IDENTIFICATION AND USE: Chlorhexidine forms solid crystals. Chlorhexidine diacetate is registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Currently, two end-use products with 2% chlorhexidine diacetate are registered for use as hard surface-treatment disinfectant/virucides. Chlorhexidine is used primarily as its salts e.g., the dihydrochloride, diacetate, and digluconate in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eyedrops, active substance in wound dressings and antiseptic mouthwashes). HUMAN EXPOSURE AND TOXICITY: Chlorhexidine diacetate is highly acutely toxic when applied to the eye. Skin reactions to chlorhexidine-acetate and chlorhexidine-gluconate were tested among eczema patients. Positive reactions were found in 52 (5.4%) of the 1,063 subjects at the initial test. Of these subjects, 29 were retested, and 21 were still found to have positive reactions. Chlorhexidine specific IgE was detected only in Japanese individuals who had experienced anaphylactic type reactions and was not detected in Japanese nurses and patients or in a group of British nurses and hospital staff, all having regular contact with chlorhexidine. All chromogens plus chlorhexidine, but not chlorhexidine alone, produced some discoloration of hydroxyapatite and human teeth. A 67-yr-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. Occupational asthma has been described in two health care workers, as a result of exposure to chlorhexidine and alcohol aerosols. Another case report describes six patients who developed urticaria, dyspnea, and anaphylactic shock due to topical application of chlorhexidine gluconate solution. Even very dilute solutions of chlorhexidine can cause marked chondrolysis of articular cartilage leading to severe permanent damage to the knee. ANIMAL STUDIES: Rabbits suffered severe ocular irritation with chlorhexidine acetate treatment. No dermal irritation was reported up to 72 hours following test article treatment in rabbits. In developmental studies no observable malformations or developmental toxicity were found at any dose level tested. Both positive and negative results have been seen in bacterial studies of the mutagenic effects of chlorhexidine; however, no mutagenic activity was seen in an in-vivo micronucleus assay or a mammalian cytogenic test using Chinese-hamster-ovary cells. No carcinogenic effects were seen in a long term animal study.
◉ Summary of Use during Lactation:Chlorhexidine has been used vaginally or topically on the abdomen or perineum prior to delivery to prevent infection. No toxicity has been reported in breastfed infants and it has clearly less toxicity compared to povidone-iodine in these situations. Topical application of chlorhexidine to the breast before and after nursing did not appear to adversely affect the breastfed infants in one study. Use of chlorhexidine oral rinse by a nursing mother is unlikely to adversely affect her infant.
◉ Effects in Breastfed Infants:A group of investigators in Belgium reviewed the results of infant thyrotropin levels on day 5 postpartum in 4745 newborn infants delivered over a 2-year period at their hospital. Infants were divided among those whose mothers had iodine overload (n = 3086) from topical povidone-iodine 10% solution during labor and delivery and those whose mothers had no iodine overload (n = 1659). Mothers had povidone-iodine applied either as a single application to 900 square cm for epidural anesthesia or 3 applications to the entire abdominal wall for cesarean section. Breastfed infants whose mothers had iodine overload had a greater risk for having elevated thyrotropin levels and requiring recall for retesting (3.2% with cesarean section and 2.7% with epidural anesthesia) compared to those who did not (0.1%). Bottle-fed infants were affected much less than breastfed infants. After replacing povidone-iodine with chlorhexidine 0.5% in 70% isopropanol for disinfection for 6 months, 1178 infants that were delivered at this institution had no increased rate of elevations in thyroid function tests and a reduced rate of recalls in breastfed infants.
In a study of mothers in Spain who received 10% povidone-iodine (n = 21) or chlorhexidine (n = 13) topically to the perineum starting immediately before the final stage of labor and daily postpartum to the episiotomy, no differences in thyrotropin, thyroxine or free thyroxine was found among their breastfed infants at day 5 to 7 postpartum.
Studies in Africa have used chlorhexidine vaginally prior to delivery in an attempt to reduce the frequency of mother-to-child transmission (MTCT) of HIV. In one, cotton soaked in 0.25% chlorhexidine solution was used to swab the vaginal walls every 4 hours from admission into labor until delivery in 4078 women. The other study used 120 mL of either 0.2% or 0.4% chlorhexidine solution as a vaginal lavage every 3 hours from admission to labor until delivery in 309 women. The average number of lavages was 2.1 (range 1 to 11). Chlorhexidine 0.25% swabs reduced MTCT in patients whose membranes ruptured more than 4 hours before delivery, but not in other women. Vaginal lavage showed a statistically nonsignificant trend towards reduction of MTCT, with the 0.4% greater than the 0.2%. Almost all of the infants in these studies were breastfed. No adverse events were reported in the infants, but follow-up related primarily to infant mortality and HIV status rather than effects of chlorhexidine.
◉ Effects on Lactation and Breastmilk:A randomized study compared 0.2% chlorhexidine in alcohol to distilled water as a spray to the breast in 200 mothers who were nursing newborns. The mothers sprayed their breasts with the liquid before and after each feeding. Mothers and infants were assessed at discharge and weekly thereafter. Discomfort and nipple trauma were less frequent in the chlorhexidine group than in the placebo group, particularly at the first assessment. Although skin flora on the breasts of the treated mothers was reduced, there was no difference in the frequency of mastitis between the treated and placebo groups. No obvious side effects occurred in the breastfed infants and there were no differences in the rates of oral thrush in infants between the treatments. A systematic review concluded that this practice is not justified based on current evidence.
Dermatotoxin - PACD (photoallergic contact dermatitis).
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
相互作用
氯己定能提高特比萘芬对念珠菌分离株的活性；在培养基中，特比萘芬-氯己定联合用药显示出协同活性。
Chlorhexidine increases the activity of itraconazole against Candida isolates; itraconazole-chlorhexidine combinations show synergistic activity in culture media.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
如果摄入了高浓度溶液，按腐蚀性物质摄入处理……，无需进行胃肠道去污处理。
1. If a highly concentrated solution is ingested, manage as a caustic ingestion ... , without gastrointestinal decontamination.
34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. /Chlorhexidine gluconate/
Percutaneous absorption of the antimicrobial agent chlorhexidine (labelled with carbon-14) was studied in rats. Less than 5% of the topically applied chlorhexidine was absorbed during a 5-day period. Excretion of absorbed radioactivity occurred mainly in the feces.
The percutaneous absorption of chlorhexidine gluconate (chlorhexidine digluconate; Hibitane) through hairless rat skin with or without stratum corneum was studied. For tests carried out on whole skin, storage in cutaneous structures after 48 hr was more important than diffusion; the reverse was observed for stripped skin. When the skin was stripped, the amount absorbed was multiplied by approximately 100, and the amount stored in skin by approximately 10. The difference in chlorhexidine diffusion observed between whole and stripped skin was related to the physicochemical characteristics of chlorhexidine. /Chlorhexidine gluconate/
To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. ... The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days.
34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. /Chlorhexidine gluconate/
Metalloporphyrins as cytochrome P450 models for chlorhexidine metabolite prediction
摘要：
The catalytic oxidation of chlorhexidine (CHX, a strong microbicidal agent) mediated by ironporphyrins has been investigated by using hydrogen peroxide, mCPBA, tBuOOH, or NaOCl as oxidant. All of these oxygen donors yielded p-chloroaniline (pCA) as the main product. The higher pCA yields amounted to 71% in the following conditions: catalyst/oxidant/substrate molar ratio of 1:150:50, aqueous medium, FeTMPyP as catalyst. The medium pH also had a strong effect on the pCA yields; in physiological pH, formation of this product was specially favored in the presence of the catalysts, with yields 58% higher than those achieved in control reactions. This provided strong evidence that CHX is metabolized to pCA upon ingestion. (c) 2012 Elsevier B.V. All rights reserved.
New Drug Delivery System for Crossing the Blood Brain Barrier
申请人：Lipshutz H. Bruce
公开号：US20070203080A1
公开（公告）日：2007-08-30
New ubiquinol analogs are disclosed, as well as methods of using these compounds to deliver drug moieties to the body.
新的泛醌类似物被披露，以及利用这些化合物将药物基团输送到人体的方法。
[EN] FUSED PYRAZOLE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLE CONDENSÉS UTILISÉS EN TANT QU'INHIBITEURS DE JAK
申请人：ALMIRALL SA
公开号：WO2017220431A1
公开（公告）日：2017-12-28
Novel fused pyrazole derivatives of Formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
[EN] PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PRMT5 CONTENANT UNE DIHYDRO- OU TÉTRAHYDRO-ISOQUINOLÉINE ET LEURS UTILISATIONS
申请人：EPIZYME INC
公开号：WO2014100730A1
公开（公告）日：2014-06-26
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
[EN] N-PYRAZOLYL CARBOXAMIDES AS CRAC CHANNEL INHIBITORS<br/>[FR] CARBOXAMIDES N-PYRAZOLYL EN TANT QU'INHIBITEURS DU CANAL CRAC
申请人：GLAXO GROUP LTD
公开号：WO2010122089A1
公开（公告）日：2010-10-28
The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.
