Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Diagnostic or test agent produces visible change in mouth
Patent
1999-05-20
2000-07-11
Dees, Jose' G.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Diagnostic or test agent produces visible change in mouth
424 111, 424 91, 544 35, A61K 4900, G01N 3100, G01N 3348
Patent
active
06086852&
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel biological stain compositions that are adapted for human in vivo topical application.
In particular the invention contemplates novel Toluidine Blue O ("TBO") dye products, products which contain TBO and specific TBO derivatives, in specific proportions.
According to another aspect, the invention pertains to new methods of manufacturing TBO compositions, including these novel TBO products.
In yet another aspect, the invention concerns in vivo methods of using such novel TBO compositions to identify suspect dysplastic, i.e., abnormal, tissue.
In still another and further aspect, the invention pertains to compositions, in vivo diagnostic methods of use thereof and processes for manufacture thereof, which are specially adapted for detecting suspect dysplastic oral tissue, especially cancerous and precancerous tissue.
The various embodiments of the invention and the practice thereof will be apparent to those skilled in the art, from the following detailed description thereof, taken in conjunction with the claims and in conjunction with the drawings, in which:
BACKGROUND OF THE INVENTION
Most oral lesions result from trauma. However, other oral lesions are dysplastic tumors, some of which may be benign, but some of which may be either cancerous or precancerous. In addition, many dysplastic lesions are small and easily missed on routine visual examination by dental clinicians.
An in vivo diagnostic test is known which identifies and delineates suspect dysplastic oral tissue. This screening test is generally described in the U.S. Pat. No. 4,321,251 to Mashberg and in the U.S. Pat. No. 5,372,801 to Tucci et al. More recently kits have been developed which make it possible for clinicians to quickly and easily administer the test, as part of other routine dental procedures, and thus identify and/or delineate suspect sites at a time when the patients are symptomless or while the dysplastic lesions are so small that they might be missed during normal visual examination. Once a suspect dysplastic lesion is identified by the Mashberg protocol, a regular biopsy sample can be taken and subjected to histological examination, to determine whether the lesion is malignant or precancerous. Kits for performing this test, containing premixed dye and rinse solutions in the proper quantities and concentrations, are licensed by Zila, Inc. and are available commercially in Canada from Germiphene, Inc. under the trademark ORASCAN.TM. and in The United Kingdom and Australia from Stafford-Miller Ltd. under the trademark "ORASCREEN.RTM.".
THE PRIOR ART
It has now been discovered that the organic dye content of the prior art TBO products which were typically commercially available, depending on the vendor, was relatively low. Typically, the combined areas of the 254 nm HPLC peaks (see HPLC procedure of Example 3),which represent the conformational isomers of TBO in these prior art products was only about .congruent.2%-75% of the combined areas of the 254 nm HPLC peaks which represent all of the TBO and TBO-related components, i.e., the two conformational isomers of TBO plus up to six TBO-related components.
Referring to FIG. 1, HPLC peaks 7 and 8 represent the two conformational isomers of TBO (shown here as the chloride salt): ##STR1## HPLC peaks 5 and 6 have been identified as the N-demethylated derivatives of the two conformational isomers of TBO: ##STR2## HPLC peaks 2 and 3 have been identifed as the N,N-demethylated derivatives of the two conformational isomers of TBO: ##STR3## The exact structures of the compounds represented by HPLC peaks 1 and 4 have not been positively determined.
At any rate, in the TBO compositions of the prior art, a typical one of which is represented in FIG. 1, the compounds represented by peaks 1-4 were present in relatively higher amounts than those of the present invention (See FIG. 2) and the compounds represented by peaks 5-8 were present in relatively lower amounts than in the TBO products of the present invention. The two N-demethylated derivatives of the conforma
REFERENCES:
patent: 4321251 (1982-03-01), Mashberg
patent: 5372801 (1994-12-01), Malmros et al.
patent: 5882627 (1999-03-01), Pomerantz
McKamey et al, J. of Pharmaceutical Sciences, vol. 64, No. 9, pp. 1456-1462, "Chromatographic Mass Spectral and Visible Light Absorption Characteristics of Toulidene Blue O & Related Dyes," Sep. 1975.
Dees Jos,e G.
Jones Dameron
Zila, Inc.
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