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Combination therapy for the treatment of bacterial infections

一种组合物、抗真菌的技术，应用在用于生物控制的化学品、抗细菌药、应用等方向，能够解决缺乏有效治疗致病菌、抗可用药物的菌株数目增加等问题

Inactive Publication Date: 2011-05-11
INTERFACE BIOLOGICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many pathogenic bacteria for which there are no effective treatments, and the number of strains resistant to available drugs continues to increase

Method used

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  • Combination therapy for the treatment of bacterial infections
  • Combination therapy for the treatment of bacterial infections
  • Combination therapy for the treatment of bacterial infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Embodiment 1: Determination of minimum inhibitory concentration (MIC)

[0113] The broth dilution method is used to quantitatively measure the activity of antimicrobial agents in vitro against a given bacterial isolate. First, a series of tubes / wells are prepared with a broth medium to which different concentrations of antimicrobial agents are added. The tubes / wells are then inoculated with a standardized suspension of the test organism. After overnight incubation at 35±2°C, the assay was performed and the minimum inhibitory concentration (MIC) was determined. Operate under sterile conditions.

[0114] Preserved cultures: Preserved cultures were maintained in MH broth containing 15% glycerol and stored at -80°C. Preserved cultures were subcultured on MH agar (MHA) and incubated overnight at 37°C.

[0115] Preparation of inoculum: A single isolated colony of the same morphological type from an MH agar plate was selected, inoculated into a sterile tube containing 25 m...

Embodiment 2

[0142] Example 2: General Synthesis of Bioactive Monomers Containing Membrane Active Antimicrobials or Fluoroquinolones

[0143] A general synthetic scheme for a bioconjugated agent (eg, a membrane-active antimicrobial (with monomeric units) or a fluoroquinolone (with monomeric units)) is set forth below in Steps A-D and Scheme A.

[0144] Step A:

[0145] To a dry 2 L round bottom flask purged with nitrogen was added ciprofloxacin hydrochloride (100 g, 301.8 mmol), trityl chloride (185.1 g, 663.9 mmol) and chloroform (1000 mL). To this stirred suspension was added triethylamine (135 mL, 965.8 mmol) dropwise, and the resulting mixture was stirred at room temperature for 4 hours, during which time a homogeneous yellow solution was obtained. The resulting solution was treated with methanol (500 mL) and stirred at 50 °C for 1.5 hours. The resulting solution was washed with water (2x 2L). The organic layer was dried over sodium sulfate, filtered, and the solvent was removed und...

Embodiment 3

[0157] Embodiment 3: the synthesis of ciprofloxacin polymer

[0158] To a dry 1 L round bottom flask purged with nitrogen was added polycaprolactone diol (200 g, 100 mmol). The flask was heated to 70°C under vacuum for 2 hours. The temperature was lowered to 65 °C, then DMSO (100 mL), dibutyltin dilaurate (3.2 mL, 5.0 mmol) and THDI (32 mL, 155 mmol) were added. The reaction mixture was stirred at 65 °C for 1 h, then a solution of 4 (38.84 g, 50 mmol) in DMSO (500 mL) and dibutyltin dilaurate (1.8 mL, 3.0 mmol) was added. The reaction was stirred for 17 hours at 65°C under an inert atmosphere. The reaction was quenched with the addition of methanol (78 mL), then kept stirring for an additional 1 hour. The polymer was transferred to a titration funnel where hexane (2 L) was added dropwise. After discarding the supernatant, the polymer was pipetted into isopropanol and hexane (2 L) was added dropwise. This process was repeated with water until precipitation occurred. The r...

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Abstract

Compositions comprising the combination of a membrane active biocide and a second agent selected from fluoroquinolones, ammoglycodies, ss-lactams, glycopeptide antibiotics, sufonamides and antifungal azoles and their use in the treatment or prevention of bacterial or fungal infections Preferred membrane active biocides are selected from chlorohexidme, polymyxin B-nonapeptide, bacitracin, aztreonam, benzlakomum salts and metal chelators The active ingredients can be in either monomer or polymeric form.

Description

technical field [0001] The present invention relates to the field of antibacterial therapy. Background technique [0002] Human use of antibiotics can be seen as a gigantic evolutionary experiment, from which incomplete natural selection can be observed in real time. Over 50 years, the number of antibiotic-resistant pathogenic and commensal bacterial genera and strains and the number of antibiotics they are resistant to has continued to increase virtually continuously worldwide. As a result, infections that are easily treatable with chemotherapy may no longer be so. It is clear that the development and spread of resistance can be attributed to the use and misuse of antibiotics. Increased resistance to antibiotic-treated bacterial infections has been widely documented and is now a recognized medical problem, especially nosocomial infections. See, eg, Jones et al., Diagn. Microbiol. Infect. Dis. 31: 379-388, 1998; Murray, Adv. Intern. Med. 42: 339-367, 1997; and Nakae, Micr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/155A01N43/80A01N47/44A01P1/00A61K31/4174A61K31/43A61K31/496A61K31/635A61K31/7036A61K38/14A61L15/46A61L15/64A61L2/16A61L27/54A61L27/58A61L29/16A61L31/14A61L31/16A61P31/04A61P31/10C08L101/02C08L101/16
CPCA61K31/155A61K31/4174A61K31/43A61K31/496A61K31/635A61K31/7036A61K38/14A61L2/16A61L15/46A61L17/005A61L27/54A61L29/16A61L31/16A61L2300/206A61L2300/404A61L2300/406A61L2300/45A61L2300/604A61P31/04A61P31/10A61K2300/00
Inventor 弗兰克·拉龙德陈汉杰西尔瓦·辛纳杜赖
Owner INTERFACE BIOLOGICS INC
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