Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
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Effects of Biodegradable Cephalexin Microspheres in Dry Cow Mastitis Therapy

젖소의 건유기 유방염 치료에 있어서 생분해 cephalexin microspheres의 효과

  • Published : 2002.06.01
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Abstract

Mastitis is the most costly disease results in lost milk production, decreased milk quality, milk discard, early culling of cows, drug costs and labor costs in dairy cow. Until now, a antibiotic administration at the end of lactation, dry cow therapy has been known the most effective and widely used mastitis control method. However, dry cow therapy do not control a new infection in the late dry and prepartum period because dry cow products have only persistent activity in the early dry period. Therefore, this study was conducted to evaluate clinical effect of sustained released biodegradable cephalexin microsphere using PLGA in bovine mastitis control during dry period. PLGA has been approved as controlled drug release system because of non-toxic, non-tissue reactive and bioerodible characteristics. This study revealed that cephalexin microsphere had a spherical shape with characteristic porous structure on the surface. Also, in vitro drug release studies are clearly observed that the release rate of cephalexin from PLGA microsphere decrease during the first 21 days after initial burst and then increase again between 3 and 4 weeks showing pulsatile releasing pattern. On the other hand, as tried in field the new infection rate, cure rate and mean SCC after parturition in cephalexin microsphere infused group were significantly differenced as compared to the control group. Accordingly, a sustained release of cephalexin from a biodegradable microsphere could make dry cow therapy more efficiently by preventing a new infection and decreasing the number of existing infection of mammary gland during dry period.

유방염은 젖소에 있어서 유량의 감소, 유질 저하로 인한 우유 폐기문제, 젖소의 도태, 치료비 및 노동력의 부담등을 초래하는 가장 경제적 손실이 큰 질환이다. 현재까지 비유기 최종 착유 후에 항생제를 주입하는 건유기 치료법이 유방염 관리에 가장 효과적이며 폭넓게 쓰이고 있는 방법으로 알려져 있다. 하지만, 건유기 치료는 건유기 주입 항생제 제품들이 건유기 초기에만 지속적인 활성을 지니기 때문에 건유기 말기와 분만 전기에 있어서의 신규 감염은 방어할 수 없다. 따라서 본 연구는 건유기 유방염 관리를 위해 PLGA를 이용한 서방형 생분해 cephalexin microsphere를 제조하여 이의 임상적 효능을 평가하고자 하였다. PLGA는 무독성의 조직 반응을 일으키지 않는 특성으로 인해 약물 방출 조절 체계의 일환으로 인정을 받아왔다. 본 연구에서 cephalexin microsphere는 표면에 특징적인 구멍을 가지고 있는 구형 모양으로 확인이 되었으며 약물 방출 시험에서 초기 과다 방출 이후로 21일간 약물의 방출이 점차 감소한 뒤 3주와 4주 사이에 2차 방출을 보이는 맥동성 방출 양상이 관찰되었다. 현장적용 시험에서는 cephalexin microsphere를 주입한 실험군에서 대조군에 비해 분만 후 신규 감염율 및 치료율, 평균 체세포 수의 변화의 측면에서 볼 때 유의성 있는 차이가 있음을 확인하였다. 따라서 생분해 microsphere를 이용한 건유기 치료법은 건유기 동안 신규 감염을 예방하고 기감염을 감소시킴으로써 종전의 건유기 치료를 좀 더 효과적으로 증진시킬 수 있을 것으로 사료된다.

Keywords

References

  1. Bulletin C-12254 Dry cow therapy Arlington VA
  2. J Contr Rel v.31 Effect of temperature on mechanism of drug release and matrix degradation of poly(d,l-lactide-co-glycilide) microsphere Aso Y;Yoshioka S;Po ALW;Terao T https://doi.org/10.1016/0168-3659(94)90248-8
  3. Pham Dev Technol v.4 Microencapsulation of antimicrobial ceftiotur drug Bodmeier C;Huagang RGW;Davidson GEH
  4. J Contr Rel v.15 Pseudoephedrine HCI microspheres formulated into an oral suspension dosage form Bodmeier R;Chen H;Tyle P;Jarosz P https://doi.org/10.1016/0168-3659(91)90104-L
  5. Int J Pharm v.51 The effect of the addition of low molecular weight poly(D,L-lactide) drug release from biodegradable poly(D,L-lactide) drug delivery system Bodmeier R;Oh KH;Chen H https://doi.org/10.1016/0378-5173(89)90068-9
  6. Third European Symposium on Controlled Drug Delivery Polimeric microparticles prepared by solvent evaporation and spray-drying techniques Bodmeier R
  7. J Pharm Pharmacol v.48 Biodegradable injectable implant systems for long term drug delivery using poly(d,l-lactide-co-glycilic) acid copolymer Chandrashekar G;Udupa N https://doi.org/10.1111/j.2042-7158.1996.tb03948.x
  8. J Contr Rel v.47 Recombinant human growth hormone poly(lactide-co-glycolic acid) (PLGA)microspheres provide a long lasting effect Cleland, JL;Duenas ET;Daugherty AL;Marian M;Yang J;Wilson M;Celniker AK;Shahzamani A;Quarmby V;Chu H;Mukku V;Mac A;Roussakis M;Gillete N;Boyd B;Yeung D;Brooks D;Maa YF;Hsu C;Jones AJS https://doi.org/10.1016/S0168-3659(96)01625-2
  9. Br Vet J v.143 no.5 Efficacy and financial valure of antibiotic treatment of bovine clinical mastitis during lactation, a review Craven N https://doi.org/10.1016/0007-1935(87)90018-2
  10. Proc. IDF Seminar on Mastitis Control. Int. Dairy Fed v.85 The role of antibiotic treatment at drying off in the control of mastitis Dodd FH;Griffin TK
  11. J Dairy Sci v.69 Management of dry cows to reduce mastitis Eberhart RJ https://doi.org/10.3168/jds.S0022-0302(86)80591-4
  12. Proc 21st Annu Mtg., Natl. Mastitis Counc New infection in the dry period Eberhart RJ
  13. Advanced Drug Delivery Review v.50 Bovine mastitis and intramammary drug delivery : review and perspectives Gruet P;Maincent P;Berthelot X;Kaltsatos V https://doi.org/10.1016/S0169-409X(01)00160-0
  14. Eur J Pharm Biopharm v.45 no.1 Biodegradable somatostain acetate containing microspheres prepared by various aqueous and non aqueous solvent evaporation techniques Herrman J;Bodmeier R https://doi.org/10.1016/S0939-6411(97)00125-2
  15. Int J Pharm v.126 Somatostatin containing biodegradable microspheres prepared by a modified solvent evaporation method based on W/O/W-multiple emulsion Herrman J;Bodmeier R https://doi.org/10.1016/0378-5173(95)04106-0
  16. J Contr Rel v.13 Biodegradable polymer systems for the sustained release of polypeptides Hutchinson FG;Furr BJA https://doi.org/10.1016/0168-3659(90)90018-O
  17. Biomaterials v.13 Controlled cisplantin delivery system using poly(d,l-lactic acid) Ike O;Schumizu Y;Wada R;Hyon SH;Ikada Y https://doi.org/10.1016/0142-9612(92)90189-U
  18. Drug Dev Ind Pharm v.24 Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches Jain R;Shah NH;Malick AW;Rhodes CT https://doi.org/10.3109/03639049809082719
  19. JAVMA v.204 no.8 Recent progress in treatment and control of mastitis in cattle: clinical update John HK;Fred D;Tyler J
  20. J Contr Rel v.33 Development of an in situ forming biodegradable poly-lactide-co-glycolide system for the controlled release of protein Lambert WJ;Peck KD https://doi.org/10.1016/0168-3659(94)00083-7
  21. Med Devices Art Org v.13 no.3;4 Microencapsulation and controlled release of insulin from polylactic acid microcapsules Lin YS;Ho TL;Chiou LH
  22. Mast Res Soc Bull v.21 The importance of new processing techniques in tissue engineering Lu L;Mikos AG
  23. J Contr Rel v.25 Gentamicin/poly(lactic acid) blends aimed at sustained release local antibiotics therapy administered per-operatively:Ⅲ. The case of gentamicin sulfate films prepared from high and low molecular weight poly(d,l-lactic acids) Mauduit J;Bukh N;Vert M https://doi.org/10.1016/0168-3659(93)90093-K
  24. In practice v.13 Intramammary treatment of mastitis in cows McKeller Q https://doi.org/10.1136/inpract.13.6.244
  25. J Dairy Sci v.54 Therapy : one component in a mastitis control system Natzke RP https://doi.org/10.3168/jds.S0022-0302(71)86131-3
  26. J Dairy Res v.17 Udder infection in the?dry period? Neave FK;Dodd FH;Henriques E https://doi.org/10.1017/S0022029900005628
  27. J Contr Rel v.25 Preparation of biodegradable nanospheres of water soluble and insoluble drugs with d,l-lactide-co-glycolide copolymer by a novel spontaneous emulsification solvent diffusion method and the drug release behavior Niwa T;Takeuchi H;Hino T;Kunou N;Kawashima Y https://doi.org/10.1016/0168-3659(93)90097-O
  28. Arch Pharm Res v.16 no.4 Assesment of biodegradability of polymeric microspheres in vivo: Poly(DL-lactic acid), poly(L-lactic acid) and poly(DL-lactide-co-glycolide) microsphere Oh IJ;Oh JY;Lee KC https://doi.org/10.1007/BF02977522
  29. J Dairy Sci v.66 Susceptibility of bovine mammary gland to infection during the dry period Oliver SP;BA Mitchell https://doi.org/10.3168/jds.S0022-0302(83)81913-4
  30. J Dairy Sci v.52 Role of therapy in mastitis control Philpot WN https://doi.org/10.3168/jds.S0022-0302(69)86633-6
  31. Refu Vet v.26 Dry cow treatment in the control of mastitis Rosenzuaig A
  32. J Microencapsulation v.12 no.1 Biodegradable microcapsules prepared by w/o/w technique: effects of shear force to make a primary w/o emulsion on their morphology and protein release Sah HK;Toddywala R;Chien YW https://doi.org/10.3109/02652049509051127
  33. J Pharm Sci v.75 Prolonged controlled -release of nafarelin, a luteinizing hormone-releasing hormon analogue, from biodegradable polymeric implants: influence of composition and molecular weight of polymer Sanders LM;Kell BA;McRae GI;Whitehead GW https://doi.org/10.1002/jps.2600750407
  34. Proc 21st Annu Mgt National Mastitis Council Antibiotic formulation for the dry period Schultze WD
  35. Proc 14th Annu Mtg Natl Mastitis Counc Dry cow therapy Schultze WD
  36. J Dairy Sci v.66 Effects of a selective regimen of dry cow therapy on intramammary infection and on antibiotic sensitivity of surviving pathogens Schultze WD https://doi.org/10.3168/jds.S0022-0302(83)81873-6
  37. Vet Rec v.79 Methods of reducing the incidence of udder infection in dry cows Smith A;Neave FK;Dodd FH;Brander GC https://doi.org/10.1136/vr.79.8.233
  38. J Dairy Res v.34 The persistence of cloxacillin in the mammary gland when infused immediately after the lasting milking of lactation Smith A;Neave FK;Dodd FH https://doi.org/10.1017/S0022029900012139
  39. J Dairy Sci v.68 Environmental pathogens and intramammary infection during the dry period Smith KL;Todhunter DA;Schoenberger PS https://doi.org/10.3168/jds.S0022-0302(85)80838-9
  40. Drug and the pharmaceutical sciences, Vol. 45, biodegradable polymers as drug delivery systems, chapter 1. controlled release of bioactive agents from lactide/glycolide polymers v.45 Swarbrick J;Langer R;Chasin M;Lewis DH
  41. J Bio Chem v.243 Biosynthesis of the peptidoglycan of bacterial cell wall. ?. inhibition of cross-linking by penicillins and cephalosporins: studies in Staphylococccus aureus in vivo Tipper DJ;Strominger JL
  42. J Dairy Sci v.58 In vitro growth of mastitis-associate streptococci in bovine mammary secretion Todhunter DA;Smith KL;Schoenberger PS
  43. Proc. 21st Annu. Mgt. Natl. Mastitis Counc Antibiotic formulation for the dry period Schultze WD
  44. J Contr Rel v.25 Controlled release of albumin from biodegradable poly(d,l-lactic) cylinders Zhang X;Wyss UP;Pichora D;Amsden B;Goosen MFA https://doi.org/10.1016/0168-3659(93)90095-M