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2-Hydroxyisocaproic acid

(Synonyms: HICA) 目录号 : GC25011

2-hydroxyisocaproic acid (HICA), an amino acid derivative, has broad antibacterial activity.

2-Hydroxyisocaproic acid Chemical Structure

Cas No.:498-36-2

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产品描述

2-hydroxyisocaproic acid (HICA), an amino acid derivative, has broad antibacterial activity.

2-Hydroxyisocaproic acid is not cytotoxic and genotoxic at concentrations <10 mg/mL. At the concentration of 1 mg/mL, 2-Hydroxyisocaproic acid is significantly less cytotoxic than calcium hydroxide.[2]

2-Hydroxyisocaproic acid reduces expression of matrix metalloproteinase 9 (MMP-9) and myeloperoxidase (MPO) in a murine chamber model of C. albicans biofilm, compared to those of chambers containing caspofungin and PBS.[3]

[1] Sakko M, et al. Mycoses. 2014 Apr;57(4):214-21. [2] Selis D, et al. J Endod. 2019 May;45(5):578-583. [3] Nieminen MT, et al. 2014 Sep;21(9):1240-5.

Chemical Properties

Cas No. 498-36-2 SDF Download SDF
别名 HICA
分子式 C6H12O3 分子量 132.16
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1 mM 7.5666 mL 37.8329 mL 75.6659 mL
5 mM 1.5133 mL 7.5666 mL 15.1332 mL
10 mM 0.7567 mL 3.7833 mL 7.5666 mL
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Research Update

Antibacterial Activity of 2-Hydroxyisocaproic acid (HICA) Against Obligate Anaerobic Bacterial Species Associated With Periodontal Disease

Microbiol Insights 2021 Oct 21;14:11786361211050086.PMID:34707364DOI:10.1177/11786361211050086.

Topical antiseptics are used to assist and further increase the effect of mechanical biofilm eradication and to potentially prevent new biofilm formation in periodontal treatment. This is of importance in treatment-resistant infections with 10% prevalence of all periodontitis cases to avoid the need for antibiotic therapy. The purpose of this study was to evaluate the antimicrobial activity of DL-2-hydroxyisocaproic acid on human pathogenic obligate anaerobic bacteria related to periodontitis. In this study antimicrobial activity of 2-Hydroxyisocaproic acid was observed against 14 bacterial reference strains and clinical isolates of obligate anaerobic bacterial species using a microdilution method in 1.25 to 160 mg/mL concentrations of 2-Hydroxyisocaproic acid. The 11 strains of bacteria included in this study are typically associated with periodontal disease; Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Parvimonas micra. Three strains of Cutibacterium acnes, normally associated with skin diseases, were tested for comparison. 90% inhibitory concentration was determined at 48 hours and minimum bactericidal concentration was determined after 72 hours incubation. The 2-Hydroxyisocaproic acid was bactericidal at ⩾160 mg/mL for all isolates tested. The reference strain of T. forsythia, and the reference strain and the clinical isolates of C. acnes were the most tolerant ones. The reference strains and clinical isolates of F. nucleatum and A. actinomycetemcomitans were killed at ⩾40 mg/mL concentration. In conclusion, topical use of 2-Hydroxyisocaproic acid could eventually be a well-tolerated and useful method in the therapy of patients with difficult-to-treat periodontal disease or other superficial infections to avoid unnecessary antibiotic use and the emergence of antibiotic resistance.

2-Hydroxyisocaproic acid is bactericidal in human dental root canals ex vivo

Int Endod J 2017 May;50(5):455-463.PMID:27004733DOI:10.1111/iej.12639.

Aim: To compare the activity of 2-Hydroxyisocaproic acid (HICA), calcium hydroxide (Ca(OH)2 ) and chlorhexidine digluconate (CHG) against Enterococcus faecalis T-75359 (root canal isolate) in the root canals of extracted human teeth. Methodology: Bacterial suspensions (108 cfu mL-1 ) were incubated in root canals with 0.9 mm diameter root blocks (n = 73) for 21 days. Bacterial penetration into dentine was analysed by the Brown and Brenn method (n = 5). Canals (n = 17/group) were medicated with 40% of HICA paste, 40% of Ca(OH)2 paste, 2% of CHG solution or 0.9% of saline solution for 7 days. Samples taken from the inner (first 0.1 mm) and deeper (second 0.1 mm) dentine, and residual roots were cultured in broth for 24 h. Bacterial growth was detected by spectrophotometry (optical density, OD) and confirmed by culture on agar. The OD data were analysed with Kruskal-Wallis and Friedman with Wilcoxon signed-rank test between and within groups, respectively, and agar culture data with Pearson chi-square with Mann-Whitney and Cochran with McNemar tests, respectively (P < 0.05). Results: Bacterial invasion into dentine tubules was confirmed. In deeper dentine, HICA inhibited >90% of bacterial growth in comparison with saline. No bacterial growth was observed in 82-100% of inner and deeper dentine samples. CHG prevented the growth in 88%, Ca(OH)2 in 59-76% and saline in 65-71%, respectively. HICA was significantly more active than Ca(OH)2 (P = 0.008) in the residual roots. The viability testing on agar showed essentially the same result. Conclusion: HICA paste exerted superior activity against E. faecalis and could have potential for root canal medication.

Evaluation of the removal of 2-Hydroxyisocaproic acid from the root canal and its effect on the bond strength of MTA

Aust Endod J 2022 Jul 19.PMID:35852919DOI:10.1111/aej.12660.

This study aimed to evaluate the removal of 2-Hydroxyisocaproic acid (HICA) from the root canal system and its effect on the bond strength of the mineral trioxide aggregate (MTA). 126 single-rooted teeth were divided into 3 experimental groups (n = 36) that were treated with double antibiotic paste (DAP), HICA and calcium hydroxide (CH) and one control group (n = 18). In the first part, 18 teeth from each experimental group (n = 54) were examined to remove HICA from the root canal. In the second part, 72 teeth (3 experimental groups (n = 54) and one control group (n = 18)) were used for the evaluation of the push-out bond strength of MTA. There was no statistically significant difference between HICA, DAP and CH residues (p > 0.05). HICA group showed significantly less push-out bond strength (p < 0.05). DAP, HICA and CH could not be removed entirely from the root canal. HICA significantly reduced the bond strength of the MTA.

2-Hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species

Mycoses 2014 Apr;57(4):214-21.PMID:24125484DOI:10.1111/myc.12145.

The amino acid derivative 2-Hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml(-1) . Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml(-1) was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad-spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections.

Antimicrobial 2-Hydroxyisocaproic acid and chlorhexidine resist inactivation by dentine

Int Endod J 2016 Apr;49(4):352-60.PMID:25944560DOI:10.1111/iej.12465.

Aim: To compare the antibacterial activity of 2-Hydroxyisocaproic acid (HICA) with currently used root canal medicaments and to examine their interactions with potential inhibitors in nutrient-deficient and nutrient-rich conditions. Methodology: First, the antibacterial activity of single concentrations of HICA, calcium hydroxide solution or slurry, chlorhexidine digluconate or acetate was tested against Enterococcus faecalis with and without potential inhibitors: dentine powder (DP), hydroxyapatite or bovine serum albumin, in a low concentration of peptone water. Relative viable counts were determined by culture at 1, 24 and 48 h. In the second set of experiments, the activity of three concentrations of HICA was evaluated against two isolates of E. faecalis with and without potential inhibitors in nutrient-rich thioglycollate broth using a modification of a standard microdilution method. The minimum bactericidal concentration was determined by culture at 1, 24 and 48 h. Results: Concentrations of ≥33 mg mL(-1) of HICA were found to be bactericidal against E. faecalis in both nutrient-deficient and nutrient-rich environments at 24- to 48-h incubation, whereas the initial activity of Ca(OH)2 slurry was lost at 48-h incubation. HICA tolerated well all tested potential inhibitors up to 19 mg mL(-1) . DP concentrations higher than this inhibited its activity in a dose-dependent manner in both environments. DP demonstrated moderate antibacterial activity, and it enhanced the otherwise limited activity of Ca(OH)2 slurry and solution. DP did not impact on the activity of chlorhexidine. Conclusions: These results support the long-term antibacterial activity of HICA and indicate its tolerance to clinically relevant concentrations of dentine and other inhibitors commonly present in the root canal system. Therefore, HICA may have potential as an interappointment medication in the treatment of root canal infections.