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Analytical methods to manage potential impurities in drug substances (의약품 중 잠재적 불순물 관리를 위한 분석법 연구 동향)

  • Park, Kyung Min;Kim, Won Mi;Ahn, Su Hyun;Lee, Ha Lim;Hwang, Su Hyeon;Lee, Wonwoong;Hong, Jongki
    • Analytical Science and Technology
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    • v.35 no.3
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    • pp.93-115
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    • 2022
  • Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

Current Status and Perspectives of Quality Improvement in Sesame (참깨 품질 연구의 현황과 문제점 및 전망)

  • Lee, Bong-Ho;Lee, Jung-Il;Park, Rae-Kyeong
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.33 no.s01
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    • pp.86-97
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    • 1988
  • Sesame(Sesamum indicum L.) is probably the most ancient oilseed crop known in the world. The seed of sesame is used in a variety of ways as food. The whole seed may be eaten raw, either roasted or parched, or fed to birds and stock. Sesame oil is used as a salad or cooking oil, in shortening, margarine and in the manufacture of soap. Minor uses are as a fixative in the perfume industry and formerly as a carrier for fatsoluble substances in pharmaceuticals such as penicillin. One of the minor constituents of sesame oil, sesamin, is used for its synergistic effect in pyrethrin insecticides, in addition of a small quantity of this substance markedly increases the effectiveness of fly sprays. The meal remaining after oil extraction can be used as and animal feed-stuff or as manure. In general sesame meal is considered to be equal to cottonseed or soybean meal as a protein supplement for livestock and poultry. It is especially high in certain amino-acids such as methionine, which is low in soybean meal, and thus can be combined with it or similar meal to form a more balanced ration. An attempt to summarize the literature review on quality improvement of sesame was made to discuss the accomplishments of the past and perspectives in the future. The reviews on quality improvement of sesame were mainly discussed in connection with the cultural practices and genetic informations in current status. The emphasis focussed on environmental variation of quality in cultural practices, such as harvest time, variety by location, climatic condition, fertilizer application, and growth regulator treatment. On the genetic variation of quality, it was discussed on variety background, mutation breeding, correlations, and inheritance of quality related characteristics. It also was discussed on relationship between quality and plant traits, storage condition or period, and seed coat color. Moreover, current research status were reviewed on some minor elements such as sesamin, oxalic acid, and trypsin inhibitor. As a results of the review, the lack of an effort to quality improvement in each utilization area was indicated as a problem area. More active efforts for the improvement of quality were also insufficient to incorporate the available genes for quality in breeding method or collection and analysis of breeding materials. Therefore, researches in the future would be recommended to emphasize on these problem areas.

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Isolation and Structural Identification of Antioxidant Substances from Ethyl Acetate Extract of Conyza canadensis (망초(Conyza canadensis) Ethyl Acetate 추출물의 항산화성 물질의 분리와 동정)

  • Hyun Sook Song
    • Journal of Naturopathy
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    • v.12 no.1
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    • pp.7-15
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    • 2023
  • Background: As a result of analyzing the components of wild Conyza canadensis, it contains physiologically active ingredients, so it is necessary to identify the compound. Purposes: It was to study the compound's molecular structure; a previous study showed that C. canadensis contains antioxidant substances. Methods: The ultrasonic pulverized lysate of C. canadensis stem and leaves was first extracted with 90% methanol and then five organic solvents. Next, the extracts was fractionated by HPLC, LC/MS chromatography, and NMR analyzers identified the molecular structure. Results: 100 g of dry C. canadensis was sonicated in 90% methanol and concentrated under reduced pressure to 11.96 g of a crude extract. Then, this crude was extracted with five types of solvents to obtain 123.8 mg of n-hexane, 448.2 mg of dichloromethane, 1047.7 mg of ethyl acetate (EA), 2563.8 mg of butanol, and 7.04 g of water. The EA extracts were fractionated by LC-MS and then re-fractionated to obtain F1 to F20. Next, the F15 was further fractionated to obtain nine fine fractions. Finally, the F17 fraction was re-fractionated to obtain ten fine fractions. As a result of LC-MS and NMR spectrometer analysis of the F15-7, the structure of this compound was confirmed as 3,5-dicaffeoylquinic acid. As a result of examining the structures of the F17-4 and F17-5 fractions, Quercetin-3-o-β-galactose was identified. In addition, the form of the F17-10 was confirmed to be 1,3,4-tri-caffeoylquinic acid. Conclusions: This study demonstrated that C. canadensis contained phenolic antioxidants, and its utilization may be expected.

In vitro Antimutagenic and Genotoxic Effects of Sophora Radix Extracts (고삼추출물의 in vitro 항돌연변이원성과 유전독성 연구)

  • Cho, Hyeon-Jo;Yoon, Hyunjoo;Park, Kyung-Hun;Lee, Je-Bong;Shim, Chang-Ki;Kim, Jin Hyo;Jeong, Mi Hye;Oh, Jin-Ah;Kim, Doo-Ho;Paik, Min-Kyoung
    • The Korean Journal of Pesticide Science
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    • v.17 no.4
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    • pp.335-342
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    • 2013
  • Sophorae radix extract (SRE) has been registered as an environment-friendly organic material that is widely used in the cultivation of crops in Korea. Matrine, the active ingredient in SRE, was reported as a toxic substance in the nervous system in mice. However, no information is available on its toxic effects in other organisms. Therefore, antimutagenicity and two kinds of genotoxicity tests (bacterial reverse mutation and chromosome aberration test) of two samples of SRE were investigated in this study. Antimutagenicity test was experimented by using bacterial reverse mutation test. In the reverse mutation test, Salmonella Typhimurim TA98, TA1535 and TA1537 were used to evaluate the mutagenic potential of SRE. Bacterial reverse mutation test was also performed on positive and negative control groups in the presence of the metabolic activation system (with S-9 mix) and metabolic non-activation system (without S-9 mix). In the chromosome aberration test, Chinese hamster lung cells were exposed to SRE for 6 or 24 hours without S-9 mix, or for 6 hours with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by SRE treatment in all strains, indicating that SRE may have antimutagenic effects. Reverse mutation was not shown at all concentrations of SRE, regardless of application of the metabolic activation system. In the chromosomal aberration test, one of the SRE sample gave a suspicious positive result at 250 ${\mu}g/ml$ in the presence of S-9 mix. For the more adequate evaluation of the genotoxic potential of SRE samples, other in vivo genotoxicity study is needed.

Factors Related with Job Satisfaction in Workers - Through the Application of NIOSH Job Stress Model - (직장인의 직무만족도 관련요인 분석 - NIOSH의 직무스트레스 모형을 적용하여 -)

  • Kim, Soon-Lae;Lee, Bok-Im;Lee, Jong-Eun;Rhee, Kyung-Yong;Jung, Hye-Sun
    • Research in Community and Public Health Nursing
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    • v.14 no.2
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    • pp.190-199
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    • 2003
  • This study was conducted to determine the factors affecting job satisfaction in workers by using the Job Stress Model proposed by the National Institute for Occupational Safety and Health (NIOSH). Data were collected from December 1 to December 30, 1999. The subjects were 2,133 workers employed at 155 work sites, who were examined using NIOSH Job Stress questionnaire translated by the Korea Occupational Safety ${\pounds}|$ Health Academy and Occupational Safety ${\pounds}|$ Health Research Institute. SAS/PC program was used for statistical analysis using descriptive analysis. Pearson's correlation coefficient, ANOVA, and Stepwise multiple regression analysis. The results of this study were as follows. 1. According to general characteristics of the subjects, job satisfaction was high in those with less number of children. 2. By work condition, job satisfaction was higher in those who were working in a permanent job position, were working with regular time basis than with shift basis, were working in regular shift hours than in changing shift hours, were working for a short period, and were working less hours and overtime works per week. 3. In terms of physical work environment, job satisfaction was significantly related to 10 physical environmental factors. In other words, job satisfaction was high in workers who were working in an environment with no noise, bright light, temperature adjusted to an appropriate level during summer and winter, humidity adjusted to an appropriate level. well ventilation, clean air, no exposure to hazardous substance during work hour, overall pleasant work environment and not crowded work space. 4. By work-related factors, job satisfaction was high in those with less ambiguity about future job and role, high job control/autonomy, and less workload. On the other hand, job satisfaction was low in those with little utilization of competencies, and much role conflict at work and workload. 5. As for the relationships between job satisfaction and the non-work related factors, job satisfaction was high in workers who were volunteering at different organizations or active in religious activities for 5-10 hours per week. 6. In the relationships between job satisfaction and buffering factors, significantly positive correlations were found between job satisfaction and factors such as support by direct superior, support by peers, and support by spouse, friend and family. 7. There were nine factors that affected job satisfaction in the workers: age, number of children, work hours per week, noise, temperature at the work site during summer, uncomfortable physical environment, role ambiguity, role conflict, ambiguity in job future, work load, no utilization of competencies and social support from direct supervisor. These nine factors accounted for 26% of the total variance in the multiple regression analysis. In conclusion. the following are proposed based on the results of this study. 1. The most important physical environmental factors affecting job satisfaction in workers were noise, role ambiguity, and work load, suggesting a need to develop strategies or programs to manage these factors at work sites. 2. A support system that could promote job satisfaction is needed by emphasizing the roles of occupational health nurses who may be stationed at work sites and manage the factors that could generate job stress. 3. Job satisfaction is one of the three acute responses to stress proposed in NIOSH job stress model (job satisfaction. physical discomfort and industrial accidents). Therefore, further studies need to be conducted on the other two issues.

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Effect of ethanol extract of Lotus Rhizome and node of Lotus Rhizome (연근과 우절 에탄올 추출물의 향장효능 검증)

  • Jang, Young-Ah;Park, So-Hyun;Kim, Bo-Ae;Park, Jong-Yi;Jeoung, Young-Ok;Lee, Jin-Tae
    • Journal of the Korean Applied Science and Technology
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    • v.34 no.3
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    • pp.657-665
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    • 2017
  • This study is for checking the possibility of Lotus Rhizome and node of Lotus Rhizome as cosmetic materials. For this we carried out biological active evaluation about anti-oxidant, anti-inflammatory and anti-wrinkle by using ethanol extract of Lotus Rhizome and node of Lotus Rhizome. We extracted Lotus Rhizome and node of Lotus Rhizome with 95% ethanol and then in order to evaluate anti-oxidant activity we treated samples by concentrations (100, 500, 1000) ${\mu}g/mL$ and carried out 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and The activity of 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) cation radical scavenging. Also, in order to evaluate effect of anti-wrinkle we carried out evaluation of Elastase inhibitory activity. To evaluate effect of anti-inflammatory we evaluated toxicity of samples through MTT assay with a macrophage (Raw 264.7 cells) and measured nitric oxide production inhibitory activity. As a result, DPPH radical scavenging activity of Lotus Rhizome and node of Lotus Rhizome at $1000{\mu}g/mL$ was 66.7% and 99.5%, respectively and ABTS + radical scavenging activity was 51.2% and 98.3% at the same concentration, respectively. Elastase inhibitory activity results showed that the nodes of the Lotus Rhizom extract excellent anti-wrinkle efficacy than Lotus Rhizom. Node of Lotus Rhizome showed higher anti-wrinkle activity than the positive the control group BHT at $1000{\mu}g/mL$ concentration. According to the result of nitric oxide production inhibitory activity, Lotus Rhizom showed 55.8% effect and nodes of the Lotus Rhizom showed 66.6% effect respectively. This showed that effect of anti-inflammatory was greater in nodes of the Lotus Rhizom extracts. As a result it suggests that Lotus Rhizome and node of Lotus Rhizome extracts can be used as natural substance of cosmetics which are safe in antioxidant, anti-inflammatory, and anti-wrinkle.

Biochemical Studies in Relation to Chance of Materials in Process of Growth of Embyro in Silkworm Eggs (Bombyx mori L.) (가잠난 배자발육과정에서 각종내용물질의 변동에 관한 생화학적 연구)

  • 임영우
    • Journal of Sericultural and Entomological Science
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    • v.13 no.1
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    • pp.23-29
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    • 1971
  • As a result of analyzing the change of material substance of all sorts biochemically and comparing the control with ${\gamma}$-ray irradiation (800${\gamma}$, 40 Min), incubating the silkworm eggs (Bombyx mori L.) as the objective in the process of growth of embyro shortly before hatching, the following conclusion has been found. 1. Ascorbic acid has shown the maximum increase of 319 r/g in the Byong B embyro stage and in other words it has increased during the period of vigorous metabolism of the materials in eggs but it has decreased before hatching after that period. 2. Triglyceride has shown the increase of 27.54 mg/g in the Byong A stage, the early period of incubation and in other words it has increased in the period of activation of cells in eggs but it has gradually decreased during the growth of embyro after that period. Great change of either total cholesterol or free cholesterol has not been shown from the early period till shortly before hatching. 3. Free fatty acid has shown the minimum decrease of 257.4$\mu$ mole/g in the Byong A stage in which triglyceride increases greatly. On the contrary, it has shown the increase of 1, 020.0$\mu$ mole/g in Ki A stage in which triglyceride decreases. As a whole, the fact that free fatty acid increases according to the growth of embyro in eggs has been found. 4. Glucose has shown the increase of 281.2 mg/g in control during tile Pigment stage and it has shown the increase of 179.6 mg/g in ${\gamma}$-ray irradiation during the same period. The difference in quantity between the former and the latter is due to the fact that the growth of embyro has been influenced by the radio active. Glucose has changed with free fatty acid and phosphorus the other way round. 5. Control organic phosphorus has shewh the increase of 5.23mg/g during the Byong B or Ki A in which organ and tissue in the emhyro has been formed. Organic phosphorus in ${\gamma}$-ray irradiation has shown the increase of 5.73mg/g during Ki B. Inorganic phosphorus has shown only a little change in the control and ${\gamma}$-ray irradiation. The phosphorus in both has shown a little quantity in the ${\gamma}$-ray irradiation in the early period of incubation. After the Ki A embyro, it has increased rapidly and it has increased till the hatching more continually than in control. The about results of the research will be helpful and instructive to the betterment and improvement, breeding and management of animals and plants.

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The difference of photosynthetic efficiency and electron transport rate by control of the red tide organism using algicidal substance and yellow clay (살조물질과 황토를 이용한 적조생물 제어에 따른광합성 효율 및 전자전달율의 차이)

  • Son, Moonho;Baek, Seung Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.4
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    • pp.2951-2957
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    • 2015
  • The development of worldwide harmful algal blooms(HAB) is a serious problem for public health and fisheries industries. To evaluate the algicidal impact on the HAB species, algicide thiazolidinedione derivative (TD49) and yellow clay were examined, which is focus on assess the algicidal effects and inhibition to photosynthesis of HAB species. To obtain the detailed information, we analyzed the viability of target species related to activity Chl. a, photosynthetic efficiency($F_v/F_m$), and electron transport rate(ETR). Culture experiment was conducted to evaluate the algicidal effects of three harmful species(raphidophyceae Heterosigma akashiwo, Chattonella marina, and dinophyceae Heterocapsa circularisquama) and one non-harmful species (cryptophyceae Rhodomonas salina). Our experiments revealed that three HAB species were easily destroyed of the cell walls after TD49 dosing. Also, they had significantly reducing values of active Chl. a, $F_v/F_m$, and ETR, due to the damage of photosystem II by inter-cellular disturbance. As a result, the algicidal effect(%) for the three HABs were as follows, in the order of greatest to the least: H. circularisquama> C. marina> H. akashiwo. However, the algicidal effect for yellow clay remained to be <30% (p>0.01), implying that it may not have damaged the photosystem II. On the other hand, non-HAB R. salina was promoted at both TD49 and yellow clay treatments. Our results demonstrated that the TD49 is a good agent for the control of HABs H. akashiwo, C. marina, and H. circularisquama, whereas the yellow clay would not be suitable for the field application based on our experimental results.

Effects of Seomaeyakssuk (Artemisia argyi H.) Vinegar on Lipid Metabolism in Rats Fed a High-Fat and High-Cholesterol Diet (섬애약쑥 식초가 고지방-고콜레스테롤 급이 흰쥐의 체내 지질대사에 미치는 영향)

  • Shin, Jeong Yeon;Kang, Jae Ran;Shin, Jung Hye;Seo, Weon Taek;Byun, Hee Uk;Choi, Jin Sang;Kang, Min Jung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.7
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    • pp.779-789
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    • 2017
  • The effects of orally administered Seomaeyakssuk (Artemisia argyi H.) vinegar on lipid metabolism in Sprague-Dawley rats fed a high-fat and high-cholesterol (HFC) diet were analyzed. The experimental animals were divided into five groups: a normal diet group (normal, N), HFC diet group (control, C), HFC diet with lovastatin at 20 mg/kg body weight (B.W.) group (positive control, PC), HFC diet with malt vinegar group (TM), and HFC diet with Seomaeyaksuk vinegar group (TS) (2 mL/kg B.W.). After 4 weeks of feeding rats the experimental diet, contents of serum total lipids and total cholesterol levels of TM and TS groups were significantly lower than those of the PC group. Triglyceride contents of the TM and TS groups were not significantly different from those of the PC group but significantly lower than those of the C group. Content of serum high density lipoprotein-cholesterol was significantly lower than that of the N group but higher than that of the C group. Low density lipoprotein-cholesterol content of serum was 190.68 mg/dL in the TS group, which was the lowest except for the N group. Aspartate transaminase and albumin transaminase activities as a measurement of liver damage index were not significantly different between the TM, TS, and C groups. Serum thiobarbituric acid reactive substance content of the TS group was reduced to a similar level as the N group but was lower than that of the C group in the liver and significantly higher than that of the N group. Antioxidant activity of the TS group was 55.69% in serum, which was a similar to that of the N group, and was 52.39% in the liver, which was not significantly different than that of the C group. From these results, we conclude that Seomaeyakssuk vinegar improves serum lipid content as a result of the complex action of vinegar, an active ingredient of Seomaeyakssuk and a product of the fermentation process.

Enzymological Evaluation of Oral Inflammation inhibitory activity by Aloe vera peel extract (Aloe vera peel 추출물에 의한 구강염증 저해 효과의 효소학적 평가)

  • Pack, Chung-Sun;Ryu, Il-Hwan;Lee, Kap-Sang
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.753-759
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    • 2001
  • To evaluate antiinflammation of Aloe vera peel, antiimflammation substances were extracted from Aloe vera peel and identified, and we investigated the effect of the its substance the inhibitory effect on the activity of hyaluoronidase, elastase, collagenase and prostaglandin endoperoxide synthase. The water extract from Aloe vera peel were successfully purified with solvent fractionation, silica gel column chromatography, preparative thin layer chromatography and UV spectrometer. Two purified active substances were identified as aloe-emodin and barbaloin by Mass Spectrometer, $^1H-NMR$ and FT-IR. Aloe-emodin and barbaloin. $IC_{50}$ values of aloe-emodin and barbaloin against hyaluronidase activity were 40 and $70\;{\mu}g/mL$, respectively. Leuckocyte elastase, which is related to the destruction of various tissue, $IC_{50}$ values of them were 50 and $60\;{\mu}g/mL$, respectively. $IC_{50}$ values of aloe-emodin and barbaloin against collagenase activity were 40 and $60\;{\mu}g/mL$, respectively. and $IC_{50}$ values of aloe-emodin and barbaloin aganist the prostaglandin endoperoxide synthase, which play an important role in inflammatory reactions, were 40 and $70\;{\mu}g/mL$, respectively. Inhibitory effects of aloe-emodin, barbaloin and aspirin against carrageenan paw edema were 74.9, 52.9 and 51.9% as inhibiton percentage, respectively, at dose of 100 mg/kg and that of indomethancin was 49.7 at dose of 10 mg/kg. Cell cytotoxicity of barbaloin against human gingival cells was lower than that of aloe-emodin. Aloe-emodin and barbaloin did not show cytotoxicity against human gingival cells at concentration of 1.0 and $5.0\;{\mu}g/mL$, However, aloe-emodin and barbaloin showed less cytotoxicity than chlorhexidine, which usually have been used as the agent of anticaries and antiinflammation. These results suggested that aloe-emodin and barbaloin from Aloe vera peel have the effect of anticaries and antiinflammation.

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