The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Inhalable Microparticles of Socheongryong-tang on Chronic Obstructive Pulmonary Disease in a Mouse Model

COPD 동물 모델에서 소청룡탕 흡입제형의 효과

  • Lee, Eung-Seok (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University) ;
  • Han, Jong-Min (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University) ;
  • Kim, Min-Hee (Dept. of Neurophysiology, College of Oriental Medicine, Daejeon University) ;
  • Namgung, Uk (Dept. of Neurophysiology, College of Oriental Medicine, Daejeon University) ;
  • Yeo, Yoon (College of Pharmacy, Purdue University) ;
  • Park, Yang-Chun (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University)
  • 이응석 (대전대학교 한의과대학 폐계내과학교실) ;
  • 한종민 (대전대학교 한의과대학 폐계내과학교실) ;
  • 김민희 (대전대학교 한의과대학 신경생리학교실) ;
  • 남궁욱 (대전대학교 한의과대학 신경생리학교실) ;
  • 여윤 (퍼듀대학교 약학대학) ;
  • 박양춘 (대전대학교 한의과대학 폐계내과학교실)
  • Received : 2013.04.23
  • Accepted : 2013.05.21
  • Published : 2013.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: This study aimed to evaluate the effects of microparticles of Socheongryong-tang (SCRT) on chronic obstructive pulmonary disease (COPD) in a mouse model. Methods: The inhalable microparticles containing SCRT were produced by spray-drying with leucine as an excipient, and evaluated with respect to the aerodynamic properties of the powder by Andersen cascade impactor (ACI). Its equivalence to SCRT extract was evaluated using lipopolysaccharide (LPS) and a cigarette-smoking (CS)-induced murine COPD model. Results: SCRT microparticles provided desirable aerodynamic properties (fine particle fraction of $49.6{\pm}5.5%$ and mass median aerodynamic diameter of $4.8{\pm}0.3{\mu}m$). SCRT microparticles did not show mortality or clinical signs over 14 days. Also there were no significant differences in body weight, organ weights or serum chemical parameters between SCRT microparticle-treated and non-treated groups. After 14 days the platelet count significantly increased compared with the non-treated group, but the values were within the normal range. Inhalation of SCRT microparticles decreased the rate of neutrophils in blood, granulocytes in peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) and level of TNF-${\alpha}$ and IL-6 in BALF on COPD mouse model induced by LPS plus CS. This effect was verified by histological findings including immunofluorescence staining of elastin, collagen, and caspase 3 protein in lung tissue. Conclusions: These data demonstrate that SCRT microparticles are equivalent to SCRT extract in pharmaceutical properties for COPD. This study suggests that SCRT microparticles would be a potential agent of inhalation therapy for the treatment of COPD.

Keywords

Acknowledgement

Supported by : 한국연구재단

References

  1. Statistics Korea. Cause of death statistics 2011. 2012; [2screens]. Available at: URL:http://kosis.kr/ups/ups_ 01List01.jsp?pubcode=YD. Accessed Sep 20, 2012.
  2. Mannino DM, Kiriz VA. Changing the burden of COPD mortality. Int J Chron Obstruct Pulmon Dis. 2006;1(3):219-33.
  3. Mannino DM. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest 2002;121:121S-26S. https://doi.org/10.1378/chest.121.5_suppl.121S
  4. Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6): 932-46. https://doi.org/10.1183/09031936.04.00014304
  5. Barnes PJ, Hansel TT. Prospects for new drugs for chronic obstructive pulmonary disease. Lancet. 2004; 364(9438):985-96. https://doi.org/10.1016/S0140-6736(04)17025-6
  6. Jung SK, Jung HJ, Kim JD, Choi HY, Park MY, Park YC, et al. Pye-gye-nae-gwa-hak. Seoul: Nado. 2011:510-1.
  7. Lee H, Kim Y, Kim HJ, Park S, Jang YP, Jung S, et al. Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease. Evid Based Complement Alternat Med. 2012;2012:769830. Epub 2012 Jun 12.
  8. Lee JG, Yang SY, Kim MH, Namgung U, Park YC. Protective effects of Socheongryong-tang on Elastase-Induced Lung Injury. J Korean Oriental Med. 2011;32(4):83-99.
  9. Yoon JM, Park YC. Protective effects of Seonpyejeongcheon-tang on Elastase-induced Lung Injury. J Korean Oriental Med. 2010;31(1):84-101.
  10. Choi HJ, Bang NY, Song BW, Kim NJ, Rhyu BH. Survey on the preference for the dosage forms of oriental herbal medicine. Kyunghee Medicine. 2004;20(1):46-57.
  11. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J. 2006;28(5):1042-50. https://doi.org/10.1183/09031936.00074905
  12. Courrier HM, Butz N, Vandamme TF. Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst. 2002;19(4-5):425-98. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v19.i45.40
  13. Zhang J. Shang-han-za-bing-lun. Shijiazhuang. Hebei Kezue Jishu Chubanshe. 1994. p.27.
  14. Jung S, Cho SJ, Moon KI, Kim HW, Kim BY, Cho SI. Effects of Socheongryong-Tang on Immunoglobulin Production in Asthmatic Mice. Kor. J. Herbology. 2008;23(1):23-8.
  15. Kim KY, Lee JH, Kim YJ, Choi SY, Kim TH, Lyu YS, et al. Anti-allergic effects of Socheongyoung-tang on RBL-2H3 mast cell and mice-mediated allergy model. Korean J. Oriental Physiology & Pathology. 2007;21(5):1260-70.
  16. Hwang WS, Lee JS, Choi JY, Jung HJ, Rhee HK, Jung SK. Two Cases of Chronic Sinusitis with Asthma Improved by Socheongryong-tang. J Korean Oriental Med. 2003;24(1):207-12.
  17. Jung SK, Heo TS, Hwang WS, Ju CY, Kim YW, Jung HJ. The Effects of Sochongryong-tang on Serum IL-4, IL-5, and IFN-$\gamma$ in asthmatic Patients. J Korean Oriental Med. 2002;23(2): 70-7.
  18. Ibrahim BM, Jun SW, Lee MY, Kang SH, Yeo Y. Development of inhalable dry powder formulation of basic fibroblast growth factor. Int J Pharm. 2010;385(1-2):66-72. https://doi.org/10.1016/j.ijpharm.2009.10.029
  19. Thiel CG. Cascade impactor data and the lognormal distribution: nonlinear regression for a better fit. J Aerosol Med. 2002;15(4):369-78. https://doi.org/10.1089/08942680260473443
  20. Nemzek JA, Bolgos GL, Williams BA, Remick DG. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res. 2001;50(10):523-7. https://doi.org/10.1007/PL00000229
  21. Hillery AM, Lloyd AW, Swarbrick J. Drug delivery and targeting; for pharmacists and pharmaceutical scientists. London:Taylor and Francis. 2001:2.
  22. Tayab ZR, Hochhaus G. Pharmacokinetic/pharmacodynamic evaluation of inhalation drugs: application to targeted pulmonary delivery system s.Expert Opin Drug Deliv. 2005;2(3):519-32. https://doi.org/10.1517/17425247.2.3.519
  23. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532-55. https://doi.org/10.1164/rccm.200703-456SO
  24. Geller DE. Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir Care. 2005;50(10):1313-21.
  25. Borgstrom L. On the use of dry powder inhalers in situations perceived as constrained. J Aerosol Med. 2001;14(3):281-7. https://doi.org/10.1089/089426801316970231
  26. Yang Y, Tsifansky MD, Shin S, Lin Q, Yeo Y. Mannitol-guided delivery of Ciprofloxacin in artificial cystic fibrosis mucus model. Biotechnol Bioeng. 2011;108(6):1441-9. https://doi.org/10.1002/bit.23046
  27. Yang Y, Tsifansky MD, Wu CJ, Yang HI, Schmidt G, Yeo Y. Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis. Pharm Res. 2010;27(1): 151-60. https://doi.org/10.1007/s11095-009-9991-2
  28. Lipworth BJ. Targets for inhaled treatment. Respir Med. 2000;94:S13-6. https://doi.org/10.1016/S0954-6111(00)80135-3
  29. Azarmi S, Lobenberg R, Roa WH, Tai S, Finlay WH. Formulation and in vivo evaluation of effervescent inhalable carrier particles for pulmonary delivery of nanoparticles. Drug Dev Ind Pharm. 2008;34(9):943-7. https://doi.org/10.1080/03639040802149079
  30. Molfino NA, Jeffery PK. Chronic obstructive pulmonary disease: Histopathology, inflammation and potential therapies. Pulm Pharmacol Ther. 2007;20(5):462-72. https://doi.org/10.1016/j.pupt.2006.04.003
  31. Yoo CG. Pathogenesis and pathophysiology of COPD. The Korean Journal of Medicine. 2009;77:383-400.
  32. Niewoehner DE, Kleinerman J, Rice DB. Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med. 1974;291(15):755-8. https://doi.org/10.1056/NEJM197410102911503
  33. Schaberg T, Haller H, Rau M, Kaiser D, Fassbender M, Lode H. Superoxide anion release induced by platelet-activating factor is increased in human alveolar macrophages from smokers. Eur Respir J. 1992;5(4):387-93.
  34. Wright JL, Cosio M, Churg A. Animal models of chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2008;295(1): L1-15 https://doi.org/10.1152/ajplung.90200.2008
  35. Wright JL, Sun JP. Effect of smoking cessation on pulmonary and cardiovascular function and structure: analysis of guinea pig model. J Appl Physiol. 1994;76(5):2163-8.
  36. Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7:CD002991.
  37. Tanino M, Betsuyaku T, Takeyabu K, Tanino Y, Yamaguchi E, Miyamoto K, et al. Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema. Thorax. 2002;57(5):405-11. https://doi.org/10.1136/thorax.57.5.405
  38. Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996;153 (2):530-4. https://doi.org/10.1164/ajrccm.153.2.8564092
  39. Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respir Res. 2006;7:53. https://doi.org/10.1186/1465-9921-7-53
  40. Foronjy R, D'Armiento J. The role of collagenase in emphysema. Respir Res. 2001;2(6):348-52. https://doi.org/10.1186/rr85

Cited by

  1. 만성폐쇄성폐질환 동물모델에 대한 射干湯 및 구성약물의 효과 vol.23, pp.2, 2015, https://doi.org/10.14374/hfs.2015.23.2.171
  2. 만성폐쇄성폐질환 및 미세먼지 유발 폐손상 동물모델에서 과루행련환의 효과 vol.38, pp.3, 2017, https://doi.org/10.22246/jikm.2017.38.3.353
  3. Effects of GHX02 on Chronic Obstructive Pulmonary Disease Mouse Model vol.39, pp.4, 2013, https://doi.org/10.13048/jkm.18040
  4. 만성폐쇄성폐질환 동물모델에서 SGX01의 폐손상 억제 효과 vol.40, pp.4, 2019, https://doi.org/10.22246/jikm.2019.40.4.567
  5. Inhibitory Effects of GGX on Lung Injury of Chronic Obstructive Lung Disease (COPD) Mice Model vol.42, pp.3, 2021, https://doi.org/10.13048/jkm.21025