Preparation and Bioavailability of Coenzyme Q10 Xylan Nanometer Suspension Agent

doi:10.7525/j.issn.1673-5102.2020.06.017

Abstract

Abstract:

A novel copolymer-supported coenzyme Q10 formed a nanometer suspension agent and increased the water solubility of CoQ10 and improved its oral bioavailability. The quercetin-Xylan（qt-xylan） copolymer coupling was used as the basis for synthesis. The single factor experiment design was adopted， and the particle size was used as the inspection condition of the single factor experiment. The factors affecting the particle size included high pressure homogenization pressure， high pressure homogenization times， copolymer concentration， mass ratio between copolymer and CoQ10， and a series of in vitro experiments were carried out. When the homogenization pressure was 60 MPa， the number of homogenization was 7， the copolymer concentration was 1 mg·mL^-1， and the mass ratio of copolymer to CoQ10 was 1∶1， it was the best preparation process for the nanometer suspension agent， and the particle size was 166.7 nm. Under the optimum technological conditions in vitro dissolution experiment，thedissolution rate of CoQ10 nanometer suspended agent coated in artificial gastric juice（SGF） and artificial intestinal juice（SIF） was 1.89 and 1.48 times that of CoQ10 active drug， respectively. The bioavailability in vivo experiments， rat were loaded on gastric CoQ10 and nanoparticle suspension agent respectively. Then the blood drug concentration， different time points in drug absorption and metabolism of rats were detected respectively. The load of CoQ10 nanometer suspending agent in rats blood drug concentration was significantly higher than that of CoQ10 technical， and the bioavailability of CoQ10 reversed-phased was improved 2.64 times.

Key words: coenzyme Q10, xylan, nanometer suspension agent, bioavailability

CLC Number:

Q552

Xiao-Xue ZHANG, Xiu-Hua ZHAO, Yan-Jie LIU, Ling-Ling WANG, Qian ZHANG. Preparation and Bioavailability of Coenzyme Q10 Xylan Nanometer Suspension Agent[J]. Bulletin of Botanical Research, 2020, 40(6): 943-950.

Figures/Tables 9

Fig.1

Fig 2

Fig 3

Fig 4

Fig 5

Fig 6

Fig.7

Fig.8

Fig.9

References 22

1	陈玉军，庞睿，葛存慧，等.提高辅酶Q10口服生物利用度的方法与思考［J］.生物技术世界，2015，（3）：115，117.
	Chen Y J，Pang R，Ge C H，et al.Method and consideration of improving oral bioavailability of coenzyme Q10［J］.Biotechnology World，2015，（3）：115，117.
2	Camilleri M，Colemont L J，Phillips S F，et al.Human gastric emptying and colonic filling of solids characterized by a new method［J］.The American Journal of Physiology，1989，257：G284-G290.
3	杨硕晔，王乐，刘娜，等.辅酶Q10长循环脂质体及冻干制剂的制备与质量控制［J］.中国药房，2016，27（22）：3115-3117.
	Yang S Y，Wang L，Liu N，et al.Preparation and quality control of coenzyme Q10 long-circulating liposomes and lyophilized preparation［J］.China Pharmacy，2016，27（22）：3115-3117.
4	林春梅，崔海信，顾微，等.纳米化阿维菌素悬浮剂的制备及部分性质研究［J］.农业环境与发展，2009，26（3）：69-72，78.
	Lin C M，Cui H X，Gu W，et al.Preparation and partial properties of nanochemical abamectin suspension agent［J］.Agro-Environment and Development，2009，26（3）：69-72，78.
5	Chen S，Zhang Y H，Qing J，et al.Core-shell nanoparticles for co-encapsulation of coenzyme Q10 and piperine：Surface engineering of hydrogel shell around protein core［J］.Food Hydrocolloids，2020，103：105651.
6	钱雪，王祖巧，韩国平，等.辅酶Q10的药理与应用［J］.食品与药品，2006，8（1）：16-19.
	Qian X，Wang Z Q，Han G P，et al.The pharmacology and clinical application of coenzyme Q10［J］.Food and Drug，2006，8（1）：16-19.
7	陈炳志，赵瑾，王超杰，等.辅酶Q10的应用概况与合成进展［J］.化学研究，1999，10（1）：29-33.
	Chen B Z，Zhao J，Wang C J，et al.The review of the synthesis and application of CoQ10［J］.Chemical Researches，1999，10（1）：29-33.
8	Mu Y Z，Fu Y M，Li J，et al.Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug［J］.Carbohydrate Polymers，2019，203：10-18.
9	陈程，冯锁民，罗国平，等.葛根总黄酮纳米混悬剂的制备及其质量评价［J］.现代中药研究与实践，2018，32（2）：37-40，44.
	Chen C，Feng S M，Luo G P，et al.Preparation and evaluation of Pueraria flavonoids in Nanosuspeusion［J］.Research and Practice on Chinese Medicines，2018，32（2）：37-40，44.
10	吴浩天，赵京华，贾德超，等.莪术醇纳米混悬剂的制备和体外释药研究［J］.沈阳药科大学学报，2017，34（8）：623-628.
	Wu H T，Zhao J H，Jia D C，et al.Preparation of curcumenol nanosuspension and in vitro drug release study［J］.Journal of Shenyang Pharmaceutical University，2017，34（8）：623-628.
11	张剑萍，郭澄.生物样品分析中的方法学验证［J］.中国药房，2008，19（31）：2469-2471.
	Zhang J P，Guo C.Bioanalytical methodology validation［J］.China Pharmacy，2008，19（31）：2469-2471.
12	Ren J L，Sun R C，Liu C F，et al.He.Synthesis and characterization of novel cationic SCB hemicelluloses with a low degree of substitution［J］.Carbohydrate Polymers，2007，67（3）：347-357.
13	李和平，李东旭，鲁勇.蔗渣木聚糖磷酸酯的合成与表征［J］.化学研究与应用，2011，23（10）：1353-1358.
	Li H P，Li D X，Lu Y.Synthesis and characterization of bagasse xylan phosphate［J］.Chemical Research and Application，2011，23（10）：1353-1358.
14	Sauraja，Kumar S U，Kumar V，et al.pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the efficient delivery of curcumin in cancer therapy［J］.Carbohydrate Polymers，2018，188：252-259.
15	Kenawi I M，Barsoum B N，Youssef M A.Drug–drug interaction between diclofenac，cetirizine and ranitidine［J］.Journal of Pharmaceutical and Biomedical Analysis，2005，37（4）：655-661.
16	朱建芬，吴祥根.纳米混悬剂的制备方法及在药剂学中应用的研究进展［J］.中国医药工业杂志，2006，37（3）：196-200．
	Zhu J F，Wu X G.Progress of the preparation and applications in pharmaceutics of Nanosuspensions［J］.Chinese Journal of Pharmaceuticals，2006，37（3）：196-200．
17	Singh A K，Pandey H，Ramteke P，et al.Nano-suspension of ursolic acid for improving oral bioavailability and attenuation of type II diabetes：A histopathological investigation［J］.Biocatalysis and Agricultural Biotechnology，2019，22：101433.
18	Alavi S，Akhlaghi S，Dadashzadeh S，et al.Green formulation of triglyceride/phospholipid-based Nanocarriers as a novel vehicle for oral coenzyme Q10 delivery［J］.Journal of Food Science，2019，84（9）：2572-2583.
19	Weber E，Gundert-Remy U.Biological availability［J］.Arzneimittel Forschung，1975，25（7a）：1158-1162.
20	杨璇.辅酶Q₁₀纳米制剂制备、表征及其生物效应研究［D］.哈尔滨：东北林业大学，2018.
	Yang X.Preparation，characterization and biological effects of coenzyme Q₁₀ nanomaterials［D］.Harbin：Northeast Forestry University，2018.
21	董英杰，艾莉，李晓怡，等.辅酶Q₁₀胶囊的药动学与人体相对生物利用度［J］.沈阳药科大学学报，2016，33（8）：659-661，666.
	Dong Y J，Ai L，Li X Y，et al.Relative bioavailability and pharmacokinetics of coenzyme Q₁₀ capsules［J］.Journal of Shenyang Pharmaceutical University，2016，33（8）：659-661，666.
22	Boedeker B H，Lojeski E W，Kline M D，et al.Ultra-long-duration local anesthesia produced by injection of lecithin-coated tetracaine microcrystals［J］.Journal of Clinical Pharmacology，1994，34（6）：699-702.

[1]	ZU Shu-Chong. Preparation Process and Bioavailability Evaluation of β-cyclodextrin Inclusion Korean Pine Seed Oil [J]. Bulletin of Botanical Research, 2020, 40(2): 314-320.
[2]	ZHAO Xue, YANG Feng-Jian, GE Yun-Long, WANG Ling-Ling, LI Wen-Gang, DENG Yi-Ping, ZHAO Xiu-Hua. Dissolution, Bioavailability and Tissue Distribution of Artemisinin Microspheres Loaded With Porous Starch [J]. Bulletin of Botanical Research, 2019, 39(4): 604-612.