炎药物的作用,可降低发炎因子肿瘤坏死因子(TNF-α)、白细胞介素(IL)的表现。
 

03

关注抗全身性发炎
在抗全身性发炎领域,绿茵生技公司近期推出一种名为专利定序19(Insumate®)的苦瓜提取物,除可以调节血糖、减少体脂与脂肪肝、降血脂,他还可被用在抗发炎的补充剂产品上[3]。厂商发布的数据可以看出,将基因转殖小鼠(发炎时会有荧光显示)分成空白组、诱导发炎组及诱导发炎组+Insumate®组,以注射发炎诱导物质(LPS)诱导发炎,发现Insumate®可有效抑制身体各器官的发炎反应,预防慢性病的发生(图一)。脑部的长期发炎反应可能与阿尔茨海默氏病的相关,已有科学指出抗肿瘤坏死因子的药物可用来治疗阿尔茨海默氏病。另外,肠道的长期发炎反应,不仅与肠道的疾病相关,在肥胖鼠的肠道细胞,发炎因子基因亦发现大量的表现。
苦瓜在传统食疗上就有清热解毒的功效,但现代人不可能每天都有机会食用去获取它的好处,科学化的专利定序19肽可以提供国人另一个选择,在繁忙中依旧能降火。

图一:专利定序19肽抗发炎结果

 

参考文章:

[1] Pahwa R, Goyal A, Bansal P, et al. Chronic Inflammation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/

[2]https://www.health.harvard.edu/staying-healthy/foods-that-fight-inflammation

[3] https://insumate.org/anti-inflammatory/?lang=zh-hans

本文

苦瓜提取物系列报道(二):增肌减脂与远离脂肪肝的好伙伴:专利定序19肽(Insumate®)

01

肥胖的影响目前我国的肥胖者已经远远超过了7,000万,超重者则超过2亿,减重保健品市场为大约60100亿[1]。根据世界卫生组织报导,肥胖会衍生出许多的慢性疾病,例如:心血管疾病、糖尿病,严重者甚至会失明[2]。导致肥胖的原因不外乎受到遗传、环境因素、心理因素、激素紊乱、饮食等因子影响,其中我国肥胖率急剧上升的推手又以少动多吃的生活型态影响最大。尤其在这波COVID-19造成的疫情下,国人更增加了许多焦虑和压力感,因此许多人会利用食物和饮料来让自己放松。

02

瘦身保健品

医学上最有效的方法为少吃多动的原则,但目前国內的饮食西化与繁忙的生活型态,规律运动对大部分人来说是一件相当困难的事。因此近年来,代餐、瘦身补充剂为相当热门的商品。根据Market Research Future预估,全球2024年的瘦身补充剂市场为400亿美金,以每年5.5%的年成长率成长。国內的减重素材为绿咖啡、荷叶萃取、蛋白粉、绿茶、咖啡因、苦橙萃取物、瓜拿那等常见原料。目前有厂商近期推出一种名为专利定序19(Insumate®)的苦瓜提取物,除可以调节血糖,还具备增肌减脂、降低脂肪肝与血脂的功效[3-7]

03

增肌减脂功效

给予高脂饮食诱发性肥胖大鼠每日专利定序1910.42 mg/kg与市售苦瓜提取52.08 mg/kg,连续喂食8周后,与对照组相比,摄入Insumate®的大鼠体脂减少28%;而摄入5倍剂量的市售苦瓜提取组,反而提高5%的体脂(图一)[8]。代表绿茵专利定序19肽苦瓜提取物,能够有效地抑制脂肪的合成,达到实质的减脂功效。此外,将腹部易累积脂肪的基因缺陷小鼠,以腹腔注射专利定序19 5 nmol/kg/week,连续4周,结果发现专利定序19肽可有效降体脂肪达25%,并增加肌肉生长,可预防糖尿病常见的肌肉萎缩与达到增肌的功效(图二)

图一:专利定序19肽降低体脂生成结果

 

图二:专利定序19肽增肌减脂之结果

降血脂与预防脂肪肝
给予高脂饮食诱发性肥胖大鼠每日专利定序19肽10.42 mg/kg,连续喂食8周后,与对照组相比,摄入专利定序19肽的大鼠可减少36%总胆固醇与39%三酸甘油脂形成(图三)。另外,喂食小鼠高脂饮食,并每周以腹腔注射专利定序19肽20 mmol/kg,连续8周后进行牺牲,取出肝脏分析专利定序19肽可有效降低肝脏脂肪堆积与减少肝脏中过氧化物的含量(图四)。

 

图三:专利定序19肽降血脂结果

图四:专利定序19肽预防脂肝结果

 

别让疫情破坏了您的好身材与好心情,在放松享受时,别忘了绿茵专利定序19肽(Insumate®)能提供给给您身材与代谢全方面的协助,在心情快乐之余,身材也能一样美丽。

参考文章:

[1] http://www.chc.org.cn/news/detail.php?id=55544

[2] https://www.who.int/health-topics/obesity#tab=tab_2

[3] A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway. J. Agric. Food Chem. 2014; 62:8952–8961.

[4]Lo HY, Ho TY, Lin C, Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem. 2013; 61:2461-2468

[5] Lo H.Y., Li C.C., Ho T.Y., Hsiang C.Y. Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein. Food Chem. 2016; 204:298–305.

[6] Hsu PK, Pan FFC, Hsieh CS. mcIRBP-19 of Bitter Melon Peptide Effectively Regulates Diabetes Mellitus (DM) Patients’ Blood Sugar Levels. Nutrients. 2020; 12:1252. 

[7] Pan F, Hsu PK, Chang WH. Exploring the Factors Affecting Bitter Melon Peptide Intake Behavior: A Health Belief Model Perspective. Risk Manag Healthc Policy. 2020; 13:2219-2226.

[8] https://insumate.org/body_shape/?lang=zh-hans

苦瓜提取物系列报道(一):植物来源之类胰岛素:专利定序19肽(Insumate)

糖尿病对我们的影响

 

根据国际医学期刊统计,我国目前的罹患糖尿病人口大约为1.14亿人,为全球最多糖尿病病人的国家,其中第二型糖尿病居多,占了我国医疗资源的8.5% [1]。但我国糖尿病的筛选率仅有30-40%,即10个人中只有34个人知道自己有糖尿病。糖尿病在我国盛行的问题主要可归咎于西方快餐、饮食不节制与少动多坐的现代生活型态影响,导致生体代谢出了问题,因此造成第二型糖尿病的产生。

02

苦瓜对糖尿病的保健

苦瓜在近年的多篇医学研究中已被发现,可作为稳定血糖的保健品开发素材,但大都研究和产品从未报导其真正作用的效性成分。绿茵生技历时10年时间从基础研究到临床研究,研发出高效性苦瓜提取产品Insumate®,里面含有与人体胰岛素受体具高亲和力的效性成分「专利定序19(mclRBP-19)」,研究成果已发表在5篇权威国际期刊[2-6]。专利定序19肽是目前除了胰岛素外,惟一能与胰岛素受体作用的天然肽,可作用在不同的胰岛素受体位置上帮助葡萄糖的调控,因此对于胰岛素药物阻抗的病人亦有调控的效果[2]

03

 

临床实验控制血糖验证

 

临床双盲实验结果显示,64位长期固定领处方签用药却控制不佳的糖尿病患受试者在服用专利定序193个月后,空腹血糖浓度可被明显改善13.74倍且空腹血糖与糖化血红蛋白的改善人数超过7(图一)[7]

 

图一:专利定序19肽于临床之控制病人血糖与糖化血红蛋白之结果

 

动物实验控制血糖验证

 

于动物实验中亦发现,专利定序19肽能够有效地控制食后的血糖数值,在两小时的作用后,血糖数值可被降低53%(图二)

图二:专利定序19肽控制动物食血糖之结果

 

专利定序19肽能达到维持血糖数值的目的,对于应用在帮助亚健康人或是糖尿病病人做为日常保健具有一定之保健作用。传统的苦瓜藉由绿茵生技独家专利提取技术保留独特的天然肽,让苦瓜提取物在维持/降血糖功效更为显着,相信此相关科学结晶能为预防慢性疾病尽一份心力。

參考文献:

[1] Luo Z, Fabre G,
Rodwin VG. Meeting the Challenge of Diabetes in China. Int J Health Policy
Manag. 2020; 9:47-52. 

[2] A novel insulin
receptor-binding protein from Momordica charantia enhances glucose uptake and
glucose clearance in vitro and in vivo through triggering insulin receptor
signaling pathway. J. Agric. Food Chem. 2014; 62:8952–8961.

[3]Lo HY, Ho TY, Lin C,
Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate
glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem.
2013; 61:2461-2468

[4] Lo H.Y., Li C.C.,
Ho T.Y., Hsiang C.Y. Identification of the bioactive and consensus peptide
motif from Momordica charantia insulin receptor-binding protein. Food Chem.
2016;204:298–305.

[5] Hsu PK, Pan FFC,
Hsieh CS. mcIRBP-19 of Bitter Melon Peptide Effectively Regulates Diabetes
Mellitus (DM) Patients’ Blood Sugar Levels. Nutrients. 2020; 12:1252. 

[6] Pan F, Hsu PK,
Chang WH. Exploring the Factors Affecting Bitter Melon Peptide Intake Behavior:
A Health Belief Model Perspective. Risk Manag Healthc Policy. 2020;
13:2219-2226.

[7]
https://insumate.org/

Insumate®- Patented Peptide Sequence mcIRBP-19: A Boon for Diabetics Says Greenyn Biotechnology

Taiwan’s biotech is gradually emerging. During the COVID-19 epidemic, we had a chance to see the advanced medical equipment and the effective preventive measures taken at the community level. The government took precautions, while private companies were introducing high-quality biotechnology products made in Taiwan. In the post-pandemic period, the world may become more sensitive to the need to strengthen prevention and improve medical treatment. The Taiwan Greenyn Group has been developing health foods for the global market for over 20 years. On Sept. 8, Greenyn Biotechnology, a member of the Greenyn Group, presented clinical results for Insumate®–Patented Peptide Sequence: mcIRBP-19.

Taiwan Greenyn Group: Chairman Wu Chia-feng (middle), CEO Luo Husan (left), and Dr. Hsu Pang-kuei (right), displaying certificates of research results.

Mr. Wu Chia Feng, Chairman of Taiwan Greenyn Group, pointed out, “Greenyn Biotechnology was established in 2012 as a subsidiary of Taiwan Greenyn Corporation. The company has many experts in medical and food biotechnology. Greenyn Biotechnology has invested heavily in research and development over the years, and finally, their products are receiving international recognition. The main goal of the company is to improve the quality of life for all people through preventive medicine.”

Among chronic diseases, the health problems caused by diabetes are particularly pervasive, and growing at an alarming rate. According to data released by the International Diabetes Federation, 463 million people were living with diabetes at the end of 2019, with related medical expenses of US$760 billion. Each year, 4.2 million people die from diabetes and its complications. With insufficient action, these numbers will continue to spiral. China, Southeast Asia, and the Western Pacific Region account for 35% of all diabetics, one third of all confirmed cases.

Dr. Yang Yi-tien (middle) of Chung Shan Medical University Hospital, which has a collaboration with Greenyn Biotechnology Corporation, displays outstanding results of randomized double-blind clinical trials.

As the company was being established nearly10 years earlier, researchers were already conducting trials on animal and human cells, and discovering that mcIRBP-19 had the potential to regulate blood sugar. Greenyn Biotechnology partnered with Chung Shan Medical University Hospital to conduct clinical trials on diabeties and functional food therapies. Professional medical teams worked tirelessly to carry out these trials, which finally obtained double approval from the Institutional Review Board (IRB). Greenyn Biotechnology confirmed on a scientific basis that a highly active extract from bitter gourd correlated with human insulin receptors. Greenyn Biotechnology called the extract “Patented Peptide Sequence: mcIRBP-19”, and the brand, “Insumate®.”

Dr. Yang Yi-Tien of Chung Shan Medical University Hospital conducted the randomized double-blind clinical trial, which confirmed that Patented Peptide Sequence: mcIRBP-19 had outstanding results on diabetic patients who undertook adjuvant therapy. The trial was conducted on 29 diabetics who were long-term patients of hypoglycemic drugs of less effectiveness. Without breaking routine drug therapy, the diabetic trials were conducted for 3 months, concluding that fasting blood sugar and glycosylated hemoglobin in the therapy group were significantly reduced. Their liver function, kidney function, and hemoglobin remained unchanged. There were no side effects of hypoglycemia and allergic gastrointestinal discomfort, which usually occur to users of oral hypoglycemic drugs. As for the control group, there was no noticeable difference. The clinical results are being submitted to an International Journal.

Taiwan Greenyn Group No.2 Factory

The unique structure of Patented Peptide Sequence: mcIRBP-19 allows for use as a pathogenic target. These results have been published in the Science Citation Index (SCI). Dr. Hsu Pang-kuei, chief of research and development at Greenyn Biotechnology, has been conducting research for more than a decade. “After many years, we discovered that mcIRBP-19 has a hypoglycemic effect on insulin-like biological activities and can bind insulin receptors. Without stimulating insulin secretion, mcIRBP-19 can participate in the body’s carbohydrate metabolism and regulate blood sugar. Besides insulin, mcIRBP-19 has been scientifically confirmed as a natural product able to bind insulin receptors to regulate blood sugar.” said Dr. Hsu. Yet another clinical trial reported that 142 diabetics who were long-term users for hypoglycemic drugs took mcIRBP-19 for 3 months, and their blood sugar indexes and glycosylated hemoglobin were well regulated. These results were published in the world-famous Journal of Nutrition.

Insumate®: mcIRBP-19 functions to regulate blood sugar, processing at low temperatures with high activity, and passing toxicity tests. This biotechnology innovation has helped Greenyn Biotechnology in obtaining 19 patent certificates and recognition from the world’s largest discovery exhibitions, the Discovery and New Products Expo (INPEX) in Pittsburgh, Pa, USA; International Discovery Exhibition of Geneva, Switzerland; and the Nuremberg International Expo (IENA) in Germany. An extensive summary of mcIRBP-19 has also been published in the Scientific Citation Index (SCI). Presently, many well-known international process manufacturers use ingredients provided by Greenyn Biotechnology to produce health foods. Greenyn Biotechnology attributes these achievements to its utmost efforts in recent years.

Insumate® –Patented Peptide Sequence: mcIRBP-19, a naturally extracted product.

As Dr. Hsu pointed out, “There are many similar products on the market, called bitter melon peptide or peptide-related peptide. But under professional tests, they are only hydrolyzed water or bitter watermelon extract. They do not contain any ingredients able to regulate blood sugar as Insumate®: mcIRBP-19. The most important thing is that strictly selected ingredients must be certified and scientifically validated locally and internationally. Only after rigorous quality testing can the product achieve its medical purpose.”

Mr. Yang Lihua, Secretary General of the Taiwan Functional Food Industry Association, said, “The Taiwan Greenyn philosophy is to rigorously pursue innovative R&D in precision medicine. We define precision medicine as a combination of prevention, healthcare, and clinical testing. Even with the support of scientific testing, improving medicine into a method of prevention takes a long time. With incredible investment and perseverance, Taiwan Greenyn has become a model for various Taiwanese industries due to continuous innovation. They have improved Taiwanese medicine into precision medicine.”

To ensure excellent product quality, Greenwyn Biotechnology has developed a comprehensive, one-stop service solution in areas such as product development, market positioning, formula design, packaging design, manufacturing design, clinical planning, marketing planning and customer service. Greenyn is dedicated to creating new futures for tomorrow’s healthy lifestyles.

Insumate®专利定序19肽 糖尿病医学再突破 台湾医疗团队临床成果亮丽

糖尿病医学再突破 台湾医疗团队临床成果亮丽

因为饮食精致、活动量少的现代生活型态,许多文明疾病成为全球公卫重大挑战。国际糖尿病联盟2019年年底公告惊人数据,全球有超过4.6亿糖尿病患者,所耗医疗成本高达7600亿美元,每年420万人因糖尿病或并发症死亡。台湾糖尿病更连续十年蝉联十大死因,患者高达230万人,根据卫福部统计,糖尿病在2018健保支出费用近300亿台币,为第2高,造成社会重大负担。为控制血糖,患者常常需要合并药物治疗,但仍有血糖控制不良及低血糖、过敏、腹痛、恶心副作用等问题,例如低血糖容易造成病人跌倒和影响生活品质,心血管疾病风险增加、失智风险增加等。绿茵生技携手中山医学大学附设医院等单位合作,完成两个IRB审核通过之糖尿病辅助治疗临床试验,成果亮丽,为糖尿病患者开发加强保养的机能辅助食品。

双盲测试研究可降空腹血糖、糖化血红蛋白

中山医学大学附设医院杨宜瑱医师公开随机、双盲测试的临床研究,实证专利定序19肽对糖尿病患调节血糖带来哪些效益。由29位服用降糖药物治疗效果不佳者进行测试,在不影响原先用药状态下,「治疗组」14位兼辅以每日600mg Insumtate®专利定序19肽,其余为对照组只给予安慰剂。3个月后「治疗组」空腹血糖降低9.7%,糖化血红蛋白降低6.3%,肝功能、肾功能、血红素无异常变化,亦无口服糖尿病药物常见的副作用,例如低血糖、过敏胃肠不适…等症状,而对照组则无显着差异。杨宜瑱表示,专利定序19肽于3个月辅助治疗成果显着,临床成果目前于国际期刊投稿中。

绿茵生技徐榜奎博士今年4月于国际知名期刊nutrients发表人体试验研究,评估专利定序19肽是否能有效调节糖尿病患者血糖。由142位长期服药却未能稳定控制血糖的二型糖尿病患者中,挑选64位为实验组服用专利定序19肽。研究结果显示,这64人在3个月内平均空腹血糖降低至118 mg/dL,糖化血色素降低至7.4%,更接近正常值。三酸甘油酯、血中尿素氮亦分别下降22.5%与4.9%,高密度胆固醇则提升5.6%,对照组则无显着差异。此人体研究显示,相对糖尿病治疗常因无效而换药以及药物常带来不适之副作用来说,专利定序19肽完全无副作用,并可有效辅助慢性糖尿病患之血糖控制。未来将进一步研究,探讨Insumate®专利定序19肽对糖尿病更深入之应用。

慎选具科学实证的专利活性成分

徐榜奎博士表示,「Insumate®专利定序19肽」在绿茵生技与学术单位至少耗时10年以上研究,宝贵的活性成分需特定专利制程与良好的生产管理,才能得到临床试验的最佳功效。而研究团队在精密分析后,发现许多标榜苦瓜胜肽或相关产品并未含有此活性成分,只是单纯苦瓜干燥磨粉或粗萃物,导致消费者权益受损。营养师王郁菁表示,专利定序19肽可作用在胰岛素受体,打开葡萄糖通道后便能调节血糖,改善糖化血红蛋白,进而调节血脂与降低体脂肪。

绿茵生技表示,Insumtate®专利定序19肽已被多篇国际SCI权威期刊刊载,并荣获19张多国专利,以及世界三大发明奖肯定。目前已授权各大厂商向绿茵购买成份制作成食品贩售。民众购买时需认明Insumtate®专利定序19肽及雷射防伪标签才是真品。

 

 

常春月刊: 苦瓜肽真能控糖?

文/徐文媛

被视为有控糖潜力的苦瓜肽,吸引许多糖尿病患关注,但是否有科学证据证明有助稳定血糖?坊间产品良莠不齐,该如何挑选?
据统计,台湾有200万人确诊糖尿病,并以每年约3万人幅度持续增加,其中超过90%是第二型糖尿病,且有越来越年轻化的趋势。因为饮食精致、活动量少的现代生活型态,肥胖问题成为全球公卫重大挑战,根据国健署调查,国内成人过重及肥胖盛行率为45.4%,而肥胖正是第二型糖尿病的重要危险因子。
目前糖尿病没有真正的治愈方法,除用药控制外,需积极控制饮食,配合运动及减重,不过,许多患者无法持续,甚至会放弃控制血糖,久而久之就会产生严重的并发症。
近年,使用天然疗法辅助控糖已成趋势。而糖尿病主要致病靶点为胰岛素受体,因此各界不断寻找可作用在胰岛素受体、替代胰岛素的天然物,但因生理机制复杂而难以实现,而许多号称植物胰岛素之产品未经科学实证,导致消费者不知该如何挑选。
有鉴于此,台湾业者与医学院合作,历经10年研究,终于从苦瓜中发现与人体胰岛素受体具高亲和力的活性成 分――「专利定序19肽」,国际统称「mclRBPTM-19」,自2013年起陆续于国际期刊共发表4篇科学研究报告,分别从细胞、动物及人体临床试验进行验效。
专利定序19肽的控糖效果研究
人体需要启动葡萄糖搬运机转,将血液中葡萄糖运送至细胞内,否则就会变成高血糖。生化专家徐榜奎博士表示,萃取 自苦瓜的专利定序19肽(mclRBPTM-19),是除了胰岛素以外,目前经科学证实可结合胰岛素受体的天然物,可维持血糖稳定;为了进一步确认效果,选择142位领取糖尿病慢性处方笺,但药物治疗效果未达理想,血糖值介于120~140的患者,在原本用药不变的情况下,3个月后抽血检查 发现,并用专利定序19肽(mclRBPTM-19)的受试组不但空腹血糖下降,糖化血红蛋白亦明显改善。
糖化血红蛋白可反映出红血球生存期间内(平均3个月)的平均血糖浓度;「平时不注意饮食控制的病人,门诊当下量测血糖数值可能是低的,但糖化血红蛋白偏高,就表示近3个月内血糖控制不稳定。」徐榜奎博士强调,当糖化血红蛋白偏高时,就有必要考虑适度的运动或辅助保健措施的介入。
上述研究报告已刊登于2020年的国际期刊《Nutrients》。另外,与中山医学大学合作,针对血糖值介于160~180患者进行的双盲试验,也证实专利定序19肽(mclRBPTM-19)有助改善血糖指标,研究报告也即将正式发表。

 

慎选具科学实证的专利成分
连续多篇研究报告的发表使苦瓜肽渐受瞩目,但徐榜奎博士表示,专利定序19 肽(mclRBPTM-19)为极宝贵的成分,需特定的制程与良好的生产管理才能得到最佳的功效,而研究团队经分析发现,坊间 许多标榜苦瓜肽的产品并未含有此成分,只是单纯苦瓜水解物或是苦瓜萃取,以致于功效不彰造成消费者权益受损,所以,选购时要特别注意。
徐榜奎博士提醒糖尿病友要在遵循医嘱用药的前提下,再评估是否需要搭配保健品辅助改善血糖,关键是要慎选具实证研究肯定的活性成分,才能真正发挥功效。

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