WO2003103569A3 - Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues - Google Patents

Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues Download PDF

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Publication number
WO2003103569A3
WO2003103569A3 PCT/US2002/017720 US0217720W WO03103569A3 WO 2003103569 A3 WO2003103569 A3 WO 2003103569A3 US 0217720 W US0217720 W US 0217720W WO 03103569 A3 WO03103569 A3 WO 03103569A3
Authority
WO
WIPO (PCT)
Prior art keywords
tbo
peaks
improved
indaminyl
indamine
Prior art date
Application number
PCT/US2002/017720
Other languages
French (fr)
Other versions
WO2003103569A2 (en
Inventor
Karl Okolotowicz
Original Assignee
Karl Okolotowicz
Zila Inc
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 Karl Okolotowicz, Zila Inc filed Critical Karl Okolotowicz
Priority to JP2004510690A priority Critical patent/JP2005535605A/en
Priority to IL16551602A priority patent/IL165516A0/en
Priority to PCT/US2002/017720 priority patent/WO2003103569A2/en
Priority to EP02739681A priority patent/EP1534346A4/en
Priority to BRPI0215775A priority patent/BRPI0215775A2/en
Priority to US10/516,352 priority patent/US20060110326A1/en
Priority to AU2002312319A priority patent/AU2002312319A1/en
Priority to MXPA04012031A priority patent/MXPA04012031A/en
Priority to CNB028290909A priority patent/CN1302815C/en
Priority to NZ537344A priority patent/NZ537344A/en
Priority to TW096101848A priority patent/TW200733956A/en
Publication of WO2003103569A2 publication Critical patent/WO2003103569A2/en
Publication of WO2003103569A3 publication Critical patent/WO2003103569A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B21/00—Thiazine dyes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/006—Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention comprises an improved process for preparing TBO drug products includes the steps: (1) synthesising an indamine; (2) converting said indamine into an S-indaminyl thiosulfate; and (3) adding an oxidizing catalyst agent, complexing agent, and an acid to said S-indaminyl thiosulfate to formulate TBO and C-4-methyl regioisomer, and derivatives thereof. The invention further comprises new compositions of matter that are useful for detecting dysplastic tissue, as well as, treating dysplastic tissue, namely, TBO products predominantly comprised of peaks eight, peak six, or a combination thereof. N,N-dimenthyl-p-phenylenediamine as a starting material results in a TBO product composition comprised of peaks eight, seven, six, and five in the approximate ratios 33:5:5:1, respectively. Whereas N-dimethyl-p-phenylenediamine as a starting material results in a TBO demetylated product composition comprised of peaks six, five, tree and two in the approximate ratio 33:5:5:1, respectively. The invention further comprises an improved PLC method for analyzing the improved TBO drug product, the improvement comprising the addition of an ion-pairing reagent in a first mobile phase and forming a second mobile phase composition comprising 5o% alcohol by volume.
PCT/US2002/017720 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues WO2003103569A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
JP2004510690A JP2005535605A (en) 2002-06-04 2002-06-04 Toluidine blue O drug and its in vivo staining of dysplastic tissue and its use in chemotherapy treatment
IL16551602A IL165516A0 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues
PCT/US2002/017720 WO2003103569A2 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues
EP02739681A EP1534346A4 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues
BRPI0215775A BRPI0215775A2 (en) 2002-06-04 2002-06-04 toluidine blue o substance (toluidine blue o) and its application for in vivo dyeing and chemotherapeutic treatment of dysplastic tissues.
US10/516,352 US20060110326A1 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vitro staining and chemotherapeutic treatment of dysplastic tissues
AU2002312319A AU2002312319A1 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues
MXPA04012031A MXPA04012031A (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues.
CNB028290909A CN1302815C (en) 2002-06-04 2002-06-04 Toluidine blue O drug substance and use thereof for in VIVO Staining and chemo therapeutic treatment of dysplastic tissues
NZ537344A NZ537344A (en) 2002-06-04 2002-06-04 Toluidine blue O drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues
TW096101848A TW200733956A (en) 2002-06-04 2002-07-22 Toluidine blue O drug substance and composition comprising the same for in vivo staining and chemotherapeutic treatment of dysplastic tissues

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2002/017720 WO2003103569A2 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues

Publications (2)

Publication Number Publication Date
WO2003103569A2 WO2003103569A2 (en) 2003-12-18
WO2003103569A3 true WO2003103569A3 (en) 2004-05-21

Family

ID=29731309

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/017720 WO2003103569A2 (en) 2002-06-04 2002-06-04 Toluidine blue o drug substance and use thereof for in vivo staining and chemotherapeutic treatment of dysplastic tissues

Country Status (9)

Country Link
EP (1) EP1534346A4 (en)
JP (1) JP2005535605A (en)
CN (1) CN1302815C (en)
AU (1) AU2002312319A1 (en)
BR (1) BRPI0215775A2 (en)
IL (1) IL165516A0 (en)
MX (1) MXPA04012031A (en)
TW (1) TW200733956A (en)
WO (1) WO2003103569A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6086852A (en) * 1997-11-13 2000-07-11 Zila, Inc. In vivo stain composition, process of manufacture, and methods of use to identify dysplastic tissue
US6194573B1 (en) * 1997-11-13 2001-02-27 Zila, Inc. Process for manufacture of in vivo stain composition

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH071257B2 (en) * 1985-09-09 1995-01-11 エスエス製薬株式会社 Simultaneous determination of water-soluble vitamins in mixed vitamin preparations
JPS6410171A (en) * 1987-07-03 1989-01-13 Shimadzu Corp Analysis of amino acid
AU661727B2 (en) * 1991-10-31 1995-08-03 Zila Biotechnology, Inc. Biological stain composition, method of preparation and method of use for delineation of epitheleal cancer
AU5357498A (en) * 1997-11-13 1999-06-07 Zila, Inc. (in vivo) stain composition, process of manufacture, and methods of use to identify dysplastic tissue
AU2000237154A1 (en) * 2000-02-28 2001-09-12 Zila, Inc. Method for detecting and killing epithelial cancer cells
JP4424838B2 (en) * 2000-08-31 2010-03-03 株式会社トクヤマ Analysis method for quaternary ammonium salts

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6086852A (en) * 1997-11-13 2000-07-11 Zila, Inc. In vivo stain composition, process of manufacture, and methods of use to identify dysplastic tissue
US6194573B1 (en) * 1997-11-13 2001-02-27 Zila, Inc. Process for manufacture of in vivo stain composition
US6372904B2 (en) * 1997-11-13 2002-04-16 Zila, Inc. Process for manufacture of in vivo stain composition

Also Published As

Publication number Publication date
JP2005535605A (en) 2005-11-24
EP1534346A2 (en) 2005-06-01
CN1627961A (en) 2005-06-15
AU2002312319A1 (en) 2003-12-22
CN1302815C (en) 2007-03-07
IL165516A0 (en) 2006-01-15
MXPA04012031A (en) 2005-03-07
BRPI0215775A2 (en) 2016-07-05
EP1534346A4 (en) 2007-07-25
WO2003103569A2 (en) 2003-12-18
TW200733956A (en) 2007-09-16

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