The Impact of AT1002 on the Delivery of Ritonavir in the Presence of Bioadhesive Polymer, Carrageenan

송건형,Natalie D. Eddington 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

New insights into the modification of the tight junctions theoretically offer the opportunity to regulate the diffusion barrier and then make it possible to investigate a permeation enhancer of low-bioavailability therapeutic agents. AT1002, a minimum biologically active fragment of zonula occludens toxin which reversibly opens intercellular tight junctions after binding to the Zonulin receptor, increased the transport of various molecular weight markers or low-bioavailability agents. The objective of this study was continuously to evaluate the permeationenhancing ability of AT1002 in the presence of the bioadhesive agent, carrageenan after intranasal administration of the antiretroviral drug, ritonavir, and the permeation enhancement ratio compared with the previous results. The permeation-enhancing effect of AT1002 was significantly promoted by the bioadhesive agent, carrageenan. The administration of ritonavir with AT1002 and carrageenan resulted in a 2.55-fold increase in AUC0-240min and a 2.48-fold increase in Cmax compared with the control group. However, AT1002 in the absence of carrageenan did not produce a statistic enhancement in the absorption of ritonavir. Hence, AT1002together with the addition of carrageenan may open a new approach of research in the tight junction modulated permeation enhancer, and allow the development of the mucosal drug delivery of therapeutic agents.

The Influence of Stabilizer and Bioadhesive Polymer on the Permeation- Enhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker

송건형,Natalie D. Eddington 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.2

Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential. Thus, this paper focused on the susceptibility of AT1002 for identifying additives to minimize the instability of AT1002, and the permeation-enhancing effect of AT1002 when co-administered with a bioadhesive polymer. The stability study showed that AT1002 were unstable in neutral to basic pH conditions and with increasing incubation time, and 5% dextrose and the 1% mixture of amino acids (arginine, cysteine, glycine) significantly minimized the instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the intranasal study of a paracellular marker, the administration of mannitol with AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17-fold increases in Cmax and AUC0-360min in the presence of carrageenan over the control. Thus, the addition of carrageenan as a bioadhesive polymer and dextrose as a stabilizer together with AT1002 may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents.

아테놀롤의 비강 및 장관 투과에 대한 C-말단 변형 밀착결합 조절제와 프룩토스 폴리머의 영향

송건형 대한약학회 2019 약학회지 Vol.63 No.1

Zonula occludens toxin has been shown to reversibly open tight junctions in endothelial and epithelial cells. The purpose of this study was to evaluate the permeation activity of C-terminal amidated fragment of Zonula occludens toxin and co-administration with a fructose polymer on enhancing the nasal and duodenal administration of atenolol. The C-terminal amidated peptide (Phe-Cys-Ile-Gly-Arg-Leu-NH2) resulted in statistically significant improvement in permeation of atenolol compared to the control in both nasal and duodenal administration. Also, the permeability enhancing effect of the C-terminal amidated peptide was significantly promoted by the fructose polymer, levan. C-terminal amidated peptide together with the addition of levan may be promising as a tight junction modulated permeation enhancer, and allow the development of the mucosal drug delivery of low bioavailability therapeutic agents.

동물 쥐에서 상·하지의 근비대를 유도하는 점증적 저항성 운동모형의 개발

채정훈,김철현,송건형 순천향대학교 기초과학연구소 2018 순천향자연과학연구 논문집 Vol.24 No.2

The purpose of this study is to develop hypertrophy-induced graded resistance model for leg muscles by modifying the ladder resistance exercise model. After modified ladder resistance exercise, thirty SD rats randomly divided control group(CON; n=15) and progressive resistance exercise group(PRT; N=10). PRT had trained progressive resistance exercise with modified ladder exercise for eight weeks. When rats had finished the 8-week resistance training program, dissected upper muscle(biceps; Bi, triceps; Tri) and hindlimb muscle(vastus lateralis; VL, tibialis anterior; TA, soleus; Sol, plantaris; Plan, extensor digitorum longus; EDL, flexor hallucis longus; FHL). Which are compared with absolute muscle weight and relative muscle weight in CON vs PRT. Exercise load is more increased 400%(pre:294±46g, post:1393±93g) in PRT group and relative muscle weight significantly more higher in VL(1258.3±145.5μg), Sol(167.3±10.2μg), Plan(444.6±25.7μg) in PRT than CON(VL(1639.2±437.9μg), Sol(181.2±15.0μg), Plan(474.9±41.2 μg) (p<0.05) but not absolute muscle weight. TA relative muscle weight is not significantly different, but relative muscle weight is higher in PRT(2.0±0.1μg) than CON(1.9±0.1μg)(p<0.05). FHL muscle weight(relative: 533.6±46.3μg, absolute: 1.3±0.1μg) is significantly higher than CON. Relative muscle(PRT: 1883±244.7μg, CON: 1679.6±247.7μg) and absolute muscle(PRT: 260.6±49.3μg, CON: 216.9±35.2μg) in upper arm(Bi, Tri) are significantly higher in PRT. According to this results, modified ladder models has hypertrophied both upper and hind limb muscles. This resistance exercise animal model is useful to find out of muscle hypertrophy mechanism. Keywords : Resistance exercise, Animal model, Upper·hind limb muscle, Muscle hypertrophy

맞춤형 기계적 외골격 보조기를 이용한 보행훈련 프로그램이 마비장애인과 간병인 삶의 질에 미치는 영향

최혁재,김규석,강성재,류제청,송건형,고창용 한국재활복지공학회 2019 재활복지공학회논문지 Vol.13 No.2

The purpose of this study is to investigate the effects of gait training program on the quality of life of the spinal cord injury and caregivers after wearing a customized body-powered mechanical exoskeletal orthosis(CBMEO). The subjects of the present study were five patients who had chronically complete thoracic spinal cord injury over two years after accident and five female family-caregivers who care for them. the quality of life for the paraplegia and caregivers were assessed through a short-form 36. The results of the caregiver showed that physical PF score increased significantly from the pri-test (17.7 ± 3.8) to post-teat (19 ± 3.5) (p<0.05). There were significant increments in mental items in VT, SF, and MH items (p<0.05). Therefore, it seems to be beneficial to improve the quality of life of caregivers by the "Gait Training Program" with CBMEO. In the future, we will be able to improve the quality of life and the continuous monitoring of health status based on the study of quality of life for the subjects with the paraplegia and caregivers. 본 연구에서는 기계적 외골격 형태의 왕복보행보조기 착용 후 적용한 보행훈련 프로그램이 척수손상장애인과 간병인의 삶에 질에 미치는 영향에 대해 규명하고자 한다. 연구대상자는 손상 후 2년 이상 경과한 흉추 수준의 완전 척수손상장애 5명과 척수장애인을 돌보는 여성 가족간병인 5명을 대상으로 연구를 진행하였다. 장애인과 간병인에 대한 삶의 질을 short-form 36 도구를 통해 사전(참가 전) 사후(1년 후) 검사를 진행하였다. 간병인에 대한 연구결과는 신체적 항목 PF 점수 사전(17.7±3.8)에서 사후(19±3.5)로 유의하게 증가하였다(p<0.05). 정신적 항목은 VT, SF, MH 항목에서 유의한 증가가 다수 나타났다(p<0.05). 따라서 맞춤형 기계적 외골격을 통한 보행훈련 프로그램이 간병인의 삶의 질 개선에 유익하다고 사료된다. 향후 삶의 질과 건강상태에 대한 지속적인 모니터링과 이에 관한 연구는 척수손상장애인과 간병인에 대한 삶의 질을 향상 시킬 수 있을 것이다.