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Background:Periodontal instrumentation is accessible to a certain limit, as subgingival calculus is difficult to remove completely in cases of deep pockets and furcation defects. Host modulating agents aim to inhibit arachidonic acid pathways, modulate MMPs, bone remodeling, and regulate immune and inflammatory responses. This systematic review aimsto find the effects of Low Dose Doxycycline (LDD) as local drug delivery systems and sub-antimicrobial dose doxycycline for the treatment of periodontal disease.Material And Methods:Electronic database searched were: Pubmed, Medline, Scopous and Ebsco was performed using MeSH terms: low dose doxycycline, subantimicrobial dose doxycycline, chemically modified doxycycline, doxycycline, doxycycline hyclate, atridox and periostat. Articles published between years 2008-2019 were reviewed. Result:A Systematic review methodology was followedand database searching was done which yields 422 records. Records from year 2008 –2019 were taken into consideration. After inclusion and exclusion accordingly, A total of 10 studies were systematically reviewed. Non surgical or surgical periodontal therapy is more effective in reducing periodontal disease when low dose doxycycline is used as an adjunct either locally or systematically delivered. Conclusion:Subantimicrobial Dose Doxycycline (SDD) is commonly accepted as a host response modifier and it Subantimicrobial Dose Doxycycline (SDD) which down regulates the activity of MMPs. Also, doxycycline provides long-term post-treatment effects. Based in the inference drawn from this systematic review, non surgical or surgical periodontal therapy is more effective in reducing periodontal disease when low dose doxycycline is used as an adjunct, delivered either locally or systematically.
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Molybdenum disulfide ( MoS2) quantum dots ( QDs) were synthesized using one-step hydrothermal method with an acceptable fluorescence property. Based on the quenching effect between doxycycline hyclate ( DOX) and MoS2QDs, a fluorescence method for detection of DOX was established. The interaction between MoS2QDs and DOX was discussed with a final proposal of the static quenching mechanism. A good linear correlation for detection of DOX using fluorescenct MoS2QDs was obtained in the concentration range of 0. 86-55. 40 μg/mL, with a detection limit of 0. 023 μg/mL (S/N=3). The fabricated sensor was applied to the detection of DOX in real samples with RSDs of less than 5% . The relative error of determination results of MoS2QDs method compared with HPLC was from -4. 5% to 0. 8% and -4. 6% to 2. 8% for DOX tablet and DOX spiked milk, respectively. The fluorescence detection of DOX in real sample using MoS2QDs was simple, rapid and reliable.
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@#This study aimed to isolate and prepare highly purified impurity C from doxycycline hyclate by a preparative HPLC method and to inspect the toxicity and in vitro antimicrobial activity of the impurity C of doxycycline hyclate. The solution of doxycycline hyclate treated with heat produced a solution containing 10% of impurity C which was firstly separated by the Sapphire C18(21. 2 mm×250 mm, 5 μm)column with 0. 1% acetic acid-acetonitrile(83 ∶17)as the mobile phase at 20 mL/min. Secondly, rotary evaporation of the eluted solution at the time of 8. 4 min was performed at 50 °C to remove organic solvent. Then the target product was prepared after freeze drying of evaporated solution adjusting pH to 1. 8 with formic acid. The target product was identified with ultraviolet absorbance(UV), infrared(IR), mass spectrometry(MS)and nuclear magnetic resonance(NMR), and its purity was be determined by HPLC. Meanwhile, cytotoxicity and genotoxicity in the Chinese hamster lung cells, toxicity on the development of zebrafish embryos and in vitro antimicrobial activity were compared among impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline. Results showed that prepared product was confirmed to be the impurity C of doxycycline hyclate. Its purity was 90. 1%, which had been the highest so far. In the cellular toxic tests and genetic toxic tests of Chinese hamster lung cells, impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline were somewhat toxic to Chinese hamster lung cells. Toxicity gradually decreased from doxycycline, impurity C of doxycycline hyclate, β-doxycycline to metacycline from -S9mix test results; toxicity gradually decreased from doxycycline, β-doxycycline, impurity C of doxycycline hyclate to metacycline from +S9mix test results; the aberration rate of all the tested related substances was less than 5%, and no obvious genotoxicity was found. According to test results of the development of zebrafish embryos, impurity C of doxycycline hyclate showed the strongest teratogenicity and lethality. Invitro antimicrobial tests revealed that impurity C of doxycycline hyclate had a weaker antimicrobial activity, and invitro antimicrobial activity potential of the tested compounds followed the order: metacycline, doxycycline, impurity C of doxycycline hyclate, β-doxycycline. Studies on safety and effectiveness indicated that impurity C of doxycycline hyclate belonged to toxic and ineffective impurity and need to be controlled individually in quality standard. A useful suggestion was given to revise the quality standard of doxycycline hyclate and its preparation in the current Pharmacopoeia of the People′s Republic of China.
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OBJECTIVE: To rapidly identify the related substances in doxycycline hyclate tablets and investigate the possible degradation pathways of doxycycline hyclate solution by 2D-LC-IT-TOF/MS. METHODS: Firstly, the chromatography was carried out using the 1stD InertSustain ™C18 (4.6 mm×150 mm, 5 μm) column and a mobile phase containing a mixture of buffer solution (0.25 mol·L-1 ammonium acetate solution-0.1 mol·L-1 ethyldiaminetetraacetic acid disodium; triethyiamine=100:10:1)-acetonitrile (85:15). Solution pH was adjusted to 8.8 with glacial acetic acid. Then a InertSustain C18 (2.1 mm×50 mm, 2 μm) column was used with 0.1% formic acid-water as mobile A and 0.1% formic acid-acetonitrile as mobile B in a gradient elution mode in 2ndD. Electrospray ionization (ESI) source was tested in both positive and negative ion modes. Nebulized gas flow was 1.5 L·min-1. Dry gas flow was 10 L·min-1. The desolvation tube temperature was kept at 200℃. Related substances were characterized according to multi-level MS behaviors. The 2D-LC-IT-TOF/MS method was employed to identify the structures of impurities in forced degradation solutions and illuminate the degradation pathways of doxycycline hyclate solution. RESULTS: A total of eight related substances were detected in doxycycline hyclate tablets. Four of them had a content of more than 0.1%, and their structures were identified to be 4-epidoxycycline, metacycline, β-epidoxycycline and 2-acetyl-2-decar-bamoyldoxycycline. The solution of doxycycline hyclate easily degraded under alkaline condition and generated an open loop compound taken off the keto group. The solution was sensitive to heat, and generated 4-epidoxycycline with a little amount of 4-epi-6-epidoxycycline; but the solution was stable under illumination and acidic condition. CONCLUSION: The established method is suitable for rapid identification of impurities in doxycycline hyclate, which can be applied as a useful analytical tool for quality control and drug process optimization of doxycycline hyclate.
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OBJECTIVE: To optimize the formulation and study the irritation of doxycycline hyclate in situ forming sustained release injection. METHODS: Doxycycline in situ forming gel (DHISFG) was prepared by using biodegradable, biocompatible PLGA and PLA as materials, and non-toxic NMP as solvent. Orthogonal design was used to optimize the gel formulation. The in vitro drug release, rheology and irritation were also studied. RESULTS: The optimal formulation of DHISFG was PLGA (Mn=10000)-NMP-doxycycline hyclate=25:65:10. The drug release from the DHISFG was 20% within 2 hours and above 90% after 10 days sustained release. The in vitro release data fit the first release and Fick diffusion mechanism. Gingival irritation test of rabbit showed no irritation. CONCLUSION: The developed DHISFG which is degradable and easy to inject could provide a new sustained release formulation to relieve the symptoms of periodontal disease such as alveolar bone absorption and tooth loss. Copyright 2012 by the Chinese Pharmaceutical Association.