Oral delivery of insulin via mesoporous carbon nanoparticles for colonic release allows glycemic control in diabetic rats

Haorong Lin,Jia Zhang,Chaochang Yu,Yan Lu,Jie Ning,Sixian Le,Yue Li,Lin‑quan Zang 한국탄소학회 2019 Carbon Letters Vol.29 No.2

In this article, a new type of mesoporous carbon nanoparticles (MCN) was fabricated as a potential oral delivery system of insulin to reduce the adverse reactions by hypodermic injection. The mesoporous carbon nanoparticles-carried insulin (MCNI) was studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR) compared with the blank MCNs. The Brunauer–Emmett–Teller (BET) method was utilized to calculate the specific surface area. The pore volume and pore size distribution (PSD) curves were calculated by Barrett–Joyner–Halenda (BJH) model. The entrapment efficiency (EE%) and loading content (LC%) of insulin onto the MCNs were determined by RP-HPLC. In vitro insulin release from MCNI was determined in simulated intestinal fluid. To evaluate the pharmacodynamics of MCNIs orally, the variation of glycemia of diabetic rats after oral administration of MCNIs was compared with the rats receiving hypodermic injection of insulin. Besides, the absorption of FITC-labeled MCNs in HCT-116 cells was tested. The results showed that there is significant difference between MCNs and MCNIs through SEM, TEM, and FT-IR. The entrapment efficiency, loading content and in vitro insulin release met the requirements of the pharmacodynamic study. The specific surface area, pore volume and pore size of MCNIs were significantly decreased compared to that of MCNs. The pharmacodynamics study showed that the blood sugar level was significantly decreased after the oral administration of MCNIs. The FITC-labeled MCNs showed significant absorption in HCT-116 cells. The MCNIs were successfully synthesized with commendable entrapment efficiency and loading content which preferably decreased the blood sugar in diabetes rats via oral administration.

Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats

Madhukar S. Dama,M. S. Dardi,V. C. Katoch,C. Varshneya 대한수의학회 2008 JOURNAL OF VETERINARY SCIENCE Vol.9 No.1

The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 μg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals. The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 μg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.

$\beta$-Glucan 투여에 의한 조피볼락(Sebastes schlegeli)의 세균성 질병에 대한 저항성 향상

박성우,김영길,최동림,Park, Sung-Woo,Kim, Young-Gill,Choi, Dong-Lim 한국어병학회 1997 한국어병학회지 Vol.10 No.2

$\beta$-Glucan을 경구 혹은 침지투여하여 조피볼락(Sebastes schlegeli)의 비특이적 방어기작을 향상시켜 세균성 질병에 대한 저항성을 증가시키는 면역자극제로서의 효과를 알아보고자 하였다. $\beta$-Glucan을 사료에 섞어 경구투여하거나 혹은 사육수에 현탁시켜 침지투여한 후 Vibrio ordalii, Staphylococcus epidermidis 및 Edwardsiella tarda를 주사하여 인위감염으로 $\beta$-glucan의 효능을 시험하였다. V. ordalii를 주사한 결과, 1% $\beta$-glucan을 30일 동안 경구투여한 시험구는 25%의 생존율을 보였으나 $\beta$-glucan을 투여하지 않은 대조구는 3일 이내에 모두 폐사하였다. S. epidermidis를 주사한 결과, 20 및 30일 경구투여구는 95%의 높은 생존율을 보였다. 그러나 E. tarda의 인위감염시 전혀 방어효과가 없었다. V. ordalii 사균혼합구 혹은 단독 침지 시험구는 주사 후 10일 동안 전혀 방어효과가 관찰되지 않았다. 이러한 결과로 볼 때 $\beta$-glucan의 경구투여는 S. epidermidis와 V. ordalii에 효과적이나 E. tarda에는 방어효과가 없는 것으로 나타났다. The effect of $\beta$-glucan as an immunostimulant to increase resistance to bacterial diseases by enhancing non-specific defense mechanism in rockfish (Sebastes schlegeli) was examined by oral and bath administration. After oral or bath administration with $\beta$-glucan, the injection challenges with Vibro ordalii, Staphylococcus epidermidis and Edwardsiella tarda were performed to assess $\beta$-glucan efficacy. After injection of V. ordalii, oral administration for 30 days with 1% $\beta$-glucan showed 25% of survival rate. But all control fish died within 3 days after the injection. After injection of S, epidermidis, oral administration group for 20 and 30 days showed a remarkably increased survival rate of 95%. But oral administration of $\beta$-glucan to rockfish did not induce protection against experimental E. tarda infection. $\beta$-Glucan bath administration with or without formalin-killed V. ordalii showed that no protection was observed at 10 days after challenge. The results show that $\beta$-glucan to rockfish was effective to increase survival rate of bacterial infections of S. epidermidis and V. ordalii but not against E. tarda.

Benzene-Induced Hematotoxicity and Myelotoxicity by Short-Term Repeated Oral Administration in Mice

Jung-Yeon Yi,Byung-Il Yoon 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.1

Exposure dose of benzene has been postulated to be critical to induce hemopoietic malignancies. By long-term inhalation of benzene, 300 ppm has been shown to be the dose that induces high frequency of leukemia with the least animal mortality in the mouse. With regard to the benzene studies, determination of the oral dose that will be corresponding to the critical inhalation dose could be important to design the experimental protocol based on oral administration. Based on the background data such as the respiratory volume, absorption factor, and so on, we, therefore, calculated a potential oral dose that is expected to be corresponding to 300 ppm of inhalation dose. The determined oral dose was 150 ㎎/㎏ B.W. We then evaluated, using C57BL/6 mice, the toxic effects of benzene on the peripheral blood and the bone marrow (BM) by oral administration of the selected dose once a day for 1 and 2 weeks. Leukocyte, red blood cell number and BM cellularity were respectively decreased to 47.8%, 72.3% and 66.7% of the respective control level by 1-week oral administration of benzene, and to 30.8%, 60.2% and 80.2% by 2-week oral administration. Changes in the leukocyte numbers were mainly due to the marked decrease of lymphocytes. According to the results, the changes of the parameters examined were generally corresponding to the change levels by the 2-week inhalation. In conclusion, the selected dose, 150 ㎎/㎏ B.W., was a reliable dose corresponding to the 300 ppm benzene inhalation, which was verified by in vivo mouse study.

Therapeutic effects of orally administrated antioxidant drugs on acute noise-induced hearing loss

Choi, C.-H.,Du, X.,Floyd, R. A.,Kopke, R. D. Harwood Academic 2014 Free radical research Vol.48 No.3

<P><I>Objective</I>. The objective of this study was to investigate the dose-dependent therapeutic effect of the orally administrated antioxidant drugs [4-hydroxy alpha-phenyl-tert-butylnitrone (4-OHPBN) and N-acetyl-L-cysteine (NAC)] on acute noise-induced hearing loss because oral administration is the most commonly used method of drug administration due to its convenience, safety, and economical efficiency. <I>Methods</I>. Thirty chinchilla were exposed to a 105 dB octave band noise centered at 4 kHz for 6 h and randomly assigned to a control group (saline only) and three experimental groups [4-OHPBN (10 mg/kg) plus NAC (20 mg/kg), 4-OHPBN (20 mg/kg) plus NAC (50 mg/kg), and 4-OHPBN (50 mg/kg) plus NAC (100 mg/kg)]. The drugs were orally administrated beginning 4 h after noise exposure and then administered twice daily for the next 2 days. Permanent auditory brainstem response threshold shifts, distortion product otoacoustic emission threshold shifts, and the percentage of missing outer hair cell were determined. <I>Results</I>. The oral administration significantly reduced permanent hearing threshold shift, distortion product otoacoustic emission threshold shift, and the percentage of missing outer hair cell in a dose-dependent manner. <I>Discussion</I>. This result demonstrates that orally administered drugs can treat acute noise-induced hearing loss in a dose-dependent manner. This suggests that oral administration was effective in treating acute noise-induced hearing loss as in intraperitoneal administration.</P>

Biodistribution study of orally administered microplastics: PET/CT study

Jang Woo Park,Heejung Kim,Eun Sang Lee,Yiseul Choi,Hye Kyung Chung,Jae Hoon Shim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Introduction: Microplastics are generated through processes such as photolysis, weathering, and abrasion of waste plastics that are discarded or left unattended after use. Recently, as microplastics have been discovered in living organisms and foods consumed by humans, related research is rapidly increasing with the main interest in toxicology and environmental sciences. Assessing the behavior of microplastics ingested with food is important to understanding the potential toxicity of microplastics in the body. PET/CT images using radioactive isotopes in behavioral evaluation have the advantage of being quantitatively evaluated. In this study, dynamic PET/CT images were acquired using orally administered microplastics (64Cu-PVC) and the behavior of microplastics in the body was evaluated. Method: ICR mouse was used to evaluate the behavior of microplastics. For PET/CT image acquisition, nano PET/CT (Mediso, Budapest, Hungary) was used and anesthetized with oxygen containing 2.0-2.5% isoflurane during image acquisition. Then, labeling the microplastic (PVC, ≤1um) bound with NH2-NODA-GA with 64Cu (t1/2=12.7hr), was orally administered by 500 μCi/100 μl. PET/CT images were obtained immediately after oral administration and at 1 hour, 3 hours, 6 hours, 24 hours, 48 hours, and 72 hours after oral administration. CT images were used to correct for scatter and acquire anatomical information. Result & Discussion: It was confirmed that the orally administered microplastic decreased by about 97% compared to the maximum after 48 hours in the intestine. And the concentration of microplastics in the liver increased up to 6 hours after oral administration, and the concentration of microplastics decreased by 41% at 72 hours. There was no significant increase (less than 0.4 %ID/g) in microplastic concentrations in the heart, lungs, brain, and muscle. And it gradually decreased after initial increase (less than 1.0 %ID/g) in kidney and bladder. As a result, microplastics, which are macromolecular compounds ingested with food, accumulate in the liver through the intestines and are slowly excreted, suggesting a high possibility of liver toxicity. In addition, it has been demonstrated that PET/CT images using radioactive materials are helpful in the study of microplastic behavior.

Metabolite profiling of gypenoside LVI in rat after oral and intravenous administration

Dao-Jin Chen,Hua-Gang Hu,Shao-Fang Xing,Huimin Liu,Xiang-Lan Piao 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.6

Gypenoside LVI, one of the major bioactivetriterpene saponins in Gynostemma pentaphyllum, has beenregarded as a potential and promising lead drug for antitumorstrategy. To better understand the pharmacologicalactivities of the component, an investigation of its in vivometabolism is important and necessary. In the presentstudy, a liquid chromatography-ion trap time of flighttandem mass spectrometry has been utilized to discoverand identify the metabolites of gypenoside LVI in rat urineafter oral and intravenous administration. Negative electrosprayionisation mass spectrometry was used to discerngypenoside LVI and its possible metabolites in urinesamples. As a result, after oral and intravenous administration,eight and six metabolites together with gypenosideLVI were detected and identified in rat urine, respectively. As metabolites of gypenoside LVI, they have never beenreported before. Deglycosylation and dehydration werefound to be the major metabolic processes of gypenosideLVI in rat.

판소리의 유네스코 <인류 구전 및 무형유산 걸작 선언> 경위와 세계문화유산으로서의 가치

최동현(Tong hyon Choe) 판소리학회 2023 판소리연구 Vol.56 No.-

이 논문은 판소리가 유네스코 <인류 구전 및 무형유산 걸작 선언(Proclamation of Masterpieces of the Oral and Intangible Heritage of Humanity)>에 선정된 경위와 세계문화유산으로서의 가치에 대해 정리하고자 집필되었다. 2008년 6월 무형문화유산 당사국 총회에서는 ‘무형문화유산 보호를 위한 협약 운영 지침’이 제정되었다. 이 지침은 총 3장으로 되어 있는바, 긴급보호목록(Urgent Safeguarding List)과 대표목록(Representative List) 등재 절차, 기금과 국제기금, 협약에 참가한 기관 및 단체 등을 자세하게 규정하였다. 이에 따라 <인류 구전 및 무형유산 걸작 선언> 사업이 시작되었다. 그 경위는 다음과 같다. 2000년 10월 17일 <인류 구전 및 무형유산 걸작> ‘정식 신청 종목 한 종목과 잠정목록 5종’을 선정하였다. 이에 앞서 ‘사단법인 유네스코 순천협회’ 이태호 회장은 2000년 7월 <건의서 - 무형문화재 구전문화(판소리), UNESCO세계문화유산 등록을 위한 사업계획(안)>을 만들었다. ‘유네스코연맹 전북협회’(회장 윤석길)에서도 2000년 9월 14일 ‘걸작 등록 추진에 따른 정책간담회’를 개최했다. 2000년 10월에는 남원에서 ‘유네스코 한국위원회’가 주최하는 ‘무형문화재 보존을 위한 워크숍’을 개최했다. 문화재청이 판소리를 <인류 구전 및 무형유산 걸작>에 신청하기로 결정한 다음 전라북도는 판소리학회와 손을 잡고 사업을 진행했다. 신청서를 작성하기 위해서 판소리학회 회장 대행을 맡고 있던 김진영 교수가 집필위원을 구성하였다. 집필위원은 김진영 교수, 최동현 교수, 김종철 교수, 김현주 교수, 박일용 교수 등 5명으로 구성되었고, 이보형 선생이 자문을 했다. 영어 번역은 서울대학교 국어국문학과 대학원생이었던 나수호(본명 Charles La Shure. 현 서울대학교 국문과 교수)에게 맡겼다. ‘관리’와 ‘실천 계획’은 문화재청 무형문화재과에 요청해서 받은 ‘한국의 무형문화재 보호정책’과 ‘보존관리와 활용에 관한 문화재 기본 계획’을 토대로 작성하였다. 전라북도와 문화재청은 2002년 2월 6일 ‘걸작 등록신청서 작성 관련 회의’를 갖고, 신청서 및 사진첩 제작은 전라북도가 담당하고, 영상물 제작은 전라남도와 문화재청이 담당하는 것으로 결정을 했다. 사진첩 제작은 ‘한국유네스코연맹 전북협회’가 맡았다. 영상물 제작은 KBS의 최공섭 PD가 담당했다. 문화재청과 외교통상부는 2002년 6월 14일 판소리의 <인류 구전 및 무형유산 걸작 선언> 후보 신청서를 제출하였다. 본래 <인류 구전 및 무형유산 걸작 선언>은 2003년 6월 30일에 이루어질 예정이었으나 지체되어 11월 7일에야 이루어졌다. 판소리가 <인류 구전 및 무형유산 걸작>으로 선언된 것을 언론이나 판소리를 좋아하는 사람들은 “창조적인 인간 천재의 걸작으로서의 뛰어난 가치”에 주목한다. 그 결과 마치 걸작 선언이 자국문화의 상대적 우수성을 국제적으로 인정받는 조치로 이해하려는 경향이 있다. 물론 그런 뛰어난 가치가 있는 것은 사실이다. 그렇지만 이것이 다른 문화에 대한 우월성을 전제로 하는 것이 아님을 깊이 인식할 필요가 있다. This paper summarizes how pansori was proclaimed a “Masterpiece of the Oral and Intangible Heritage of Humanity” by UNESCO and its value as world cultural heritage. In June 2008, UNESCO’s General Assembly of the Parties to Intangible Cultural Heritage enacted the “Guidelines for the Operation of the Convention for the Protection of Intangible Cultural Heritage.” These guidelines consist of three chapters: the first stipulates in detail the procedures for registration, an urgent safeguarding list, and representative list; the second concerns funds and international funds; and the third chapter lists the institutions and organizations participating in the agreement. Accordingly, the Proclamation of Masterpieces of the Oral and Intangible Heritage of Humanity project was launched. The process for pansori was as follows. On October 17, 2000, one officially applied list and five provisional lists of Masterpieces of Human Oral and Intangible Heritage were selected. Prior to this, in July 2000, Lee Tae-ho, the Chairman of the UNESCO Suncheon Association, created a plan for registration of pansori as UNESCO World Heritage. On September 14, 2000, the UNESCO Federation Jeonbuk Association (Chairman Yoon Seok-gil) held a “policy meeting according to the promotion of masterpiece registration.” In October 2000, a workshop hosted by the UNESCO Korean Committee was held to preserve intangible cultural properties. After the Cultural Heritage Administration decided to apply for the registration of pansori as a Masterpiece of Human Oral and Intangible Heritage, Jeollabuk-do teamed up with the Pansori Society to implement the project. In order to complete the application, Professor Kim Jin-young, who was acting chairman of the Pansori Society, formed a writing committee consisting of five members: Professors Kim Jin-young, Choi Dong-hyun, Kim Jong-chul, Kim Hyun-joo, and Park Il-yong, with Lee Bo-hyung consulting. The English translation was entrusted to Na Soo-ho (real name Charles La Shure), currently professor of the Department of Korean Language and Literature, Seoul National University, and at that time a graduate student in the Department of Korean Language and Literature, Seoul National University. The management and action plans were prepared based on “Korea’s Intangible Cultural Heritage Protection Policy” and “Basic Cultural Heritage Plan on Preservation Management and Utilization,” received upon request from the Intangible Cultural Heritage Division of the Cultural Heritage Administration. Jeollabuk-do and the Cultural Heritage Administration held a meeting on February 6, 2002, where it was decided that Jeollabuk-do would be in charge of the applications and photo albums, while Jeollanam-do and the Cultural Heritage Administration would produce the videos. The photoalbums were produced by the Korean UNESCO Federation Jeonbuk Association. KBS producer Choi Gong-seop was responsible for producing the video. On June 14, 2002, the Cultural Heritage Administration and the Ministry of Foreign Affairs and Trade submitted an application for pansori to be included in the Proclamation of Masterpieces of the Oral and Intangible Heritage of Humanity. The proclamation was originally scheduled to take place on June 30, 2003, but it was delayed and only took place on November 7. When pansori was declared a “Masterpiece of Oral and Intangible Heritage of Humanity,” the media and pansori lovers noted the statement of its “outstanding value as a masterpiece of creative human genius.” Furthermore, there is a tendency for a masterpiece declaration to be taken as an internationally recognized measure of the relative excellence of its culture. Of course, while it is true that this recognition indicates great worth, it is necessary to remember that this does not presuppose superiority over other cultures.

Oral Administration of Novel Oriental Medicine, KIOM-C, Protect against Influenza Virus

김은하,이준한,송민석,백윤희,최영기,마진열 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.3

The influenza virus is one of the important respiratory risks affecting humans which require effective treatments. Some oriental medicines are currently treated for common cold as well as influenza infection. Previous studies have reported that the therapeutic properties of oriental medicines are able to treat psoriasis antiasthmatic and atopic dermatitis. In this study, we investigated the therapeutic properties of the novel herbal medicine, KIOM-C, for the treatment of influenza virus infection by oral administration. KIOM-C is an active natural biological compound from herbal-marine origin. The results showed that oral administration of mice with KIOM-C could confer a survival benefit against Type A influenza virus infection. Daily oral administration of KIOM-C delayed the death in infected mice for three days against mouse adapted H3N2 (A/Philippines/2/82). However, it protected more than 60% of mice from lethal infection of 2009 pandemic H1N1 (A/Korea/CJ01/2009) influenza virus. In addition, lung viral titers were significantly reduced at 7 days of post infection (~100 times) compared with mock-treated mice and viruses were cleared at 9 dpi only in KIOM-C treated groups. This study demonstrated that the novel herbal medicine, KIOM-C, have the potentials as a herbal remedy against influenza A viruses.

Oral Administration of Novel Oriental Medicine, KIOM-C, Protect against Influenza Virus

Jin Yeul Ma, Eun Ha Kim, Jun Han Lee, Min-Suk Song, Yun Hee Baek, Young Ki Choi 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.2

The influenza virus is an important respiratory risk affecting humans, and effective treatments are needed. Some oriental medicines are currently applied for treatment of common colds as well as influenza infection. Previous studies have reported that the therapeutic properties of MA-128 are effective for treatment of psoriasis antiasthmatic and atopic dermatitis. In this study, we investigated the therapeutic properties of the novel herbal medicine, MA-128, for treatment of influenza virus infection by oral administration. MA-128 is an active natural biological compound from herbal-marine origin. The results showed that oral administration of MA-128 in mice could confer a survival benefit against Type A influenza virus infection. Daily oral administration of MA- 128 resulted in delayed death in infected mice for three days against mouse adapted H3N2 (A/Philippines/2/82). However, it protected more than 60% of mice from lethal infection of 2009 pandemic H1N1 (A/Korea/CJ01/2009) influenza virus. In addition, lung viral titers were significantly reduced at seven days post infection (~100 times) compared with mock-treated mice and viruses were cleared at 9 dpi only in the MA-128 treated groups. This study demonstrated the potential of the novel herbal medicine, MA-128, as an herbal remedy against influenza A viruses.