경구용 약물 제형의 유당 함량과 유당불내증 환자의 임상적 의의

천영주(Young Ju Cheon),임성실(Sung Cil Lim) 대한약학회 2017 약학회지 Vol.61 No.4

Although lactose is also widely used as an excipient in oral formulations, the amount of ‘hidden’ lactose in drugs still has not been identified. We investigated the ‘hidden’ lactose in 1,109 oral solid formulations in formulary of a gen-eral hospital in Seoul. The investigation is conducted from Oct. 2015 to Jan. 2016. Firstly, we retrieved the 1,109 items through two databases (KIMS©, Druginfo©) to know whether lactose is contained or not. Out of 1,109 items, 501 items were lactose-containing drugs (LCDs). We confirmed the amount of lactose of 228 items by mailing from each manufactures of LCDs. Then we calculated the ingested daily amount of lactose. The range of lactose amounts on each LCD was 7.4-601.4 mg. The average amount of lactose per formulation was as follows; 93.4(7.4−383.1) mg for tablets, 91.8(8.3−187.3) mg for capsules, 344.9(88.4−601.4) mg for granules, and 175.0 mg for powder. When LCD was taken usual dosage, the ingested maximum lactose per day was 1,804.3 mg, and 500 mg or more (504.0−1,804.3) for six items, and less than 300 mg for remaining 222 items. This result suggests that clinical symptoms of lactose intolerance may not induce by one LCD, but may occur by combination therapy with various LCDs. Therefore, if the patient shows symptoms of lactose intolerance after taking the drug, it is also necessary to check that the drug contains lactose or to replace with LFD. And the man-ufacturer should provide accurate information about the lactose content, and also do well to apply alternative excipient besides lactose in the manufacture.

대장균에서 lactose를 이용한 수용성 재조합 인간 상피 세포 성장 인자의 생성

박세철,권태종,고인영,유광현 한국산업미생물학회 1998 한국미생물·생명공학회지 Vol.26 No.1

재조합 인간상피세포 성장인자(rhEGF)가 E. coli BL21(pYHB101) 균주를 사용하여 발현되었다. 10 g/L glucose를 첨가한 변형된 MBL 배지를 사용하여 10μM IPTG/lactose로 2시간 동안 유도배양한 후 27℃에서 48시간 동안 배양하였을 때 44.5 ㎎/L의 rhEGF가 발현되었다. 상기의 결과는 E. coli BL21(pYHB101)를 사용하여 rhEGF를 발현시 lactose를 IPTG와 동일한 유도 물질로 사용가능하다는 것을 시사하는 것이다. 회분식 배양에서 glucose를 10 g/L 첨가한 변형된 MBL 배지에 유도물질로 10μM lactose를 사용하였으며 28시간 동안 배양하였을 때 최대 45 ㎎/L의 rhEGF가 발현되었다. 유가식 배양에서 정지기에 0.5%(w/v) lactose와 0.25%(w/v) yeast extract를 첨가하였을 때 160 ㎎/L의 rhEGF가 발현되었으며 94.3%가 분비되었다. 이에 비하여 유도기에 lactose를 첨가한 경우는 120 ㎎/L의 rhEGF가 발현되었으며 cytoplasm으로 발현된 불용성 봉입체의 비율은 20.9%에 달하였다. 이것은 lactose의 첨가시기가 E. coli BL21(pYHB101)로부터 soluble rhEGF의 생성에 중요하다는 것을 확인한 결과이다. Recombinant human epidermal growth factor (rhEGF) was produced by E. coli BL21 (DE3) harboring a plasmid pYHB101. The production of rhEGF was 44.5 ㎎/L when the E. coli BL21 (pYHB101) was cultured at 27℃ for 48 hr in the modified MBL medium containing 10 ㎍/L glucose with 10μM IPTG/lactose induction at 2 hr after inoculation. It was shown that lactose is able to induce the rhEGF expression of E. coli BL21 (pYHB101) with the same efficiency as IPTG. In the batch culture system, when induced with 10μM lactose, E. coli BL21 (pYHB101) produced maximum 45 ㎎/L of the rhEGF at 28 hr culture in the modified MBL medium containing 10 g/L glucose. In teh semi-fed batch culture system, the volumetric yield was 160 ㎎/L when the culture was added with 0.5% (w/v) lactose and 0.25% (w/v) yeast extract in the late logarithmic phase and 94.3% of rhEGF was secreted as soluble form. However, when the culture was added with them in the early logarithmic phase, the volumetric yield was 120 ㎎/L and 20.9% of rhEGF was found in cytoplasmic insoluble aggregated. It was found that the addition time of lactose was important for production of soluble rhEGF from E. coli BL21 (pYHB101).

The role of lactose carrier on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation

Lee, Hyo-Jung,Lee, Hong-Goo,Kwon, Yong-Bin,Kim, Ju-Young,Rhee, Yun-Seok,Chon, Jinmann,Park, Eun-Soek,Kim, Dong-Wook,Park, Chun-Woong Elsevier 2018 European journal of pharmaceutical sciences Vol.117 No.-

<P><B>Abstract</B></P> <P>In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier. In all of the carrier-based formulations, the flow properties were improved compared with bosentan microparticles alone, in the following order spray-dried, sieved and milled lactose. The aerodynamic characteristics of each were evaluated by particle image velocimetry and Andersen cascade impactor™. Depending on the lactose carrier type, particle dispersion showed different flow characteristics. In the spray-dried lactose, the formulation was dispersed fast in the only frontal direction, while the milled and sieved lactose formulations formed a relatively slower S-shaped and fountain-shaped flow stream, respectively. In addition, milled and sieved lactose formulations showed that the drug particles were readily liberated from the lactose carrier, and demonstrated significantly higher aerosol performance than spray-dried lactose.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Streptococcus의 유당분해에 대한 자일리톨의 효과

신강호,양규호,최남기,김선미,오종석 大韓小兒齒科學會 2004 大韓小兒齒科學會誌 Vol.31 No.2

자일리톨은 탄소 5개가 있는 탄수화물로 치아우식증을 억제할 목적으로 사용되는 자당 대체물이다. 본 논문은 구강 중요 세균인 Streptococcus mutans, Streptococcus oralis, Streptococcus salivarius에서 유당분해에 대한 자일리톨의 작용을 관찰하고자 하였다. 세균에 대한 유당과 자일리톨의 병합효과를 보기 위하여 분광광도계를 이용한 흡광도를 측정하였고 생균수 검사를 실시하였다. Streptococcus mutans 또는 β-galactosidase에 의한 유당분해에 대한 자일리톨 효과를 보기 위하여 thin layer chromatography와 lactose-PTS activity test를 실시하여 다음과 같은 결과를 얻었다. 1. 유당과 자일리톨을 병합 첨가한 배지에 Streptococcus mutans를 배양하면 배양액 흡광도가 배양 8시간에 증가하지 않다가 배양 24시간에 증가하였다. 배양 8시간에서의 생균수도 유당 단독보다 유당과 자일리톨 병합 첨가 시 적게 나타났다. 2. 유당과 자일리톨을 병합 첨가한 배지에 Streptococcus oralis, Streptococcus salivarius를 배양하면 배양액 흡광도가 배양 8시간에 증가하지 않다가 배양 24시간에 증가하였다. 3. 배지에 유당 단독으로 첨가할 때보다도 유당과 자일리톨을 병합 첨가한 배지에 Streptococcus mutans를 8시간 배양하면 thin layer chromatography상 남아있는 유당이 많았으나, 배양 24시간에는 모든 유당이 분해되었다. 4. 배지에 유당 단독으로 첨가할 때보다도 유당과 자일리톨을 병합 첨가한 배지에서 Streptococcus mutans의 lactose-PTS 활성도가 낮았다. 5. 배지에 유당 단독으로 첨가할 때보다도 유당과 자일리톨을 병합 첨가한 배지에 β-galactosidase 사용시 thin layer chromatography상 유당이 많았다. 이상의 결과는 자일리톨이 Streptococcus의 유당 이용을 억제함을 시사하였다. Xylitol is a 5-carbons carbohydrate, which can be replaced with sucrose for preventing dental caries. To study the effect of xylitol on the fermentation of lactose in bacteria, the important oral bacteria such as Streptococcus (S.) mutans, S. oralis and S. salivarius were studied. The optical density using spectophotometer and the cell concentration were assessed to evaluate the combined effect of lactose and xylitol against the bacteria. Thin layer chromatography and lactose-PTS activity test were performed to evaluate the effect of xylitol on the fermentation of lactose in S. mutans and by β-galactosidase with the following results. 1. The optical density of Streptococcus mutans culture was not increased for 8 hours-incubation in the media added with lactose and xylitol, but was increased at 24 hours-incubation. The number of viable cells at 8 hours-incubation was smaller in the media containing lactose and xylitol in comparison with lactose only. 2. The optical densities of Streptococcus oralis culture and Streptococcus salivarius culture were not increased for 8 hours-incubation in the media added with lactose and xylitol, but were increased at 24 hours-incubation. 3. When Streptococcus mutans was incubated for 8 hours in the media added with lactose and xylitol. the amount of remained lactose was larger compared with the media added with lactose only. But all lactose was fermented in both media after 24 hours-incubation. 4. When Streptococcus mutans was incubated in the media added with lactose and xylitol, the activity of lactose-PTS was higher compared with the media added with lactose only. 5. When β-galactosidase was incubated in the media added with lactose and xylitol, the amount of remained lactose was larger compared with the media added with lactose only. These results indicated that xylitol inhibited the fermentation of lactose by Streptococcus.

호알칼리성 Bacillus sp.의 Lactose 투과와 이용성

윤성식,김창민,양융,유주현 한국산업미생물학회 1991 한국미생물·생명공학회지 Vol.19 No.2

호알칼리성 Bacillus sp. YS-309의 lactose 투과와 이용에 관하여 연구하였다. 실험결과 lactose의 투과는 항생물질의 종류에 따라서 영향을 받았으며 tetracycline이 촉진효과가 가장 우수하였고 valinomycin은 대조구와 비슷하였다. Lactose 배지에서 자란 starved cell의 PEP-potential도 glucose나 galactose를 이용할 때보다 낮게 측정되었다. 따라서 lactose 투과는 PEP의 존재나 phosphorylation과는 무관하게 일어나며 세포막에는 carrier protein이 존재하는 점이 시사되었다. 한편, 세포내로 들어온 lactose는 β-galactosidase에 의해 분해되어 glucose는 빠르게 이용되나 galactose는 세포내에 축적되었다. 또 세포내 축적된 galactose나 배지 중의 lactose 및 galactose는 glucose가 존재할 때는 이용되지 않고 glucose가 소모되면 비로소 이용되는 것으로 나타났다. Glucose와 galactose는 β-galactosidase 합성에 영향을 미쳤으며, glucose는 0.2%, galactose는 0.05∼0.1% 이상의 농도로 배지에 존재할 때 효소합성을 저해하였다. 정확한 기전은 알 수 없으나 세포내 glucose와 galactose는 각각 β-galactosidase 생성의 repressor와 inducer로 작용하는 것으로 생각되며 glucose의 β-galactosidase 합성에 대한 catabolite repression은 cAMP 첨가에 의해 해소되지 못하였다. To study the reduced growth and synthesis, previously reported, of β-galactosidase of alkalophilic Bacillus sp. YS-309 at the higher lactose concentration of 0.5%(w/v) in the medium, lactose transport and utilization were examined. The results showed that lactose transport was influenced by the addition of four kinds of antibiotics, and tetracycline stimulated most but not valinomycin. PEP-potentials of the cells grown on lactose was estimated lower than the cells on glucose and on galactose. Thus, the transport of lactose was independent of intracellular PEP and phosphorylation reactions, and was thought to be uptaked directly or oxidized in part in the transport process. In the other hand, once lactose was uptaked into the cells, it was hydrolyzed by β-galactosidase to glucose and galactose. The former was metabolized fast but the latter was accumulated. Galactose and lactose were not utilized until glucose was mostly depleted in the medium. The β-galactosidase synthesis decreased in the presence of glucose over 0.2% and galactose over 0.05 to 0.1%, respectively. In conclusion, it was considered for glucose as a repressor and galactose as a inducer for -galactosidase synthesis even though the mechanisms were not elucidated. Catabolite repression of glucose on the enzyme synthesis was not relieved by the addition of exogeneous cAMP.

Rahnella aquatilis를 이용한 Lactan gum 생산에서 탄수화물 대사

나건,이성호,이기영 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.4

Rahnella aquatilis에 의해 생산되는 lactan gum은 고점성 물질로 의가소성 유동거동을 보인다. pH가 7.0으로 제어된 발효조 배양에서 lactose나 sucrose같은 2당을 기질로 삼았을 때의 lactan 생산량은 glucose나 galactose같은 단당의 경우보다 2배 이상의 큰 값을 보였다. 초기탄소원 농도가 45 g/l인 lactose와 sucrose의 lactan gum 생산량은 27, 28g/l로 60% 이상의 수율을 보였다. Lactose를 glucose와 galactose로 가수분해시키는 β-galactosidase의 활성은 lactose와 galactose를 기질로 사용하였을 때 유도되었고 lactose를 기질로 사용한 경우 최고 4000U/ml까지의 큰 값을 보였다. 그러나 초기 탄소원이 혼합 탄소원 I (glucose+galactose)인 경우 단당(glucose, galactose)의 경우에 비해 lactan gum 수율이 높았고 45 g/l의 lactose와 비슷하였다. β-galactosidase의 반응이 필요하지 않은 혼합탄소원 I의 경우에서 lactose로의 lactan gum 생산능과 비슷한 값을 보인 것으로 보아 β-galactosidase에 의한 lactose 분해반응은 율속 단계가 아닌 것으로 판단된다. 초기 탄소원을 혼합 탄소원 Ⅱ(glucose+ fructose)으로 하였을 때 총 탄소원의 소비속도는 sucrose보다 늦었으며 glucose의 소비가 fructose의 소비보다 빨랐다. Lactan gum produced by Rahnella aquatilis is a high viscous, anionic polysaccharide and has shear thinning behaviour. Lactan gum yield and concentration was greater on disaccharides such as lactose and sucrose than on monosaccharides such as glucose and galactose. When initial carbon source concentration was 45 g/l sucrose or lactose, the microorganisms produced 26 g/l and 27 g/l of lactan, respectively with a yield more than 60%. β-Galactosidase, hydrolying lactose into galactose and glucose, was induced by lactose or galactose. When initial carbon source was 45 g/l of mixed carbon I (glucose:galactose=1:1), lactan gum concentration was higher than that from 45 g/l of monosaccharide (glucose or galactose) but was similar to the result from 45 g/l of lactose. Therefore, lactose hydrolysis reaction by β-galactosidase does not seem to be rate determining step in lactan gum biosynthesis. When initial carbon source was 45 g/l of mixed carbon Ⅱ (glucose:fructose=1:1), total carbon source consumption rate was slower than that from sucrose, but glucose consumption rate was faster than that from fructose.

장내세균의 락토오스 분해 유전자 확인 연구

고유라,김가은,현성희 국제차세대융합기술학회 2023 차세대융합기술학회논문지 Vol.7 No.12

유당 분해능을 확인하는 시험은 대표적으로 MacConkey 배지 배양과 ONPG 시험이다. 그러나 일부 균주 들은 유당을 분해함에도 두 시험의 생화학적 성상이 다르게 나타난다. 이에 그람 음성 장내세균 중 Escherichia coli를 포함한 12개 균주를 사용하여 유당 분해 능력을 확인하였다. 유당의 빠른 발효능력은 MacConkey 배지에서, 유당의 느린 분해능력은 ONPG disk를 사용하여 확인하였다. 12개 균주의 DNA를 추출하여 PCR 증폭과 증폭산물 의 염기서열분석법으로 Lac Z와 Lac Y 유전자를 확인하였다. Escherichia coli 외 4개의 균주에서는 MacConkey 배 지 양성과 ONPG 시험 양성으로 두 유전자가 모두 확인되었다. Edwardsiella tarda 외 4개의 균주는 MacConkey 배지 음성과 ONPG 시험 음성으로 두 유전자 모두 확인되지 않았다. Serratia marcescens는 MacConkey 배지 음성 과 ONPG 시험 양성으로 β-galactosidase 유전자는 확인되었으나 lactose permease 유전자는 확인되지 않았다. 본 연구에서 이러한 유당 분해 능력의 차이는 Lac Z (β-galactosidase)와 Lac Y (lactose permease) 두 가지 유전 자의 존재 유무에 따라 다르다는 것을 확인하였다. Tests for lactose degrading abilities are typically MacConkey medium culture and ONPG test. However, Some enterobacteriacaes show different biochemical properties of the two tests even though they degrade lactose. Lactose degradation ability was confirmed using 12 strains, including Escherichia coli. The rapid fermentation ability of lactose was observed through proliferation and color changes of neural red, which is a pH meter in MacConkey agar medium. The low fermentation ability of lactose was observed through ONPG disk. DNA of 12 strains, including Escherichia coli, was extracted and Lac Z and Lac Y genes were confirmed by PCR amplification and sequencing of amplified products. In five strains including Escherichia coli, both β-galactosidase and lactose permease genes were identified as MacConkey agar and ONPG test were both positive. In four other strains including Edwardsiella tarda, MacConkey agar and ONPG test both negative, and neither β-galactosidase nor lactose permease genes were identified. Serratia marcescens was negative for MacConkey agar and positive for ONPG test, and not lactose permease gene, but β-galactosidase gene was identified. Klebsiella pneumoniae is MacConkey agar positive and ONPG test positive, and both β-galactosidase and lactose permease genes have been identified, but it degrades lactose slowly. In this study, it was confirmed that the difference in lactose degradation ability depends on the presence or absence of two genes, Lac Z (β-galactosidase) and Lac Y (lactose permease).

과민성 장 증후군에서 유당 불내성의 의의

박기락(Ki Lack Park),박근용(Keun Yung Park),강영우(Young Woo Kang) 대한내과학회 1996 대한내과학회지 Vol.51 No.5

N/A Objectives: Some proportion of Korean patients with irritable bowel syndrome may have lactose intolerance as the prevalence of lactose intolerance in Korea is very high. This study was undertaken to determine the prevalence of lactose intolerance in Korean adults with the irritable bowel syndrome and the relationship between lactose intolerance and history of milk intolerance. Methods: 50 patients with the irritable bowel syndrome were tested for lactose intolerance by measurement of breath hydrogen excretion after ingestion of 50g of lactose. Results: 33 of the 50 patients (66%) had lactose intolerance. Twenty of 33 subjects with a history of milk intolerance had positive lactose hydrogen breath test, and thirteen of 17 subjects without it had also positive result. Therefore, there was no significant relationship between lactose intolerance and history of milk intolerance (p>0.05). Conclusion: Korean adults with irritable bowel syndrome need to be screened by lactose hydrogen breath test.

유당분해율에 따른 저지방 유당분해우유의 품질 특성

정다혜 ( Da Hye Jeong ),신용국 ( Yong Kook Shin ),강신호 ( Shin Ho Kang ) 한국유가공기술과학회 2017 Journal of Dairy Science and Biotechnology (JMSB) Vol.35 No.1

본 연구에서는 유당분해율에 따른 저지방우유의 이화학적 특성을 비교해 보고자 하였으며, 유당 함량과 빙점 값의 상관 공식을 도출하여 유당분해 제조공정상 유당분해 정도를 쉽고 빠르게 예측하고자 하였다. 우유의 빙점은 특히 유당 함량과 염류와 같은 미네랄의 변화에 따라 큰 영향을 받는다고 알려져 있는데, 본 실험에서도 10℃에서 시간이 경과함에 따라 유당이 서서히 분해되고 빙점 값도 함께 떨어짐을 확인하였다. 따라서, y=-50.416x+767.91(R²=0.9866, x값은 유당함량(g/100 mL), y값은 빙점 값(m℃))과 같은 상관식을 도출하였다. 단, 유당분해우유의 제조공정, 분해조건, 원유의 특성에 따라 다소 차이는 있을 수 있으나, 공정 표준화된 제품에는 쉽게 적용할 수 있을 것으로 보인다. 유당분해우유는 살균 방법 또는 장기간 저장 중에 마일라드 반응, 갈변화, 풍미 등에 영향을 받는다고 알려져 있으나, 이화학적 특성 분석 결과에서 유당분해율에 따른 샘플 간의 우유 단백질, 유지방, 무지유 고형분, 총 고형분, pH, 산도 값에 유의 차는 없었다(p<0.05). 또한, 색도값과 입자 크기에서도 유당분해율에 따른 샘플 간 다소 차이는 있으나, 뚜렷한 경향은 보이지 않았다. 단, 유지방 함량에 따른 입자크기는 유의적인 차이를 보였다(p<0.05). 본 연구에서는 유당분해율에 따른 저지방우유의 품질 특성을 파악할 때, 장기간 보관 중에 따른 이화학적 변화를 살펴보지 않았다는데 한계가 있다. 따라서, 향후 유당분해우유 품질에 영향을 줄 수 있는 요인인 저장 기간을 달리한 이화학적 특성을 살펴 제품에 다양하게 적용할 수 있는 방안을 모색하면 좋을 것으로 사료된다. The market for lactose-hydrolyzed milk is growing due to an increased awareness of lactose intolerance, and increased market interest for modified milk with health claims. The aim of this study was to compare the quality characteristics of 2% lactose-hydrolyzed milk with its lactose hydrolysis rate, with the goal of applying the method to dairy product monitoring in the future. We observed that the freezing point of milk significantly decreased with increasing lactose hydrolysis rate. A linear relationship was found between lactose concentration and freezing point, following the equation (y=-50.416x + 767.91). However, no significant changes were observed in other physicochemical properties of the milk (pH, titratable acidity, total solids and color) (p<0.05). In conclusion, we could predict the residual lactose content quickly and easily in 2% low fat milk by measuring its freezing point. This could represent an easy means for assessing the lactose hydrolysis rate of dairy products.

유당불내증에 효과적인 유당이 없는 낙농 유제품의 개발: 현재와 미래

천정환 ( Jung-whan Chon ),서건호 ( Kun-ho Seo ),정동관 ( Dongkwan Jeong ),송광영 ( Kwang-young Song ) 한국낙농식품응용생물학회(구 한국유가공학회) 2020 Journal of Dairy Science and Biotechnology (JMSB) Vol.38 No.1

Lactose intolerance is a pathophysiological phenomenon caused by a deficiency of the enzyme lactase present in human intestines. Changes in intestinal digestion and colon fermentation after the intake of lactose-containing products cause diarrhea and other clinical discomforts. Therefore, lactose intolerance can be easily ameliorated by consuming lactose hydrolyzed milk and dairy products. In the recent years, lactose-free dairy products have provided lactose intolerant consumers with several options, due to an improvement in the quality and an increase in the variety of products. Currently, the manufacturing of lactose-free products also represents the fastest growing sector in the dairy industry. This review, thus, aims to provide an overview of the current availability and prospects of lactose-free dairy products, and also discuss the potential benefits of the development of a variety of lactose-free dairy foods.