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Details for Patent: 5,225,433

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Details for Patent: 5,225,433

Title: Treatment of tumors using chlorins
Abstract:To obtain tumor-selective, photosensitizing drugs useful in the localization of neoplastic tissue and treatment of abnormal neoplastic tissue such as tumors, one of two methods is used. In the first method, a hydrolyzed mixture of the products of reaction of hematoporphyrin with acetic acid and sulfuric acid is cycled through a microporous membrane system to exclude low molecular weight products. In the second method, drugs are synthesized or derived from other pyrrole compounds. The drugs: (1) include two covalently bound groups, each with four rings, some of which are pyrroles such as phlorins, porphyrins, chlorins, substituted pyrroles, substituted chlorins or substituted phlorins, each group being arranged in a ring structure, connected covalently to another group and have a triplet energy state above 37.5 kilocalories per mole; (2) are soluble in water, forming an aggregate of over 10,000 molecular weight in water and have an affinity for each other compared to serum protein such that 10 to 100 per cent remain self aggregated in serum protein; and (3) are lipophyllic and able to disaggregate and attach to cell plasma, nuclear membrane, mitochondria, lysosomes and tissue. The drug obtained by the first method has an empirical formula of approximately C.sub.68 H.sub.70 N.sub.8 O.sub.11 or C.sub.68 H.sub.66 N.sub.8 O.sub.11 Na.sub.4. Neoplastic tissue retains the drug after it has cleared normal tissues and illumination results in necrosis. Moreover, other photosensitizing materials may be combined with a carrier that enters undesirable tissues and cells of the reticular endothelial system such as macrophages. These photosensitizing materials: (1) must have a triplet energy state above 3.5 kilocalories per mole; (2) cannot be easily oxidized; and (3) not physically quench any required energy state. Preferably, this photosensitizing material should be li RIGHTS IN THE U.S. GOVERNMENT This invention was made with federal support under research grants CA 30840-01 and CA 16717 and contract No. 1-CM-97311, awarded by the National Career Institute, U.S. Department of Health and Human Services. The Government has certain rights to this invention.
Inventor(s): Dougherty; Thomas J. (Grand Island, NY), Potter; William R. (Grand Island, NY), Weishaupt; Kenneth R. (Sloan, NY)
Assignee: Health Research, Inc. (Buffalo, NY)
Filing Date:Jul 02, 1991
Application Number:07/724,749
Claims:1. A composition of matter comprising:

a substance including, as its active ingredient, a molecule with at least one chlorin;

said molecule having the formula: ##STR3## said molecule being photosensistizing, having the capability of localizing in and being retained in tumor cells for a longer time than normal tissues and not being completely disaggregated by serum protein.

2. A process for the in vivo destruction of tumors comprising the steps of:

injecting a chlorin into a host having undesirable tissue;

waiting for a predetermined period of time; and

illuminating the undesirable tissue with light at predetermined intensity.

3. A process in accordance with claim 2 wherein the time delay between the injection and illumination is within a range of about 3 hours to 7 days.

4. A process in accordance with claim 3 wherein said intensity of illumination is at least 5 mw per square centimeter for an extended period of time, but no greater than 750 mw per square centimeter for twenty minutes.

5. A process according to claim 4 in which said step of illuminating said host includes the step of transmitting radiation through a light conductor to a location adjacent to the area to be treated and transmitting the radiation through a diffuser onto the area being treated.

6. A process for the in vivo destruction of tumors comprising the steps of:

injecting a substance including as its active ingredient, a molecule with at least one chlorin into a host having undesirable tissue;

waiting for a predetermined period of time; and

illuminating the undesirable tissue with light at predetermined intensity.

7. A process in accordance with claim 6 wherein the time delay between the injection and illumination is within a range of about 3 hours to 7 days.

8. A process in accordance with claim 7 wherein said intensity of illumination is at least 5 mw per square centimeter for an extended period of time, but no greater than 750 mw per square centimeter for twenty minutes.

9. A process according to claim 8 in which said step of illuminating said host includes the step of transmitting radiation through a light conductor to a location adjacent to the area to be treated and transmitting the radiation through a diffuser onto the area being treated.
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