Doxycycline hyclate
(Synonyms: 多西环素盐酸盐半乙醇半水合物; Doxycycline hydrochloride hemiethanolate hemihydrate; WC2031) 目录号 : GC13456
A broad-spectrum tetracycline antibiotic
Cas No.:24390-14-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Glioma Cells：LNT-229, G55, and U343 glioma cells |
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Preparation Method |
Doxycycline hyclate was dissolved in water (stock 1 mg/mL). The following concentrations were analyzed: 0.0, 0.1, 1, 10 g/mL. Cell growth using crystal violet staining (CV) was measured after incubation under standard conditions. |
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Reaction Conditions |
Doxycycline hyclate 0.01, 0.1, 1 or 10 µg/mL for 4 days |
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Applications |
Doxycycline hyclate affected growth of glioma cells only under high concentrations (10 µg/mL). |
| Animal experiment [2]: | |
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Animal models |
Mouse model of P. berghei malaria (Female Swiss Webster mice average of 20 g body weight) |
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Preparation Method |
Doxycycline hyclate 10 mg/kg and 50 mg/kg once daily; dissolved in PBS in a total volume of 100 μl; intraperitoneally |
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Dosage form |
10 mg/kg and 50 mg/kg, 4days |
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Applications |
In mouse model of P. berghei malaria, Doxycycline hyclate exhibited potent antimalarial activity at 50 mg/kg and activity was suboptimal at 10 mg/kg. |
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References: [1]. Luger AL, Sauer B, et,al. Doxycycline Impairs Mitochondrial Function and Protects Human Glioma Cells from Hypoxia-Induced Cell Death: Implications of Using Tet-Inducible Systems. Int J Mol Sci. 2018 May 17;19(5):1504. doi: 10.3390/ijms19051504. PMID: 29772845; PMCID: PMC5983704. [2]. Rothan HA, Mohamed Z, et,al. Inhibitory effect of doxycycline against dengue virus replication in vitro. Arch Virol. 2014 Apr;159(4):711-8. doi: 10.1007/s00705-013-1880-7. Epub 2013 Oct 19. PMID: 24142271. |
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Doxycycline hyclate is a derivative of tetracycline and possesses the activities of anti-inflammatory and antimicrobial. Doxycycline hyclate is an orally active and broad-spectrum metalloproteinase (MMP) inhibitor[5].Doxycycline hyclate treatment reduces MMP-8 and -9 levels and inhibits expression of tissue MMP-2 and MMP-9. Moreover, treatment with doxycycline hyclate significantly reduces the incidence of intracranial aneurysms. Doxycycline hyclate has also been reported to be an anti-inflammatory agent based on its inhibition of matrix metalloproteinases. In addition, doxycycline has potent antimalarial activity with IC50 value of 320nM at 96h in vitro[2 3].
Doxycycline hyclate inhibits dengue virus replication in vitro with a temperature-dependent manner. The IC50 value is 52.3μM at 37°C and 26.7μM at 40°C. It inhibits the dengue virus via inhibiting the NS2B-NS3 serine protease of the virus[5]
The ability of doxycycline hyclate to cause severe mitonuclear protein imbalance in glioma and astroglial cells, especially at high concentrations. Doxycycline hyclate had no effect on cell growth at concentrations regularly used to induce gene expression. Only the highest tested concentration of doxycycline hyclate (10 ug/mL) impaired cell growth[4].In human cell lines, commonly used concentrations of doxycycline hyclate change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption[7].Doxycyline can inhibit the viability and proliferation of breast cancer cells and BCSCs, decrease mammosphere forming efficiency, migration and invasion, and EMT of breast cancer cells. Expression of stem cell factors were also significantly downregulated after doxycycline hyclate treatment[8]
In mouse model of P. berghei malaria, Doxycycline hyclate exhibited potent antimalarial activity at 50 mg/kg and activity was suboptimal at 10 mg/kg [1].Doxycycline hyclate treatment inhibits the activity of tissue MMP and attenuates the decrease in the collagen content in aortas of mice haploinsufficient for collagen III, as well as prevents the development of stress-induced vessel pathology. The results suggest that doxycycline hyclate merits clinical testing as a treatment for vEDS(The vascular form of Ehlers-Danlos syndrome)[6]
References:
[1]: Rothan HA, Mohamed Z, et,al.Inhibitory effect of doxycycline against dengue virus replication in vitro. Arch Virol. 2014 Apr;159(4):711-8. doi: 10.1007/s00705-013-1880-7. Epub 2013 Oct 19. PMID: 24142271.
[2]:Maradni A, Khoshnevisan A, et,al. Role of matrix metalloproteinases (MMPs) and MMP inhibitors on intracranial aneurysms: a review article. Med J Islam Repub Iran. 2013 Nov;27(4):249-54. PMID: 24926188; PMCID: PMC4011417.
[3]:Draper MP, Bhatia B, et,al. In vitro and in vivo antimalarial efficacies of optimized tetracyclines. Antimicrob Agents Chemother. 2013 Jul;57(7):3131-6. doi: 10.1128/AAC.00451-13. Epub 2013 Apr 29. PMID: 23629719; PMCID: PMC3697387.
[4]: Luger AL, Sauer B, et,al. Doxycycline Impairs Mitochondrial Function and Protects Human Glioma Cells from Hypoxia-Induced Cell Death: Implications of Using Tet-Inducible Systems. Int J Mol Sci. 2018 May 17;19(5):1504. doi: 10.3390/ijms19051504. PMID: 29772845; PMCID: PMC5983704.
[5]: Manchado E, Weissmueller S, et,al. A combinatorial strategy for treating KRAS-mutant lung cancer. Nature. 2016 Jun 30;534(7609):647-51. doi: 10.1038/nature18600. Epub 2016 Jun 22. PMID: 27338794; PMCID: PMC4939262.
[6]: Briest W, Cooper TK, et,al. Doxycycline ameliorates the susceptibility to aortic lesions in a mouse model for the vascular type of Ehlers-Danlos syndrome. J Pharmacol Exp Ther. 2011 Jun;337(3):621-7. doi: 10.1124/jpet.110.177782. Epub 2011 Mar 1. PMID: 21363928; PMCID: PMC3101011.
[7]: Ahler E, Sullivan WJ, et,al. Doxycycline alters metabolism and proliferation of human cell lines. PLoS One. 2013 May 31;8(5):e64561. doi: 10.1371/journal.pone.0064561. PMID: 23741339; PMCID: PMC3669316.
[8]: Zhang L, Xu L, et,al. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer. Cell Cycle. 2017 Apr 18;16(8):737-745. doi: 10.1080/15384101.2016.1241929. Epub 2016 Oct 18. PMID: 27753527; PMCID: PMC5405729.
Doxycycline hyclate是四环素的衍生物，具有抗炎和抗菌活性。 Doxycycline hyclate 是一种具有口服活性的广谱金属蛋白酶 (MMP) 抑制剂[5]。Doxycycline hyclate 治疗可降低 MMP-8 和 -9 水平并抑制组织 MMP-2 和 MMP-9 的表达。此外，用盐酸多西环素治疗可显着降低颅内动脉瘤的发生率。据报道，多西环素海克酸盐是一种基于其对基质金属蛋白酶的抑制作用的抗炎剂。此外，多西环素具有有效的抗疟活性，体外96h的IC50值为320nM[2 3]。
Doxycycline hyclate 在体外以温度依赖性方式抑制登革热病毒复制。 IC50 值在 37°C 时为 52.3μM，在 40°C 时为 26.7μM。它通过抑制病毒的NS2B-NS3丝氨酸蛋白酶来抑制登革热病毒[5]
盐酸多西环素在胶质瘤和星形胶质细胞中引起严重线粒体核蛋白失衡的能力，尤其是在高浓度时。在常规用于诱导基因表达的浓度下，强力霉素海克酸盐对细胞生长没有影响。只有最高测试浓度的盐酸多西环素 (10 ug/mL) 会损害细胞生长[4]。在人类细胞系中，常用浓度的盐酸多西环素会改变基因表达模式，并伴随着将新陈代谢向更快速的方向转变糖酵解表型，表现为乳酸分泌增加和耗氧量减少[7]。多西环素可抑制乳腺癌细胞和 BCSCs 的活力和增殖，降低乳腺球形成效率、迁移和侵袭以及乳腺癌细胞的 EMT。多西环素hyclate处理后干细胞因子的表达也显着下调[8]
在 P. berghei 疟疾小鼠模型中，盐酸多西环素在 50 mg/kg 时表现出有效的抗疟活性，而在 10 mg/kg 时活性次优 [1]。盐酸多西环素处理抑制组织 MMP 并减弱胶原蛋白 III 单倍体不足的小鼠主动脉中胶原蛋白含量的减少，并防止应激诱导的血管病理学的发展。结果表明，盐酸多西环素作为治疗 vEDS（埃勒斯-当洛斯综合征的血管形式）值得进行临床试验[6]
| Cas No. | 24390-14-5 | SDF | |
| 别名 | 多西环素盐酸盐半乙醇半水合物; Doxycycline hydrochloride hemiethanolate hemihydrate; WC2031 | ||
| 化学名 | (4S,4aR,5S,5aR,6R,12aR)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-3,4,4a,5,5a,6,12,12a-octahydrotetracene-2-carboxamide hydrochloride | ||
| Canonical SMILES | O=C(C1=C(O)[C@]2(O)[C@]([C@@H](O)[C@@]3([H])C(C2=O)=C(O)C4=C(O)C=CC=C4[C@@H]3C)([H])[C@H](N(C)C)C1=O)N.Cl | ||
| 分子式 | C23H29ClN2O9 | 分子量 | 512.94 |
| 溶解度 | ≥ 22.15 mg/mL in DMSO, ≥ 49.2 mg/mL in Water with ultrasonic | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9495 mL | 9.7477 mL | 19.4955 mL |
| 5 mM | 0.3899 mL | 1.9495 mL | 3.8991 mL |
| 10 mM | 0.195 mL | 0.9748 mL | 1.9495 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Minocycline and Doxycycline: More Than Antibiotics
Curr Mol Pharmacol2021;14(6):1046-1065.PMID: 33568043DOI: 10.2174/1874467214666210210122628
Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications. The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline. Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords 'minocycline and doxycycline'. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and the number of other non-antibiotic effects were compiled for minocycline and doxycycline.
Doxycycline
Ther Drug Monit1982;4(2):115-35.PMID: 7048645DOI: 10.1097/00007691-198206000-00001
The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.
Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats
Oxid Med Cell Longev2021 Apr 17;2021:4681041.PMID: 33959214DOI: 10.1155/2021/4681041
The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect of Dx on inflammatory cell recruitment and production of inflammatory mediators via in vitro and in vivo analysis. In addition, we analyzed neovascularization, extracellular matrix deposition, and antioxidant potential of Dx on cutaneous repair in Wistar rats. Male animals (n = 15) were divided into three groups with five animals each (protocol: 72/2017), and three skin wounds (12 mm diameter) were created on the back of the animals. The groups were as follows: C, received distilled water (control); Dx1, doxycycline hyclate (10 mg/kg/day); and Dx2, doxycycline hyclate (30 mg/kg/day). The applications were carried out daily for up to 21 days, and tissues from different wounds were removed every 7 days. Our in vitro analysis demonstrated that Dx led to macrophage proliferation and increased N-acetyl-β-D-glucosaminidase (NAG) production, besides decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and metalloproteinases (MMP), which indicates that macrophage activation and COX-2 inhibition are possibly regulated by independent mechanisms. In vivo, our findings presented increased cellularity, blood vessels, and the number of mast cells. However, downregulation was observed in the COX-2 and PGE2 expression, which was limited to epidermal cells. Our results also showed that the downregulation of this pathway benefits the oxidative balance by reducing protein carbonyls, malondialdehyde, nitric oxide, and hydrogen peroxide (H2O2). In addition, there was an increase in the antioxidant enzymes (catalase and superoxide dismutase) after Dx exposure, which demonstrates its antioxidant potential. Finally, Dx increased the number of types I collagen and elastic fibers and reduced the levels of MMP, thus accelerating the closure of skin wounds. Our findings indicated that both doses of Dx can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.
Tailored Doxycycline Hyclate Loaded In Situ Gel for the Treatment of Periodontitis: Optimization, In Vitro Characterization, and Antimicrobial Studies
AAPS PharmSciTech2021 Feb 17;22(3):77.PMID: 33595740DOI: 10.1208/s12249-021-01950-x
Currently, periodontitis is treated by oral dosage forms (antibiotics) which shows systemic side effects and failed to reach the therapeutic concentration (above minimum inhibitory concentration, MIC) in the periodontal pocket. The present study aimed to overcome the above issues, by designing tailored doxycycline hyclate laden in situ gel by Poloxamer 407, chitosan, and polyethylene glycol 600. The in situ gel-forming system has attracted attention owing to its ability of sustained drug release above MIC, easy administration (syringeability), and high drug retention (localization) in the periodontal cavity. The Box-Behnken design (BBD) was used to tailor and optimize the concentration of Poloxamer 407 (X1 = 14.3%), chitosan (X2 = 0.58%), and polyethylene glycol 600 (X3 = 1.14%) to achieve sufficient syringeability (149 N), t90% (1105 min), and viscosity at non-physiological condition (512 cps) and physiological condition (5415 cps). The optimized in situ gel was clear and isotonic (RBCs test). The gelation temperature of the optimized in situ was 34 ± 1°C with sufficient mucoadhesive strength (26 ± 2 dyn/cm2), gel strength (29 ± 2 sec), and texture profile for periodontal application. The in vitro drug release studies showed sustain release from optimized in situ gel (24h) in comparison to marketed gel (7h). The antimicrobial activity (cup plate technique) of the in situ gel was equivalent to the marketed doxycycline gel, which suggests that the doxycycline hyclate retained its antimicrobial efficacy when formulated as in situ gelling system. In conclusion, BBD was effectively utilized to optimize in situ gel with minimum level of polymers to achieve the required characteristics of the in situ gel for sustaining drug delivery to treat periodontitis.
Development of doxycycline hyclate suppositories and pharmacokinetic study in rabbits
Eur J Pharm Sci2020 Jan 15;142:105141.PMID: 31706017DOI: 10.1016/j.ejps.2019.105141
Doxycycline hiclate is a broad spectrum antibiotic widely used in human and veterinary medicine. The inability to perform the parenteral administration of drugs and the lack of oral preparations can be mentioned as difficulties in the treatment of animals in the domestic environment. In this scenario, the aim of this study was to investigate the bioavailability of the drug by rectal route, to propose a potential suppository formulation containing 25 mg of doxycycline as an alternative to the available injectable formulations. Hydrophilic and lipophilic suppositories were prepared, in polyethylene glycol (S-PEG) or cocoa butter (S-CBT), respectively. The suppositories were prepared and evaluated concerning visual characteristics, content, average weight, melting range, content uniformity and in vitro release. A stability study was performed and the two most stable formulations were submitted to a pharmacokinetic study in rabbits. The bioavailability of the suppositories was compared to the data of the intravenous (i.v.) formulation. PEG suppository showed 49.13% bioavailability and CBT 51.43% with Cmax equal to 2.06 ± 2.96 µg.mL-1 and 1.54 ± 0.28 µg.mL-1, respectively. The data obtained suggest that rectal administration may become another method of administration of doxycycline in the treatment of bacterial infections.