Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues.
Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a significant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease.
This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow the researchers to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.

开始日期2013-09-01

申办/合作机构

Mayo Clinic

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100 项与羟脯氨酸相关的转化医学

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100 项与羟脯氨酸相关的专利（医药）

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项与羟脯氨酸相关的文献（医药）

2015-09-01·Journal of dermatological science2区 · 医学

(2R/S,4R)-2-(2,4-Dihydroxyphenyl)thiazolidine-4-carboxylic acid prevents UV-induced wrinkle formation through inhibiting NF-κB-mediated inflammation

2区 · 医学

Letter

作者: Kim, Dae Hyun ; Son, Sujin ; Ullah, Sultan ; Lee, Eun Kyeong ; Moon, Hyung Ryong ; Chung, Ki Wung ; Lee, Bonggi ; Yun, Hwi Young ; Chung, Hae Young ; Han, Yu Kyeong ; Moon, Kyoung Mi ; An, Hye Jin ; Ha, Young Mi ; Chun, Pusoon

This study examined inhibitory effects of (2R/S,4R)-2-(2,4-dihydroxyphenyl)thiazolidine-4-carboxylic acid on wrinkle formation using Hs27 human dermal fibroblasts and HR-1 hairless mouse.In this study Hs27 human dermal fibroblasts were pretreated with MHY384 followed by UVA exposure and type 1 procollagen concentration in culture medium was measured using an ELISA kit.This study resulted that, (2R/S,4R)-2-(2,4-Dihydroxyphenyl)thiazolidine-4-carboxylic acid prevented UV-induced wrinkle formation through inhibiting NF-κB-mediated inflammation using Hs27 human dermal fibroblasts and HR-1 hairless mouse.This study concluded that MHY384 could be potentially used to prevent wrinkle formation and would be a novel additive for anti-aging cosmetics.

2015-06-01·Urolithiasis

A single-blind, parallel trial of l-hydroxyproline in healthy adult subjects

Letter

作者: Ayako Kamimura ; Saori Akiduki ; Koji Morishita ; Haruo Ito

As calcium oxalate is the most common constituent of urinary stones animal model of the urolithiasis has been established by feeding l-hydroxyproline, an endogenous precursor of oxalate. However, the influence of oral l-hydroxyproline on human urinary oxalate excretion has not been clearly demonstrated. We herein report a clinical study examining the influence of daily ingestion of l-hydroxyproline on urinary oxalate levels with a focus on measuring oxalic acid excreted in the urine. In detail, we performed a single-blind, parallel designed study at Sta. Rosa Hospital and Medical Center, Philippines. This study was approved by the hospital review board and was in compliance with the Declaration of Helsinki. Forty healthy subjects (20 males and 20 females, 33.4 ± 9.4 years of age, who has no history of kidney disease) were divided into 4 groups with 10 subjects in each group with same sex ratio. l-Hydroxyproline doses of 0, 500, 1000 and 2000 mg were taken daily after breakfast for 12 weeks. Prior to and during each scheduled examination, subjects were reminded to refrain from intake of oxalate-rich foods and to drink more than 1 L of water per day. Medical interviews, physical examinations, vital sign measurements, anthropometric measurements, blood examinations and 24-h urine sample collections were conducted every 4 weeks at the hospital. A male and two female subjects were withdrawn from this study because of pregnancy or urinary tract infection so the final number of subjects was 37. Informed consent was obtained from qualified individuals. The baseline characteristics of subjects of each group were not different statistically. No adverse events were observed throughout the trial period except for a few symptoms like itchiness or headache which were self-reported from subjects, but the relationships with the test material were denied by the principle investigator. On the 24-h urine test, almost no markers changed, but there was a significant change in total l-hydroxyproline excretions in the 2000 mg l-hydroxyproline group compared to control group at the point of 8 weeks after first intake. Moreover, oxalic acid levels also increased significantly in the 2000 mg group at the point of 8 and 12 weeks after first intake. However, all values returned to basal values after 4 weeks from the last l-hydroxyproline intake (Table 1). Various dietary factors can change urine oxalate excretion; one is a high-protein diet. Many studies have addressed urinary oxalate excretion after high-protein intake, but conclusions are still uncertain. For example, Knight et al. [1] not only showed significant changes in urinary oxalate with 5 and 10 g of gelatine administered to healthy subjects, but also indicated that the high-protein diet did not influence total daily urinary oxalate excretion [2]. Collagen contains approximately 10 % of l-hydroxyproline, and the daily turnover of collagen in humans is estimated to be 2–3 g/day so the metabolism of l-hydroxyproline will be 240–420 mg [1]. In this study, the urinary oxalate level following 500 or 1000 mg/day l-hydroxyproline ingestion did not change compared with control but 2000 mg/day l-hydroxyproline ingestion increased the urinary oxalate excretion, but the values did not exceed the level of stone forming individuals with a mean oxalate excretion 40 mg/day [2]. As noted, there are various opinions on the association of dietary and urinary oxalate. Recently, it was reported that the Dietary-Approaches to Stop Hypertension (DASH)-style diet is more effective in reducing calcium oxalate supersaturation than a low-oxalate diet, although it includes a lot of fruits and vegetables which contain much oxalate [3]. Thus, the influence of the diet in conjunction with oxalate is still unclear in human metabolism. Moreover, we found no accumulation of l-hydroxyproline and oxalate in the withdrawal period same as the animal model. The metabolic significance of l-hydroxyproline is still unclear and further investigation is warranted. Table 1 Urinalysis results of 24-h urine sample

2013-12-01·Bioorganic & medicinal chemistry3区 · 医学

Peptide conjugates of 4-aminocyclophosphamide as prodrugs of phosphoramide mustard for selective activation by prostate-specific antigen (PSA)

3区 · 医学

Article

作者: Longqin Hu ; Yongying Jiang

In our continued effort to develop prodrugs of phosphoramide mustard, conjugates of 4-aminocyclophosphamide (4-NH2-CPA) with three PSA-specific peptides were synthesized and evaluated as substrates of PSA. These include conjugates of cis-(2R,4R)-4-NH2-CPA with a tetrapeptide Succinyl-Ser-Lys-Leu-Gln-OH, a hexapeptide Succinyl-His-Ser-Ser-Lys-Leu-Gln-OH, and a pentapeptide Glutaryl-Hyp-Ala-Ser-Chg-Gln-OH. These conjugates were cleaved by PSA efficiently and exclusively after the expected glutamine residue to release 4-NH2-CPA, the activated prodrug form of phosphoramide mustard. The cleavage was most efficient for the pentapeptide conjugate 3 (Glutaryl-Hyp-Ala-Ser-Chg-Gln-NH-CPA), which showed a half-life of 55 min with PSA, followed by the hexapeptide conjugate 2 (Succinyl-His-Ser-Ser-Lys-Leu-Gln-NH-CPA) and the tertrapeptide conjugate 1 (Succinyl-Ser-Lys-Leu-Gln-NH-CPA) with half-lives of 6.5 and 12h, respectively. These results indicate a potential of the conjugate 3 as an anticancer prodrug of phosphoramide mustard for selective PSA activation.

项与羟脯氨酸相关的新闻（医药）

2023-06-18

·蒲公英Ouryao

鹿胶、鹿角胶粉等3饮片炮制规范征求意见

‍‍来源：辽宁药监局整理：wangxinglai20042023年06月16日，辽宁药监局发布了中药饮片炮制规范征求意见，涉及三个品种分别为鹿骨粉、鹿胶、鹿角胶粉，公示期截止2023年6月30日。主要内容为规范我省中药饮片炮制方法和质量要求，省药品监督管理局组织制修订了鹿骨粉等三个中药饮片炮制规范，现向社会公开征求意见。请2023年6月30日前，将相关意见反馈至电子邮箱：lnfdazhuce@163.com。 01 鹿骨粉鹿骨粉Lugu FenCERVI OS POWDER本品为鹿科动物马鹿Cervus elaphus Linnaeus或梅花鹿Cervus nippon Temminck骨骼的干燥粉末。【性状】本品为类白色至浅黄色粉末。气微腥，味微咸，嚼之有颗粒感。【炮制】取原药材，除去残余筋肉，洗净，破碎、脱脂，灭菌，干燥，粉碎，混匀，分装，即得。【鉴别】取本品粉末20g，加水100ml，超声处理30分钟，滤过，滤液减压浓缩至干，残渣加50%的乙醇1ml溶解作为供试品溶液。另取甘氨酸对照品，加50%乙醇制成每1ml含0.5mg的溶液，作为对照品溶液。照薄层色谱法（《中国药典》2020年版四部通则0502）试验，分别吸取上述供试品和对照品溶液各2µl，点于同一硅胶G薄层板上，以水饱和正丁醇-冰醋酸-水（8:3:1）为展开剂，展开，取出，晾干，喷以2%茚三酮试液，在105℃加热至斑点显色清晰。供试品色谱中，在与对照品色谱相应的位置上，显相同颜色的斑点。【检查】外观均匀度取本品适量，置光滑纸上，平铺约5cm2，将其表面压平，在明亮处观察，应色泽均匀，无花纹与色斑。水分照水分测定法（《中国药典》2020年版四部通则0832第二法）测定，不得过9.0%。粒度照粒度和粒度分布测定法（《中国药典》2020年版四部通则0982第二法）测定，全部通过五号筛，通过六号筛的粉末不得少于75%。微生物限度取本品适量，照中药饮片微生物限度检查法（《中国药典》2020年版四部通则1108）测定，需氧菌总数不得过105cfu/g，霉菌和酵母菌总数不得过103cfu/g，大肠埃希菌（1g）、沙门菌（10g）不得检出，耐胆盐革兰阴性菌不得过104cfu/g。【浸出物】照水溶性浸出物测定法项下的热浸法（《中国药典》2020年版四部通则2201）测定，不得少于5.0%。【性味与归经】甘、温，归肝、肾经。【功能与主治】补虚羸，强筋骨，除风湿，止泻痢，生肌敛疮。用于肾虚腰痛，风湿痹痛，四肢疼痛，泻痢，瘰疬，疮毒。【用法与用量】酒调、吞服或冲泡服用，日用量15～30g，每日3次，每次5～10g。或遵医嘱。【贮藏】密封，防潮。 02 鹿胶鹿胶LujiaoCERVI CORII COLLA 本品为鹿科动物马鹿 Cervus elaphus Linnaeus 或梅花鹿Cervus nippon Temminck的皮经水煎煮、浓缩制成的固体胶、固体胶粉。【性状】鹿胶本品呈长方形块、方形块或丁块，棕色至黑褐色，有光泽。质脆而硬，断面光亮，碎片对光照呈半透明状。气微，味微甘。鹿胶粉本品为黄棕色至棕褐色粉末。气微，味微甘。【炮制】鹿胶将鹿皮去毛，切块洗净，分次水煎，滤过，合并滤液，滤液浓缩至稠膏状，分别加入适量的黄酒、冰糖及豆油，熬至胶状时，冷凝，切块，晾干，包装，即得。鹿胶粉将鹿皮去毛，切块洗净，分次水煎，滤过，合并滤液，浓缩，分别加入适量的黄酒、冰糖及豆油，熬至胶状时，干燥，粉碎，混匀，分装，即得。【鉴别】取本品4g粉末，加50%的乙醇50ml，超声处理15分钟，滤过，滤液减压浓缩至干，残渣加50%的乙醇1ml溶解作为供试品溶液。另取甘氨酸对照品，加50%乙醇制成每1ml含0.5mg的溶液，作为对照品溶液。照薄层色谱法（《中国药典》2015年版四部通则0502）试验，吸取供试品溶液和对照品溶液各2µl，点于同一硅胶G薄层板上，以水饱和正丁醇-冰醋酸-水（8:3:1）为展开剂，展开，取出，晾干，喷以2%茚三酮试液，在105℃加热至斑点显色清晰。供试品色谱中，在与对照品色谱相应的位置上，显相同颜色的斑点。【检查】水分照水分测定法（《中国药典》2020年版四部通则0832第二法）测定，鹿胶不得过15.0%，鹿胶粉不得过10.0%。总灰分照灰分测定法（《中国药典》2020年版四部通则2302）测定，不得过3.0%。水不溶物取本品1.0g，精密称定，加水5ml，加热溶解，将溶液移入已恒重的10ml离心管中，用温水5ml分3次冼涤，洗液并入离心管中，摇匀。置40℃水浴保温15分钟，离心（转速为每分钟2000转）10分钟，去除管壁浮油，倾去上清液，沿壁加入温水至刻度，离心，如法清洗3次，倾去上清液，离心管在105℃加热2小时，取出，置干燥器中冷却30分钟，精密称定，计算，即得。本品水中不溶物不得过2.0%。粒度鹿胶粉照粒度和粒度分布测定法（《中国药典》 2020年版四部通则0982 第二法）检查，全部通过五号筛，通过六号筛的粉末不得少于70%。微生物限度取本品适量，照中药饮片微生物限度检查法（《中国药典》2020年版四部通则1108）测定，需氧菌总数不得过105cfu/g，霉菌和酵母菌总数不得过103cfu/g，大肠埃希菌（1g）、沙门菌（10g）不得检出，耐胆盐革兰阴性菌不得过104cfu/g。【性味与归经】咸，温。归肝、肾经。【功能与主治】补肾固精，强筋健骨。用于身体瘦弱，腰酸，耳鸣，头晕目眩，虚弱久嗽，痰中带血，虚喘气短，妇女经血不调，崩漏，带下。【用法与用量】鹿胶烊化兑服，日用量6～9g。或遵医嘱。鹿胶粉酒调、吞服或冲泡服用，日用量6～9g，每日2～3次，每次3g，或遵医嘱。【贮藏】密封、防潮。 03 鹿角胶粉鹿角胶粉Lujiaojiao Fen CERVI CORNUS COLLA POWDER本品为鹿科动物马鹿 Cervus elaphus Linnaeus 或梅花鹿Cervus nippon Temminck的角经水煎煮、浓缩、干燥，粉碎制成的固体胶粉。【性状】本品为黄棕色至棕褐色粉末。气微，味微甜。【炮制】将鹿角锯段，漂泡洗净，分次水煎，滤过，合并滤液，离心，浓缩（可加适量黄酒、冰糖和豆油）至稠膏状，干燥，粉碎，混合、分装，即得。【鉴别】取本品粉末0.1g，加1%碳酸氢铵溶液50ml，超声处理30分钟，用微孔滤膜滤过，取续滤液100μl，置微量进样瓶中，加胰蛋白酶溶液10μl（取序列分析用胰蛋白酶，加1%碳酸氢铵溶液制成每1ml中含1mg的溶液，临用时配制），摇匀，37℃恒温酶解12小时，作为供试品溶液。另取鹿角胶对照药材0.1g，同法制成对照药材溶液。照高效液相色谱法-质谱法（《中国药典》2020年版四部通则0512和《中国药典》2020年版四部通则0431）试验，以十八烷基硅烷键合硅胶为填充剂（色谱柱内径2.1mm）；以乙腈为流动相A，以0.1%甲酸溶液为流动相B，按下表中的规定进行梯度洗脱；流速为每分钟0.3ml。采用质谱检测器，电喷雾正离子模式（ESI+），进行多反应监测（MRM），选择质荷比（m/z）765.4（双电荷）→554.0和m/z765.4（双电荷）→733.0作为检测离子对。取鹿角胶对照药材溶液，进样5μl，按上述检测离子对测定的MRM色谱峰的信噪比均应大于3：1。时间（分钟）流动相A（%）流动相B（%）0～255→2095→8025～4020→5080→50吸取供试品溶液5μl，注入高效液相色谱-质谱联用仪，测定。以质荷比（m/z）765.4（双电荷）→554.0和m/z765.4（双电荷）→733.0离子对提取的供试品离子流色谱中，应同时呈现与对照药材色谱保留时间一致的色谱峰。【检查】水分取本品1g，精密称定，加水2ml，加热溶解后，置水浴上蒸干，使厚度不超过2mm，照水分测定法（《中国药典》2020年版四部通则0832第二法）测定，不得过10.0%。总灰分照灰分测定法（《中国药典》2020年版四部通则2302）测定，不得过3.0%。重金属取总灰分项下的残渣，依法检查（《中国药典》2020年版四部通则0821第二法），不得过30mg/kg。砷盐取本品1.0g，加氢氧化钙1g，混合，加少量水，搅匀，干燥后，先用小火烧灼使炭化，再在500～600℃炽灼使完全灰化，放冷，加盐酸5ml与水2ml，依法检查（《中国药典》2020年版四部通则0822），不得过2mg/kg。水不溶物取本品1.0g，精密称定，加水10ml，加热溶解，将溶液移入已恒重的10ml离心管中，离心，去除管壁浮油，倾去上清液，沿管壁加入温水至刻度，离心，如法清洗3次，倾去上清液，离心管在105℃加热2小时，取出，置干燥器中冷却30分钟，精密称定，计算，即得。水不溶物不得过2.0%。外观均匀度取本品适量，置光滑纸上，平铺约5cm2，将其表面压平，在明亮处观察，应色泽均匀，无花纹与色斑。粒度照粒度和粒度分布测定法（《中国药典》2020年版四部通则0982 第二法）检查，全部通过五号筛，通过六号筛的粉末不少于70%。微生物限度取本品适量，照中药饮片微生物限度检查法（《中国药典》2020年版四部通则1108）测定，需氧菌总数不得过105cfu/g，霉菌和酵母菌总数不得过103cfu/g，大肠埃希菌（1g）、沙门菌（10g）不得检出，耐胆盐革兰阴性菌不得过104cfu/g。【含量测定】照高效液相色谱法（《中国药典》2020年版四部通则0512）测定。色谱条件与系统适用性试验以十八烷基硅烷键合硅胶为填充剂；以乙腈-0.1mol/L醋酸钠溶液（用醋酸调节pH值至6.5）（7：93）为流动相A，以乙腈-水（4：1）为流动相B，按下表中的规定进行梯度洗脱；检测波长为254nm。柱温为43℃。理论板数按L-羟脯氨酸峰计算应不低于4000。时间（分钟）流动相A（%）流动相B（%）0～11100→930→711～13.993→887→1213.9～1488→8512→1514～2985→6615→3429～3066→034→100对照品溶液的制备取L-羟脯氨酸对照品、甘氨酸对照品、丙氨酸对照品、L-脯氨酸对照品适量，精密称定，加0.1mol/L盐酸溶液制成每1ml含L-羟脯氨酸70μg、甘氨酸0.14mg、丙氨酸60μg、L-脯氨酸70μg的混合溶液，即得。供试品溶液的制备取本品粗粉约0.25g，精密称定，置25ml量瓶中，加0.1mol/L盐酸溶液20ml，超声处理（功率300W，频率40kHz）30分钟，放冷，加0.1mol/L盐酸溶液至刻度，摇匀。精密量取2ml，置5ml安瓿中，加盐酸2ml，150℃水解1小时，放冷，移至蒸发皿中，用水10ml分次洗涤，洗液并入蒸发皿中，蒸干，残渣加0.1mol/L盐酸溶液溶解，转移至25ml量瓶中，加0.1mol/L盐酸溶液至刻度，摇匀，即得。精密量取上述对照品溶液和供试品溶液各5ml，分别置25ml量瓶中，各加0.1mol/L异硫氰酸苯酯（PITC）的乙腈溶液2.5ml，1mol/L三乙胺的乙腈溶液2.5ml，摇匀，室温放置1小时后，加50%乙腈至刻度，摇匀。取10ml，加正己烷10ml，振摇，放置10分钟，取下层溶液，滤过，取续滤液，即得。测定法分别精密吸取衍生化后的对照品溶液与供试品溶液各5μl，注入液相色谱仪，测定，即得。本品按干燥品计算，含L-羟脯氨酸不得少于6.6%、甘氨酸不得少于13.3%、丙氨酸不得少于5.2%、L-脯氨酸不得少于7.5%。【性味与归经】甘、咸，温。归肾、肝经。【功能与主治】温补肝肾，益精养血。用于肝肾不足所致的腰膝酸冷，阳痿，遗精，虚劳羸瘦，崩漏下血，便血，尿血，阴疽肿痛。【用法与用量】酒调、吞服或冲泡服用。日用量3～6g，每日1～2次，每次3g。或遵医嘱。【贮藏】密封，防潮。‍

诊断试剂

100 项与羟脯氨酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	羟脯氨酸	-	DB08847

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
原发性高草酸尿症	临床2期	美国	National Institutes of Health	2013-09-30
肾钙质沉着症	临床2期	美国	National Institutes of Health	2013-09-30
草酸钙肾石病	临床2期	美国	National Institutes of Health	2013-09-30
高草酸尿症	临床2期	美国	Mayo Clinic	2013-09-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASN2014	N/A	高草酸尿症	-	Hydroxyproline	鬱憲網鑰鏇廠簾淵淵顧(顧膚遞鑰範蓋築網鹹襯) = 艱鹽窪夢鏇夢糧齋觸淵選願衊蓋繭獵構獵網構 (構壓餘艱衊願齋選簾鑰, 11) 更多	积极	2014-11-11
ASN2012	N/A	-	4	Hydroxyproline	獵鑰壓鏇鏇膚膚鏇鹹餘(憲構遞顧憲鏇觸夢範遞) = 獵艱蓋艱餘壓鹹淵築憲膚製蓋簾膚憲鹹憲蓋憲 (衊鏇鑰範衊夢選顧衊齋, 3.7) 更多	-	2012-10-30
2073 (AUA2012)	N/A	肾石病	8	DIETARY HYDROXYPROLINE (Control diet)	網艱鹹蓋憲鬱廠衊齋廠(構淵醖鏇簾衊齋繭鏇遞) = 壓鏇壓淵蓋網蓋積壓廠獵齋廠願觸積壓鹽願繭 (醖鏇膚獵簾鏇鬱衊淵艱 )	-	2012-04-01
2073 (AUA2012)	N/A	肾石病	8	DIETARY HYDROXYPROLINE (10% hydroxyproline diet)	網艱鹹蓋憲鬱廠衊齋廠(構淵醖鏇簾衊齋繭鏇遞) = 顧鹹鏇鹹遞積網繭簾築獵齋廠願觸積壓鹽願繭 (醖鏇膚獵簾鏇鬱衊淵艱 )	-	2012-04-01