盐酸米诺环素络合物温敏凝胶的制备及初步评价

doi:10.16431/j.cnki.1671-7236.2022.12.033

Abstract

Abstract: 【Objective】 The aim of this experiment was to prepare a complexed temperature-sensitive gel capable of local delivery of minocycline hydrochloride.【Method】 Minocycline hydrochloride complexes formed with calcium ions were loaded into a temperature-sensitive gel formed by poloxamer 407 (P407) and poloxamer 188 (P188). Its temperature sensitivity, characterized structure, drug content, stability, in vitro release effect and antibacterial properties were then investigated.【Result】 The temperature-sensitive gel of minocycline hydrochloride complex was prepared [JP2]with the formula of minocycline 0.25 g, P407 8 g, P188 1.5 g, CaCl₂ 0.01 g, [JP]acetic acid adjusted to pH 4.0±0.2 and deionized water in 50 mL of gel, and the appearance of minocycline hydrochloride complex temperature-sensitive gel showed a light yellow clarified solution with uniform transparency.The temperature-sensitive performance was good (gelling occurred at 31 ℃), the grid of pores formed by the gel was dense and uniformly distributed, the average particle size was 11.5 nm and the zeta potential was -3.8 mA, and the in vitro release time was up to 48 h, which was significantly longer compared with that of the raw materials.In the antibacterial performance test, the concentration of minocycline hydrochloride complex was the same as that of the raw materials.In the antibacterial performance test, the inhibition ability of minocycline hydrochloride complex warming gel did not decrease, and the antibacterial time in vitro was longer compared with that of the raw materials, the inhibition effect was good.【Conclusion】 In this study, a temperature-sensitive gel of minocycline hydrochloride complex was successfully prepared.The simulated in vitro release test and in vitro inhibition curve showed that the gel could significantly prolong the drug action time and improve the drug utilization, providing a new way of drug delivery for the clinical use of minocycline hydrochloride.

Key words: temperature-sensitive gel; minocycline hydrochloride; ion-pairing complexation; antibacterial effect

CLC Number:

S859

WANG Tianyang, MA Bei, DING Ze, DONG Tianzhen, LIU Junfeng. Preparation and Preliminary Evaluation of Minocycline Hydrochloride Complex Temperature-sensitive Gel[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(12): 4854-4865.

References

[1] ORYLSKA-RATYNSKA M, PLACEK W, OWCZARCZYK-SACZONEK A.Tetracyclines——An important therapeutic tool for dermatologists[J].International Journal of Environmental Research and Public Health, 2022, 19(12):7246-7259.
[2] GARRIDO-MESA N, ZARZUELO A, GÁLVEZ J.Minocycline:Far beyond an antibiotic[J].British Journal of Pharmacology, 2013, 169(2):337-352.
[3] GUNAWAN H, FALDIAN Y, HINDRITIANI R.Beneficial effect of minocycline as additional treatment to prednisone for pustular erythema nodosum leprosum[J].International Medical Case Reports Journal, 2022, 15:263-268.
[4] ENTEZARI Z, JAHANABADI S.Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice:Involvement of 5-ht3 receptor[J].Drug Research, 2022, 72(5):268-273.
[5] SAVADELIS M D, DAY K M, BRADNER J L, et al.Efficacy and side effects of doxycycline versus minocycline in the three-dose melarsomine canine adulticidal heartworm treatment protocol[J].Parasit Vectors, 2018, 11(1):671-678.
[6] WEI C, LIU Y, JIANG A, et al.A pharmacovigilance study of the association between tetracyclines and hepatotoxicity based on food and drug administration adverse event reporting system data[J].International Journal of Clinical Pharmacy, 2022, 44(3):709-716.
[7] MANCANO M A.ISMP adverse drug reactions:Minocycline-induced drug fever without skin rash lupus erythematosus-like eruption induced by hydroxyurea cardiotoxicity and fever induced by clozapine denosumab-induced hepatotoxicity severe cardiotoxicity induced by bevacizumab[J].Hospital Pharmacy, 2018, 53(2):93-95.
[8] DRAKE L, REYES-HADSALL S, BARBIERI J S, et al.New developments in topical acne therapy[J].American Journal of Clinical Dermatology, 2022, 23(2):125-136.
[9] SUNG J H, HWANG M R, KIM J O, et al.Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan[J].International Journal of Pharmaceutics, 2010, 392(1-2):232-240.
[10] RUAN H, YU Y C, LIU Y, et al.Preparation and characteristics of thermo responsive gel of minocycline hydrochloride and evaluation of its effect on experimental periodontitis models[J]. Drug Delivery, 2016, 23(2):525-531.
[11] LU H D, RUMMANEETHORN P, RISTROPH K D, et al.Hydrophobic ion pairing of peptide antibiotics for processing into controlled release nanocarrier formulations[J].Molecular Pharmaceutics, 2018, 15(1):216-225.
[12] LAMBS L, BRION M, BERTHON G.Metal ion-tetracycline interactions in biological fluids.Part 3.Formation of mixed-metal ternary complexes of tetracycline, oxytetracycline, doxycycline and minocycline with calcium and magnesium, and their involvement in the bioavailability of these antibiotics in blood plasma[J]. Agents and Actions, 1984, 14(5-6):743-750.
[13] JOSHI Y M, KWAK J C.The binding of divalent metal ions to polyelectrolytes in mixed counterion systems.Ⅱ.Dextransulfate-Mg²⁺ and dextransulfate-Ca²⁺ in solutions containing added NaCl or KCl[J].Biophysical Chemistry, 1981, 13(1):65-75.
[14] ZHANG Z, WANG Z, NONG J, et al.Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications[J].Biofabrication, 2015, 7(1):15006-15019.
[15] ZHOU W, DUAN Z, ZHAO J, et al.Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing[J].Bioactive materials, 2022, 17(1):1-17.
[16] 胡丹蕾, 杨钮钮, 张傲雪, 等.介孔材料的合成及其在药物传递中的研究进展[J].中国畜牧兽医, 2021, 48(4):1498-1505. HU D L, YANG N N, ZHANG A X, et al.Advance in synthesis and applications of mesoporous materials as drug delivery system[J].China Animal Husbandry & Veterinary Medicine, 2021, 48(4):1498-1505.(in Chinese)
[17] 中国兽药典委员会.中华人民共和国兽药典:2020版一部[M].北京:中国农业出版社, 2021. CHINA VETERINARY PHARMACOPOEIA COMMITTEE.Veterinary Pharmacopoeia of the People's Republic of China:2020 Edition Ⅰ[M].Beijing:China Agriculture Press, 2021.(in Chinese)
[18] 宋庆翠, 汤震, 仇益群.米诺环素胶囊对人体相对生物利用度的研究[J].中国药业, 2001, 2:27-28. SONG Q C, TANG Z, QIU Y Q.Study on the relative bioavailability of minocycline capsules in humans[J].China Pharmaceuticals, 2001, 2:27-28.(in Chinese)
[19] 刘宝玲, 楚品品, 李春玲, 等.猪链球菌临床分离株对四环素类抗生素的耐药性和耐药基因分析[J].中国畜牧兽医, 2022, 49(7):2796-2804. LIU B L, CHU P P, LI C L, et al.Analysis of resistance and resistance genes of Streptococcus suis clinical isolates to tetracyclines[J]. China Animal Husbandry & Veterinary Medicine, 2022, 49(7):2796-2804.(in Chinese)
[20] BAHRAMI F, MORRIS D L, POURGHOLAMI M H.Tetracyclines:Drugs with huge therapeutic potential[J]. Mini Reviews in Medicinal Chemistry, 2012, 12(1):44-52.
[21] GOODHART G L.Further evidence for the role of bivalent cations in human polymorphonuclear leukocyte locomotion:Recovery from tetracycline-induced inhibition in the presence of cation ionophores[J].Journal of the Reticuloendothelial Society, 1979, 25(5):545-554.
[22] ZHANG Q M, XU W, SERPE M J.Optical devices constructed from multiresponsive microgels[J].Angewandte Chemie (International ed.in English), 2014, 53(19):4827-4831.
[23] LU C, LIU M, FU H, et al.Novel thermosensitive in situ gel based on poloxamer for uterus delivery[J].International Journal of Pharmaceutics, 2015, 77:24-28.
[24] HONEDER C, ENGLEDER E, SCHÖPPER H, et al.Sustained release of triamcinolone acetonide from an intratympanically applied hydrogel designed for the delivery of high glucocorticoid doses[J].Audiology & Neurootology, 2014, 19(3):193-202.
[25] YONG C S, OH Y K, JUNG S H, et al.Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol[J].European Journal of Pharmaceutical Sciences, 2004, 23(4-5):347-353.
[26] 严昊, 冯建远, 张子仪, 等.纳米抗体的制备与临床应用研究进展[J].中国畜牧兽医, 2021, 48(2):685-694. YAN H, FENG J Y, ZHANG Z Y, et al.Progress in preparation and clinical application of nanobody[J]. China Animal Husbandry & Veterinary Medicine, 2021, 48(2):685-694.(in Chinese)
[27] WU L, CHEN W, LI F, et al.Sustained release of minocycline from minocycline-calcium-dextran sulfate complex microparticles for periodontitis treatment[J].Journal of Pharmaceutical Sciences, 2018, 107(12):3134-3142.

Preparation and Preliminary Evaluation of Minocycline Hydrochloride Complex Temperature-sensitive Gel

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