[go: up one dir, main page]

WO2013015774A1 - Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique - Google Patents

Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique Download PDF

Info

Publication number
WO2013015774A1
WO2013015774A1 PCT/US2011/045063 US2011045063W WO2013015774A1 WO 2013015774 A1 WO2013015774 A1 WO 2013015774A1 US 2011045063 W US2011045063 W US 2011045063W WO 2013015774 A1 WO2013015774 A1 WO 2013015774A1
Authority
WO
WIPO (PCT)
Prior art keywords
phenyl ring
carbohydrate
substituted
meta
substituent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2011/045063
Other languages
English (en)
Inventor
Daniel Aicher
Volker Albrecht
Burkhard Gitter
Christian B. W. STARK
Arno Wiehe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ceramoptec GmbH
Biolitec Pharma Marketing Ltd
Original Assignee
Ceramoptec GmbH
Biolitec Pharma Marketing Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ceramoptec GmbH, Biolitec Pharma Marketing Ltd filed Critical Ceramoptec GmbH
Priority to BR112013001577-2A priority Critical patent/BR112013001577B1/pt
Priority to CN201180038608.8A priority patent/CN103096887B/zh
Priority to MX2013000876A priority patent/MX352281B/es
Priority to PL11869827T priority patent/PL2616065T3/pl
Priority to JP2014521602A priority patent/JP6041360B2/ja
Priority to EP11869827.3A priority patent/EP2616065B1/fr
Priority to IL224380A priority patent/IL224380A/en
Publication of WO2013015774A1 publication Critical patent/WO2013015774A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/409—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings

Definitions

  • the invention relates generally to photodynamic therapy and more
  • glyco-substituted dihydroxychlorins or glyco-substituted ⁇ - functionalized chlorm derivatives as photosensifizers for the treatment and prevention of microbial infectious diseases in human and animals.
  • Photodynamic therapy is one of the most promising new techniques now being explored for use in a variety of medical applications, and particularly is a well-recognized treatment for the destruction of tumors.
  • Photodynamic therapy uses light and a photosensitizer (a dye) to achieve its desired medical effect.
  • Antimicrobial photodynamic therapy is a very promising, relatively new method for combating bacterial infections even for resistant strains. Fortunately, no resistance to photodynamic destruction has been reported to be acquired by bacteria nor is it likely since the "killing species" is oxygen. Bacterial cells treated with photosensitizers were shown to be successfully killed by photo illumination. Due to the obvious differences between bacteria and malignant cells, photosensitizers with a different mode of action were needed for an antimicrobial PDT.
  • a major problem for the use of anti-microbial PDT is a blocking action of the components of the blood whose presence decreases the activity of photosensitizers.
  • a high bactericidal photodynamic activity in PBS buffer could be decreased remarkably when blood serum or blood is added.
  • photosensitizers and the effectiveness of PDT against bacterial infection is to conjugate a photo sensitizer with a ligand-vector, which specifically binds to receptors on the surface of a target cell.
  • ligand-vector which specifically binds to receptors on the surface of a target cell.
  • US Patent No. 6,977,075 by Hasan et al discloses a method of killing intracellular pathogens using antibiotics and PDT.
  • the intracellular pathogens are targeted using conjugated photosensitizers.
  • Targeting moiety used are molecules or a macromolecular structure that target macrophages or that interacts with a pathogen. Effectiveness of the conjugate against Gram-negative bacteria, and, in complex environment is not disclosed.
  • US Patent No. 6,462,070 by Hasan et al. discloses a photo sensitizer conjugated to polylysine which is linked to a histatin targeting moiety to treat disorder of the oral cavity infected by microorganism. These materials have trouble working in the presence of body fluids, such as saliva, blood, etc.
  • US Patent No. 5,466,681 describes a variety of conjugates useful for the treatment of infectious diseases due to pathogenic microorganisms.
  • the conjugates comprise at least one agent coupled to a microorganism receptor - a carbohydrate vector, which is able to bind selectively to a microorganism.
  • This patent discloses a conjugate comprising at least one agent that is an anti-infective, which couples to a microorganism receptor.
  • Agents such as antibiotics, synthetic drugs and steroids are mentioned. Since photosensitizers do not themselves interact with microbes, they are not considered agents as described in this patent and were not disclosed therein.
  • Chlorins are porphyrin derivatives, in which one double bond of the aromatic system in ⁇ - position is absent. Many current photosensitizers are not efficient enough as they have low absorption in the red region of the spectrum. Chlorins have the advantage that they possess an intense absorption in the red and near-infrared region of the electromagnetic spectrum which allows a deeper penetration of the light into the tissue. US Patent No. 7,022,843B1 by
  • MacAlpine et al discloses a variety of ⁇ , T-dihydroxy /wesosubstituted chlorins as photosensitizers but do not offer guidance for treatment of microbial infectious diseases.
  • International Publication No. WO 2010/033678 by Wiehe et al. disclose unsymmetrically meso-substituted po hyrins and chlorins for diagnostic and PDT applications, including viral or infection diseases, however their effectiveness for both Gram-positive and Gram-negative bacteria in complex medium is not clearly conveyed.
  • molecular conjugates which can actively target both Gram-positive and Gram-negative bacteria. Also they need to work under in vivo conditions, where typically blood and other body fluids are present, to use with patients directly to help protect them from deleterious
  • the present invention provides antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals.
  • the key to these conjugates is connecting dihydroxychlorins and / ⁇ functionalized chlorins to carbohydrate moieties.
  • the present invention effectively works to combat infections caused by Gram-positive and Gram-negative bacteria, including their resistant strains.
  • they are also effective in complex environments, including blood, serum and other body fluids which are present in patient's body.
  • microorganisms in human and animals is also provided.
  • Figure 1. shows one embodiment of photodynamic inactivation using 5 0J5-tris-(3- ⁇ -D-glucosyl henyl)-20-[3,5-bis-(trifluoromethyl)-phen l]-po ⁇ hyrin
  • Figure 2.- shows one embodiment of photodynamic inactivation using 5,10,15-tris-(3-p-D-gIucosylphe ⁇
  • Figure 3. shows one embodiment of photodynamic inactivation using 5,10, 15 ris-(3- -D-galactosylphenyl)-20-[3,5-bis-(trifiuoromethyl)-phenyl]-l 7, 18- dihydroxy- 17, 18-chlorin.
  • Figure 4.- shows one embodiment of photodynamic inactivation using 5 , 10, 15-tri s-(3 -a-D-mannosy lphenyl)-20 - [3 ,5-bis-(trifl uoromethyl)-pheny 1 J - 17, 18- dihydroxy- 17, 18-chlorin.
  • Figure 5. shows one embodiment of photodynamic inactivation using 5,10,1 -tris-(3- -D-lactosylphenyl)-20-[3 ,5-bis-(trifluoromethyl)-phenyl]- 17,18- dihydroxy- 17, 18-chlorin.
  • Figure 6.- shows one embodiment of photodynamic inactivation using 5,10,15,20-tetrakis-(3-p-D-glucosylphenyl)-7,8-dihydroxy-7,8-chlorin.
  • Figure 7 shows one embodiment of photodynamic inactivation using 5, 10,15,20-tetrakis-(3-p-D-glucosyIphenyl)-7,8-dihydroxy-7,8-bis-(trifluoromethyl)- 7, 8-chlorin.
  • a photodynamic method for inactivation/reduction of bacteria in a complex environment is disclosed.
  • Successfully combating bacterial infection in complex media present in vivo, like serum plasma or blood has shown to be one of the most difficult goals as seen in the prior art.
  • antimicrobial photodynamic therapy is used to target pathogenic microorganisms using conjugated photosensitizers to treat various infectious diseases and also to induce photo- destruction in the complex media normally found in vivo for real patients.
  • conjugated photosensitizers to treat various infectious diseases and also to induce photo- destruction in the complex media normally found in vivo for real patients.
  • One of the main advantages of the molecular conjugates disclosed herein is their ability to target both Gram-positive and Gram-negative bacteria, including their resistant strains.
  • the molecular conjugates comprise photosensitizers connected to carbohydrate moieties.
  • conjugates of carbohydrates disclosed herein are used to improve the specificity for microorganisms.
  • the selectivity of the conjugate ' s targeting moiety allows an increased targeting effect of the photosensitizer, minimizing the dosage and potential adverse side-effects.
  • conjugated photosensitizers of present invention enhance the effectiveness of prior art biologically active compounds, offering a deeper penetration due to their higher absorption at long wavelength of the red and near-infrared region of the electromagnetic spectrum.
  • conjugates provided by the present invention have the advantage that they are easily produced. Starting from chemically stable porphyrin or the glycosylation can be achieved by using trichloroacetimidates as glycosyl donors.
  • a carbohydrate and dihydroxychlorin conjugate compound for eliminating/reducing/destroying pathogenic microorganisms in complex environments of real patients has the general formula:
  • R is a substituent comprising one or more carbohydrate groups.
  • a conjugate of a carbohydrate and a dihydroxychl for eliminating microor anisms is based on the formulas 1 or 2:
  • R is a substituent comprising one or more carbohydrate groups
  • R 1 is a substituted or unsubstituted alkyl or fluoroalkyl group consisting of 1-15 carbon atoms, a phenyl ring, or a phenyl ring with one or more substituent X in the ortho-, meta- or para-position of the phenyl ring.
  • the substituent X is OH, -COOH, - NH- 2 , -CF 3, -F, -COOY, -NHY, -OY, -NH-Z-COOH, and -CO-Z-NH 2
  • the substituent Z are peptides or oligopeptides.
  • a conjugate of a carbohydrate and a dihydroxychlorin for eliminating microorganisms is based on the formula 3:
  • R is a substituent comprising one or more carbohydrate groups;
  • R is a substituted or unsubstituted alkyl, alkenyl, alkynyl or fluoroalkyl group consisting of 1 -15 carbon atoms, a phenyl ring, or a phenyl ring with one or more substituent X.
  • the substituent X of the phenyl ring is either in the ortho-, meta- or para-position of the phenyl ring and is OH, -COOH, -NH 2 , -CF 3> -F, -COOY, - ⁇ , -OY, -NH-Z- COOH, or -CO-Z-NH 2 .
  • R 1 is a substituted or unsubstituted alkyl, alkenyL alkynyl, or fluoroalkyl group consisting of 1-15 carbon atoms, or a phenyl ring substituted with one or more CF 3 -groups either in the ortho-, meta- or /rara-position of the phenyl ring.
  • the carbohydrate and a dihydroxychlorin conjugate compound for eliminatin pathogenic microorganisms is based on the formulas 4 or 5:
  • R is a substituent comprising one or more carbohydrate groups
  • R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, or fluoroalkyl group consisting of 1-15 carbon atoms, a phenyl ring, or a phenyl ring with one or more substituents X either in the ortho-, meta- or ⁇ xzra-position of the phenyl ring
  • the substituent X is OH, -COOH, -NH 2 , -CF 3 , -F, -COOY, -NHY, -OY, -NH-Z-COOH, or -CO-Z-NH 2
  • Z are peptides or oligopeptides.
  • a conjugate compound for destroying, eliminating, and/ or reducing pathogenic microorganisms in complex environments is based on the formulas 1 or 2; wherein R is a substituent comprising one or more carbohydrate groups; R 1 is a substituted or unsubstituted alkyl or fluoroalkyl group consisting of 4- 15 carbon atoms, or a phenyl ring with one or more substituents X either in the meta- or /jora-position of the phenyl ring.
  • the substituent X is OH, -COOH, -N3 ⁇ 4, or -CF 3 .
  • the conjugate compound is based on the formulas 4 or
  • R is a substituent comprising one or more cai'bohydrate groups
  • R 1 is s a substituted or unsubstituted alkyl or fluoroalkyl group consisting of 4-15 carbon atoms, or a phenyl ring with one or more substituent X in the meta- or para-position of the phenyl ring.
  • the substituent X is OH, -COOH, -N3 ⁇ 4, or -CF 3.
  • R 2 is a substituted or unsubstituted alkyl, alkenyl, a alkynyl, or fluoroalkyl group consisting of 1-15 carbon atoms, or a phenyl ring substituted with one or more CF 3 -groups either in the ortho-, meta- or 3 ⁇ 4/ra-position.
  • a compound for eliminating/reducing microorganisms is based on the formula 1:
  • R 1 is a phenyl ring with a substituent X either in the meta- or para- position, and is a glucosyl, galactosyl, mannosyl, 2-acetamidoglucosyl, lactosyl, cellobiosyl, maltosyl or 3,4,6-trideoxy-3-(dimethylamino)-D-xy/o-hexopyranosyl substituent.
  • a compound for eliminating/reducing microorganisms is based on the formul 2:
  • R 1 is a substituted or unsubstituted alkyl or fluoroalkyl group consisting of 4-1 carbon atoms, or a phenyl ring with one or more substituent X either in the meta- or para-position.
  • the substituent X is selected from the group consisting of OH, -CO OH, -N3 ⁇ 4, and -CF 3 .
  • R is a phenyl ring with a substituent Y either in the meta- or para-position, and is a glucosyl, galactosyl, mannosyl, 2- acetamidoglucosyl, lactosyl, cellobiosyl, maltosyl or 3,4,6-trideoxy-3- (dimethylamino)-D-rv/o-hexopyranosyl substituent.
  • a carbohydrate and a ⁇ functionalized chlorin compound is based on the formula 1 ;
  • R is a phenyl ring with a substituent X either in the meta- or para-posi tion, and is a glucosyl, galactosyl, mannosyl, 2-acetamidoglucosyI, lactosyl, cellobiosyl, maltosyl or 3,4,6-trideoxy-3 ⁇ (dimethylamino)-D- y/o-hexopyranosyl substituent.
  • R 2 is a substituted or unsubstituted alkyl, alkenyl, alkynyl or fluoroalkyl group consisting of 1 -15 carbon atoms, or a phenyl ring substituted with one or more CF 3 -groups either in the ortho-, meta- or para-position.
  • a conjugate compound for eliminating/destroying/reducing pathogenic microorganisms is based on the formulas 1 or 2:
  • R 1 is a substituted or unsubstituted alkyl or fluoroalkyl group consisting of 4-15 carbon atoms, or a phenyl ring with one or more substituent X either in the meta- or para- position; and R 2 is a phenyl ring with a substituent Y either in the meta- or ara-position.
  • the substituent Y is a glucosyl, galactosyl, mannosyl, 2- acetamidoglucosyi, lactosyl, cellobiosyl, maltosyl or 3,4,6-trideoxy-3- (dimethylamino)-D-r /o-hexopyranosyl substituent.
  • R is a substituted or unsubstituted alkyl, alkenyl, alkynyl or fluoroalkyl group consisting of 1-15 carbon atoms, or a phenyl ring substituted with one or more CFs-groups either in the ortho-, meta- or ?flra-position.
  • mactivation/reduction/elimination of pathogenic microorganisms comprises the steps of selecting a molecular conjugate, selected from the previously described conjugate compounds, with a vector component targeting the microorganisms to be eliminated; introducing or administrating the vectored molecular conjugate to an environment containing pathogenic microorganisms, including Gram- positive and Gram-negative bacteria, in real patient complex environments like blood, serum and saliva, comprises the steps of selecting a molecular conjugate, selected from the previously described conjugate compounds, with a vector component targeting the microorganisms to be eliminated; introducing or administrating the vectored molecular conjugate to an environment containing pathogenic
  • the incubation time varies depending on many factors.
  • the contaminated medium is incubated for 90 min before being irradiated with 652 nm laser at 100 J/cm 2 to initiate photo-destruction of bacterial cells.
  • the conjugated photo sensitizer can be
  • the conjugated photosensitizer can be administered topically.
  • Example 2
  • dichloromethane/pyridine 1 :1 (26 ml). After stirring for 30 minutes at 0 °C and additional 2 hours at room temperature, a saturated solution of sodium bisulfite in water/methanol 1:1 (25 ml) was added and the mixture was stirred for 18 h. The reaction mixture was filtered through Celite and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was purified by flash chromatography with dichloromethane/methanol 95:5 as eluent, followed by recrystallization from dichloromethane/aqueous methanol.
  • dichloromethane/pyridine 1 :1 (15 ml). After stirring for 30 minutes at 0 °C and additional 2 hours at room temperature, a saturated solution of sodium bisulfite in water/methanol 1 :1 (25 ml) was added and the mixture was stirred for 18 h. The reaction mixture was filtered through Celite and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was purified by flash chromatography with dichloromethane/methanol 95:5 as eluent, followed by recrystallization from dichloromethane/aqueous methanol.
  • osmium tetroxide 100 mg, 0.39 mmol was added to a stirred solution of 5,10,15 ; 20-tetrakis-[3-(2,3,4,6-tetraacetyl- -D-glucosyl)-phenyl3- porphyrin (455 mg, 0.23 mmol) in dicliloromethane/pyridine 1 :1 (26 ml).
  • dicliloromethane/pyridine 1 :1 26 ml
  • a saturated solution of sodium bisulfite in water/methanol 1 : 1 25 ml was added and the mixture was stirred for 18 h.
  • reaction mixture was filtered through Celite and dried over anhydrous sodium sulfate.
  • the solvent was evaporated and the residue was purified by flash chromatography with dichloromethane/methanol 95:5 as eluent, followed by recrystallization from dichloromethane/aqueous methanol.
  • 5,10, 15,20-Tetrakis-(3- (2,3,4,6-tetraacetyl-p-D-glucosyl)-phenyl]-7,8-dihydroxy-7,8-chlorin (184 mg, 40%) was obtained as a violet crystalline solid after recrystallization from
  • the organisms used in our studies were two members of the microflora wounds; Staphylococcus aureus DSM 11729, Gram-positive; and Pseudomonas aeruginosa DSM 1117, Gram-negative.
  • Gram-positive bacteria are particularly susceptible to photodynamic inactivation whereas Gram-negative bacteria are significantly more resistant to many commonly used photosensitizers.
  • Gram-positive and Gram-negative bacterial cells in complex media e.g. blood, plasma, blood serum, saliva
  • complex media e.g. blood, plasma, blood serum, saliva
  • Cultures cells are suspended in sterile phosphate-buffered saline (PBS) or sterile PBS supplemented with 10% sterile horse blood serum.
  • the final OD (Optical Density) at 600 nra, 1 cm in all cases was 0.03.
  • the bacterial suspensions are placed into sterile black well plates with clear bottoms. Concentrations of photosensitizer used in the study were as follows: 100 ⁇ , 10 ⁇ and 1 ⁇ .
  • the samples are exposed to laser light of 652 nm, power set 0.5 W, and irradiation time of 85 s. With the irradiation time, the resulting energy fluency is of about 100 J/cm 2 .
  • Control plates contained no photosensitizer and are not exposed to laser light. The control samples for dark toxicity are only exposed to photosensitizer without any illumination.
  • CFU/ml colony-forming units
  • FIG. 1 shows the activity of a porphyrin glycoconjugate and Figures 2 - 7 show the activity of chlorin glycoconjugates.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des conjugués moléculaires antimicrobiens destinés au traitement et à la prévention de maladies infectieuses provoquées par des microorganismes pathogènes chez les humains et les animaux. La clé de la réalisation de ces conjugués réside dans la liaison entre, d'une part des dihydroxy-chlorines glyco-substituées ou des chlorines Bêta-fonctionnalisées, et d'autre part des groupes fonctionnels glucides. Ces conjugués s'avèrent très efficaces dans la lutte contre les infections bactériennes provoquées par les bactéries Gram-positives et Gram-négatives, y compris leurs souches résistantes. On remarquera en outre que ces conjugués sont également efficaces dans des environnements complexes, notamment le sang, le sérum, et d'autres fluides corporels présents dans le corps d'un patient. L'invention concerne également leur utilisation pour lutter contre des microorganismes pathogènes chez les humains et les animaux.
PCT/US2011/045063 2010-07-22 2011-07-22 Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique Ceased WO2013015774A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
BR112013001577-2A BR112013001577B1 (pt) 2010-07-22 2011-07-22 conjugados de carboidrato e dihidroxiclorina
CN201180038608.8A CN103096887B (zh) 2010-07-22 2011-07-22 用于抗微生物光动力疗法的糖取代的二羟基‑二氢卟酚和β‑官能化二氢卟酚
MX2013000876A MX352281B (es) 2010-07-22 2011-07-22 Dihidroxi-clorinas glico-sustituidas y clorinas beta-funcionalizadas para terapia fotodinamica anti-microbiana.
PL11869827T PL2616065T3 (pl) 2010-07-22 2011-07-22 GLIKO-PODSTAWIONE DIHYDROKSYCHLORYNY I ß-FUNKCJONALIZOWANE CHLORYNY DO PRZECIWDROBNOUSTROJOWEJ TERAPII FOTODYNAMICZNEJ
JP2014521602A JP6041360B2 (ja) 2011-07-22 2011-07-22 抗菌性光線力学療法のための、糖−置換ジヒドロキシ−クロリン及びβ−官能化クロリン
EP11869827.3A EP2616065B1 (fr) 2010-07-22 2011-07-22 Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique
IL224380A IL224380A (en) 2010-07-22 2013-01-23 Dihydroxy-chlorins are conserved in glyco group and activated chlorine in beta position for anti-microbial photodynamic therapy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US61/366,718 2010-07-22
US201161366718P 2011-07-22 2011-07-22

Publications (1)

Publication Number Publication Date
WO2013015774A1 true WO2013015774A1 (fr) 2013-01-31

Family

ID=47601393

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/045063 Ceased WO2013015774A1 (fr) 2010-07-22 2011-07-22 Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique

Country Status (1)

Country Link
WO (1) WO2013015774A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130041307A1 (en) * 2011-08-12 2013-02-14 Ceramoptec Industries, Inc. Application of beta-functionalized dihydroxy-chlorins for pdt
JP2015030703A (ja) * 2013-08-02 2015-02-16 公立大学法人名古屋市立大学 光線力学療法のための新規糖連結光感受性物質
EP3626268A1 (fr) 2018-09-24 2020-03-25 Westfälische Wilhelms-Universität Münster Systèmes porteurs scissibles par la lumière à particules de polymère pour thérapie photodynamique
PL446667A1 (pl) * 2023-11-07 2024-06-03 Politechnika Warszawska Glikoporfiryny typu A4 i sposób ich otrzymywania
PL445313A1 (pl) * 2023-06-22 2024-12-23 Politechnika Warszawska Glikoporfiryny i sposób ich otrzymywania

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2709491A1 (fr) 1993-09-03 1995-03-10 Centre Nat Rech Scient Nouveaux dérivés de porphyrines et leurs applications notamment en thérapeutique.
US5466681A (en) 1990-02-23 1995-11-14 Microcarb, Inc. Receptor conjugates for targeting penicillin antibiotics to bacteria
US20040259810A1 (en) 2001-07-19 2004-12-23 David Grierson Porphyrin derivatives for photodynamic therapy
US7022843B1 (en) 1999-04-14 2006-04-04 The University Of British Columbia β,β′-dihydroxy meso-substituted chlorins, isobacteriochlorins, and bacteriochlorins
US20070059316A1 (en) * 2003-09-23 2007-03-15 Pallenberg Alexander J Singlet oxygen photosensitizers activated by target binding enhancing the selectivity of targeted pdt agents
US20090149525A1 (en) * 2004-11-16 2009-06-11 Universidade De Coimbra Novel derivatives of porphyrin, particularly chlorins and/or bacteriochlorins, and uses thereof in photodynamic therapy
WO2010033678A2 (fr) 2008-09-18 2010-03-25 Ceramoptec Industries, Inc. Nouveau procédé et application de porphyrines méso-substituées de façon non symétrique et de chlorines pour thérapie photodynamique
WO2012012809A2 (fr) 2010-07-22 2012-01-26 Ceramoptec Gmbh Application de chlores-dihydroxy β-fonctionnalisés pour tpd

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5466681A (en) 1990-02-23 1995-11-14 Microcarb, Inc. Receptor conjugates for targeting penicillin antibiotics to bacteria
FR2709491A1 (fr) 1993-09-03 1995-03-10 Centre Nat Rech Scient Nouveaux dérivés de porphyrines et leurs applications notamment en thérapeutique.
US7022843B1 (en) 1999-04-14 2006-04-04 The University Of British Columbia β,β′-dihydroxy meso-substituted chlorins, isobacteriochlorins, and bacteriochlorins
US20040259810A1 (en) 2001-07-19 2004-12-23 David Grierson Porphyrin derivatives for photodynamic therapy
US20070059316A1 (en) * 2003-09-23 2007-03-15 Pallenberg Alexander J Singlet oxygen photosensitizers activated by target binding enhancing the selectivity of targeted pdt agents
US20090149525A1 (en) * 2004-11-16 2009-06-11 Universidade De Coimbra Novel derivatives of porphyrin, particularly chlorins and/or bacteriochlorins, and uses thereof in photodynamic therapy
WO2010033678A2 (fr) 2008-09-18 2010-03-25 Ceramoptec Industries, Inc. Nouveau procédé et application de porphyrines méso-substituées de façon non symétrique et de chlorines pour thérapie photodynamique
WO2012012809A2 (fr) 2010-07-22 2012-01-26 Ceramoptec Gmbh Application de chlores-dihydroxy β-fonctionnalisés pour tpd

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
V. SOL; P. BRANLAND; R. GRANET; C. KALDAPA; B. VEMEUIL; P. KRAUSZ: "Nitroglycosylated meso arylporphyrins as Photoinhibitors of Gram positive Bacteria", BIOORG. MED. CHEM. LETT., vol. 8, 1998, pages 3007 - 3010, XP004141864, DOI: doi:10.1016/S0960-894X(98)00536-8

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130041307A1 (en) * 2011-08-12 2013-02-14 Ceramoptec Industries, Inc. Application of beta-functionalized dihydroxy-chlorins for pdt
US9156849B2 (en) * 2011-08-12 2015-10-13 Biolitec Pharma Marketing Ltd Application of β-functionalized dihydroxy-chlorins for PDT
JP2015030703A (ja) * 2013-08-02 2015-02-16 公立大学法人名古屋市立大学 光線力学療法のための新規糖連結光感受性物質
EP3626268A1 (fr) 2018-09-24 2020-03-25 Westfälische Wilhelms-Universität Münster Systèmes porteurs scissibles par la lumière à particules de polymère pour thérapie photodynamique
WO2020064701A1 (fr) 2018-09-24 2020-04-02 Westfälische Wilhelms-Universität Münster Systèmes porteurs photoclivables à particules polymères pour thérapie photodynamique
PL445313A1 (pl) * 2023-06-22 2024-12-23 Politechnika Warszawska Glikoporfiryny i sposób ich otrzymywania
PL446667A1 (pl) * 2023-11-07 2024-06-03 Politechnika Warszawska Glikoporfiryny typu A4 i sposób ich otrzymywania

Similar Documents

Publication Publication Date Title
US9308185B2 (en) Glyco-substituted dihydroxy-chlorins and β-functionalized chlorins for anti-microbial photodynamic therapy
Kustov et al. Synthesis and investigation of novel chlorin sensitizers containing the myristic acid residue for antimicrobial photodynamic therapy
Xiao et al. In vitro and in vivo demonstration of ultraefficient and broad-spectrum antibacterial agents for photodynamic antibacterial chemotherapy
JP4786182B2 (ja) 新規化合物およびその用途
DK2125026T3 (en) FORMATIONS BASED ON bridged POLYCYCLIC COMPOUNDS FOR INHIBITION AND RELIEF OF DISEASES
WO2013015774A1 (fr) Dihydroxy-chlorines glyco-substituées et chlorines bêta-fonctionnalisées pour thérapie antimicrobienne photodynamique
Mottais et al. Antibacterial and transfection activities of nebulized formulations incorporating long n-alkyl chain silver N-heterocyclic carbene complexes
EP3011972B1 (fr) Composition médicinale favorisant la synthèse de la protoporphyrine ix
Mills et al. Riboflavin-vancomycin conjugate enables simultaneous antibiotic photo-release and photodynamic killing against resistant Gram-positive pathogens
US20080206736A1 (en) Flavin n-oxides: new anti-cancer agents and pathogen eradication agents
JP6041360B2 (ja) 抗菌性光線力学療法のための、糖−置換ジヒドロキシ−クロリン及びβ−官能化クロリン
US20090030257A1 (en) Anti-microbial photodynamic therapy
Bharadwaj et al. Role of Gold Nanoparticles Against Multidrug Resistance (MDR) Bacteria: An Emerging Therapeutic Revolution
EP3983486A1 (fr) Petits dérivés cationiques d'ortho-5,15-di-hétéroaryl-porphyrines et leurs applications dans la photoinactivation de micro-organismes
WO2020196891A1 (fr) Médicament polymère
WO2009014524A2 (fr) Thérapie photodynamique antimicrobienne
US20220025185A1 (en) Specifically glyco-substituted porphyrins and chlorins for photodynamic therapy
WO2016028633A2 (fr) Complexes métal de transition-porphyrine et méthodes de traitement les utilisant
WO2022074014A1 (fr) Composés à base de tétrapyrrole et leurs formulations pour une thérapie antimicrobienne
WO2016110754A1 (fr) Finafloxacine à utiliser dans le traitement d'infections des voies urinaires
WO2013027040A1 (fr) Oligosaccharides cycliques pour l'utilisation dans le traitement et la prévention d'une infection bactérienne

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201180038608.8

Country of ref document: CN

ENP Entry into the national phase

Ref document number: 2014521602

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2013/000876

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 224380

Country of ref document: IL

REEP Request for entry into the european phase

Ref document number: 2011869827

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2011869827

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11869827

Country of ref document: EP

Kind code of ref document: A1

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112013001577

Country of ref document: BR

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 112013001577

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20130122