WO2012036585A1 - Composition pharmaceutique à action antimicrobienne pour administration parentérale, et procédé de production - Google Patents

Composition pharmaceutique à action antimicrobienne pour administration parentérale, et procédé de production Download PDF

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Publication number
WO2012036585A1
WO2012036585A1 PCT/RU2011/000320 RU2011000320W WO2012036585A1 WO 2012036585 A1 WO2012036585 A1 WO 2012036585A1 RU 2011000320 W RU2011000320 W RU 2011000320W WO 2012036585 A1 WO2012036585 A1 WO 2012036585A1
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Prior art keywords
beta
silicon dioxide
lactam
nanostructured silicon
weight
Prior art date
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PCT/RU2011/000320
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English (en)
Russian (ru)
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WO2012036585A8 (fr
Inventor
Виктор Львович ЛИМОНОВ
Константин Валентинович ГАЙДУЛЬ
Александр Валерьевич ДУШКИН
Original Assignee
Limonov Viktor Lvovich
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Application filed by Limonov Viktor Lvovich filed Critical Limonov Viktor Lvovich
Priority to UAA201203809A priority Critical patent/UA103118C2/ru
Priority to CN2011800044095A priority patent/CN103096896A/zh
Priority to AU2011302724A priority patent/AU2011302724C1/en
Priority to NZ598831A priority patent/NZ598831A/xx
Priority to EP11825509.0A priority patent/EP2620152A4/fr
Priority to MX2012010535A priority patent/MX2012010535A/es
Priority to CA2785228A priority patent/CA2785228A1/fr
Priority to US13/390,151 priority patent/US20130164337A1/en
Priority to JP2013528146A priority patent/JP2013537190A/ja
Priority to BR112012023964A priority patent/BR112012023964A2/pt
Publication of WO2012036585A1 publication Critical patent/WO2012036585A1/fr
Publication of WO2012036585A8 publication Critical patent/WO2012036585A8/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the invention relates to antimicrobial pharmaceutical preparations and technologies for their preparation and can be used in medicine and veterinary medicine for the treatment of infectious and inflammatory diseases, as well as in the pharmaceutical industry for the production of medicines.
  • Beta-lactams include drugs (natural and semisynthetic penicillins, cephalosporins, cefamycins, carbapenems and monobactams), which have a common fragment in the chemical structure of the beta-lactam ring, which determines the antimicrobial activity and a number of common properties of this group of drugs [1].
  • beta-lactams have a wide spectrum of antimicrobial activity and high antimicrobial activity, however, the resistance of microorganisms to many of them develops relatively quickly due to their production of specific beta-lactamase enzymes (extended-spectrum beta-lactamases, class C chromosome beta-lactamases, etc. ) hydrolyzing the beta-lactam ring, which deprives these drugs of antibacterial properties and leads to the development of resistant strains of microorganisms [2].
  • beta-lactamase inhibitors clavulanic acid, sulbactam, tazobactam, etc.
  • a number of effective combined antibacterial beta-lactam drugs of the penicillin and cephalosporin series amoxicillin / clavulanic acid, ampicillin / sulbacanum piperacillin / tazobactam, cefoperazone / sulbactam, etc.
  • beta-lactamase inhibitors clavulanic acid, sulbactam, tazobactam, etc.
  • inhibitor-protected drugs were not effective enough, since at a high level production by pathogenic microorganisms beta-lactamases, the above inhibitors do not completely protect antibiotics from hydrolysis.
  • the carbapenems that are resistant to many beta-lactamases also do not completely solve the problem of microbial resistance to these antibiotics, since their widespread use for the treatment of severe infections leads to the formation of multi-resistant P. aeruginosa strains [3].
  • beta-lactams in infections caused by various microorganisms is associated not only with the negative effect of beta-lactamases, but also with the limited ability of these drugs to concentrate locally in the focus of infectious inflammation and penetrate into macrophages, in which the phagocytosed pathogens of many infectious and inflammatory diseases are deposited and from the severity of their functional state, which The level of antimicrobial resistance depends on the degree of measure [4, 5].
  • the essence of the invention lies in the fact that in order to enhance the therapeutic efficacy of beta-lactams, it is proposed to use SiCte (silicon dioxide) nanoparticles, which, differing in pharmacologically advantageous properties of biocompatibility, biodistribution, biodegradation and low toxicity (regardless of the severity of the structure's porosity), can serve as carrier of antibiotics for intracellular delivery to macrophages, which are concentrated in the foci of inflammation observed in the lungs, liver, kidney x, spleen, lymph nodes, heart, skin, bladder and other organs of mammals (i.e., significantly increase the concentration of antibiotics in infected areas), and to stimulate antimicrobial activity of these cells of the immune system, thereby significantly enhancing the therapeutic effect of antimicrobials in the treatment of infectious and inflammatory diseases [13, 14, 15, 16, 17, 18, 19, 20, 21].
  • the invention solves the problem of creating a pharmaceutical composition of antimicrobial action for injection based on the use of antibiotics from the group of beta-lactams and nanoparticles of silicon dioxide, which has increased therapeutic efficacy (compared with conventional beta-lactams, which are considered as a prototype in this invention) in the treatment of infectious inflammatory diseases.
  • a pharmaceutical composition of antimicrobial action for injection which contains a beta-lactam antibiotic and highly dispersed nanostructured silicon dioxide in a weight ratio of (10-75): 1.
  • the problem is also solved by the fact that the proposed method for producing a pharmaceutical composition of antimicrobial action for injection, comprising mixing beta-lactam antibiotics with other components, according to which a beta-lactam antibiotic in powder form is mixed with highly dispersed nanostructured silicon dioxide powder in a weight ratio of (10 -75): 1, and the resulting mixture is machined by impact-abrasion.
  • the therapeutic efficacy of the proposed pharmaceutical composition is enhanced if the resulting mixture is machined by impact-abrasion such that the proportion of highly dispersed nanostructured silicon dioxide particles having a size of not more than 5 ⁇ m is at least 25%.
  • beta-lactam antibiotics were used, provided by the Russian pharmaceutical company ABOLmed LLC (penicillins: carbenicillin; cephalosporins: cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefopezzone, cefenfexfam; cefefexfon; cefefexfon; cefcefimzone; cefzefzone; cefzefzone; meropenem; monobactam: aztreonam).
  • BHS1O2 nanostructured silicon dioxide
  • the drug “Polysorb” pharmaceutical group: enterosorbing agent; active substance: silicon dioxide
  • Polisorb CJSC complex organic compound
  • a similar drug is produced by the Ukrainian company ZAO Biofarma under the trade name Silix [12].
  • composition composition is based on the phenomenon of reversible sorption of beta-lactam molecules by nano- and micro-sized particles of BHSi02, as well as a decrease in the size of BHS1O2 microparticles upon mechanical activation of its mixtures with beta-lactam substances by intense impact-abrasion mechanical stresses.
  • the inventive method for producing the above pharmaceutical composition by mechanically activating a powder mixture of a beta-lactam antibiotic and BHS1O2 by intensive shock-abrasion action makes it possible to increase the proportion of finely dispersed (less than 5 ⁇ m) particles of BHS1O2 on which beta-lactam molecules are adsorbed and which are phagocytized mainly by macrophages [10,19].
  • a mixture of the above substances in a weight ratio of beta-lactam antibiotic: BHS1O2 equal to (10-75): 1 is subjected to mechanical activation by impact-abrasion until the weight fraction of the finely dispersed fraction is increased to no less than 25%.
  • Fig. 1 and Fig. 2 The particle size distribution of the aqueous suspension of the composition using the example of a ceftriaxone: BHS1O2 mixture equal to 30: 1 by weight, measured on a Micro-Sizer 201 laser granulometer, is shown in Fig. 1 and Fig. 2.
  • Injectable colloidal solutions for parenteral administration (by dilution by any known method adopted for beta-lactams), consisting of finely dispersed particles of BHS1O2 with molecules of one or another beta-lactam, reversibly sorbed on their surface, are prepared from the obtained powder composition.
  • Table 1 shows the data (obtained by high performance liquid chromatography - HPLC) on the degree of sorption of various beta-lactam antibiotics on BHS1O2 particles after mechanical activation of the antibiotic: BHS1O2 composition in a weight ratio of 30: 1, which suggests that highly dispersed nanostructured silicon dioxide can be used for parenteral administration of antimicrobial and other drugs that can be adsorbed onto nanoparticles and microparticles of this inorganic substance for delivery to areas of inflammation, tumor growth, regeneration, healing, scarring, etc., i.e. in areas of increased presence of macrophages, with the goal of deliberately increasing the local (including intracellular) concentration of the pharmaceutical product and, accordingly, enhancing the therapeutic effect.
  • compositions a mechanochemical approach was used, which consists in processing a mixture of solid components by intense mechanical stresses - pressure and shear deformations, which are realized mainly in various types of mills that carry out impact-abrasive effects on substances.
  • the method used to obtain mixtures allows one to significantly avoid chemical decomposition, achieve complete homogeneity of the powder components in comparison with the preparation of mixtures by simple mixing of the components, or by evaporation of their solutions, and, as a result, determines the high pharmacological activity of the pharmaceutical composition.
  • the mechanical processing of powdered mixtures is carried out in rotary, vibration or planetary mills.
  • grinding media can be used balls, rods, etc.
  • compositions prepared by the claimed method have significantly increased therapeutic efficacy in the treatment of bacterial sepsis caused by Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, compared with the original antibiotics.
  • Example 1 Obtaining a solid composition beta-lactam antibiotic is a highly dispersed nanostructured silicon dioxide.
  • a mixture of beta-lactam antibiotic and BHSi0 2 in weight ratios of 10: 1, 20: 1; 30: 1 and 40: 1 by weight are processed for 1, 2 and 4 hours in a rotary ball mill.
  • the data on the particle size distribution of aqueous suspensions of the obtained compositions and the HPLC analysis of the content of antibiotics in them (in% of the initial substance) are given in table. 2.
  • Granulometric composition of aqueous suspensions and antibiotic content in various compositions are provided.
  • A3TpeoHaM BHSi0 2 (30: 1), 21.7 39.4 53.6 97
  • the selected conditions for obtaining the proposed composition can increase to the required value (at least 25% of the total weight) the fraction of the finely dispersed fraction of BHSi0 2 (particle size less than 5 microns) and thus avoid chemical decomposition of the antibiotic.
  • beta-lactam antibiotics cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefoperazone, cefoperazone / sulbactam, ceftazidime, cefepime, cefoxitin, aztreone, meropenem, carbenicillin
  • Microorganisms Staphylococcus aureus (ATCC N ° 25923 F-49), Escherichia coli (ATCC JYQ25922 F-50), Pseudomonas aeruginosa (ATCC 27853 F-51).
  • Pseudomonas aeruginosa at a dose of 5x10 CFU / mouse or a suspension of a daily culture of Staphylococcus aureus at a dose of 10 10 CFU / mouse or a suspension of a daily culture of Escherichia coli at a dose of 8x10 8 CFU / mpp.
  • the control group was administered physical. solution (0.9% sodium chloride solution) in a volume of 0.8 ml.
  • antibiotics and various pharmaceutical compositions at a dose of 100 mg / kg diluted in 0.25 ml of physiological saline were injected intravenously daily for 3 days once a day.
  • the control group of mppey was injected with saline in a volume of 0.25 ml according to the same scheme.
  • MeponeHeM / BHSi0 2 90.6% (29/32) 95.0% (38/40) 95.1% (39/41)
  • beta-lactam antibiotic highly dispersed nanostructured silica (BHSi0 2 ) in a weight ratio of 30: 1.
  • Rational antimicrobial pharmacotherapy // Guide for practitioners. Under the general editorship of V.P. Yakovlev, S.V. Yakovlev. - M .: Litterra, 2003 .-- 1008 p.

Abstract

L'invention se rapporte au domaine de la pharmacologie, de la médecine, de la médecine vétérinaire et de l'industrie pharmaceutique, et concerne notamment un procédé de production de préparation antimicrobiennes complexes originales pour administration parentérale, qui possèdent une efficacité thérapeutique accrue lors du traitement de formes lourdes de maladies infectieuses et inflammatoires. Ces compositions pharmaceutiques comprennent contiennent en qualité de substance active des antibiotiques bêta-lactames et du dioxyde de silicium à haute dispersion nano-structuré selon des proportions allant de 10:1 à 75:1 en poids, respectivement. Les particules de silicium présentes dans la composition constituent des moyens de transport des molécules d'antibiotiques vers les phagocytes, ce qui permet d'augmenter spécifiquement la concentration de préparations antimicrobiennes dans les zones d'inflammation, et de niveler sensiblement le phénomène de résistance aux antibiotiques des microorganismes. Ce procédé de production de composition pharmaceutique consiste à mélanger la substance de l'antibiotique bêta-lactame avec du dioxyde de silicium à haute dispersion nano-structuré, et se caractérise en ce que le mélange des substances susmentionnées dans des proportions allant de 10:1 à 75:1 en poids, respectivement, est soumis à un traitement mécanique en appliquant des actions de choc et d'attrition jusqu'à ce que la part en poids de la fraction à dispersion fine (< 5 microns) atteigne au moins 25 %. Le mélange ainsi obtenu est utilisé pour préparer des solutions à injecter.
PCT/RU2011/000320 2010-09-13 2011-05-11 Composition pharmaceutique à action antimicrobienne pour administration parentérale, et procédé de production WO2012036585A1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
UAA201203809A UA103118C2 (ru) 2010-09-13 2011-05-11 Фармацевтическая композиция антимикробного действия для парентерального введения и способ ее получения
CN2011800044095A CN103096896A (zh) 2010-09-13 2011-05-11 供不经肠投药的抗菌用药物组合物及其制造方法
AU2011302724A AU2011302724C1 (en) 2010-09-13 2011-05-11 Pharmaceutical composition with antimicrobial activity for parenteral administration and process for preparing same
NZ598831A NZ598831A (en) 2010-09-13 2011-05-11 Pharmaceutical composition with antimicrobial activity for parenteral administration and process for preparing same
EP11825509.0A EP2620152A4 (fr) 2010-09-13 2011-05-11 Composition pharmaceutique à action antimicrobienne pour administration parentérale, et procédé de production
MX2012010535A MX2012010535A (es) 2010-09-13 2011-05-11 Composicion farmaceutica con actividad antimicrobiana para administracion parenteral y procedimiento de produccion de la misma.
CA2785228A CA2785228A1 (fr) 2010-09-13 2011-05-11 Composition pharmaceutique a action antimicrobienne pour administration parenterale, et procede de production
US13/390,151 US20130164337A1 (en) 2010-09-13 2011-05-11 Antimicrobial action pharmaceutical composition for parenteral administration and its production process
JP2013528146A JP2013537190A (ja) 2010-09-13 2011-05-11 非経口投与のための抗菌作用を有する医薬組成物及びその製造方法
BR112012023964A BR112012023964A2 (pt) 2010-09-13 2011-05-11 composição farmacêutica de ação antimicrobiana para administração parenteral e processo de produção da mesma

Applications Claiming Priority (3)

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EA201001449 2010-09-13
RU201001449 2010-09-13
EA201001449A EA021874B1 (ru) 2010-09-13 2010-09-13 Фармацевтическая композиция антимикробного действия для парентерального введения и способ ее получения

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WO2012036585A8 WO2012036585A8 (fr) 2012-10-04

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CN (1) CN103096896A (fr)
AU (1) AU2011302724C1 (fr)
BR (1) BR112012023964A2 (fr)
CA (1) CA2785228A1 (fr)
EA (1) EA021874B1 (fr)
MX (1) MX2012010535A (fr)
NZ (1) NZ598831A (fr)
WO (1) WO2012036585A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2377985C2 (ru) 2006-12-25 2010-01-10 Сергей Михайлович Юдин Средство для лечения инфекционных болезней, вызванных множественно-устойчивыми бактериями

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040058360A (ko) * 1996-02-29 2004-07-03 후지사와 야꾸힝 고교 가부시키가이샤 합성 감미료
JP2010500340A (ja) * 2006-08-11 2010-01-07 パナセア バイオテック リミテッド 活性成分を送達するための粒子、その製造方法、および組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2377985C2 (ru) 2006-12-25 2010-01-10 Сергей Михайлович Юдин Средство для лечения инфекционных болезней, вызванных множественно-устойчивыми бактериями

Non-Patent Citations (28)

* Cited by examiner, † Cited by third party
Title
"Antibacterial medicaments", 2004, «MEDICINE» PUBLISHING», pages: 944
A.E. GULIAEV; B.A. ERMEKBAEVA; G.Y. KIVMAN: "Nanoparticles as targeted antibiotic transport (review", CHEMICAL AND PHARMACEUTICAL MAGAZINE, 1998, pages 3 - 6
A.M. MAYANSKY: "Nizhny Novgorod: Nizhny Novgorod State Medical", 1999, ACADEMY PUBLISHING, article "Microbiology for physicians (pathogenetic microbiology essays", pages: 400
ABEYLATH S.C. ET AL.: "Drug delivery approaches to overcome bacterial resistance to beta-lactam antibiotics", EXPERT OPIN. DRUG DELIV., vol. 5, no. 9, 2008, pages 931 - 949, XP008167290, Retrieved from the Internet <URL:http://www.ncbi.nim.nih.gov/pubmed/18754746> [retrieved on 20110822] *
ABEYLATH S.C.; TUROS E: "Drug delivery approaches to overcome bacterial resistance to ?-lactam antibiotics", EXPERT OPINION ON DRUG DELIVERY, vol. 5, 2008, pages 931 - 949
BASTUS N.G.; SANCHEZ-TILLO E.; PUJALS S. ET AL.: "Peptides conjugated to gold nanoparticles induce macrophage activation", MOLECULAR IMMUNOLOGY, vol. 46, 2009, pages 743 - 748
CHUIKO A.; PENTYUK A.; SHTAT'KO E.; CHUIKO N.: "Medical aspects of application of highly disperse amorphous silica // Surface Chemistry in Biomedical and Environmental Science", MATHEMATICS, PHYSICS AND CHEMISTRY, vol. 228, 2006, pages 191 - 204
ECKHARDT C.; FICKWEILER K.; SCHAUMANN R. ET AL.: "Therapeutic efficacy of moxifloxacin in a murine model of severe systemic mixed infection with E.coli and B.fragilis", ANAEROBE, vol. 9, 2003, pages 157 - 160
F.F. CHUYKO: "Medical chemistry and clinical use of silica dioxide", 2003, NAUKOVA DUMKA, pages: 416
IZDATELSTVO NFAU ET AL.: "Promyshlennaya tekhnologiya lekarstv pod red. prof. V.I.", CHUESHOVA, vol. 1, 2002, pages 45 - 46, XP008167292 *
LUCARELLI M.; GATTI A.M.; SAVARINO G. ET AL.: "Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles", EUROPEAN CYTOKINE NETWORK, vol. 15, 2004, pages 339 - 346
M.D. MASHKOVSKY: "Medicaments", vol. 2, 2001, NOVAYA VOLNA PUBLISHING, pages: 608
MOHAMED N. SELEEM ET AL.: "Silica-Antibiotic Hybrid Nanoparticles for targeting Intracellular Pathogens.", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 53, no. 10, October 2009 (2009-10-01), pages 4270 - 4274, XP055101084, Retrieved from the Internet <URL:http://aac.asm.org/cgi/content/abstract/53/10/4270> [retrieved on 20110829] *
N.A. PIATAEV; A.N. BELIAEV; M.D. ROMANOV; I.S. KOTLOV: "Pharmacons directed cell assosiated transport", 2007, MORDOVIA UNIVERSITY PUBLISHING, pages: 140
PARK J-H.; GU L.; MALTZAHN G. ET AL.: "Biodegradable luminescent porous silica nanoparticles for in vivo applications", NATURE MATERIALS, vol. 8, 2009, pages 331 - 336
PERNIS B.: "Silica and the immune system", ACTA BIOMED., vol. 76, no. 2, 2005, pages 38 - 44
PINTO-ALPHANDARY H.; ANDREMONT A.; COUVREUR P.: "Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, vol. 13, 2000, pages 155 - 168
RAI A.; PRABHUNE A.; PERRY C.C.: "Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings", JOURNAL OF MATERIALS CHEMISTRY, vol. 20, 2010, pages 6789 - 6798
ROSEMARY M.J. ET AL.: "Investigations of the Antibacterial Properties of Ciprofloxacin@ Si02", LANGMUIR, vol. 22, 2006, pages 10125 - 10129, XP002606517 *
ROSEMARY M.J.; MACLAREN I.; PRADEEP T.: "Investigation of antibacterial properties of ciprofloxacin@Si02", LANGMUIR, vol. 22, 2006, pages 10125 - 10129
SCHAUMANN R.; BLATZ R.; BEER J. ET AL.: "Effect of moxifloxacin versus imipenem/cilastatin treatment on the mortality of mice infected intravenously with different strains of Bacteroides fragilis and Escherichia coli", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 53, 2004, pages 318 - 324
See also references of EP2620152A4 *
SELEEM M.N.; MUNUSAMY P.; RANJAN A ET AL.: "Silica-antibiotic hybrid nanoparticles for targeting intracellular pathogens", ANTIMICROBIAL. AGENTS AND CHEMOTHERAPY, vol. 53, 2009, pages 4270 - 4274
TASCIOTTI E.; LIU X.; BHAVANE R. ET AL.: "Mesoporous silica particles as a multistage delivery system for imaging and therapeutic applications", NATURE NANOTECHNOLOGY, vol. 3, 2008, pages 151 - 157
ULBRICH W.; LAMPRECH A.: "Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases", JOURNAL ROYAL SOCIETY INTERFACE, vol. 7, no. 1, 2010, pages S55 - S66
V.P. YAKOVLEV; S.V. YAKOVLEV; M.: LITTERRA: "Practitioners' Guidance. Under the general editorship", 2003, article "Efficient antibacterial pharmaceutical", pages: 1008
WANG, YANG.: "Antibiotic-conjugated polyacrylate nanoparticles: New opportunities for development of anti-MRSA agents.", THESES AND DISSERTATIONS, PAPER 2746, 2006, pages 49, XP055101062, Retrieved from the Internet <URL:http:scholarcommons.usf.edu/etd/2746> *
ZOLNIK B.S.; GONZALEZ-FERNANDEZ A.; SADRIEH N.; DOBROVOLSKAIA V.: "Minireview: Nanoparticles and the immune system", ENDOCRINOLOGY, vol. 151, 2010, pages 458 - 465

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Publication number Publication date
NZ598831A (en) 2013-11-29
WO2012036585A8 (fr) 2012-10-04
AU2011302724C1 (en) 2012-11-29
BR112012023964A2 (pt) 2016-08-02
CA2785228A1 (fr) 2012-03-22
CN103096896A (zh) 2013-05-08
AU2011302724B2 (en) 2012-06-28
AU2011302724A1 (en) 2012-05-03
MX2012010535A (es) 2012-11-16
EA021874B1 (ru) 2015-09-30
JP2013537190A (ja) 2013-09-30
EA201001449A1 (ru) 2012-02-28

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