《口服液態玻尿酸之臨床應用》由会员分享，可在线阅读，更多相关《口服液態玻尿酸之臨床應用（54页珍藏版）》请在金锄头文库上搜索。
1、口服液態玻尿酸之臨床應用前馬偕醫院神經科主治醫師仁欣診所院長蔡正浩2024/8/1玻尿酸的用途與困境玻尿酸的用途與困境口服玻尿酸的吸收口服玻尿酸的吸收皮膚領域皮膚領域退化性關節炎退化性關節炎防老化的應用防老化的應用2024/8/1The repeat disaccharide of hyaluronan, -D-glucuronic acid-beta-1, 3-N-acetylglucosamine-beta-1,4- (B) 玻尿酸三維立體結構藍色帶代表親水部位,紅色帶代表疏水部位.呈白色，爲無定形固體，無臭無味，有強吸濕性，溶於水，不溶於有機溶劑。 玻尿酸分子化學結構與物理特性Glucu
2、ronic acidN-acetylglucosamine2024/8/1保水性: 1公克的玻尿酸可以吸收500c.c.1000c.c的水分，相當於5001000倍吸水能力2024/8/1玻尿酸的醫療用途醫學領域應用一般外科人造皮膚、傷口敷料、尿失禁治療劑、止血劑(Hemostat)皮膚科皮膚除皺及修補、化妝保養品、皮膚水嫩光滑骨科退化性關節炎之治療口腔外科口腔組織修補及再生婦產科婦女停經後症狀之改善心臟血管外科血管及心瓣膜修補眼科白內障和青光眼手術、眼角膜移植、人淚液、乾眼症整型外科隆鼻、隆乳、豐唇、器官組織整形及修補藥物遞送藥物的局部性遞送2024/8/1目前玻尿酸在各種治療上的障礙 過去
3、的經驗因分子量太大，口服、錠劑普遍效果不佳 只針對施打玻尿酸的位置，無法全面的保養皮膚 退化性關節炎（OA）玻尿酸進行關節腔注射：打會痛、打完尚有腫脹痛，病人看到針頭會怕 縫隙小，有傷到神經之危險，恐引起醫療糾紛 提前被代謝掉，健保給付有斷層很高比例的病人吃維骨力沒有效果2024/8/1有沒有其他有效安全的選擇?如果玻尿酸可以改善如果玻尿酸可以改善吸收不良吸收不良的問的問題以題以口服型式補充口服型式補充 ，而以，而以內內生性的生性的方式達到需要之部位，那這種治療方式達到需要之部位，那這種治療方式是否對方式是否對某些病患某些病患來來說說是一個更是一個更好的選擇好的選擇?!2024/8/1玻尿酸的
4、用途與困境玻尿酸的用途與困境口服玻尿酸的吸收口服玻尿酸的吸收皮膚領域皮膚領域退化性關節炎退化性關節炎防老化的應用防老化的應用2024/8/1口服玻尿酸的吸收實驗一在口服在口服在口服在口服3030分鐘後，即可在血液中偵測到分鐘後，即可在血液中偵測到分鐘後，即可在血液中偵測到分鐘後，即可在血液中偵測到該報告證明口服玻尿酸可以順利被哺乳類吸收，堆積於血液，肌肉，硬骨組織，排出體外者僅小於5%This study examined the absorption, excretion and distribution of radiolabeled hyaluronan (HA) after a sin
5、gle oral administration in Wistar rats and Beagle dogs. To date its therapeutic use has been limited to injections or topical applications, but there is no data on pharmacokinetics after oral intake. The gamma emitting isotope 99mtechnetium (Tc) was coupled to HA Less than 5% of the radioactivity ap
6、peared in feces after 72 hours in rats. Radioactivity was seen in blood, muscles, salivary glands and bone as early as 30 minutes, and peaked 4-6 hours in all non-alimentary tissues examined after oral administration. There were transient increases in radioactivity in shoulder joints and vertebrae 4
7、 hours after oral administration of HA in both rats and Beagle dogs. Residence time (t) in Beagle blood was 0.0134 hours. These results demonstrate that HA is absorbed and distributed to organs and joints after a single oral administration. (FASEB, 2004). A. G. Schauss, L. G. Balogh, A. G. Polyak, D
8、. G. Mathe, R. G. Kiraly and G. G. Janoki American Institute for Biosocial and Medical Research, Inc and National Institute for Health. 2024/8/1日本的報告證明口服玻尿酸可以順利被哺乳類小腸絨毛吸收，在口服三小時內吸收比率高達80%以上，殘留於消化道之玻尿酸小於16%。口服玻尿酸的吸收實驗二2024/8/1口服玻尿酸的吸收實驗三Studyonabsorptionofhyaluronicacidafteranoraladministrationinrats
9、2005年23期蒋秋燕 , 凌沛学 , 黄思玲 , 林洪 , 张天民 , JIANG Qiu-yan , LING Pei-xue , HUANG Si-ling , LIN Hong , ZHANG Tian-min 目的探讨透明质酸口服吸收的机制.方法采用放射免疫法测定大鼠单剂量口服透明质酸溶液和3种单糖(D-葡糖醛酸、N-乙酰氨基葡糖及两者等摩尔配比)溶液后血清中透明质酸的浓度,用梯形法计算AUC.结果生理盐水对照组和D-葡糖醛酸组的血清中透明质酸没有出现峰值;透明透明质酸酸组在口服后在口服后约2h,出出现明明显的透明的透明质酸吸收峰酸吸收峰;另外两个单糖组在口服后7 h左右,出现一个明
10、显的透明质酸合成峰.透明质酸组的AUC013 h为2 417ghL-1,实测max为187.6gL-1,tmax为2.0 h.结论透明透明质酸口服后可以被机体吸收酸口服后可以被机体吸收,且能以非且能以非单糖的形式被机体吸收糖的形式被机体吸收. 2024/8/1口服玻尿酸只有少量會被酵素分解成醣類及熱量，玻尿酸口服後在腸道的吸收率可以達到 7090 %人體雙盲臨床實驗證實口服玻尿酸，4小時後血液中HA含量開始增加，12小時後達到最高峰比對照組高出 70倍，顯示口服玻尿酸的生理利用率及吸收率極佳連續服用28天後可以達到最穩定的濃度與代謝 HA 在人體的吸收研究2024/8/1口服玻尿酸之美國專利U
11、nited States Patent 6,924,273August 2, 2005 Chondroprotective/restorative compositions and methods of use thereof AbstractThe instant invention provides a method of treating or preventing osteoarthritis, joint effusion, joint inflammation and pain, synovitis, lameness, post operative arthroscopic su
12、rgery, deterioration of proper joint function including joint mobility, the reduction or inhibition of metabolic activity of chondrocytes, the activity of enzymes that degrade cartilage, the reduction or inhibition of the production of Hyaluronic acid, said method comprising orally administering to
13、a mammalian species a therapeutically effective amount of Hyaluronic Acid or pharmaceutically acceptable salts thereof. Additionally, compositions containing hyaluronic acid; chondroitin sulfate, and glucosamine sulfate in a paste formulation are also disclosed which can be administered on their own
14、 or can be used as a feed additive. 2024/8/1如果玻尿酸可口服吸收在皮膚美容上是否有幫助?!2024/8/1玻尿酸的用途與困境玻尿酸的用途與困境口服玻尿酸的吸收口服玻尿酸的吸收皮膚領域皮膚領域退化性關節炎退化性關節炎防老化的應用防老化的應用2024/8/1玻尿酸在皮膚之作用(1)(1)表皮層表皮層表皮層表皮層epidermisepidermis(2)(2)真皮層真皮層真皮層真皮層dermisdermis(3)(3)玻尿酸玻尿酸玻尿酸玻尿酸HAHA(4)collagen(4)collagen膠原蛋白膠原蛋白膠原蛋白膠原蛋白 玻尿酸流失後的肌膚會使真皮層的
15、含水量降低，漸漸失去彈性與光澤，同時對陽光、環境的傷害，肌膚自我修護力也下降，進一步生成皺紋、黑斑等。玻尿酸補充細胞間的基質與活性消除皺紋，軟化肌膚2024/8/1施打玻尿酸在皮膚之應用Hyaluronic acid injection can be used to improve the skins contour and reduce depressions in the skin due to acne, scars, injury or lines. Immediately or within a few hours after injection thesitemayberedand
16、swollen. This usually disappears within a week. Another one or two treatments (at least a week apart) may be necessary to achieve the desired correction. Hyaluronic acid implantation is not permanent. Like natural hyaluronic acid, manufactured hyaluronic acid once injected into the skin will gradual
17、ly break down and be absorbed by the body. In most cases, the hyaluronic acid augmentation usually lasts between 6-9 months. Compared to collagen implants hyaluronic acid appears to have a longer augmentation effect, possibly lasting 2 to 3 times longer than the average collagen implant. To maintain
18、 the initial results, repeat hyluronic acid injections or top-up treatments will be necessary. Most people following this protocol have 2 to 3 treatments per year. 2024/8/1以口服singledose的方式投與裸鼠，結果顯示玻尿酸在八小時之後就被傳送到全身，主要分布於皮膚當中，睪丸、關節，並可在體內持續72小時以上。細胞實驗的結果，玻尿酸的濃度越高，細胞分化，進行吞噬作用、釋放發炎反應激素的效用也越大。顯示玻尿酸具有活化免疫系
19、統的功能。玻尿酸以口服方式確實可被哺乳類吸收，再分布於特定部位發揮其功能。細胞實驗證實小分子玻尿酸可以調控免疫系統的活性Data on file, VGH-TC台灣 台中榮總 口服玻尿酸之研究2024/8/1餵食螢光HA的動物試驗追蹤結果照片左邊的為沒有餵食螢光HA的大白鼠（對照組），），右邊的大白鼠為餵食0.5 mg螢光HA，經過48小時後的螢光偵測結果 照片左邊的為沒有餵食螢光HA的大白鼠（對照組），），右邊的大白鼠為餵食0.5 mg螢光HA，經過72小時後的螢光偵測結果Data on file, VGH-TC2024/8/1玻尿酸與膠原蛋白玻尿酸在人體的組織內:膠原蛋白如同鋼筋玻尿酸如同
20、水泥穩定組織架構維持細胞活性膠原蛋白玻尿酸在軟骨組織中的聚集作用2024/8/1玻尿酸幫助膠原蛋白合成之研究Hyaluronicacidcounteractsinterleukin-1-inducedinhibitionofcollagenbiosynthesisinculturedhumanchondrocytesAbstractAlthough, hyaluronic acid (HA) is used in the treatment of osteoarthritis for 30 years, the mechanism of its protective action on col
21、lagen metabolism disturbances in tissues during inflammation is not known. Therefore, the present study was undertaken to evaluate the mechanism of IL-1 action (inductor of experimental inflammation) on deregulation of collagen biosynthesis in cultured human chondrocytes and the effect of HA on the
22、process. IthasbeenfoundthatIL-1stronglyinducedinhibitionofcollagenbiosynthesis,whileHAcounteractedtheprocess. The mechanism of this phenomenon was found at both transcriptional and post-transcriptional level. IL-1 was found to down regulate the expression of mRNA for type II collagen and to inhibit
23、prolidase activity, an enzyme that plays an important role in collagen biosynthesis at post-translational level. HA was shown to counteract the IL-1-dependent inhibition of both processes. During experimental inflammation of chondrocytes cultured in 0.1% FBS there was no differences in the expressio
24、n of 1-integrin independently of cell number and the presence of HA in growth medium. In chondrocytes cultured in 5% FBS, IL-1 up-regulated the expression of 1-integrin receptor while HA abolished the effect. The data suggest that HA-dependent up-regulation of collagen biosynthesis in IL-1-treated c
25、hondrocytes may involve stimulation of prolidase activity in serum starved cells and may also originate at the transcriptional level in the cells cultured in standard conditions. Source / Source2006,vol.54,PharmacologicalresearchISSN1043-6618,pp.275-2817page(s)(article) 2024/8/1玻尿酸加速fibroblast之增生Hya
26、luronanfacilitatestransforminggrowthfactor-beta1-mediatedfibroblastproliferation.This study aims to understand the role of the matrix polysaccharide hyaluronan(HA)ininfluencingfibroblastproliferationandtherebyaffectingwoundhealingoutcomes. To determine mechanisms that underlie scarred versus scar-fr
27、ee healing, patient-matched dermal and oral mucosal fibroblasts were used as models of scarring and non-scarring fibroblast phenotypes. Specifically, differences in HA generation between these distinct fibroblast populations have been examined and related to differences in transforming growth factor
28、-beta(1) (TGF-beta(1)-dependent proliferative responses and Smad signaling. There was a differential growth response to TGF-beta(1), with it inducing proliferation in dermal fibroblasts but an anti-proliferative response in oral fibroblasts. Both responses were Smad3-dependent. Furthermore, the two
29、fibroblast populations also demonstrated differences in their HA regulation, with dermal fibroblasts generating increased levels of HA, compared with oral fibroblasts. Inhibition of HA synthesis in dermal fibroblasts was shown to abrogate the TGF-beta(1)-mediated induction of proliferation. Inhibiti
30、on of HA synthesis also led to an attenuation of Smad3 signaling in dermal fibroblasts. J Biol Chem. 2008 Mar 7;283(10):6530-45. Epub 2008 Jan 2. 2024/8/1補充玻尿酸可多方保養肌膚填補肌膚間隙肌膚光澤白皙促進血液循環肌膚年輕水嫩增進肌膚彈性撫平皺紋老化活化纖維母細胞增生膠原蛋白超級保水功能皮膚長效保濕玻尿酸2024/8/1如果玻尿酸可口服吸收在退化性關節炎是否有幫助?!2024/8/1玻尿酸的用途與困境玻尿酸的用途與困境口服玻尿酸的吸收口服玻尿
31、酸的吸收皮膚領域皮膚領域退化性關節炎退化性關節炎防老化的應用防老化的應用2024/8/1退化性關節炎多發生於45歲以上的中老年人身上。根據統計，在台灣隨著年齡的增加，罹患退化性關節炎的比例隨之增加：年齡 罹患退化性關節炎 30391%404910%505940%606950%70以上70%退化性關節炎 (OA)2024/8/1骨關節炎 (Arthritis)軟骨裂解的產物會導致滑液囊的慢性發炎反應。滑液囊中的吞噬細胞產生細胞媒介物，包括 interleukin 1 (IL-1)、tumor necrosis factor-alpha、metalloproteinase 會回到軟骨處，直接破壞組
32、織或刺激軟骨細胞產生更多的metalloproteinase。最後，關節的結構遭受改變，為了穩定關節，便發生補償性的硬骨增生2024/8/1骨關節發炎時相關之物質2024/8/1補充可使用之玻尿酸以恢復關節液的彈性和黏度。活化纖維母細胞之活性,使玻尿酸之合成再開始抑制發炎反應中IL-1的作用,使軟骨細胞及膠原蛋白維持增加減少OA 病人的疼痛感治療退化性關節炎之策略 Osteoarthritis2024/8/1Osteoarthritis Treatment過去20年，內科醫生對骨關節炎病患的治療是採取直接注射 HA 至膝蓋的關節液，因為這些病患的身體中原本就存在骨關節處的 HA 較薄一層，當關
33、節活動摩擦時會感疼痛，而額外補充注射 HA 能豐厚關節保護層，暫時抑制疼痛約幾天至幾星期，一些文獻的研究目地皆是探討 HA 在這種醫療方式上扮演的角色 Sundblad L. Glycosaminoglycans and glycoproteins in synovial fluid. In: Balazs EA, Jeanloz RW, editors. The amino sugars. The chemistry and biology of compounds containing amino sugars, vol. IIA. New York: Academic Press 196
34、5:229-50. Wobig M, Bach G, Beks P, Dickhut A, Runzheimer J, Schwieger G, et al. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan. Clin Ther 1999;21:1549-62. Weiss C, Balazs EA, St.
35、 Onge R, Denlinger JL. Clinical studies of the intraarticular injection of HealonR (sodium hyaluronate) in the treatment of osteoarthritis of human knees. Osteoarthritis symposium. Palm Aire, Fla., October 20-22, 1980. Semin Arthritis Rheum. 1981;11(suppl 1): 143-4.目前治療關節炎(OA)普遍的方式2024/8/1注射玻尿酸患者與注射
36、placebo之比較A controlled, randomized, double-blind, parallel-design multicentre study J. Karlsson, L. S. Sjgren1 and L. S. Lohmander2 2024/8/1玻尿酸幫助膠原蛋白合成之研究Hyaluronicacidcounteractsinterleukin-1-inducedinhibitionofcollagenbiosynthesisinculturedhumanchondrocytesAbstractAlthough, hyaluronic acid (HA) is
37、 used in the treatment of osteoarthritis for 30 years, the mechanism of its protective action on collagen metabolism disturbances in tissues during inflammation is not known. Therefore, the present study was undertaken to evaluate the mechanism of IL-1 action (inductor of experimental inflammation)
38、on deregulation of collagen biosynthesis in cultured human chondrocytes and the effect of HA on the process. IthasbeenfoundthatIL-1stronglyinducedinhibitionofcollagenbiosynthesis,whileHAcounteractedtheprocess. The mechanism of this phenomenon was found at both transcriptional and post-transcriptiona
39、l level. IL-1 was found to down regulate the expression of mRNA for type II collagen and to inhibit prolidase activity, an enzyme that plays an important role in collagen biosynthesis at post-translational level. HA was shown to counteract the IL-1-dependent inhibition of both processes. During expe
40、rimental inflammation of chondrocytes cultured in 0.1% FBS there was no differences in the expression of 1-integrin independently of cell number and the presence of HA in growth medium. In chondrocytes cultured in 5% FBS, IL-1 up-regulated the expression of 1-integrin receptor while HA abolished the
41、 effect. The data suggest that HA-dependent up-regulation of collagen biosynthesis in IL-1-treated chondrocytes may involve stimulation of prolidase activity in serum starved cells and may also originate at the transcriptional level in the cells cultured in standard conditions. Source / Source2006,v
42、ol.54,PharmacologicalresearchISSN1043-6618,pp.275-2817page(s)(article) 2024/8/1玻尿酸加速fibroblast之增生Hyaluronanfacilitatestransforminggrowthfactor-beta1-mediatedfibroblastproliferation.This study aims to understand the role of the matrix polysaccharide hyaluronan(HA)ininfluencingfibroblastproliferationa
43、ndtherebyaffectingwoundhealingoutcomes. To determine mechanisms that underlie scarred versus scar-free healing, patient-matched dermal and oral mucosal fibroblasts were used as models of scarring and non-scarring fibroblast phenotypes. Specifically, differences in HA generation between these distinc
44、t fibroblast populations have been examined and related to differences in transforming growth factor-beta(1) (TGF-beta(1)-dependent proliferative responses and Smad signaling. There was a differential growth response to TGF-beta(1), with it inducing proliferation in dermal fibroblasts but an anti-pr
45、oliferative response in oral fibroblasts. Both responses were Smad3-dependent. Furthermore, the two fibroblast populations also demonstrated differences in their HA regulation, with dermal fibroblasts generating increased levels of HA, compared with oral fibroblasts. Inhibition of HA synthesis in de
46、rmal fibroblasts was shown to abrogate the TGF-beta(1)-mediated induction of proliferation. Inhibition of HA synthesis also led to an attenuation of Smad3 signaling in dermal fibroblasts. J Biol Chem. 2008 Mar 7;283(10):6530-45. Epub 2008 Jan 2. 2024/8/1玻尿酸幫助軟骨細胞合成之研究TheeffectofhyaluronicacidonIL-1-
47、inducedchondrocyteapoptosisinaratmodelofosteoarthritisThe purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1) and explore its mechanism. HAcouldinhibitIL-1-inducedchondrocyteapoptosis in our cell c
48、ulture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. ThisstudyshowsthatHAcouldsuppressinadose-dependentwaychondrocyteapoptosisinourIL-1-induc
49、edosteoarthritismodel. ThesuppressionofinflammatorycytokineactivitywithinthejointmightbeoneimportantmechanismoftheclinicalactionofHAinthetreatmentofOA. 2008 Orthopaedic Research Society. J Orthop Res 2024/8/12024/8/12024/8/1OAKnee:excitabilityofnociceptorsofarticularnerves,nerveimpulses&nervesensiti
50、vity:hyperalgesic,spontaneouslydischarge,sensitivetonon-noxiousjointmovementHA:decreasedongoingnerveactivity&movementevokednerveactivity,nerveimpulsedecreased60%ofcontrol,impulsedischargeandfiringfrequencydecreasedto65%and45%ofcontrolIonchannelsdecreasedmechanicalsensitivityRatmodel:abnormalgait:att
51、enuationofprostaglandinE2,bradykininsynthesisDirectorindirecteffectsonsubstanceP(excitatoryaminoacids,prostaglandins,NO)Hyaluronanandnociception口服玻尿酸之臨床有效性Effectofanaturalextractofchickencombswithahighcontentofhyaluronicacid(Hyal-JointR)onpainreliefandqualityoflifeinsubjectswithkneeosteoarthritis:ap
52、ilotrandomizeddouble-blindplacebo-controlledtrialPublished:21January2008Nutrition Journal 2008,7:3doi:10.1186/1475-2891-7-3Methods:Twentysubjectsaged40yearswithkneeosteoarthritis (pain for at least 15 days in the previous month, symptoms present for 6 months, Kellgren/Lawrence score 2) participated
53、in a randomized double-blind controlled trial. Ten subjects received AP (80 mg/day) and 10 placebo for 8 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and quality of life by the Short Form-36 (SF-36v2) were administered at baseline and after 4 and 8 weeks of treat
54、ment.ConclusionDaily supplementation with HA from a natural extract of chicken combs (Hyal-Joint), 80 mg/day for 8 weeks, appeared to be effective in subjects with knee osteoarthritis for decreasing pain, improving physical function, and enhancing several aspects of quality of life. 2024/8/1玻尿酸跟維骨力的
55、差別?如果您已經有皺紋，表示合成玻尿酸的能力已經減退，如果人體合成速率已減低吃再多的葡萄糖胺或許效果不彰。Glucuronic acidN-acetylglucosamine口服玻尿酸跟維骨力的差別2024/8/1口服液態玻尿酸作為半成品玻尿酸的結構主要由:N-acetyl-D-glucosamine D-glucuronic acid平均分子量介於100萬到1000萬Dalton之間一個雙醣 N=1時分子量為415Da如果要合成到關節腔需要的玻尿酸 大約550萬Da, 那大概要幾個unit ?答案是 132532024/8/1小孩、年輕女性合成玻尿酸的情況2024/8/1中、老年婦女合成玻尿
56、酸的情況2024/8/1中、老年婦女使用口服小分子玻尿酸後，合成玻尿酸的情況2024/8/1半成品的玻尿酸 可口服吸收 並在合成大分子玻尿酸上比起使用葡萄糖胺來的有效活化了纖維母細胞 並使軟骨細胞的凋亡減緩 故可在骨關解腔內合成黏度夠高的高分子玻尿酸HA有抑制IL-1之作用，藉此可減少collagen及chondrocyte的生合成被抑制之作用，相對的使代謝速率及生成速率達成平衡HA可降低因OA引起的疼痛口服玻尿酸可以達成治療骨關節炎的目標2024/8/1玻尿酸可口服吸收,是否可預防老化及婦女停經後症候群?!2024/8/1玻尿酸的用途與困境玻尿酸的用途與困境口服玻尿酸的吸收口服玻尿酸的吸收皮
57、膚領域皮膚領域退化性關節炎退化性關節炎防老化的應用防老化的應用2024/8/125歲的玻尿酸含量只有嬰兒期的65%到了60歲只剩25%玻尿酸流失是老化的指標2024/8/1玻尿酸的故事The startling ABC News Prime Time Live TV program (Nov. 2000) in which Connie Chung (宗毓華) went to Yuzurihara, Japan (the village of long life ) and showed pictures of people who were in their 80s and 90s, and
58、 who had flawless skin (no wrinkles, no age spots), flexible joints, good eyesight (few wore glasses) and a full head of hair. Some had even habitually worked in the sun much of their lives, smoked tobacco and drunk copious amounts of sake. A World Health Organization (WHO) survey of 990 villages an
59、d towns in Japan found Yuzurihara had the oldest population. There are 10 times more people living beyond the age of 80 in Yuzurihara than any place in the United States. This report came on the heels of the WHO announcement that the Japanese live the most disease-free years of any country in the wo
60、rld. 2024/8/1Progeria早老症症狀症狀:(1)典型的鳥型頭，且為禿頭。 (2)身材矮小，體重不足。(3)四肢瘦且關節變得明顯。(4)皮下脂肪減少。(5)梨狀胸，且鎖骨短。(6)青筋突出。(1)臨床實驗室檢查：尿中玻尿酸尿中玻尿酸值值會增加會增加2024/8/1Progeria早老症In very young children with a disease called progeria, HA is excreted in the urine at a rate 17 times that of healthy children. These progeria kids, a
61、t age 2 and 3, look like they are old, very old. They have facial wrinkles, they are bald, and they have cataracts(白內障). Progeria serves as evidence that aging is not a function of the number of birthdays but a process involving the loss of HA. Lose HA and a person will look old, regardless of his o
62、r her birth date. 2024/8/1排卵期玻尿酸大量生成，導致血液和表皮玻尿酸量增加生理週期荷爾蒙變化2024/8/1Estrogen對皮膚HA生合成的影響The mechanism of estrogen-induced increase in hyaluronic acid biosynthesis, with special reference to estrogen receptor in the mouse skin.Uzuka M, Nakajima K, Ohta S, Mori Y.The increase in hyaluronic acid and wate
63、r contents induced by estradiol treatment in the mouse skin was dependent on dose and the number of treatments of estradiol. The anti-estrogen administered together with estradiol blocked the increase in hyaluronic acid content produced by treatment with estradiol alone. It was suggested that the an
64、ti-estrogen may act as an antagonist by competing for the cytoplasmic estrogen receptor on increase in hyaluronic acid synthesis. It was observed that the sensitivity in increase in hyaluronic acid biosynthesis by estradiol was related to the age of the mouse and the content of the cytoplasmic estro
65、gen receptor in the mouse skin. It was suggested that there was a possible relationship between the increase in hyaluronic acid and cytoplasmic estrogen receptor in the mouse skin. Biochim Biophys Acta. 1980 Jan 17;627(2):199-206.Related Articles, LinksBiochim Biophys Acta. 1980 Jan 17;627(2):199-20
66、6.Related Articles, Links2024/8/1Estrogen對皮膚HA合成酵素的影響Inductionofhyaluronicacidsynthetasebyestrogeninthemouseskin.Uzuka M, Nakajima K, Ohta S, Mori Y.Hyaluronic acid synthetase activity was measured in male mouse skin following the topical application of estradiol in vivo. The enzyme activity increas
67、ed in parallel with the hyaluronic acid content of the skin, and showed a similar response in the skin of ovariectomized female mice. The increase in enzyme activity was reduced by the anti-estrogen agents, tamoxifene citrate and clomiphene citrate, which block competitively the binding of estrogen
68、to the estrogen receptor. The increase in hyaluronic acid synthetase activity was also reduced by topical application of cycloheximide or by subcutaneous injection of actinomycin D. The results suggest that the stimulation of hyaluronic acid synthesis in mouse skin in response to estrogen treatment
69、is mediated through estrogen receptors and involves the induction of the enzyme hyaluronic acid synthetase.Biochim Biophys Acta. 1981 Apr 3;673(4):387-93. Links2024/8/1玻尿酸對婦女停經症狀之改善Many women taking oral HA supplements have reported that their hot flashes and symptoms of menopause have abated with u
70、se. This is not surprising. Women have been advised that oral estrogen supplementation doesnt prevent disease, and may in fact slightly increase the risk of disease. An alternative to estrogen would be oral HA. Why do women have beautiful skin? Because estrogen elevates HA levels in the skin and bod
71、y. Once natural estrogen production has ceased (menopause), the natural alternative would be oral HA. 2024/8/11989年的一項研究提到人會因年齡的增加而造成腦部玻尿酸的流失，解釋了為什麼腦部會因年齡增長而縮小(CIBA Foundation Symposium 143: 208-20, 1989)。50歲的成人平均的腦重量為3 磅，15 年之後的腦重量大約只有 2.6 磅。50歲65歲腦重量3 磅腦重量2.6 磅腦部玻尿酸Relation between HA content in brain and brain weight2024/8/1
