中藥五苓散對復發型草酸鈣結石患者之前瞻性研究; Prospective study of Wu-Ling-San Formula prophylaxis against recurrent calcium oxalate nephrolithiasis
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(4) ύЎᄔा ύ୯ᙴᛰεᏢύՋᙴ่ӝᙴᏢࣴ܌ز ࣴزғ : ݅ػቼ ࡰᏤ௲ : ഋؙӓ ௲ قǺύ୯ᙴᛰεᏢഋؙӓ௲ϐࣴزჴǴϖऴණܭᡏѦჴᡍϷނ၂ᡍϐ ύǴޑዴԖڋለ่້ԋǵᏉکԋߏϐфਏǶҁჴᡍϐҞޑջࣁᔈҔύ ᛰϖऴණǴࣴځزჹܭൺวࠠለ่້ҡޣϐ่ҡߦϷڋӢηϐቹៜǹа යפрୋբҔեЪԖਏϐБٰݤႣ่ٛҡϐൺวǶ ჴᡍБݤǺ ჴᡍಔ 5 ΓǴϖऴණ 2g ВΟԛࡕܺҔǴӅܺҔঁДǴ٠ӭ സНᆢВֿໆ>2000ccǶჹྣಔ 5 ΓǴ๏ϒӼኃᏊ 2g ВΟԛࡕܺҔǴӅ ܺҔঁДǴ٠ӭസНᆢВֿໆ>2000ccǶᢀჸܺځᛰϷܺᛰࡕঁДϐ Ոనᔠǵֿనᔠǵဎ X ӀϷ᠌ຬॣݢᔠϐᡂϯǴࢂցԖཥғԋϐ่ ҡϷܭՈనᆶֿనύࢂցౢғᡂϯǶीϩճҔ SPSS ೬ᡏՉ t-test ीǴ p ॶ<0.05 ᇡࣁܭीᏢڀԖᡉϐৡ౦Ƕ ่݀Ǻ10 ՏੰΓύǴ ܄ت7 Տ(70%)Ǵζ܄ΟՏ(30%)Ƕѳ֡ԃស 50.7 ྃ(40 Կ 59 ྃ) Ƕჴᡍಔ 5 ΓϐֿໆᡂϯࣁǴܺҔ 2260²434 డϲ/ϺǴܺҔࡕ 2580²526 డϲ/Ϻ(ᡂϯԭϩК 14.1%)Ƕჹྣಔ 5 ΓϐֿໆᡂϯࣁǴܺҔ 2660²844 డϲ/ ϺǴܺҔࡕ 2660²850 డϲ/Ϻ(ᡂϯԭϩК-0.1%)ǶٿಔКၨวύᛰϖऴණޑዴ ૈቚу่ҡੰϐ௨ֿໆ(t ᔠۓǴp ॶλ ܭ0.05)ǴԶቚу௨ֿໆჹ่ҡϐႣٛڀ Ԗ҅य़ϐշǶќБय़Ǵύᛰϖऴණ٠คဉगၰڈᐟੱ܈ރႝှ፦Ѩᑽϐݩ วғǹՈమύႝှ፦ǵطϷфૈࡰኧ٠คܴᡉϐᡂϯǶ ่ፕǺύᛰϖऴණёૈࣁୋբҔեЪԖਏϐύᛰёᔈҔܭႣ่ٛҡϐൺวȄᆶ ᖏதᔈҔ่ܭҡϐᘗᘔለႇણ҃КၨวǴύᛰϖऴණ٠คဉगၰڈᐟੱރ วғǹᆶᖏதᔈҔ่ܭҡϐճֿᏊКၨวǴύᛰϖऴණ٠คႝှ፦Ѩᑽϐ ݩวғǶ٬Ҕύᛰϖऴණёа٬ለ่້ҡੰϐֿໆቚу٠ႴᓰੰΓӭസН.
(5) аቚуֿໆǶ܌аჹܭሡߏයܺҔ่ҡႣٛᛰޑނൺวࠠለ่້ҡޣԶقǴ ҁБӝբࣁᢀჸߏයܺҔႣٛਏ݀ޑύᛰБᏊǶ ᜢᗖຒǺለ້ǹֿၡ่ҡǹύᛰǹϖऴණǹ่ҡ.
(6) Ҟ. ᒵ. ಃക ……………………………………ق.1 ಃΒക Ў……………………………...2 ಃΟക ᆶБ…………………………ݤ...5 ಃѤക ่݀…………………………………...7 ಃϖക ፕ…………………………………..8 ಃϤക. ่ፕ………………………………….11. კ߄…………………………………………….12 ୖԵЎ……………………………………….14 मЎᄔा……………………………………….16 Γᡏ၂ᡍीჄቩਡЎҹ……………………….18 ࣴزीฝቩਡЎҹ…………………………….51 ࣴزीฝයύൔ…………………………….72 բޣᙁᐕ……………………………………….78 ᖴຒ…………………………………………….80.
(7) ಃകʳ ق Urinary stone disease affects 9.6% of the total population in Taiwan, which includes 4.3% of females and 14.5% of males [1]. The recurrent rate ranges from 35% within 5 years and after first treatment to 74% within 10 years [2]. A number of medical treatments have been reported to prevent the recurrence of urinary stone, including encouraging patients to take more fluid, nutrient supplements and diet control [3]. In recent years, the most popular medication for preventing calcium oxalate nephrolithiasis is potassium citrate [4, 5, 6, 7] Potassium citrate effectively reduces the recurrence rate of calcium oxalate nephrolithiasis [4, 5]. However, potassium citrate has tendency to irritate gastric mucosa, and this problem can limit patient acceptability. In published clinical trials of potassium citrate, incidence of gastrointestinal adverse incidence ranged from 9 to 17% [6, 7]. On the other hand, medicinal herbs are widely accepted by many people in Taiwan and in Chinese societies elsewhere. We previously reported that WLS effectively inhibited the process of calcium oxalate nucleation, crystallization and aggregation in vitro and in vivo [8, 9]. These findings inspired us to clarify the nephrolithiasis prevention effects of WLS in a clinical trail. In this study, we examined the efficacy of Wu-Ling-San formula (WLS) prophylaxis for preventing recurrent calcium oxalate nephrolithiasis. We analyzed the changes in urine output, body weight and biochemical parameters of urine and serum. We are trying to find out a lower side effect drug for calcium oxalate nephrolithiasis prevention. 1.
(8) ಃΒകʳ Ў ֿၡ่ҡࢂԛֿܭၡགࢉǴಃΒதֿࣽݜޑـ੯ੰǴՠځԋӢ ޑፄᚇǵݯᕍ֚ޑᜤǵᙴᕍԋҁޑǴࠅᇻεֿܭၡགࢉǶᏵߥӺ ीǴѠӦԖ5Կ10ʝޑΓමᑡ่ڙ҅܈ҡϐधǶԖъа ੰޑΓܭ5Կ10ԃ໔ൺวǶԃ15ʘൺวǶൺวӧΎԃϣଯ ၲ60% [1]ǶӧѠ่ҡϐՉऊ9.6%(܄تऊ14.5%Ϸζ܄ऊ4.3%) [1]Ƕவᙴᕍၗྍޑᢀᗺٰ࣮ǴѠӦऊԖ2301ΓαǴࠅԖຬၸ 130Ѡ࿗ҡᐒǹΨ൩ࢂᇥǴѳ֡ԭΓαᏱԖ6Ѡ࿗ҡᐒǶԃ ܭ࿗ҡޑԋҁຬၸሹऍߎǴऊ՞଼ߥᕴᚐޑ4% [8]ǶࣁΑ෧Ͽᙴᕍ ԋҁϐǴ܌аॺךѸ൨פрঁԖਏԶёՉޑБٰݤႣ่ٛҡ ϐൺวǶᗨฅҞςԖදၹᔈҔܭႣ่ٛҡϐᛰࣁނᘗᘔለႇણ҃Ǵ ՠࢂځϝԖ9%-17%Їଆဉगၰόϐёૈ[܄4]Ƕ. ֿၡ่ҡܭύᙴڂᝤၩᆀϐࣁϙҡరϙ܈ϙࣳరϙˎʳ ੱځ ރхࡴΑֿύԖҡǵှֿੵภǵֿύԖՈ܈ቃਗ਼ဈภǶӧύᙴڂᝤ ၩύǴԖӭБᏊёݯᕍֿၡ่ҡǴځύхࡴΑϖऴණǶϖऴණനԐ ၩܭՋϡΟШइҗҸඳ܌ጓቪϐϙൣፕϙǴځచЎࣁʳ Ϙύ॥ วǴʳ ϤΎВόှԶྠǴԖ߄္ǴటНǴНΕ߾ӗޣǴʳ ӜГ Нʳ Ǵʳ ϖऴණЬϐǶൣԠрԶޣǴϖऴණЬϐϙϘൣፕϙύ ၩځಔԋࣁϙऴΜΖሏȐѐҜȑ!ᐛᘞٿϤሏ!қҀ!ΜΖሏ!ἐ 2.
(9) ऴΜΖሏ!ਦ݄ъٿȐѐҜȑϙǶԶനԐၩϖऴණᔈҔݯܭᕍֿၡ ่ҡࣁՋϡΜϤШइҗЦޭጓቪϐ”ຓྗݯᛣ”[8, 9]Ƕ. ϖऴණܭύᙴϐᔈҔࣁНဍϐᏊǴᖐΥНྒྷϣଶ܌ठНဍي ख़ǵλߡόճǴࣣё٬ҔǴᖏҔܭགߵԖ༾ǵαǵཀྵǵλ ߡόճǴჹ࡚ܭᄌ܄ݹǵݹطǵᆮાݹǵ࡚܄ဉगݹǵНᘞǵН ဍ܈ဎЋೌࡕ௨ֿ֚ᜤ֡Ԗਏ [24, 25]ǶӧжᛰᏢБय़Ǵϖऴ ණڀԖճֿϷלբҔǶճֿբҔёߦֿݜၰ่ҡ௨рǴځύ ऴǵἐऴǵқҀǵᐛᘞ֡ԖճֿբҔǶԶਦ݄ᙖׯ๓ՈనൻᕉǴЀځ ࢂ᠌ՈనൻᕉǴуமճֿբҔ [24, 25]ǶЪלբҔёڋགࢉ܄ ่ҡԋǴځύਦ݄ჹࢬՉ܄གߵੰࢥǵݹޤౚǵฟ੯ఎǵεဉ ఎԖբҔǴऴᎇගనჹߎՅဟౚǵεဉఎԖڋ բҔǶќѦਦ݄ǵᐛᘞჹဉगѳྖԼԖှยբҔǴёᔅշᒡֿᆅѳྖ ԼܫǴߦֿݜၰ่ҡ௨р [24, 25]Ƕ ӧύ୯ᙴᛰεᏢഋؙӓ௲ϐࣴزΨࡰрǴϖऴණܭᡏѦ၂ᡍϐ ύǴܭόӕᐚࡋ6.25ǵ12.5ǵ25 ک50 mg/mlΠёڋ344ǵ387ǵ543 Ϸ943%ޑለ่້ਡϐԋǴՠࢂჹ่ਡϐԋߏ٠คڋϐբ ҔǶӧќБय़Ǵϖऴණܭ12.5ǵ25ک50 mg/mlޑᐚࡋϐΠǴёڋ 74.24ǵ75.05ک92.49%ޑለ่້ϐᏉբҔǹࡺӧᡏѦ၂ᡍ่ޑ ፕࣁϖऴණޑዴԖڋለ่້ԋکᏉϐфਏǴ܈ჹܭለ 3.
(10) ่້ҡϐႣٛԖځфਏ [9]Ƕӧഋؙӓ௲ϐނჴᡍύΨຓჴǴӧ ΌΒᎇᗯ१εқႵᇨวϣለ่້ҡϐኳಔύ;ӧҔΌΒᎇНޑ εႵ᠌ಔᙃϪТёวλᆅϐઇᚯǵཞϷวݹϸᔈǶԶϖऴණ ᗯ१ಔǴځϣ่ϐܴ߾ݩᡉ෧ᇸǶа่؈ᑈࡰኧٰ߄ҢǴե ᐚࡋϖऴණಔ (375 mg/kg )Кჹྣಔࡰኧёவ1.40फ़Կ0.46ǹଯᐚࡋ ϖऴණಔ (1,125 mg/kg )Кჹྣಔࡰኧёவ1.40फ़Կ0.45ǶᕴᢀٰᇥǴ ϖऴණёԖਏڋჴᡍނ᠌ϐለ่້Ϸ่ҡϐԋ(pॶ ܭ0.035) [8]Ƕ Ӣֿၡ่ҡࢂଯൺวϐ੯ੰǴӵคϷਔϐೀǴᇸ߾ੵ ภǵՈֿǴख़߾Їଆ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁ ჴࣁ؈ख़ϐॄᏼǹҁჴᡍϐҞޑջࣁᔈҔύᛰϖऴණǴࣴځزჹ ܭൺวࠠለ่້ҡޣϐ่ҡߦϷڋӢηϐቹៜǹаයפр ୋբҔեЪԖਏϐБٰݤႣ่ٛҡϐൺวǴаᅽቶεϐ่ҡੰ ဂǶ. 4.
(11) ಃΟക ᆶБݤ Preparation of Wu-Ling-San Formula Extracts The formula of Wu-Ling-San (WLS) consists of five herbs including Rhizoma alismatis, Poria cocos Wolf, Polyporus umbellatus Fries, Rhizoma Atractylodis Macrocephalae and Ramulus Cinnamomi Cassiae; the weight of each is in a ratio of 4:3:3:3:2. The fine powder formula used in this study was provided by the Koda pharmaceutical company (Taichung, Taiwan). Aqueous extracts of WLS formula were prepared by putting 100g of formula into a bottle containing 500ml distilled water; the solution was then heated for 15 min in an autoclave at 121°C. Then resulting jellies-like product was dissolved in distilled water to a final volume of 750 ml and stored at 4°C for 7 days. Next, the solution was centrifuged at 1,500 rpm for 10 min. The concentration of the extract was measured by weighing 1 ml of the supernatant which had been dried in a 60°C oven for 1 day (82 mg/ml). Finally, the crude drugs (6, 4.5, 4.5, 4.5 and 3 gm respectively) were concentrated to 4gm net weight (crude drug:net drug=5.625:1). The placebo was made with starch and caramel, the appearance of which was similar to WLS formula. The packing of the placebo and the WLS formula were identical. Study Protocol This experimental protocol was approved by the Institutional Review Board of Show Chwan Memorial Hospital (IRB, SCMH No: 960202). This was a prospective pilot study that evaluated the WLS formula effect on 10 patients with recurrent calcium oxalate nephrolithiasis. The patients with malignant tumor with bony metastasis, hyperthyroidism, psychosis, 5.
(12) renal tubular acidosis, anatomical abnormalities, chronic urinary tract infection, osteoporosis, gout, chronic diarrhea or pregnancy were excluded. The patients were randomized divided into two groups. The medication group took 2 gm Wu-Ling-San formula three times daily for 1 month. The control group took 2 gm placebo formula three times daily for 1 month. The patients were asked to drink enough fluid to urinate at least 2 L daily during the study period. At entry before treatment a 24-hr urine sample was collected from every patient, who was kept on a random diet, for measurement of calcium, uric acid, PH and total urine volume. A venous serum sample was collected for calcium, phosphorus, creatinin, sodium, GOT, GPT, potassium and urine acid. At the beginning and 1 month later, image follow-up a single KUB film and renal ultrasonography was taken in all patients. We calculate the sum of the long-axis diameter of the largest stone and stone numbers for further statistical analysis. The long-axis diameter of the largest stone, less than 1 cm stone get 1 point, 1-2 cm stone get 2 point, larger than 2cm stone get 3 point. About the stone numbers, 1 or less 1 stone get 1 point, two stones get 2 point and more than 2 stones get 3 point. Statistical analysis was performed using the Student’s t-test, p<0.05 was considered statistically significant.. 6.
(13) ಃѤക ่݀ A total of 10 patients were enrolled, of whom 7 (70%) were men and 3 (30%) were women. All the patients completed the study. The mean age was 50.7 years (range 40 to 59). The patients reported a lifetime total of 3 to 6 (average 4.2) stone episodes. The patients had undergone 2 to 3 (average 2.5) stone procedures. There were no differences in baseline data between the two groups, including age, male/female ratio, stone severity index, urolithiasis procedures and BMI (Table 1). The baseline urine output level was 2260±434 ml/day in Wu-Ling-San formula (WLS) group and 2660±844 ml/day in placebo group. After treatment with Wu-Ling-San formula group, the mean urine output level increased to 2580r526ml/day (percentage of change, 14.1%). With placebo therapy, the mean decreased slightly to 2660r850ml/day (percentage of change, -0.1%). Comparing the two groups, WLS group significantly increased the urine output (student t-test, p<0.05). No patient complained of side effects,. including. fatigue,. dizziness,. impotence,. musculoskeletal. symptoms, or gastrointestinal disturbance. The serum liver function, renal function, electrolyte and urinary parameters were found to have no significant change in both groups (Table 2). No significant differences in urine calcium, urine pH value, serum calcium or phosphorous at the beginning of the study were noted between the groups.. 7.
(14) ಃϖക ፕ Many traditional Chinese medicine (TCM) are used to treat urolithiasis, Wu-Ling-San (WLS) is one of those [10, 11, 12]. To the best of our knowledge, the possible mechanism of WLS used in antilithic remains unclear. Some studies have suggested that macromolecules may be involved in the antilithic mechanism of WLS [8]. One of the components of WLS, Alisma orientalis, has been shown to inhibit the stone formation process [13, 14]. Yin et al. reported that Alisma inhibited the growth and aggregation of CaOx crystals in vitro and the renal calcium content decreased in Alisma treated rats [15]. In addition, Suzuki et al also reported that Alisma orientalis (also named as Takusha) strongly suppressed crystal formation, growth and aggregation of CaOx crystals in vitro[16]. Furthermore, several studies have shown that this herb significantly. decreased. the. formation. of. CaOx. deposits,. and. downregulated the expression of inter-alpha-trypsin inhibitor and bikunin [17]. Yashimura et al in another in vitro study also noted that WLS significantly inhibited CaOx crystallization in human urine [18]. Liu et al reported that in reducing CaOx crystals, WLS also suppressed the development of hydroxylapatite renal calcinosis in rats fed on a high phosphorus diet [19]. Our previous study already concluded that WLS effectively inhibits the process of CaOx nucleation, crystallization and aggregation in vitro and in vivo [8, 9]. All of these reports suggest that WLS may be a useful drug for preventing renal stones. WLS is a TCM formula mainly used for treatment of uremia, dropsy, nephrosis and to promote urination. The formula for WLS was first 8.
(15) recorded in the book “Shang Han Lun” (Treatise of Cold-induced Disorders) written by Zhong-Jing Zhang. The original indications for WLS were symptoms of headache, fever, voiding difficulty, irritability, strong thirst with vomiting immediately after drinking and a floating pulse [8]. Treating urinary stone disease by WLS was recorded in the book written by Ken-Tang Wang entitled “Zheng Zhi Zhun Sheng” (standards of patterns and treatment) during the Ming Dynasty (later sixteenth century). Since that time, the WLS formula has been used as a usual prescription for treating urinary difficulties and febrile diseases because of its diuretic properties [20]. This study is the Wu-Ling-San (WLS) clinical trail for calcium oxalate stone prevention. The baseline urine output level was 2260±434 ml/day in Wu-Ling-San formula (WLS) group and 2660±844 ml/day in placebo group. After treatment with Wu-Ling-San formula group, the mean urine output level increased to 2580r526ml/day (percentage of change, 14.1%). With placebo therapy, the mean decreased slightly to 2660.0r850ml/day (percentage of change, -0.1%). Comparing both groups, WLS group significantly increased the urine output (student t-test, p<0.05). The results of this study have confirmed that Wu-Ling-San Formula is effective in increasing urine output in recurrent calcium oxalate stone formers.. Hydration and increase of urine output are effective methods. in stone prevention [21]. Other popular stone prevention drugs, like Potassium Citrate, have a number of side effects like gastrointestinal disturbances, and it may be improved if diluted in a large glass of water [4, 22]. Loop agents such as the thiazides, may induce hypokalemic, hypochloremic, metabolic 9.
(16) alkalosis and it may be treated with potassium chloride replacement. Thiazide diuretics also have been linked to glucose intolerance, which may be an effect of hypokalemia rather than the diuretic itself. Thiazides may lead to hyponatremia which may cause permanent neurologic damage [23]. In the contrast, Wu-Ling-san did not have any of the side effects like gastrointestinal adverse, electrolyte imbalance or malaise in our series. An interesting finding from our study was the overall good compliance with the instruction to urinate 2 L daily. All the patients met the goal, including WLS group and placebo group. That may be because we educated the patients about the WLS possible antilithic mechanism and the diuretic effect. One should drink enough fluid to urinate at least 2 L daily during the study period for reaching the best effect of WLS. In view of cost-effect, the Wu-Ling-San formula cost was only 10.2 USD/month. The potassium citrate cost was 40.9 USD/month. The limitation of this study is that we did not examine the oxalate and citrate levels in urine. The significance of the study is also limited due to the small number of subjects included.. 10.
(17) ಃϤകʳ. ่ፕ. Traditional Chinese herb medicine (Wu-Ling-San Formula) is a promising adjunct to surgical and medical management of kidney stones. It might be better accepted by patients, when compared with potassium citrate, because of the lower gastrointestinal disturbance. However, in the case of Wu-Ling-San Formula versus hydration group, the urinary parameters did not improve with Wu-Ling-San Formula. Active therapy with Wu-Ling-San Formula did have a positive effect on the urine volume without electrolyte imbalance. Patients need ongoing education and encouragement to meet the goals of urinary output, and treatment with Wu-Ling-San Formula might help patients reach these goals.. 11.
(18) კ߄ Table 1. Patient’s data of the study. Wu-ling-san group. Men(n). 4. Placebo group. P value. 3 1.000. Women(n). 1. 2. Mean age (years). 49.8r3.8. 51.60r7.89. 0.548. Urolithiasis. 2.60r0.55. 2.40r0.55. 0.690. Stone severity index. 3.80r1.10. 3.40r0.55. 0.421. BMI. 26.31r3.01. 26.28r3.01. 1.000. procedure. BMI: body mass index. 12.
(19) Table 2. Urinary parameters at baseline and after treatment with Wu-ling-san formula and placebo Wu-ling-san group pretreatment. Placebo group. Post-treatment. %of. pretreatment. Post-reatment. change. %of change. 2260r434*. 2580r526*. 14.1r9.1̺. 2660r844. 2660.0r850. -0.1r3.4̺. Serum GOT. 23.0r4.2. 23.8r5.2. 3.5r13.4. 18.8r1.8. 18.2r2.2. -3.2r7.1. Serum GPT. 25.2r2.2. 26.6r3.8. 6.4r18.9. 20.2r4.1. 20.4r5.0. 0.3r10.6. Serum K. 4.26r0.40. 4.30r0.24. 1.8r13.4. 4.04r0.18. 3.96r0.27. -02.0r4.5. Serum CL. 105.2r1.3. 104.2r2.4. -1.0r1.8. 105.4r2.2. 105.0r2.3. -0.4r1.4. Serum Ca. 8.96r0.37. 9.16r0.67. 2.3r7.8. 250.5r43.5. 269.1r60.9. -1.7r2.3. Serum P. 2.82r0.56. 3.12r0.27. 13.2r17.4. 3.02r0.93. 2.80r0.68. -5.6r7.8. Urine Ca. 288.4r170.9. 351.4r192.4. 63.2r117.0. 250.5r43.5. 269.1r60.9. 7.3r14.9. Urine UA. 685.6r372.2. 823.2r148.0. 61.7r117.0. 753.1r252.2. 744.3r272.5. -2.2r10.1. Urine Cr. 59.9r23.9. 71.6r24.3. 70.9r180.0. 57.3r16.6. 58.2r15.1. 2.6r5.8. Urine PH. 6.80r0.45. 6.60r0.55. -2.9r6.4. 6.00r0.771. 6.40r0.55. 8.0r17.9. Urine Ccr. 98.8r28.4. 112.2r34.1. 25.6r67.1. 97.1r17.7. 100.2r14.6. 3.8r5.3. Stone severity. 3.8r1.1. 3.4r0.9. -9.0r12.5. 3.4r0.5. 3.2r0.4. Urine volume(ml/day). index. Data presented as mean ̈́SD *p<0.05 versus pretreatment ̺ % of change between groups < 0.05 (Student t test). 13. -5.0r11.2.
(20) ୖԵЎ 1. Lee YH, Huang WC, Tsai JY, Lu CM, Chen WC, Lee MH, Hsu HS, Huang JK and Chang LS. Epidemiological studies on the prevalence of upper urinary calculi in Taiwan. Urol Int 2002; 68: 172-177. 2. Uribarri J, Man S and Carroll JH. The first kidney stone. Ann Int Med 1989; 111: 1006–1009. 3. Lewandowski S and Rodgers AL. Idiopathic calcium oxalate urolithiasis: risk factors and conservative treatment. Clin Chim Acta 2004; 45: 17–34. 4. Whalley NA, Meyers AM, Martins M and Margolius LP. Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia. Brit J Urol 1996; 78: 10-14. 5. Hofbauer J, Hobarth K, Szabo N and Marberger M. Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis: a prospective randomized study. Brit J Urol 1994; 73: 362-365. 6. Ettinger BC, Pak Y, Citron JT, Thomas C, dams-Huet B and Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol 1997; 158: 2069–2073. 7. Barcelo P, Wuhl O, Servitge E, Rousaud A and Pak CY. Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol 1993; 150: 1761-1764. 8. Tsai CH, Chen YC, Chen LD, Pan TC, Ho CY, Lai MT, Tsai FJ and Chen WC. A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats. Urol Res 2008; 36:17-24. 9. Chen YC, Ho CY, Chen LD, Hsu SF and Chen WC. Wu-Ling-San formula inhibits the crystallization of calcium oxalate in vitro. Am J Chin Med 2007; 35:533–541. 10. Das I, Gupta SK and Ansari SA. In vitro inhibition and dissolution of calcium oxalate by edible plant Trianthema monogyna and pulse Macrotyloma uniXorum extracts. J Cryst Growth 2005; 273:546–554. 11. Freitas A, Gohel MD and Wong SP. Chinese herbal medicines and there efficacy in treating renal stones. Urol Res 2006; 34:365–372. 12. Freitas AM, Schor N and Boim MA. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int 2002; 89: 829-834. 13. Cao ZG, Liu JH and Zhou SW. The effect of the active constituents of Alisma orientalis on renal stone formation and bikunin expression in rat urolithiasis 14.
(21) model. Matl Med J China 2004; 84:1276–1279. 14. Yasui T, Fujita K and Sato M. The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model. Urol Res 1999; 27:194–199. 15. Yin CP, Liu JH and Zhang YS. Effects of Alisma orientalis Juzep on calcium oxalate crystallization in vitro and calcium oxalate renal stone in rats. Acta Univ Med Tongji 1997; 26:99–101. 16. Suzuki K, Kawamura K and Tsugawa R. Formation and growth inhibition of calcium oxalate crystals by Takusha (Alismati rhizoma). Scanning Microsc 1999; 13:183–189. 17. Cao ZG, Liu JH and Zhou SW. Effect of alisma orientalis extract on renal stone formation and the expression of inter-alphatrypsin inhibitor in rat urolithiasis model. Chin J Exp Surg. 2004; 21:295–297. 18. Yashimura K, Miake O and Okuyama A. Effect of chorei-to and gorei-san on calcium oxalate crystallization in human urine. Hinyokika Kiyo 1998; 44:13–16. 19. Liu QL, Sato S and Kishikawa T. Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats. Med Electron Microsc 2001; 34: 103–114. 20. Chen YH, Tsai FJ and Chen WC. Phytotherapies for urolithiasis. Research Signpost. 2008:17-38. 21. Patrick Y, Walsh C, Alan B and Retik .Campbell's urology. 8th ed 2002: 3230-3260. 22. Koff SG, Paquette EL, Cullen J, Gancarczyk KK, Tucciarone PR and Schenkman NS. Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology 2007; 69:1013-1016. 23. Greenberg A. Diuretic complications. Am J Med Sci 2000; 319:10-24. 24. ࣥࡲ؟ΕࣥࡲؓΕࣥན Κխᢐᢐᖂ ഏمᒳ塢 ( )ק1995Κ228-229 25. ࣔޘΚֱᕪᖂ ഏمխഏ᠔ᢐઔߒࢬ ( )ק1999: 201-202. 15.
(22) मЎᄔा Objectives: Wu-Ling-San formula has been proved to have a preventive effect on the treatment of calcium oxalate nephrolithiasis both in vitro and in vivo. In this study, we examined the efficacy of Wu-Ling-San formula prophylaxis for preventing recurrent calcium oxalate nephrolithiasis. Methods: This was a prospective clinical study that evaluated the 24-hour urine parameters of 10 patients with kidney stones. All patients with a history of recurrent calcium oxalate nephrolithiasis who were aged 40 to 59 years old. The patients were asked to drink enough fluid to urinate at least 2 L daily during the study period. A 24-hour urine collection was performed to establish the baseline levels of multiple urinary parameters before taking the medicine. The patients were randomized divided into two groups. The medication group took 2 gm Wu-Ling-San formula three times daily for 1 month. The control group took 2 gm placebo formula three times daily for 1 month. All the patients received 24-hour urine collection was performed of multiple urinary parameters after complete the study. The serum liver, renal function and electrolyte was also collected. Results: A total of 10 patients were enrolled, of whom 7 (70%) were men and 3 (30%) were women. All the patients completed of the study. The mean age was 50.7 years old (range 40 to 59). The patients reported a lifetime total of 3 to 6 (average 4.2) stone episodes. The patients had undergone 2 to 3 (average 2.5) stone procedures. The baseline urine. 16.
(23) output level was 226˃̈́ˇˆˇʳml/day in Wu-Ling-San formula (WLS)group and 2660̈́ˋˇˇʳml/day in placebo group. After treatment with Wu-Ling-San formula group, the mean urine output level increased to 2580r526ml/day (percentage of change, 14.1%). With placebo therapy, the. mean decreased slightly to 2660.0r850ml/day (percentage of change, -0.1%). Compare with both group, WLS group significantly increased the urine output. (student t-test, p<0.05). No patient complain of side effects, including fatigue, dizziness, impotence, musculoskeletal symptoms, or gastrointestinal disturbance. The serum liver function, renal function, electrolyte and urinary parameters were no significant change in both groups. Conclusions: Wu-Ling-San formula is a promising adjunct to surgical and medical management of kidney stones. Compare with potassium citrate, they might be better accepted by patients than medications taken three times daily because of the lower gastrointestinal disturbance. Active therapy with Wu-Ling-San Formula did have a positive effect on the urine volume without electrolyte imbalance. Patients need ongoing education and encouragement to meet the goals of urinary output, and treatment with Wu-Ling-San Formula might help patients reach these goals. Keywords Calcium oxalate; Urinary Stone; Traditional Chinese medicine, Wu-Ling-San Formula; Nephrolithiasis. 17.
(24) Ver.1.4. 16/May/2007. Γᡏ၂ᡍہቩ ذइۺᙴଣࣴزीฝਜ. ԃ. ࡋǺΐΜϤ. ीฝӜᆀǺύᛰϖऴණჹለ่້ҡޣϐ่ҡ ߦӢηϷڋӢηޑቹៜ. ࣴزख़ᗺǺɍՋᙴᖏزࣴɍύᙴࣴزɎύՋᙴ ่ӝࣴز. ҙፎൂՏǺذइۺᙴଣֿݜѦࣽ. Ь ΓǺ݅ػቼ. ᙴৣᛝӜǺ 18.
(25) ذइۺᙴଣΐΜϤԃࡋਢࣴزीฝਜ! ύЎǺύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ. ीฝӜᆀ. ीฝጓဦǺ. मЎǺ! The influence of Wu-ling-San on the promotive and inhibitory factors for stone. formation in patients with calcium oxalate stone ՉൂՏ ذइۺᙴଣֿݜѦࣽ ࣴزሦୱ ύՋᙴ่ӝࣴز. ीฝᜪձ. Ɏཥቚीฝ. ɍុۯीฝ. Ӣֿၡ่ҡࢂଯൺวϐ੯ੰǴӵคϷਔϐೀǴᇸ߾ੵภǵՈֿǴख़߾Їଆ ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁჴࣁ؈ख़ϐॄᏼ 1ǹҁჴᡍϐҞޑ ࣴزख़ᗺ. ջࣁᔈҔύाϖऴණǴࣴځزჹܭൺวࠠለ่້ҡޣϐ่ҡߦϷڋӢηϐቹ ៜǹаයפрୋբҔեЪԖਏϐБٰݤႣ่ٛҡϐൺวǴаᅽቶεϐ่ҡੰဂǶ. ीฝ܄፦ ɍ୷ᘵ. ɎᔈҔࣴز Ծ. Չයज़. ɍزࣴೌמ. 96/7/1. ɍೌמቶ. ଆ. ҁԃࡋीฝǺ. ɍՉࡹଛӝ. ɍځд. Ծ. 96/7/1. ଆ. Կ. 97/6/30. З. ӄำीฝǺ Կ. 96/12/31 З. ӄԃीฝǺཥѠჾϖΜѤѤίԭΒΜϡ ԃ ࡋ. ࣴ زҙፎߎᚐ Ьᆅᐒᜢ Չीฝ Չीฝ ፎ༤ΠӈσՉԃࡋϐਡۓኧǵҁԃࡋϐҙፎኧǵаࡕӚ ਡߎۓᚐ ۓݤႣᆉ ،ᆉኧ ԃࡋϐႣኧ. ΓΚ ȐΓ. Γ٣. ୍ ᆢៈ ਓၮ ഢ ᆅ. ȑ 96 ԃ ၮҔ. 3. 544120. 15000. ɎԾՉࣴ ز100 ʘ д. ɍࣚૼہ. ʘ. 529120 ɍૼہᏢࣚ. ʘ. ɍೌמЇ. ʘ. БԄ. ɍځ. ЍрҞ. ɍதЍр! ! ! ! ! щϡȐ! ! ʘȑ. Ⴃԋ݀. ϭೌמ౽ᙯ. ৎ. ɍೌמЇ. . ɍ୍ܺೌמ. ৎ. ɍೌמൔ. . ϭճᕇள. . ɍ ҹ . . ɎፕЎว߄. 1 ጇ. ɍཥ ౢ ࠔ. . ϭၗૻᘉණ. Γ. ;Γωػ. Γ. ɍځ. ʘ ɍၗҁЍр! ! ! ! ! щϡȐ! ! ʘȑ. д. ीฝЬ ݅ػቼ Γ. ᙍᆀ Ьݯᙴৣ. ႝ၉. 0966230701 E-Mail [email protected] om.tw. ीฝՉ ݅ػቼ ᖄ๎Γ. ႝ၉ 0966230701. . 047296805. 19. E-Mail [email protected] om.tw.
(26) ມǵीฝᄔाǺፎᄔॊҁीฝϐҞޑᆶჴࡼБݤϷᜢᗖຒ. ύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ ύЎᄔाᇥܴ ֿၡ่ҡࢂԛֿܭၡགࢉǴಃΒதֿࣽݜޑـ੯ੰǴՠځԋӢޑፄᚇǵ ݯᕍ֚ޑᜤǵᙴᕍԋҁޑǴࠅᇻεֿܭၡགࢉǶᏵߥӺीǴѠӦԖ 5 Կ 10ʝޑΓමᑡ่ڙ҅܈ҡϐधǶԖъаੰޑΓ ܭ5 Կ 10 ԃ໔ ൺวǶԃ 15ʘൺวǶൺวӧΎԃϣଯၲ 60%Ƕ1 Ӣֿၡ่ҡࢂଯൺวϐ੯ੰǴӵคϷਔϐೀǴᇸ߾ੵภǵՈֿǴ ख़߾Їଆ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁჴࣁ؈ख़ϐॄ ᏼǹҁჴᡍϐҞޑջࣁᔈҔύᛰϖऴණ 9-10Ǵࣴځزჹܭൺวࠠለ่້ҡ ޣϐ่ҡߦϷڋӢηϐቹៜ 11ǹаයפрୋբҔեЪԖਏϐБٰݤႣٛ ่ҡϐൺวǴаᅽቶεϐ่ҡੰဂǶ ჴᡍБࣁݤჴᡍಔ 40 ΓǴϖऴණ 2g ВΟԛࡕܺҔǴӅܺҔΟঁДǴ ٠ӭസНᆢВֿໆ>2000ccǶჹྣಔ 40 ΓǴ๏ϒӼኃᏊ 2g ВΟԛࡕ ܺҔǴӅܺҔΟঁДǴ٠ӭസНᆢВֿໆ>2000ccǶᢀჸܺځᛰϷܺᛰ ࡕکΟঁДϐՈనᔠǵֿనᔠǵဎ X ӀϷ᠌ຬॣݢᔠϐᡂϯǴࢂ ցԖཥғԋϐ่ҡϷܭՈనᆶֿనύࢂցౢғᡂϯǶ ीϩճҔ SPSS ೬ᡏՉ t-test ीǴp ॶ<0.05 ᇡࣁܭीᏢڀԖᡉ 20.
(27) ϐৡ౦Ƕ ᜢᗖຒǺϖऴණǵ่ҡႣٛǵለ่້ҡ. 21.
(28) ୖǵीฝϣ ǵीฝጔଆǺፎ௶ॊҁीฝౢғϐङඳϷख़ा܄ ֿၡ่ҡࢂԛֿܭၡགࢉǴಃΒதֿࣽݜޑـ੯ੰǴՠځԋӢޑፄᚇǵ ݯᕍ֚ޑᜤǵᙴᕍԋҁޑǴࠅᇻεֿܭၡགࢉǶᏵߥӺीǴѠӦԖ 5 Կ 10ʝޑΓමᑡ่ڙ҅܈ҡϐधǶԖъаੰޑΓ ܭ5 Կ 10 ԃ໔ ൺวǶԃ 15ʘൺวǶൺวӧΎԃϣଯၲ 60%Ƕ1 ϖऴණܭύᙴϐᔈҔࣁНဍϐᏊǴᖐΥНྒྷϣଶ܌ठНဍيख़ǵλߡ όճǴࣣё٬ҔǴᖏҔܭགߵԖ༾ǵαǵཀྵǵλߡόճǴჹ࡚ܭ ᄌ܄ݹǵݹطǵᆮાݹǵ࡚܄ဉगݹǵНᘞǵНဍ܈ဎЋೌࡕ௨ֿ֚ᜤ֡ ԖਏǶ ӧжᛰᏢБय़ǴϖऴණڀԖճֿϷלբҔ 9-10ǶճֿբҔёߦ ֿݜၰ่ҡ௨рǴځύऴǵἐऴǵқҀǵᐛᘞ֡ԖճֿբҔǶԶਦ݄ᙖׯ๓ ՈనൻᕉǴЀࢂځ᠌ՈనൻᕉǴуமճֿբҔ 9-10Ƕ ЪלբҔёڋགࢉ ่܄ҡԋǴځύਦ݄ჹࢬՉ܄གߵੰࢥǵݹޤౚǵฟ੯ఎǵεဉఎ ԖբҔǴऴᎇගనჹߎՅဟౚǵεဉఎԖڋբҔ 9-10ǶќѦ ਦ݄ǵᐛᘞჹဉगѳྖԼԖှยբҔǴёᔅշᒡֿᆅѳྖԼܫǴߦֿݜၰ ่ҡ௨р 9-10Ƕ ԜѦӧύ୯ᙴᛰεᏢഋЎᲑ௲ϐࣴزΨჴǴϖऴණܭᡏѦ၂ᡍϐύǴ ޑዴԖڋለ่້ԋǵᏉکԋߏϐфਏǶ ܭЎύ 11Ǵለ่້ҡϐߦӢηхࡴΑֿనύϐ້ᚆηǵለਥᚆηǴ 22.
(29) ڋӢηхࡴΑֿనύϐᗔᚆηǵᘗᘔለਥᚆηǶ Ӣֿၡ่ҡࢂଯൺวϐ੯ੰǴӵคϷਔϐೀǴᇸ߾ੵภǵՈֿǴ ख़߾Їଆ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁჴࣁ؈ख़ϐॄ ᏼǹҁჴᡍϐҞޑջࣁᔈҔύᛰϖऴණǴࣴځزჹܭൺวࠠለ่້ҡޣϐ ่ҡߦϷڋӢηϐቹៜ 11ǹаයפрୋբҔեЪԖਏϐБٰݤႣ่ٛҡ ϐൺวǴаᅽቶεϐ่ҡੰဂǶ. 23.
(30) ΒǵीฝҞޑǺፎ⒕煭␆浣⒦承ҁीฝ܌ाၲԋϐҞаϷ܌ाֹԋϐπբ ҞǴᔈᗉխݱޜϐ௶ॊǶ ҁࣴޑزҞޑΏύᛰϖऴණჹֿၡ่ҡႣٛޑਏ݀Ƕҁࣴࣁزය ԃǴஒϩࣁΟයǴයႣۓՉπբҞӵΠǺ ಃය(1-2 ঁД)ǺύᛰᇙբϷࣴزշ૽ግǴ٬ࣴزշዕੱރୢ߄ڔǴ٠ ዴۓբࢬำǶ ಃΒය(2-9 ঁД)ǺᑔᔠੰǴ٠ᆶᛰނǶՏۓޣයௗڙֿၡ่ҡຑǴ ٠ܜՈϷᡍֿǴаᢀჸܺځᛰࡕϐᡂϯǶ ಃΟය(10-12 ঁД)ǺᖏኧᏵǴՉीϩǴ٠ኗቪࣴزൔ. 24.
(31) ΟǵჴࡼБݤϷՉᡯǺፎᇡาᎅࣔჴࡼҁԃࡋीฝ܌௦ҔϐБݤϷᡯǴࣴ زीฝᔈ၁ಒᇥܴࣴزीǵၗԏϷϩБݤǶ 9 ࣴزीǺ ¾ ՉБԄǺProspective Study ¾ ჹྣಔᒿᐒϩଛϐѳՉಔࣴز ¾ ޓϯБԄǺൂޓ ¾ ᒿᐒϩࢴǺ٩ႝတኧ߄ᒿᐒᒧڗǴ٠ᇙԋߞ࠾ੰٮΓڗܜǶ 9 ڙ၂ޣǺ ɊᒧྗǺ 1.ለ่້ҡੰ(ϐϐ่ҡϩࣁለ่້ҡ) 2.Ԗੱރϐ่ҡൺวεٿܭԛ Ɋ௨ନྗ 2-8Ǻ 1.. ൾ܄ဍዦٳମᙯ౽. 2.. ୋҘރဏфૈϗ. 3.. ᆒઓ੯. 4.. λᆅለՈੱ. 5.. سֿݜ่ᄬ౦த. 6.. ᄌֿ܄ၡགࢉ. 25.
(32) 7.. ମ፦౧ޣ. 8.. ภ॥. 9.. ᄌ܄ဎᘞ. 10. ᚶѫ 11. طфૈό٫ޣ ɊʳଏрᐒڋǺ 1. ӵڙ၂ܭޣ၂ᡍύวғ่ҡൺวϐݩǴջಖЗҁ၂ᡍǴ٠җ ीฝЬΓ٩ֿၡ่ҡೀচ߾ࣁִځ๓ೀǶ 2. ӵڙ၂ܭޣ၂ᡍύวғᚶѫϐݩǴᗨฅϖऴණۘคठ྾जϐ ൔᏤǴՠ㵝ӼӄଆـǴջಖЗҁ၂ᡍǶ 3. ӵڙ၂ܭޣ၂ᡍύวғᅪ՟ჹϖऴණၸ௵ϐݩǴջಖЗҁ၂ ᡍǴ٠җीฝЬΓ٩ᛰނၸ௵ೀচ߾ࣁִځ๓ೀǶ Ɋʳڙ၂ޣኧҞǺ 80 ΓǴх֖ჴᡍಔ 40 ΓϷჹྣಔ 40 Γ. 26.
(33) 9 ࣴزБݤǺ 9 ჴᡍಔ: 1. ϖऴණ 2g ВΟԛࡕܺҔǴӅܺҔΟঁДǶ ӭസНᆢВֿໆ>2000ccǶ 9 ჹྣಔ: ӼኃᏊ 2g ВΟԛࡕܺҔǴӅܺҔΟঁДǶ ӭസНᆢВֿໆ>2000ccǶ. 9 ᛰނёૈϐୋբҔ 9Ǻ ¾ Ҟёٮ᎙ϐЎǴჹܭϖऴණ٠คୋբҔϷόؼϸᔈϐวғǶ ¾ ϖऴණϐᐛᘞǴځᆯણ 1~2g/kg షܭႩύᗯεқႵΟঁДǴܭᡉ༾᜔ ΠطಒझϷ߈Ԕλᆅϐᡂ܄ǴՠԜჴᡍ࠻ᏊໆᇻεܭݯᕍᏊໆǶՠ 㵝ӼӄଆـǴطфૈό٫ࡌޣϮуΕԜ၂ᡍǶќуΕҁ၂ᡍϐڙ၂ ޣѸௗۓڙයϐطфૈᔠǶ ¾ ϖऴණҞܭё᎙ϐЎǴ٠คठ྾ज܄ǴՠࣁӼӄଆـǴܭჴᡍ ය໔ᚶѫޣǴಖЗҁჴᡍǶ ¾ ӢӚΓᡏ፦όӕǴҺՖᛰ֡ނԖёૈวғၸ௵ϸᔈǴރੱځхࡴܺᛰࡕआ ੶ǵҜጥཝǵⶁഞ੶ǵࣗ߾֚֎ڥᜤǴӵԖၸ௵ຝวғǴፎҥջଶЗ ܺᛰᆶीฝЬΓೱ๎Ƕ. 27.
(34) 9 ၂ᡍ܌ाϐᖏᢀჸǺ Ε၂ᡍϐ୷ҁᔠхࡴ 2-8Ǻ ՈనᔠǺGOT, GPT, BUN, CR, NA, K, CL, UA, SUGER(AC),CA,P ֿనᔠǺ24HRS URINE Ccr, CALCIUM, Mg, URIC ACID, CITRATE, OXALATE,P ဎ X ӀϷ᠌ຬॣݢᔠǶ ၂ᡍঁДϷΟঁДࡕ 2-8Ǻ ՈనᔠǺGOT, GPT, BUN, CR, NA, K, CL, UA, SUGER(AC),CA,P ֿనᔠǺ24HRS URINE Ccr, CALCIUM, Mg, URIC ACID, CITRATE, OXALATE,P ဎ X ӀϷ᠌ຬॣݢᔠǶ 9 ीϩǺ ճҔ SPSS ೬ᡏՉ t-test ीǴp ॶ<0.05 ᇡࣁܭीᏢڀԖᡉϐৡ౦Ƕ. 28.
(35) Ѥǵख़ाୖԵЎǺ References •. 1.Lee, Y.H., W.C. Huang, J.Y. Tsai, C.M. Lu, W.C Chen., M.H. Lee, H.S. Hsu, J.K. Huang and L.S.Chang. Epidemiological studies on the prevalence of upper urinary calculi in Taiwan. Urol. Int. 68: 172-177, 2002.. •. 2. Whalley, N. A., Meyers, A. M., Martins, M. and Margolius, L. P.: Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia. Brit. J. Urol., 78: 10, 1996.. •. 3. Cicerello, E., Merlo, F., Gambaro, G., Maccatrozzo, L., Fandella, A., Baggio, B. and Anselmo, G.: Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J. Urol., 151: 5, 1994.. •. 4. Hofbauer, J., Hobarth, K., Szabo, N. and Marberger, M.: Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis: a prospective randomized study. Brit. J. Urol., 73: 362, 1994.. •. 5.Ettinger, B., C.Y. Pak, J.T. Citron, C. Thomas, B. dams-Huet and A. Vangessel. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J. Urol. 158: 2069–73, 1997.. •. 6. Barcelo, P., Wuhl, O., Servitge, E., Rousaud, A. and Pak, C. Y. C.: Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J. Urol., 150: 1761, 1993.. •. 7. Freitas, A.M., N. Schor, M.A. Boim. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU. Int. 89: 829-834, 2002.. •. • •. 8. Kato Y, Yamaguchi S, Yachiku S, Nakazono S, Hori J, Wada N, Hou K. Changes in urinary parameters after oral administration of potassium-sodium citrate and magnesium oxide to prevent urolithiasis. Urology. Jan;63(1):7-11.2004 9. ࣥࡲ؟ΕࣥࡲؓΕࣥན Κխᢐᢐᖂ ഏمᒳ塢 1995Κ228-9 10. ࣔޘΚֱᕪᖂ ഏمխഏ᠔ᢐઔߒࢬ 1999: 201-202. • •. 11. Patrick C. Walsh; Alan B. Retik .Campbell's urology. 8th ed 2002: 3230-3260 12. UTSUNOMIYA MΔKOIDE TΔYAMAGUCHI SΔet al.The effect of kompou medicine on the growth and aggregation of calcium oxalate crystal in vitro. Acta Urol Jpn. 37 ΰ10α:1097.1101.1991.. •. 13. KAWAMURA KΔMORIYAMA MΔNAKAJIMA CΔet al.The inhibi-tory effects of Takusha on the formationΔgrowth and aggregation of calcium oxalate crystal in vitro..Acta. 29.
(36) Urol Jpn.39(8α:695-700.1998. •. 14.YASUI TΔFUJITA KΔSATOMΔet al.The effect of takushaΔa kampo medicineΔon renal stone formation and osteopontin expression in a rat urolithiasis model. .Urol Res..27 ΰ3α:194-199.1999.. 30.
(37) ϖǵԃࡋႣۓࡋǺа Gantt Chart ߄ҢҁԃࡋϐՉࡋǴຑᥛࢤૠᓮჄ٨։ڣ ച۩ၞ৫֗ีᗨၞ৫Ƕ ڣ৫ Дԛ ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ. ಃ ഢຏ. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Д. Д. Д. Д. Д. Д. Д. Д. Д. Д. Д. Д. πբҞ ύᛰྗഢ ࣴزշ૽ግ ᑔᒧڙ၂ޣ ۓයܜՈ ֹԋӚෳۓ ϩኧᏵ ኗቪൔ. πբՉࡋಕीԭϩК 5%. 10% 15% 20% 30% 40% 50% 60% 70% 80% 90%. ՉࡋಕीԭϩК. ϩԃಕᑈࡋК. 31. 100%.
(38) ϤǵΓΚଛǺᜪձឯፎϩձ༤ቪЬΓǵڐӕЬΓǵࣴزǵҺࣴز շǵঋҺࣴزշǶࣴزշӵ҂ዴۓΓᒧǴۉځӜឯё༤ቪࡑငǶ ЬΓǵڐӕЬΓǵࣴزሡߕԄΜѤϐᏢᐕᇥܴਜǶ. ᜪ. ձ ۉ. ЬΓ. Ӝ. ᙍ ӧҁीฝϣᏼҺϐ␆浣πբ܄፦ǵҞϷጄൎ. ݅ػቼ Ьݯᙴৣ ჴᡍϐՉǵΓ૽ግǵၗǵीϩǵ ੰᐕଓᙫǵፕЎኗቪ. ڐӕЬ. ݅प ֿ ݜѦ ࣽ ՉࡹڐፓǵፕЎࡰᏤ. Γ ঋҺࣴ. ߏ ࡑင. ၗǵीϩǵੰᐕଓᙫ. زշ. 32.
(39) ᜪ ձ ۉ. Ȑ v ȑЬΓ. Ӝ. ݅ػቼ. Ꮲ. Ȑ ȑڐӕЬΓ. ܄ձ. ت. Ȑ. ȑࣴزΓ. рғԃДВ. 1974/12/12. ᐕȐځख़ाޣ༤ቪȑ Ꮲ. ਠ. Ӝ. ᆀ. Ꮲ. ύ୯ᙴᛰεᏢ. Տ. ᙴᏢγ. ଆّԃД. ߏ. 1993/7~2000/6. ֿݜѦࣽ Ѡчଭିᙴଣ . Րଣᙴৣǵ ᕴᙴৣ. ֿݜѦࣽ੯ੰ. 2000/7~2005/6. ᐕȐፎࡪ୍ܺਔ໔Ӄࡕׇ༤ቪᆶගीฝԖᜢϐᐕȑ ܺ. ୍. ᐒ. ᄬ. Ϸ. ൂ. Տ. ᙍ. ҺǺᄆϯذᙴଣֿݜѦࣽ. ϐ࣬ᜢࣴزीฝ ߈ϖԃϣමୖᆶ. ी. ฝ. Ӝ. ᆀ. Ьݯᙴৣ. ᆀ. ଆّԃД 2005/7~ّϞ. ଆّԃД. ᅽѭষМᚯੴᝄख़ࡋࡰኧϐྗዴࡋ ࣴز. ಃբޣ. ଭିᙴଣ. 2003/7~2005/ 7. ମࣧ๚ϣচว܄రЃՈᆅዦࣴز. ಃբޣ. ଭିᙴଣ. 2001/6~2003/ 6. ीฝЍජᐒᜢ. ଆّԃД. ीฝЍජᐒᜢ. ଆّԃД. ी. ฝ. Ӝ. ᆀ. ᜢࣴزीฝ ҙፎύϐ࣬. ीฝЍජᐒᜢ. ᜢࣴزीฝ Չύϐ࣬. ीฝϣᏼҺπբ. ी. ฝ. Ӝ. ᆀ. . . ҙ ፎ . ࣴزΓᛝകǺ. ЬΓᛝകǺ 33.
(40) ᜪ. ձ. ۉ. Ӝ. Ȑ. ȑЬΓ. ݅प. Ꮲ. Ȑ vȑڐӕЬΓ ܄ձ. ت. Ȑ. ȑࣴزΓ. рғԃДВ. ᐕȐځख़ाޣ༤ቪȑ Ꮲ. ਠ. Ӝ. ᆀ. Ꮲ. Տ. ଆّԃД. ύ୯ᙴᛰεᏢ. ᙴᏢγ. Ѡчଭିᙴଣ. ֿݜѦࣽ Րଣᙴৣǵ. ߏ. ֿݜѦࣽ੯ੰ. ᕴᙴৣ . ᐕȐፎࡪ୍ܺਔ໔Ӄࡕׇ༤ቪᆶගीฝԖᜢϐᐕȑ ܺ. ୍. ᐒ. ᄬ. Ϸ. ൂ. Տ. ᙍ. ҺǺᄆϯذᙴଣֿݜѦࣽ. ᆀ. ЬҺ. ฝ ߈ϖԃϣමୖ ᜢࣴزीฝ Չύϐ࣬. ी. ฝ. Ӝ. ᆀ. ी. ฝ. Ӝ. ᆀ. ीฝϣᏼҺπ բ. . . ଆّԃД 200~ّϞ. ीฝЍජᐒᜢ. ଆّԃД. ीฝЍජᐒᜢ. ଆّԃД. ᜢࣴزीฝ ҙፎύϐ࣬. Predictor of to Dutasteride therapy in Taiwan BPH patient. 500000. Sexuality and management of BPH with Alfuzosin (SAMBA). 500000. Sanofi Aventis company. 7/2006~6/200 7. ҙ ፎ . ीฝЍජᐒᜢ. ଆّԃД. ी. ฝ. Ӝ. ᆀ. ࣴزΓᛝകǺ. Taiwan continence 7/2006~6/200 society 7. ЬΓᛝകǺ. 34.
(41) ፄቩቩཀ(߄ـ96.03.02) ीჄӜᆀ. ύᛰϖऴණჹֿၡ่ҡႣٛϐᘳزࣴ܄. ЬΓ. ݅ػቼ. ୍ܺൂՏ/ᙍᆀ ذइۺᙴଣֿݜѦࣽ IRB ҙፎጓဦ 960202 ቩޣǺ 1. ٩ЬΓޑเᙟǴҁࣴޑزҞޑςҗᢀჸϖऴණڋᏊ่ҡޑൺวᙯࣁᢀჸ ϖऴණࢂցׯᡂֿޑޣύ่ҡڋӢηϷߦӢηǶჹࣴزीฝԶقǴ೭ ࢂࡐख़εׯޑᡂǶࡌЬΓࢂցزࣴׯ׳ᚒҞࣁ“ύᛰϖऴණჹለ่້ҡ ޣϐֿన่ҡߦӢηϷڋӢηޑቹៜ”ǴӵԜωૈଛӝࣴزҞޑǶӕਔ ЬΓѸஒֿၰ่ҡߦϷڋӢηޑЎԵၩܭीฝጔଆύǴᇥܴ ೭٤Ӣηჹֿ่ҡޑቹៜǶќѦǴᗨූࣴزҞޑςԖׯᡂǴՠीฝਜύࣴޑ زҞ(ޑP6)ǵीฝᄔाύزࣴޑҞ(ޑP4)Ϸڙ၂ޣӕཀਜύزࣴޑҞޑϐϣ ֡ሡख़ཥׯ׳Ƕ 2. ҁࣴزीฝޑҞޑςࣁׯ׳ᢀჸϖऴණჹ่ҡڋϷߦӢηޑቹៜǹӧเ ᙟύΨගډाᢀჸڙ၂ֿޣύᘗᘔለਥǵለਥǵ້ǵᕗޑᡂϯǴՠჴᡍБ ݤύ٠คෳֿۓύᕗϐҞǴࢂցѸံӈǶ. ቩޣΒǺ 1. IRB ቩཀ ـ2ǴPI ،ۓаᢀჸڙ၂ޣϐ”В”ֿໆǾीϩǴՠࣴز БݤΏ،ܺۓҔ 3 ঁДǴόֿޕనஒӵՖ௦ǻ. ᡏቩ่݀Ǻ! ɍӕཀ!!!!!5অ҅ࡕӕཀ!!!!ɍόӕཀ! ! ፎ،زࣴۓЬΓࢂցሡӈৢୖуΓᡏ၂ᡍہ! ɍሡӈৢ!!5όሡӈৢ! ሡӈৢচӢǺɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕ !. 35.
(42) ፄቩਢҙፎ߄(96.03.02) IRB ጓဦ. ीฝጓဦ. 960202. ԏЎВය ीฝᚒҞ. ύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ. ࣴزԋ. ύЎۉӜ. मЎۉӜ. ႝ၉/ϩᐒ. e-mail. ЬΓ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᖄ๎Γ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᡂ׳Ўҹ. Ɏीฝਜ. Ɏڙ၂ޣӕཀਜ Ɏঁਢൔ߄. ހҁ. Ver.1.2. Ver.1.2. Вය. 2/Mar/2007 2/Mar/2007. ڙ၂ޣΓ ኧ. 90 Γ. ಃԛଌቩВය. ଌቩԛኧ. ɍಃΒԛቩ ɎಃΟԛቩ ɍʳ ಃѤԛቩ. നࡕԛଌቩВය. ҙፎރᄊ. ɎזೲቩȐ༾λ൯ࡋᡂ׳ȑ ɍʳ ቩȐຬၸ༾λ൯ࡋᡂ܈׳ᡂޑ׳ᚒቹៜڙ၂ޑޣӒᓀ܄ȑ. IRB ཀـ. ٩ЬΓޑเᙟǴҁࣴޑزҞޑςҗᢀჸϖऴණڋᏊ่ҡޑൺวᙯࣁ ᢀჸϖऴණࢂցׯᡂֿޑޣύ่ҡڋӢηϷߦӢηǶჹࣴزीฝ ԶقǴ೭ࢂࡐख़εׯޑᡂǶࡌЬΓࢂցزࣴׯ׳ᚒҞࣁ“ύᛰϖऴණ ჹለ่້ҡޣϐֿన่ҡߦӢηϷڋӢηޑቹៜ”ǴӵԜωૈଛ ӝࣴزҞޑǶӕਔЬΓѸஒֿၰ่ҡߦϷڋӢηޑЎԵ ၩܭीฝጔଆύǴᇥܴ೭٤Ӣηჹֿ่ҡޑቹៜǶќѦǴᗨฅࣴزҞޑ ςԖׯᡂǴՠीฝਜύزࣴޑҞ(ޑP6)ǵीฝᄔाύزࣴޑҞ(ޑP4)Ϸڙ ၂ޣӕཀਜύزࣴޑҞޑϐϣ֡ሡख़ཥׯ׳Ƕ. PI ӣᙟ. 1. ςزࣴׯ׳ᚒҞࣁ“ύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷ ڋӢηޑቹៜȹǶ 2. ЎٰྍςቚӈܭीฝጔଆύǶ 3. ڙ၂ޣӕཀਜύزࣴޑҞޑϐϣςख़ཥׯ׳Ƕ. ɍʳ ЬΓЋн. Ver.1.2 2/Mar/2007. ᖴᖴாᝊϐཀـǼ 36. 96 ԃ 02 Д 02 В 96 ԃ 03 Д 04 В.
(43) অࡕׯ. 1.Ӣֿၡ่ҡࢂଯൺวϐ੯ੰǴӵคϷਔϐೀǴᇸ߾ੵภǵ ՈֿǴख़߾Їଆ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁჴࣁ ؈ख़ϐॄᏼ 2ǹҁ ҁჴᡍϐҞޑջࣁᔈҔύाϖऴණǴࣴځزჹܭൺว ࠠለ่້ҡޣϐ่ҡߦϷڋӢηϐቹៜǹаයפрୋբҔե ЪԖਏϐБٰݤႣ่ٛҡϐൺวǴаᅽቶεϐ่ҡੰဂǶ! (ीฝਜύزࣴޑҞ ޑp4ǵीฝᄔाύزࣴޑҞ ޑp5)! 3/!ܭЎύ 22Ǵ ለ่້ҡϐߦӢηхࡴΑֿనύϐ້ᚆηǵለਥ ᚆηǴڋӢηхࡴΑֿనύϐᗔᚆηǵᘗᘔለਥᚆηǶ! (ीฝਜύीฝጔଆ p5) 4/ҁჴᡍϐҞޑջࣁᔈҔύᛰϖऴණ. :.21. Ǵࣴ ࣴځزჹܭൺวࠠለ่້ҡ. ޣϐ่ҡߦϷڋӢηϐቹៜ 11ǹаයפрୋբҔեЪԖਏϐБ ٰݤႣ่ٛҡϐൺวǴаᅽቶεϐ่ҡੰဂǶ! )ڙ၂ޣӕཀਜύزࣴޑҞ ޑp1) IRB ཀـ. 3. ҁࣴزीฝޑҞޑςࣁׯ׳ᢀჸϖऴණჹ่ҡڋϷߦӢηޑቹ ៜǹӧเᙟύΨගډाᢀჸڙ၂ֿޣύᘗᘔለਥǵለਥǵ້ǵᕗޑ ᡂϯǴՠჴᡍБݤύ٠คෳֿۓύᕗϐҞǴࢂցѸံӈǶ. PI ӣᙟ. ܭጓቪਔᒪᅅǴςံǴᖴᖴாᝊϐཀـǼ. অࡕׯ. Ε၂ᡍϐ୷ҁᔠхࡴ 3.9Ǻ! ՈనᔠǺHPU-!HQU-!CVO-!DS-!OB-!L-!DM-!VB-! TVHFS)BD*-DB-Q! ֿనᔠǺ35IST!VSJOF!Dds-!DBMDJVN-!Nh-!VSJD!BDJE-! DJUSBUF-!PYBMBUF-Q Q! ဎ Y ӀϷ᠌ຬॣݢᔠǶ! ၂ᡍঁДϷΟঁДࡕ 3.9Ǻ! ՈనᔠǺHPU-!HQU-!CVO-!DS-!OB-!L-!DM-!VB-! TVHFS)BD*-DB-Q! ֿనᔠǺ35IST!VSJOF!Dds-!DBMDJVN-!Nh-!VSJD!BDJE-! DJUSBUF-!PYBMBUF-Q Q! ဎ Y ӀϷ᠌ຬॣݢᔠǶ! (ीฝਜύीฝጔଆ p9). IRB ཀـ. IRB ቩཀ ـ2ǴPI ،ۓаᢀჸڙ၂ޣϐ”В”ֿໆǾीϩǴՠ ࣴزБݤΏ،ܺۓҔ 3 ঁДǴόֿޕనஒӵՖ௦ǻ. PI ӣᙟ. চ߾ӵ݀ڙ၂ޣёᒵ 3 ঁДύϐВֿໆӆуаѳ֡ϐࣁന٫Ǵՠ ԵໆډՉय़ჹڙܭ၂ޣၨᜤၲԋǴࡺᔕаܺᛰϷܺᛰࡕکΟঁ 37.
(44) Дϐ 24 λਔֿໆࣁྗ(Ӣڙ၂ޣѸԏܺᛰϷܺᛰࡕکΟঁДϐ 24 λਔֿనڙᔠ*ǶᖴᖴாᝊϐཀـǼ. 38.
(45) ፄቩቩཀ(߄ـ96.03.16) ीჄӜᆀ. ύᛰϖऴණჹለ่້ҡߦޣӢηϷڋӢηޑቹៜ. ЬΓ. ݅ػቼ. ୍ܺൂՏ/ᙍᆀ ذइۺᙴଣֿݜѦࣽ IRB ҙፎጓဦ 960202 ቩޣǺ 1.ҁࣴزፄቩς٩ाࣁׯ׳ȸύᛰϖऴණჹለ่້ҡߦޣӢηϷڋ ӢηޑቹៜȹǴՠࢂڙ၂ޣӕཀਜϐႣය၂ᡍਏ݀(p2)ࠅϝߥ੮ࣁȸ෧ե่ҡൺ วϷ่ҡϐғԋȹǴԜᔈঅ“ࣁׯϖऴණёफ़ե่ҡғԋӢη܈ගϲ่ҡڋ Ӣη”Ƕ 2.ࣴزीฝࡕׯ׳ǴࣴزᚒҞޑमЎᆶύЎόֹӄ಄ӝ(ـीฝਜ p3)ࡌࣁׯ׳ ȸThe influence of Wu-ling-San on the promotive and inhibitory factors for stone formation in patients with calcium oxalate stone”ǴၨࣁӝەǶ. ቩޣΒǺ 1. 24h ϐֿనᇆǴஒӵՖᆶڙ၂ޣၲԋӅǻ. ᡏቩ่݀Ǻ! ɍӕཀ!!!!!5অ҅ࡕӕཀ!!!!ɍόӕཀ! ! ፎ،زࣴۓЬΓࢂցሡӈৢୖуΓᡏ၂ᡍہ! ɍሡӈৢ!!5όሡӈৢ! ሡӈৢচӢǺɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕɕ ! !. 39.
(46) ፄቩਢҙፎ߄(96.03.16) IRB ጓဦ. ीฝጓဦ. 960202. ԏЎВය ीฝᚒҞ. ύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ. ࣴزԋ. ύЎۉӜ. मЎۉӜ. ႝ၉/ϩᐒ. e-mail. ЬΓ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᖄ๎Γ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᡂ׳Ўҹ. Ɏीฝਜ. Ɏ ڙ၂ ޣӕ ཀ Ɏঁਢൔ߄. ɍʳ ЬΓЋн. ਜ ހҁ. Ver.1.3. Вය. 16/Mar/2007 16/Mar/2007. ڙ၂ޣΓ ኧ. 90 Γ. ಃԛଌቩВය. ଌቩԛኧ. ɍಃΒԛቩ ɍಃΟԛቩ ɎಃѤԛቩ. നࡕԛଌቩВය. ҙፎރᄊ. ɎזೲቩȐ༾λ൯ࡋᡂ׳ȑ ɍʳ ቩȐຬၸ༾λ൯ࡋᡂ܈׳ᡂޑ׳ᚒቹៜڙ၂ޑޣӒᓀ܄ȑ. IRB ཀـ. ቩޣǺ ҁࣴزፄቩς٩ाࣁׯ׳ȸύᛰϖऴණჹለ่້ҡߦޣӢηϷ ڋӢηޑቹៜȹǴՠࢂڙ၂ޣӕཀਜϐႣය၂ᡍਏ݀(p2)ࠅϝߥ੮ࣁ ȸ෧ե่ҡൺวϷ่ҡϐғԋȹǴԜᔈঅ“ࣁׯϖऴණёफ़ե่ҡғԋ Ӣη܈ගϲ่ҡڋӢη”Ƕ. PI ӣᙟ. Ⴃය၂ᡍਏ݀ς”ࣁ҅׳ϖऴණёफ़ե่ҡғԋӢη܈ගϲ่ҡڋӢ η”Ƕ ᖴᖴாᝊϐཀـǼ. IRB ཀـ. ࣴزीฝࡕׯ׳ǴࣴزᚒҞޑमЎᆶύЎόֹӄ಄ӝ(ـीฝਜ p3)ࡌ ࣁׯ׳ȸThe influence of Wu-ling-San on the promotive and inhibitory factors for stone formation in patients with calcium oxalate stone”Ǵၨࣁӝ ەǶ. Ver.1.3. Ver.1.3 16/Mar/2007. 40. 96 ԃ 02 Д 02 В 96 ԃ 03. Д 16 В.
(47) PI ӣᙟ. मЎᚒҞςࣁׯ׳ȸThe influence of Wu-ling-San on the promotive and inhibitory factors for stone formation in patients with calcium oxalate stone” ᖴᖴாࡰޑᏤǼ. IRB ཀـ. ቩޣΒǺ 24h ϐֿనᇆǴஒӵՖᆶڙ၂ޣၲԋӅǻ. PI ӣᙟ. ஒҗ PI ᒃԾᆶڙ၂ޣှញ٠ྎ೯ǴӢҁჴᡍҞࣁޑᢀჸϖऴණࢂցёफ़ ե่ҡғԋӢη܈ගϲ่ҡڋӢηǴࡺѸܭ၂ᡍϷکΟঁДਔ ԏ 24hr ֿనڙᔠǴԜှញϐπբϷӅѸܭᛝुڙ၂ޣӕཀਜϐ ֹԋǴӵڙ၂ޣϝคݤଛӝǴջคݤуΕҁ၂ᡍीჄǶ ᖴᖴாࡰޑᏤϷᝊϐཀـǼǼ. 41.
(48) ᐉᤜ࣠ຏव।. IRB ᒳᇆ. 960202. ૠټጠ. խᢐնཋኙ౻Ꭸၩف൛ृআၞڂ֗ڂࠫލऱᐙ. ᄎᤜཚڻ. 96 ڣ৫รԲڻᄎᤜ. ᐉᤜ࣠. ɍʳ μுνΚு࿇ءᄎٵრᜯݩᇢ᧭ᢞࣔ Ϯ. Գ. ᄎᤜֲཚ. ࣥߛᐜ. 96 ڣ04 ִ 21 ֲ. μଥإ৵ுν Κଥإ৵ΔᆖᐉࡡᐉຏመΔு࿇ٵრᜯݩ ᇢ᧭ᢞࣔ. ɍʳ μଥإ৵ᓤᐉνΚ༼IRBՀڻᄎᤜᐉ ɍʳ μլுνΔطΚ_________________ ɍʳ ᓮૠԳ٨ஂףԳ᧯ᇢ᧭ࡡᄎᄎᤜΔطΚ__________ ދปધᙕ. ᚨଥإ. 1. 2.. ு__0__ป ଥإ৵ு__11_ป. 3.. ଥإ৵ᓤᐉ__0__ป. 4.. լு__0__ป. 5.. ࣋ඵ__0__ป. ૠΚ 1. ઔߒૠࡳطԿิิࠟګޏΚኔ᧭ิնཋΔኙᅃิڜᐣᕪΖᑌ ءᑇ ิޢط30 ԳΔ᜔٥ 90 ԳΔ ګޏ2 ิΔ ิޢ40 ԳΖ 2. նཋኙ࣍ቃفய࣠ऱ֮ܫᓮ٨נΖ 3. ԵΕඈೈයٙΔ࠹ᇢृಯנᖲࠫᓮᇖךᎅࣔΖ ࠹ᇢृٵრ 1. ֮ဲشڗՑ֏Ζ 2. ኙ࣍౻ᎨၩفऱఐԳΔិ឴Ꭸሧऱए᛭ڶԫࡳګயΔ܀նཋऱ ए᛭ய࣠ؾছࡸ˿˿˸̊ آˀ˷̂˶̈̀˸́̇Δڕ܃۶࠹ڇᇢृٵრՂ༉ᨃ࠹ ᇢृԱᇞףהԵᇢ᧭৵ױڶ౨൷࠹նཋΕࢨڜᐣᕪۖॺិ឴Ꭸ ሧए᛭ΔۖᣋრףԵઔߒΛնཋए᛭ऱய࣠ΕᢞᖕؘႊܧΖ 3. ܫव࠹ᇢृΔٺጟֱऄऱቃګயڕ۶ΛٵழᨃהवሐΔףԵᇢ ᧭৵լਢ۞הطաެࡳהୌԫጟए᛭ֱऄΔۖਢૠԳאᙟ ᖲֱڤ։Δຍࠄᇷಛך։ܫवΖ 4. ኙွܶץՖࢤΔ࣠ڕᡖ؋༉ඈೈΔೈԱگூছඈೈᡖ؋Δگூ৵ᇢ ᧭ཚၴؘႊܫव࠹ᇢृආ࠷ᝩ؋ൻਜΔڂնཋኙ઼ࠝऱᐙآ वΖ 42.
(49) 5. ʻԲʼቃཚᇢ᧭ய࣠Κψնཋ܅૾ױڂګسفࢨ༼֒ڂࠫލف ω Δ۶ᘯڂګسفΕڂࠫލຍᇩاฒլᚩΖᓮଥإΖਢ ܡଥګޏϙቃف༚࿇ࢨ૾܅ف༚࿇ऱᖲϙΖ 6. ࠹ᇢृٵრՂᏁᏺ ˇ˅ ף՛ழऱᜤሽᇩΖ ᓤᐉ࿓ݧ. 1. ᓮࠉՂ૪ᐉრߠΔאψᓤᐉூعᓮ।ωດයڃΖ 2. ଥޏΔؘႊΚאψษ ษ᧯+ڗցጻࢍ+ࢍᒵωᑑقΖ 3. ᓤᐉழᓮലಬᐉ֮ٙ堚ΕᓤᐉعᓮΕଥإ৵ૠΕ࠹ᇢृٵ რԫڤԿٝബڃԳ᧯ᇢ᧭ࡡᄎఽΖ 4. ڶڕጊംᓮၞԫޡፖ⊺ટெᜤΔሽᇩΚ7256166 ᠏ 66088Ζ. ٚࡡټ. ֲټཚ. 43. ___ֲ___ִ___ڣ.
(50) ፄቩਢҙፎ߄(96.05.16) IRB ጓဦ. ीฝጓဦ. 960202. ԏЎВය ीฝᚒҞ ύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ ࣴزԋ ύЎۉӜ. मЎۉӜ. ႝ၉/ϩᐒ. e-mail. ЬΓ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᖄ๎Γ. ݅ػቼ. ! Eugene Lin!. 0966230701. [email protected]. ᡂ׳Ўҹ Ɏीฝਜ. Ɏ ڙ၂ ޣӕ ཀ Ɏঁਢൔ߄. ɍʳ ЬΓЋн. ਜ ހҁ. Ver.1.4. Вය. 16/May/2007 16/May/2007. Ver.1.4. Ver.1.4 16/May/2007. ڙ၂ޣΓ 80 Γ ኧ. ಃԛଌቩВය. ଌቩԛኧ ɍಃΒԛቩ ɍಃΟԛቩ ɎಃѤԛቩ. നࡕԛଌቩВය. 96 ԃ 02 Д 02 В 96 ԃ 05 Д 16 В. ҙፎރᄊ ɎזೲቩȐ༾λ൯ࡋᡂ׳ȑ ɍʳ ቩȐຬၸ༾λ൯ࡋᡂ܈׳ᡂޑ׳ᚒቹៜڙ၂ޑޣӒᓀ܄ȑ IRB ཀزࣴ ـीҗচۓΟಔׯԋٿಔǺჴᡍಔϖऴණǴჹྣಔӼኃᏊǶኬҁኧ җಔ 41 ΓǴᕴӅ :1 ΓǴׯԋ 3 ಔǴಔ 51 ΓǶ! PI ӣᙟ. ीฝਜϩςঅࣁׯǺჴᡍБࣁݤჴᡍಔ 51 ΓǴϖऴණ 3h ВΟԛ ࡕܺҔǴӅܺҔΟঁДǴ٠ӭസНᆢВֿໆ?3111ddǶჹྣಔ 51 ΓǴ๏ϒӼኃᏊ 3h ВΟԛࡕܺҔǴӅܺҔΟঁДǴ٠ӭസНᆢ Вֿໆ?3111ddǶ ᖴᖴாᝊϐཀـǼ. IRB ཀ ـϖऴණჹܭႣ่ٛҡਏ݀ޑЎൔፎӈрǶ!. PI ӣᙟ. •. ीฝਜ Sfgfsfodf ϩǺ • 9. ࣥࡲ؟ΕࣥࡲؓΕࣥན Κխᢐᢐᖂ ഏمᒳ塢 199ˈΚ ˅˅ˋˀˌ •. ˄˃ˁʳ ࣔޘΚֱᕪᖂ ഏمխഏ᠔ᢐઔߒࢬ 1999: 201-202 44.
(51) • •. 11. Patrick C. Walsh; Alan B. Retik .Campbell's urology. 8th ed 2002: 3230-3260 12. UTSUNOMIYA MΔKOIDE TΔYAMAGUCHI SΔet al.The effect of kompou medicine on the growth and aggregation of calcium oxalate crystal in vitro. Acta Urol Jpn. 37 ΰ10α:1097.1101.1991.. •. 13. KAWAMURA KΔMORIYAMA MΔNAKAJIMA CΔet al.The inhibi-tory effects of Takusha on the formationΔgrowth and aggregation of calcium oxalate crystal in vitro..Acta Urol Jpn.39(8α:695-700.1998.. •. 14.YASUI TΔFUJITA KΔSATOMΔet al.The effect of takushaΔ a kampo medicineΔon renal stone formation and osteopontin expression in a rat urolithiasis model. .Urol Res..27 ΰ3α:194-199.1999.. ᖴᖴாᝊϐཀـǼ IRB ཀ ـયΕǵ௨ନచҹǴڙ၂ޣଏрᐒڋፎံкᇥܴǶ!. PI ӣᙟ. ɊᒧྗǺ! 2/ለ่້ҡੰ)ϐϐ่ҡϩࣁለ่້ҡ*! 3/Ԗੱރϐ่ҡൺวεٿܭԛ! 3.9 Ɋ௨ନྗ Ǻ! 2/ൾ܄ဍዦٳମᙯ౽! 3/ୋҘރဏфૈϗ! 4/ᆒઓ੯! 5/λᆅለՈੱ! 6/سֿݜ่ᄬ౦த! 7/ᄌֿ܄ၡགࢉ! 8/ମ፦౧!ޣ 9/ภ॥! :/ᄌ܄ဎᘞ! 21/ᚶѫ! 22/طфૈό٫!ޣ ɊଏрᐒڋǺ! 2/ӵڙ၂ܭޣ၂ᡍύวғ่ҡൺวϐݩǴջಖЗҁ၂ᡍǴ٠җीฝЬ Γ٩ֿၡ่ҡೀচ߾ࣁִځ๓ೀǶ! 3/ӵڙ၂ܭޣ၂ᡍύวғᚶѫϐݩǴᗨฅϖऴණۘคठ྾जϐൔᏤǴ 45.
(52) ՠ㵝ӼӄଆـǴջಖЗҁ၂ᡍǶ! 4/ӵڙ၂ܭޣ၂ᡍύวғᅪ՟ჹϖऴණၸ௵ϐݩǴջಖЗҁ၂ᡍǴ٠ җीฝЬΓ٩ᛰނၸ௵ೀচ߾ࣁִځ๓ೀǶ! ! ᖴᖴாࡰޑᏤϷᝊϐཀـǼ IRB ཀڙ ـ၂ޣӕཀਜЎӷҔຒाαᇟϯǶ! ! PI ӣᙟ. ςӄय़ख़ཥঅ҅ڙ၂ޣӕཀਜ٠ஒځαᇟϯǶ ᖴᖴாࡰޑᏤϷᝊϐཀـǼ!. IRB ཀ ـჹܭለ่້ҡੰޑΓǴᘗᘔለႇݯޑᕍԖۓԋਏǴՠϖऴණݯޑᕍ ਏ݀Ҟۘ҂ xfmm.epdvnfouǴգӵՖӧڙ၂ޣӕཀਜ൩ᡣڙ၂ޣΑှ дуΕ၂ᡍࡕԖёૈाௗڙϖऴණǵ܈ӼኃᏊԶߚᘗᘔለႇݯᕍǴԶᜫ ཀуΕࣴزǻϖऴණݯᕍޑਏ݀ǵᏵѸևǶ! ! PI ӣᙟ. ςڙܭ၂ޣӕཀਜύቚӈǺ! ¾ ϖऴණёफ़ե่ҡϐൺวǶ ¾ ϖऴණܭύᙴϐᔈҔࣁНဍϐᏊǴჹ࡚ܭᄌ܄ݹǵݹطǵᆮ ાݹǵ࡚܄ဉगݹǵНᘞǵНဍ܈ဎЋೌࡕ௨ֿ֚ᜤ֡ԖਏǶ ¾ ӧжᛰᏢБय़ǴϖऴණڀԖճֿϷלբҔǶ ¾ ճֿբҔёߦֿݜၰ่ҡ௨рǴځύऴǵἐऴǵқҀǵᐛᘞ֡ ԖճֿբҔǶԶਦ݄ᙖׯ๓ՈనൻᕉǴЀࢂځ᠌ՈనൻᕉǴуம ճֿբҔǶ ¾ ЪלբҔёڋགࢉ่܄ҡԋǴځύਦ݄ჹࢬՉ܄གߵੰࢥǵ ݹޤౚǵฟ੯ఎǵεဉఎԖբҔǴऴᎇගనჹߎ ՅဟౚǵεဉఎԖڋբҔǶ ¾ ϖऴණύޑਦ݄ǵᐛᘞჹဉगѳྖԼԖှยբҔǴёᔅշᒡֿᆅѳ ྖԼܫǴߦֿݜၰ่ҡ௨рǶ ¾ ԜѦӧύ୯ᙴᛰεᏢഋЎᲑ௲ϐࣴزΨჴǴϖऴණܭᡏѦ၂ᡍ ϐύǴޑዴԖڋለ่້ԋǵᏉکԋߏϐфਏǶ! ¾ ϖऴණऊё෧ե 30-40%ϐ่ҡൺวǶ! ¾ Sfgfsfodf! :/!݅ےѿǵ݅ےѳǵ݅ඳர!ǺύᛰᛰᏢ!୯ҥጓᓔ!2::6Ǻ339.: 21/!ᖴܴǺБᏊᏢ!୯ҥύ୯ᙴᛰࣴ!܌ز2:::;!312.313! 22/!Qbusjdl!D/!Xbmti<!Bmbo!C/!Sfujl!/Dbnqcfmm(t!vspmphz/!9ui fe!. 46.
(53) 3113;!4341.4371! 12. UTSUNOMIYA MΔKOIDE TΔYAMAGUCHI SΔet al.The effect of kompou medicine on the growth and aggregation of calcium oxalate crystal in vitro. Acta Urol Jpn. 37ΰ10α:1097.1101.1991. 13. KAWAMURA KΔMORIYAMA MΔNAKAJIMA CΔet al.The inhibi-tory effects of Takusha on the formationΔgrowth and aggregation of calcium oxalate crystal in vitro..Acta Urol Jpn.39(8α:695-700.1998. 14.YASUI TΔFUJITA KΔSATOMΔet al.The effect of takushaΔa kampo medicineΔon renal stone formation and osteopontin expression in a rat urolithiasis model. .Urol Res..27ΰ3α:194-199.1999. ! ᖴᖴாࡰޑᏤϷᝊϐཀـǼǼ! IRB ཀڙޕ ـ၂ޣǴӚᅿБޑݤႣٛԋਏӵՖǻӕਔाᡣдޕၰǴуΕ၂ᡍࡕ όࢂҗдԾρ،ۓдाবᅿݯᕍБݤǴԶࢂीฝЬΓаᒿᐒБԄϩ ଛǴ೭٤ၗૻाкϩޕǶ! ! PI ӣᙟ. ςڙܭ၂ޣӕཀਜύቚӈ! 2/ ϐᘗᘔለႇણ҃ऊё෧ե 21.61&ϐ่ҡൺวǶ! 3/ ϖऴණऊё෧ե 41.51&ϐ่ҡൺวǶ! 4/ ൂપസН٠ᆢВֿໆ?3111dd ऊё෧ե 26&ϐ่ҡൺวǶ! 5/ ࣁᆢࣴ࠼ޑزᢀ܄Ǵॺך٣Ӄஒಔձးुӧߞ࠾ύǴாӕཀу ΕࣴزਔǴڗܜঁߞ࠾،ۓாஔڙবಔݯᕍǴԶόࢂாԾҗ ᒧाуΕবಔǴӕਔாόޕၰாϩଛډবಔǶ! ! ᖴᖴாࡰޑᏤϷᝊϐཀـǼǼ!. IRB ཀ ـჹຝх֖ζ܄Ǵӵ݀ᚶѫ൩௨ନǴନΑԏਢ௨ନᚶѫǴԏਢࡕ၂ᡍය ໔Ѹڙޕ၂ޣ௦ڗᗉѫࡼǴӢࣁϖऴණჹजޑٽቹៜ҂ޕǶ! ! PI ӣᙟ. ςڙܭ၂ޣӕཀਜύቚӈଏрᐒڋǺ! ӵڙ၂ܭޣ၂ᡍύวғᚶѫϐݩǴᗨฅϖऴණۘคठ྾जϐൔᏤǴՠ 㵝ӼӄଆـǴջಖЗҁ၂ᡍǶ! ! 47.
(54) ᖴᖴாࡰޑᏤϷᝊϐཀـǼ!. Ȩϖऴණёफ़ե่ҡғԋӢη܈ගϲ IRB ཀڙ ـ၂ޣӕཀਜύ)Β*Ⴃය၂ᡍਏ݀Ǻ ่ҡڋӢηȩ ǴՖᒏ่ҡғԋӢηǵڋӢη೭ѡ၉࣮҇όᔉǶፎঅ ҅ǶࢂցঅׯԋȹႣ่ٛҡൺว܈फ़ե่ҡൺวޑᐒȹ! PI ӣᙟ. ςڙܭ၂ޣӕཀਜύ)Β*Ⴃය၂ᡍਏ݀ǺҁჴᡍϐҞޑջࣁᔈҔύᛰϖ ऴණǴႣ่ٛҡൺว܈फ़ե่ҡൺวޑᐒǶ! ᖴᖴாࡰޑᏤϷᝊϐཀـǼ!. IRB ཀڙ ـ၂ޣӕཀਜሡाቚу 35 λਔޑᖄ๎ႝ၉Ƕ! ! PI ӣᙟ. ςڙܭ၂ޣӕཀਜύቚӈ 35 λਔޑᖄ๎ႝ၉ 0933090403! ᖴᖴாࡰޑᏤϷᝊϐཀـǼ!. 48.
(55) ذ इ ۺᙴ ଣ ᖏ ၂ ᡍ ڙ၂ ӕ ཀ ਜ ၂ᡍӜᆀǺύᛰϖऴණჹለ่້ҡޣϐ่ҡߦӢηϷڋӢηޑቹៜ ՉൂՏǺ. ذᙴଣֿݜѦࣽ. ၂ᡍЬΓǺ. ݅ػቼ. ᖄ๎ႝ၉Ǻ 04-7813888 ext 72128. ᙴৣ. ࣴزीჄᜅշޣǺ ذइۺᙴଣ ڙ၂ۉޣӜǺ. ੰᐕဦዸǺ. ܄ձǺ ೯ૻӦ֟Ǻ. ԃសǺ. ᖄ๎ႝ၉Ǻ ᆙ࡚ᖄ๎ΓǺ(ᆙ࡚ݩރϐೀ) ऩԖҺՖᆙ࡚ݩǵ্ǵୋբҔځ܈дό൨தيޑᡏݩރӧ၂ᡍය໔วғǴፎ୍Ѹҥڅ ᖄ๎аΠႝ၉Ǻ ၂ᡍЬΓۉӜǺ ݅ػቼ ႝ၉Ǻ 04-7813888 ext 72128 24 λਔᆙ࡚ᖄ๎ΓǺ ႝ၉Ǻ 0933090403. ᙴৣ. ݅ػቼ ᙴৣ. () ၂ᡍҞޑǺ ֿၡ่ҡࢂঁଯൺวϐ੯ੰǴӵ݀ؒԖϷਔϐೀǴᇸ߾ੵภǵՈֿǴख़߾Ї ଆ௳Ոੱǵ૰ᆃٳวੱǴჹܭᙴᕍϷޗԋҁჴࣁ؈ख़ϐॄᏼǹҁࣴزҞޑӧ ύᛰϖऴණჹܭႣ่ٛҡൺว܈फ़ե่ҡൺวᐒޑਏ݀Ƕ (Β) Ⴃය၂ᡍਏ݀Ǻ ¾ ϖऴණёफ़ե่ҡϐൺวǶ ¾ ϖऴණܭύᙴϐᔈҔࣁНဍϐᏊǴჹ࡚ܭᄌ܄ݹǵݹطǵᆮાݹǵ࡚܄ဉगݹǵ НᘞǵНဍ܈ဎЋೌࡕ௨ֿ֚ᜤ֡ԖਏǶ ¾ ӧжᛰᏢБय़ǴϖऴණڀԖճֿϷלբҔǶ ¾ ճֿբҔёߦֿݜၰ่ҡ௨рǴځύऴǵἐऴǵқҀǵᐛᘞ֡ԖճֿբҔǶԶਦ ݄ᙖׯ๓ՈనൻᕉǴЀࢂځ᠌ՈనൻᕉǴуமճֿբҔǶ ¾ ЪלբҔёڋགࢉ่܄ҡԋǴځύਦ݄ჹࢬՉ܄གߵੰࢥǵݹޤౚǵฟ੯ఎ ǵεဉఎԖբҔǴऴᎇගనჹߎՅဟౚǵεဉఎԖڋբҔǶ ¾ ϖऴණύޑਦ݄ǵᐛᘞჹဉगѳྖԼԖှยբҔǴёᔅշᒡֿᆅѳྖԼܫǴߦݜ ֿၰ่ҡ௨рǶ ¾ ԜѦӧύ୯ᙴᛰεᏢഋؙӓ௲ϐࣴزΨჴǴϖऴණܭᡏѦ၂ᡍϐύǴޑዴԖڋ 49.
(56) ለ่້ԋǵᏉکԋߏϐфਏǶϖ ϖऴණऊё෧ե 30-40%ϐ่ҡൺวǶ (Ο) يЈёૈᏤठϐୋբҔǵό܈ӒᓀǺ ¾ Ҟёٮ᎙ϐЎǴჹܭϖऴණ٠คୋբҔϷόؼϸᔈϐวғǶ ¾ ϖऴණϐᐛᘞǴځᆯણ 1~2g/kg షܭႩύᗯεқႵΟঁДǴܭᡉ༾᜔ΠطಒझϷ ߈Ԕλᆅϐᡂ܄ǴՠԜჴᡍ࠻ᏊໆᇻεܭݯᕍᏊໆǶՠ㵝ӼӄଆـǴطф ૈό٫ࡌޣϮуΕԜ၂ᡍǶќуΕҁ၂ᡍϐڙ၂ޣѸௗۓڙයϐطфૈᔠǶ ¾ ӢӚΓᡏ፦όӕǴҺՖᛰ֡ނԖёૈวғၸ௵ϸᔈǴރੱځхࡴܺᛰࡕआ੶ǵҜጥཝ ǵⶁഞ੶ǵࣗ߾֚֎ڥᜤǴӵԖၸ௵ຝวғǴፎҥջଶЗܺᛰᆶीฝЬΓೱ๎Ƕ ϖऴණҞܭё᎙ϐЎǴ٠คठ྾ज܄ǴՠࣁӼӄଆـǴܭჴᡍය໔ᚶѫޣǴ ፎޕ٠ಖЗҁჴᡍǶ. (ϖ) ځдёૈݯޑᕍϷځᇥܴǺ ¾ ჹܭለ่້ҡޑޣǴёаܺҔᘗᘔለႇણ҃٠ӭസНǴϐᘗᘔለႇણ҃ऊё ෧ե 10-50%ϐ่ҡൺวǶ ¾ ӭസН٠ۓයଓᙫǴൂપസН٠ᆢВֿໆ>2000cc ऊё෧ե 15%ϐ่ҡൺวǶ (Ϥ) ځдёૈޑཞѨ܈ճǺ ாคሡॄᏼᆶҁࣴزԖᜢϐᛰނҔϷᚐѦғԋϐᔠෳҔǶ (Ύ) ୖуҁࣴزीჄڙ၂ঁޣΓஒߥډڙៈ ¾ ҁࣴزीჄϐՉᐒᄬஒᆢៈாӧࣴزၸำύᔈளϐǶ ¾ ாӧࣴزၸำύёᒿਔᄖӣӕཀǴଏр၂ᡍǴόѸၸЬΓӕཀǴЪόЇଆҺՖ όඍ܈זቹៜځВࡕޑᙴᕍྣ៝Ƕ ¾ ӵ݀วҺՖཥޑၗૻԖёૈቹៜாᝩុୖᆶᖏ၂ᡍޑཀᜫਔǴா܈ாۓݤޑж ΓջਔޕǶ ¾ ӵ݀ӵாӢҺՖҗటύЗࣴزϐୖᆶǴፎᖄ๎ࣴزЬΓ ܈24 λਔᆙ࡚ᖄ๎ΓǶ ¾ ذइۺᙴଣஒӧ܌ࡓݤೕጄϐำࡋϣຎாϐၗࣁᐒஏǶாҭᕕှࣴزᜅշޣȐቷ ȑǵፁғᆶذइۺᙴଣΓᡏ၂ᡍہࣣԖᔠຎாޑၗǶ (Ζ) ڙ၂ޣᖂܴਜ аޑၗૻςӛךᇥܴǴךԖᐒ၌ୢԜीฝޑԖᜢୢᚒǴךςΑှЪӕཀୖᆶԜ ࣴزीჄǶӵ݀ךаࡕԖୢᚒǴךёаᆶذइۺᙴଣػ݅ޑቼᙴৣᖄ๎Ƕ ɍ၂ᡍЬΓ ۉӜǺ ڙ၂ޣᛝӜ ི҅ۉӜǺ. ɍڐӕЬΓ. ɍࣴزжΓ. ᛝӜǺ. ᛝӜВයǺ. ᛝӜǺ. ᛝӜВයǺ. 50.
(57) Ver.1.6. 28/Jul/2007. ᄆᔭذइۺᙴଣࣴزीฝਜ. ԃ. ࡋǺΐΜϤ. ीฝӜᆀǺύᛰϖऴණჹለ่້ҡޣϐ่ҡ ߦӢηϷڋӢηޑቹៜ. ࣴزख़ᗺǺɍՋᙴᖏزࣴɍύᙴࣴزɎύՋᙴ ่ӝࣴز. ҙፎൂՏǺᄆᔭذइۺᙴଣֿݜѦࣽ. Ь ΓǺ݅ػቼ. ᙴৣᛝӜǺ. 51.
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