No abstract

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by food and drug administration (FDA) as harmless adjuvant and is largely used in drug systems delivery. The aim of the study was to use the TPGS polymer as a drug release model to regulate the release of the anesthetic xylazine-ketamine in order to minimize therapeutically reference dose, avoid side effects, and improve efficacy. The study performed on 15 adult local breed male rabbits, divided into 3 groups with same number which injected intramuscularly with single dose of suggested anesthetics. Heart rate, respiratory rate, degree of muscle relaxation, onset of action and stages of anesthesia were evaluated, also induction of anesthesia, surgical anesthesia and recovery time were recorded. Nanoprecipitation technique was optimal method for preparing small particle size as well as reduce dose for therapeutic effect. Small and large dose was showed perfect analgesic and muscle relaxant activity of xylazine-ketamine drugs. Ketamine 30 mg and xylazine 10 mg loaded PLGA showed elevation of conciseness period as well as increase muscle relaxant. Ketamine 30 mg and xylazine 10 mg loaded PLGA reduce heart rate but onset of action delayed when compared with reference drug. The process of nanoprecipitation was ideal for forming small particle sizes and reducing the dosage for therapeutic effects. PLGA loaded with ketamine-xylazine demonstrated improved cycle concentration (walk time) as well as improved muscle relaxant, finally the protocol created an excellent anesthetic combination for induction of general anesthesia.

Wounds are defined as the cellular and anatomical destruction of tissues that can be caused by chemical, physical, microbiological, thermal, or immunological damage, leading to skin rupture. 1 Wound healing is one of the most complex biological processes, with four overlapping phases: hemostasis, inflammation, proliferative, and maturation. These phases lead to the regeneration of new tissue. In burn injuries, blood coagulation occurs due to damaged capillaries, followed by inflammation. 2,3 The global cost of wound care averaged 2.8 billion dollars in 2014 and is expected to reach 3.5 billion dollars by 2021. 4 A 2018 analysis

Prepare new derivatives 5-(3-Fluoro-biphenyl-2-yl)-7-nitro-1,3-dihydro-benzo[e] [1,4]diazepin-2-ol (88)and 5-Nitro-2’-(7-nitro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-biphenyl-3-carboxylic acid (89)compound from clonazepam and identified by spectrum of 13C-NMR and showed spectrum 1H-NMR . Clonazepam has massive adverse effect on prostate,lung,liver,kidney and spleen 3-new derivatives 5-(3-Fluoro-biphenyl-2-yl)-7-nitro-1,3-dihydro-benzo[e] [1,4]diazepin-2-ol (88) has limited effect and there is no clear changes in most organs studies.4-5-Nitro-2’-(7-nitro-2-oxo-2,3-dihydro-1Hbenzo[e][1,4]diazepin-5-yl)-biphenyl-3-carboxylic acid (89)compound has significant adverse effect but still less potent than clonazepam. OBJECTIVE To characterization and synthesis of new drugs related to clonazepam as well as to overcome massive adverse effect of clonazepam and increase the potency and half live of drugs.

D-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) has been approved as a safe pharmaceutical adjuvant by FDA, and several drug delivery systems (DDS) based on TPGS have been developed. TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, vaccine system adjuvant, nutritional supplement, film plasticizer, anticancer reagent, and so on, are discussed in this review. Consequenly, TPGS can inhibit ATP-dependent P-glycoprotein activity and act as a potent excipient that promotes the efficiency of delivery and the therapeutic effect of drugs. Inhibition of P-gp occurs through mitochondria-dependent inhibition of the P-gp pump. Many of the latest studies address the use of TPGS for many poorly water-soluble or permeable drugs in the manufacture of nanodrugs or other formulations. In addition, it has been reported that TPGS shows a robust improvement in chylomicron secretion at low concentrations and improves intestinal lymphatic transport, which would also boost the potential of drug absorption. It also indicates that there are still many problems facing clinical translation of TPGS-based nanomedicines, requiring a more deep evaluation of TPGS properties and a future-based delivery method.