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브라디키닌 수용체 발현 및 길항제개발에 관한 연구

  • 정성현;이은순
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.146-146
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    • 1993
  • 신장에서 브라디키닌(Bradikinin, BK)의 생리적 역할을 규명하기 위한 첫 단계로 토끼신장 근위세뇨관의 일차배양세포를 이용, BK 수용체를 ($^3$H) BK를 이용하여 수용체결합실험을 함과 아울러 세포배양과정에서 여러 성장인자들의 BK 수용체발현에 미치는 영향을 관찰하였다. 첫째, 토끼 신장의 피질, 수질 및 근 위세뇨관 둥 각 부위에 대한 BK 수용체결합 실험결과 신수질 부분에 가장 많은 BK 수용체가 발견되었으며 이때 해리항수는 0.52 nM, 그리고 최대결합부위는 mg 단배질당 112.5 fmol이었다. 둘째, serum free 배지에서 insulin, transferrin 그리고 hydrocortisone이 성장인자로 사용될 때 BK 수용체발현이 가장 높았으며 이 중 인슐린에 가장 큰 영향을 받았다. 한편 인슐린의 최적농도를 결정하는 실험의 결과 5 $\mu\textrm{g}$/ml매서 가장 높은 수용체발현을 나타내었으며 그 이상에서는 별다른 차이를 보이지 못했다. 세째, 위의 세 성장인자에 prostaglandin E$_1$이나 triiodothyronine을 첨가시 BK 수용체발현은 오히려 저하되었다. 네째, fetal bovine serum (FBS)과 위의 세 성장인자간의 수용체발현능을 비교한 실험에서 세포배양 후 첫 일주일에는 FBS가 세 성장인자보다 약간 나은 수용체발현능을 나타내었으나 그후 이주째에는 세 성장인자가 BK 수용체발현에 더 적절한 요소임을 보여주었다. 이상의 결과로 보아 토끼 근위세뇨관 상피세포에서의 BK 수용체발현은 세포성장인자로 insulin, transferrin, hydrocortisone 중 insulin에 가장 큰 영향을 받는것으로 보이며, 이들 세가지 성장인자는 serum free 배지에서 세포성장 및 기능에 많은 영향을 주는 것으로 생각된다.prolidine이 $K_{M}$ /K$_{H}$ 비가 가장 높았고 diphenidol이 가장 낮았다. 이상의 결과로 보아 항 histamine제의 muscarinic receptor 차단작용은 이들 약물의 항 alleragy 효과에 필요한 작용이 아니며 본 실험에서 추정된 항 histamine제의 H$_1$-receptor와 muscarinic receptor에 대한 상대적 역가는 이들 약물의 선택과 평가에 중요한 지표가 될수 있을 것으로 생각된다.ing ischemic insults. The nature of the receptor is being explored by molecular genetic techniques, and we have recently cloned two of the major subunits; some of the data will be presented.LIFO, 우선 순위 방식등을 선택할 수 있도록 확장하였다. SIMPLE는 자료구조 및 프로그램이 공개되어 있으므로 프로그래머가 원하는 기능을 쉽게 추가할 수 있는 장점도 있다. 아울러 SMPLE에서 새로이 추가된 자료구조와 함수 및 설비제어 방식등을 활용하여 실제 중형급 시스템에 대한 시뮬레이션 구현과 시스템 분석의 예를 보인다._3$", chain segment, with the activation energy of carriers from the shallow trap with 0.4[eV], in he amorphous regions.의 증발산율은 우기의 기상자료를 이용하여 구한 결과 0.05 - 0.10 mm/hr 의 범위로서 이로 인한 강우손실량은 큰 의미가 없음을 알았다.재발이 나타난 3례의 환자를 제외한 9례 (75%)에서는 현재까지 재발소견을 보이지 않고 있다. 이러한 결과는 다른 보고자들과 유사한 결과를

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Bioequivalence Test of Triflusal Capsules (트리플루살 캅셀의 생물학적 동등성 평가)

  • 박정숙;이미경;박경미;김진기;임수정;최성희;민경아;김종국
    • Biomolecules & Therapeutics
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    • v.9 no.4
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    • pp.291-297
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    • 2001
  • The bioequivalence of two triflusal products was evaluated with 20 healthy volunteers following single oral dose according to the guidelines of Korea Food and Drug Administration (KFDA). Trisa $l^{R}$ capsule (Whanin Pharm. Corp., Korea) and Disgre $n^{R}$ capsule (Myung-In Pharm. Corp., Korea) were used as test product and reference product, respectively. Both products contain 300 mg of trifusal. One capsule of test product or reference product was orally administered to the volunteers, respectively, by randomized two period crossover study (2$\times$2 Latin square method). Blood samples were taken at predetermined time intervals for 4 hours and the determination of trifusal was accomplished using semi-microbore HPLC equipped with automated column switching system. The analytical method with HPLC was validated according to the Bioanalytic Method Validation guideline by F7A prior to determining the plasma samples. The pharmacokinetic parameters (AU $C_{0-4h}$ $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for statistical analysis of parameters. As a result of the assay validation, the limit of quantification of trifusal in human plasma by current assay procedure was 50 ng/ml using 500 $\mu$l of plasma. The accuracy of the assay was from 97.76% to 116.51% while the intra-day and inter-day coefficient of variation of the same concentration range was less than 15%. Average drug concentration at the designated time intervals and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05). The difference of mean AU $C_{olongrightarrow4hr}$, $C_{max}$, and $T_{max}$ between the two products (2.92, 4.39, and -2.44%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $C_{olongrightarrow4hr}$ and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different from each other (p>0.05). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two products of triflusal were bioequivalent.quivalent.ent.ent.

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Pharmacokinetics and tissue residues of ivermectin in swine

  • Park, Kwon-moo;Park, Jln-bong;Li, Long-hua;Han, Seong-kyu;Lee, Hye-sook;Park, Jong-myung;Chang, Byoung-sun;Lee, Mun-han;Ryu, Pan-dong
    • Korean Journal of Veterinary Research
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    • v.39 no.2
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    • pp.257-266
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    • 1999
  • Ivermectin is a widely used broad spectrum antiparasitic agent in veterinary medicine. In this work, we examined the pharmacokinetic parameters and the tissue residue profile of a new injectable formulation of ivermectin developed for pigs. The plasma ivermectin levels reached the peak at about 9 and 2 hours after the administrations in young and adult pigs, respectively. But the elimination half-life (3-3.5 days) and the $C_{max}$ values (24~28 ng/ml) were not significantly different between young and adult pig groups. When compared to the reference formulation, the $C_{max}$ of test formulation was higher and $T_{1/2}$ values were shorter than those of the reference formulation, respectively. The tissue residue levels were dose- and time-dependent and were higher in the liver and fat, than in the other tissues such as the injection sites, the kidney, intestine, muscle, plasma (4~74 ng/g) at the 7th day after the administration of both formulations of ivermectin. Then, the mean tissue ivermectin levels at the 21st day after the administration in all the tissues decreased to 7.4 and 25% of the 7th day levels in the test and reference formulations, respectively. In general, the tissue levels of ivermectin in the animals treated with the test formulation decreased more rapidly than those with the reference formulation. The tissue to plasma distribution ratio (T/P ratio) of ivermectin was higher in the liver and fat than other tissues. The T/P ratio in the liver of animals treated with the test formulation was somewhat higher than that in the animals treated with the reference formulation. Taken together, the results of pharmacokinetic and tissue residue studies indicate that the test formulation of ivermectin for subcutaneous injection is comparable to the reference formulation, but unique in that it has higher peak plasma concentrations, shorter elimination half-life and higher T/P ratio in the liver than the reference formulation.

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Ultrasonographic appearance of the gestational structures throughout accurately timed pregnancy in Korea Jin-do dogs II. Estimation of gestational age by measurement of the fetal and extra-fetal structures (진도개에서 임신일령에 따른 임신구조물의 초음파상 II. 태아 및 태아외구조물의 측정에 의한 임신일령의 추정)

  • Son, Chang-ho;Shin, Chang-rok;Kang, Byong-kyu;Choi, Han-sun
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.247-254
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    • 1996
  • Serial ultrasonographic examinations were performed on 9 pregnant Korea Jin-do dog from days 15 to 60 to determine the size of gestational structures throughout pregnancy. Gestational age was timed from the day of ovulation (Day 0), which was estimated to occur when plasma progesterone concentration was first increased above 4.0 ng/ml. Extra-fetal structures were measureable from days 17 to 49. Outer uterine diameter increased from $7.0{\pm}0.7$ ($mean{\pm}SD$)mm at day 17 to $54.0{\pm}2.2mm$ at day 49 and inner chorionic cavity diameter increased from $3.0{\pm}0.7mm$ at day 17 to $37.5{\pm}0.6mm$ at day 49. Uterine wall thickness increased from $2.8{\pm}0.4mm$ at day 17 to $8.3{\pm}0.5mm$ at day 49, placental thickness increased from $1.0{\pm}0.1mm$ at day 22 to $5.7{\pm}0.2mm$ at day 49 and length of chorionic cavity or zonary placenta increased from $5.5{\pm}1.3mm$ at day 20 to $52.3{\pm}2.2mm$ at day 49. Inner chorionic cavity diameter, outer uterine diameter and placental length each increased at a linear rate through day 37, after which time, each had a marked plateau in growth. Of the extra-fetal structures, inner chorionic cavity diameter was the most accurate for estimation of gestational age until day 37. Fetal structures were measureable from days l7 to 60. Crown-rump length, increased from $3.0{\pm}0.7mm$ at day 22 to $118.7{\pm}3.1mm$ at day 49, fetal body diameter increased from $4.0{\pm}0.7mm$ at day 25 to $55.8{\pm}1.7mm$ at day 60 and fetal head diameter increased from $4.3{\pm}0.6mm$ at day 26 to $29.8{\pm}0.8mm$ at day 60. Of the fetal structures, fetal head diameter was the most accurate for estimation of gestational age from day 37 until day 60.

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Serum Concentration of Major Minerals, Trace Elements, Lipids and Fatty Acids Composition Related to Whole Cow's Milk Feeding in Infancy & Young Childhood (생우유 과량섭취와 관련된 영유아의 혈청 무기질과 미량원소 함량 및 지질조성)

  • 안홍석;배현숙;박성혜;정은정;오경환
    • Korean Journal of Community Nutrition
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    • v.2 no.4
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    • pp.477-485
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    • 1997
  • This study was conducted to determine the effect of large amounts of whole cow's milk intake on serum levels of minerals and lipids. Subjects were normal infants who were brought to the pediatric hospital for vaccination at the age of 7-26 months after birth, living in Eumsung-Choongbuk area. The serum concentrations of the imnerals(calcium, phosphorus, magnesium, iron, zinc and copper), lipids and fatty acids composition were analyzed in 38 infants which consumed large amount of whole cow's milk(over 700ml/day). The results obtained are summarized as follows : 1) The mean levels of calcium, phosphorus and magnesium in the serum of the total subjects were 7.56$\pm$0.51mg/dl, 11.12$\pm$0.72mg/dl and 1.62$\pm$0.13mg/dl respectively. The serum concentrations of iron, zinc and copper in total subjects averaged 72.42$\pm$1.62$\mu\textrm{g}$/dl, 76.29$\pm$3. 62$\mu\textrm{g}$/dl and 86.44$\pm$2.98$\mu\textrm{g}$/dl respectively. 2) The mean serum concentrations of triglyceride, total cholesterol, HDL and LDL in the total number of subjects were 96.84$\pm$9.22mg/dl, 133.45$\pm$6.30mg/dl, 32.79$\pm$1.77mg/dl and 81.29$\pm$4.81mg/dl respectively. 3) The average percentages of SFA, MUFA and PUFA inth total serum fatty acids were 38.98$\pm$2.42$\%$, 25.82$\pm$0.98$\%$ and 37.30$\pm$1.09$\%$ respectively and the mean$w6/w3$fatty acids ratio was 13.48. In general, the levels of serum minerals and $\omega$3 fatty acid composition in the subjects of this study, who were whole cow's milk fed infants were lower than those reported in breast milk or formula fed infants. Therefore, the intake of large amount of whole cow's milk in the weani ng period should be controlled and adequate for the infant's nutritional status. (Korean J Community 2(4) : 477-485, 1997)

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Breeding on a new cultivar of golden Flammulina velutipes 'Auram' (황금색 팽이 신품종 '아람' 육성)

  • Im, Ji-Hoon;Jang, Kab-Yeul;Oh, Youn-Lee;Oh, MinJi;Raman, Jegadeesh;Kong, Won-Sik
    • Journal of Mushroom
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    • v.17 no.4
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    • pp.218-223
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    • 2019
  • Flammulina velutipes, known as winter mushroom or Enokitake, is an important edible mushroom in Korea. In 2017, approximately 28,000 tons of this mushroom were produced in Korea, putting its output at the third place, behind the oyster and king oyster mushrooms. Despite its high production, F. velutipes has the lowest distribution rate of domestic cultivars, estimated to be about 28 percent. To increase the income of farms and provide more options to consumers, we developed a new golden domestic cultivar 'Auram'. 'Auram' was bred by mating two monokaryotic strains isolated from ASI 4103 and ASI 4111. Auram has bright golden, hemispheric shaped caps, and light brown stipes, making it strikingly different from the control. The optimum mycelial growth temperature was 25℃, but Auram mostly displayed higher mycelial growth than the control in a wide range of temperatures. The yield of Auram (257.4 ± 13.5 g) was high, and the period of fruit body growth was also a couple of days ahead in bottle cultivation, compared with the control. Auram received a more favorable evaluation from farms and distributors than the control for its appearance, because the fruit body of Auram had an attractive golden color, and the spotted cap often seen in the control was not observed.

Studies on the Hematologic Values and Blood Chemistry Values of Korean Native Ogolgye 1. Hematologic Values for Korean Native Ogolgye (한국재래오골계의 혈액상 및 혈액화학치에 관한 연구 - 1. 오골계의 혈액상에 관하여)

  • Rhee Han-Gie;Park Oak-Youn
    • Journal of the korean veterinary medical association
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    • v.20 no.4
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    • pp.233-238
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    • 1984
  • This experiment was conducted to investigate normal hematologic value of RBC, Hb, PCV, WBC, MCV, MCHC, thrombcyte, differential leukocyte count and diameter of RBC, with 10 males and 10 females of the 182 days- Korean Native Ogolgye designated the number

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Epidural Ketamine for postoperative Analgesia -Comparison with Epidural Morphine- (경막외케타민 주입을 이용한 술후 통증관리 -경막외몰핀과의 비교-)

  • Kim, Han-Soo;Baik, Seong-Wan;Kim, Inn-Se;Chung, Kyoo-Sub
    • The Korean Journal of Pain
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    • v.1 no.2
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    • pp.192-198
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    • 1988
  • Sixty patients, of ASA physical status class I for elective operations in the lower abdomen, perineum, or lower extremities, were studied in a comparative prospective trial to evaluate the efficacy of epidural morphine and ketamine for postoperative analgesia. They were divided into two groups: an epidural morphine sulfate group (EMS group; 30 patients), and an epidural ketamine hydrochloride group (EKH group; 30 patients). Indwelling epidural catheters were placed in the patients' lumber areas (L3-4) and then all patients were anesthetized with thiopental, nitrous oxide, and halothane. After the patients had fully recovered from the anesthesia, the analgesic agents were administered epidurally via the catheter when the patients complained of pain in the postoperative period. The groups were given either 0.1 mg/kg of morphine sulfate or 0.5 mg/kg of ketamine hydrochloride administered in a volume of 10 ml of normal saline. Patients were observed for the onset and duration of postoperative analgesia and for other effects. Total doses were $5.7{\pm}0.6\;mg$ of morphine sulfate in the EMS group and $27.9{\pm}3.3\;mg$ of ketamine hydrochloride in the EKH group. The onset of analgesia was detectable within 35 min.($23.5{\pm}6.3$ min) in 86.7% (26 cases) of the EMS group and within 10 min. ($7.8{\pm}3.7$ min.) in 76.7% (23 cases) of the EKH group. Mean duration of postoperative analgesia was $22.3{\pm}2.1\;hr$. in the EMS group. In the EKH group, the duration of analgesia was shorter and variable, the range of duration was from 2 hr. to 24 hr., Cardiopulmonary changes were statistically insignificant ih both groups. Side effects such as nausea, vomiting, urinary retention, pruritus, dizziness, and headache were observed in EMS group. In the EKH group, there was no discomfort except dizziness (3 cases) and headache (1 case). Epidural ketamine was a safe technique for postoperative analgesia, but because of the variability and relative shortness in the duration of analgesia the use of this technique will require further clinical trials.

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The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

  • Moon, Jee Youn;Choi, Sang Sik;Lee, Shin Young;Lee, Mi Kyung;Kim, Jung Eun;Lee, Ji Eun;Lee, So Hyun
    • The Korean Journal of Pain
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    • v.29 no.2
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    • pp.110-118
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    • 2016
  • Background: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods: Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl $1,000{\mu}g$; Group B, fentanyl $500{\mu}g$ + nefopam 200 mg; and Group C, fentanyl $500{\mu}g$ + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results: Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions: The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.

Inhibition of Enzymatic Degradation of Leucine Enkephalin and $[D-Ala^2]$-Leucine Enkephalinamide in Various Rabbit Mucosal Extracts by Inhibitors (효소 억제제에 의한 토끼의 점막 추출액중 로이신엔케팔린 및 [D-알라$^2$-로이신엔케팔린아미드의 분해 억제)

  • Chun, In-Koo;Park, In-Sook;Hyun, Jeen
    • Journal of Pharmaceutical Investigation
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    • v.26 no.3
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    • pp.175-185
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    • 1996
  • To inhibit the enzymatic degradation of leucine enkephalin (Leu-Enk) and its synthetic analog. $[D-ala^2]$-leucine enkephalinamide (YAGFL), in the nasal, rectal and vaginal mucosal and serosal extracts of rabbits, effects of enzyme inhibitors such as amastatin (AM), puromycin (PM), thiorphan (TP), thimerosal (TM), EDTA, N-carboxymethyl-Phe-Leu (CPL), phenylethyl alcohol (PEA), phenylmercuric acetate (PMA), benzalkonium chloride (BC) and modified cyclodextrins, alone or in combination, were observed by assaying the pentapeptides staying intact during incubation. Mucosa extracts were prepared by exposing freshly-excised mucosal specimens mounted on Valia-Chien cells to isotonic phosphate buffer while stirring. The degradation of Leu-Enk and YAGFL followed the apparent first-order kinetics. The half-lives (mean) in the nasal, rectal and vaginal mucosal extracts were found to be 1.07, 0.33 and 1.14 hr for Leu-Enk, and 16.9, 6.2 and 6.8 hr for YAGFL, respectively. AM or PM, which is an aminopeptidase inhibitor, did not show a sufficient inhibition of Leu-Enk $(50\;{\mu}g/ml)$ degradation in all kinds of extracts. $Dimethyl-{\beta}-cyclodextrin\;(DM-{\beta}-CyD)$ decreased the degradation rate constants of Leu-Enk about 2 or 3 times, comparing with no additive. However, the use of mixed inhibitors of AM $(50\;{\mu}M)$/TM (0.25 mM)/EDTA (5 mM) resulted in a full stabilization of Leu-Enk by decreasing the degradation rate constants 67.3, 161.3 and 113.8 times far the nasal, rectal and vaginal mucosal extracts, respectively, comparing with no inhibitor. With mixed inhibitors, Leu-Enk remained intact more than 90% after 6 hr-incubation. In the stabilization of YAGFL, hM, TP or CPL alone showed little efffct, and some additives demonstrated a considerable inhibition of YAGFL degradation in the rank order of TM > BC > EDTA. However, the addition of mixed inhibitors such as TM (0.5 mM) and EDTA (5 mM) into the extracts protected YAGFL from the degradation by more than 85% even after 24 hr-incubation, suggesting almost complete inhibition of YAGFL degradation in the extract. On the other hand, $DM-{\beta}-CyD\;or\;hydroxypropyl-{\beta}-cyclodextrin$ (10%) were also found to retard enzymatic degradation rates of YAGFL markedly, and resulted in staying intact more than 80% of YAGFL in the nasal and vaginal mucosal extracts, and more than 60% in the rectal mucosal extract after 16 hr-incubation.

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