Patent JPS6442010A successfully refreshed from Google Patents.
EP0161606A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Drug, and methods of preparing and using it for treatment of tumors
Assignee: Health Research Inc
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Filing: 1985-05-06
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Granted: —
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Expires: 2005-05-06
Abstract
Abstract The technical field of the invention relates to: (1) certain photosensitive substances used with lasers for discovery and destruction of tumors; (2) methods of making the substances; (3) use of the substances; and (4) certain light-delivery equipment used with the substance. To obtain tumor-selective, photosensitizing substances 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. 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 lipophilic. The substance is injected into the patient, clears normal tissue and then neoplastic tissue is irradiated using lasers. Laser equipment includes a light conductor and transmitting head with light differing surface and feedback path for radiated light related to dosage.
Inventors
- 👤 Kenneth R. Weishaupt
- 👤 Thomas J. Dougherty
- 👤 William R. Potter
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 07:44
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/40; A61B; A61B5/00; A61B5/41; A61B5/411; A61B5/414; A61B5/416; A61K41/00; A61K41/0057; A61K41/0071; A61N; A61N5/00; A61N5/06; A61N5/0601; A61N5/0613; A61N5/062; A61P; A61P35/00; A61P43/00; C; C07; C07D; C07D519/00; G; G02; G02B; G02B6/00; G02B6/24; G02B6/26; G02B6/262; G02B6/42; G02B6/4201; G02B6/4204; A61B5/0059; A61B5/0071; A61B5/0082; A61B5/0084; G02B6/4298; Y; Y10; Y10S; Y10S607/00; Y10S607/901
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
96 words
A composition of matter comprising a substance including as its active ingredient, a molecule which is photosensitizing, has the capability of localizing in and being retained in tumor cells for a longer time than in normal tissues; and not completely disaggregating in the serum protein characterized in that said high molecular weight aggregate comprises molecules having two groups, each group being arranged in a ring structure and that at least 50 percent of the molecules in the active ingredient in the substance form a high molecular weight aggregate of more than 10,000 in an aqueous medium.
Claim 2
Dependent Claim
96 words
A composition of matter comprising a substance including as its active ingredient, a molecule which is photosensitizing, has the capability of localizing in and being retained in tumor cells for a longer time than in normal tissues; and not completely disaggregating in the serum protein characterized in that said high molecular weight aggregate comprises molecules having two groups, each group being arranged in a ring structure and that at least 50 percent of the molecules in the active ingredient in the substance form a high molecular weight aggregate of more than 10,000 in an aqueous medium.
Claim 3
Dependent Claim
27 words
A composition of matter according to claim 1 characterized in that at least some of the porphyrins forming the high molecular weight aggregate have the molecular formula:
Claim 4
Dependent Claim
18 words
A composition of matter according to claim 2 characterized in that said groups are covalently bound to Rl.
Claim 5
Dependent Claim
33 words
A composition of matter in accordance with any of claims 1 - 3 characterized in that said substance has an empirical formula of approximately C 68 H 70 N 8 O 11 .
Claim 6
Dependent Claim
33 words
A composition of matter in accordance with any of claims 1 - 3 characterized in that said substance has an empirical formula of approximately C 68 H 66 O 11 Na 4 .
Claim 7
Dependent Claim
16 words
A composition of matter according to claim 1 characterized in that the molecule is a phlorin.
Claim 8
Dependent Claim
19 words
A composition of matter in accordance with claim 6 characterized in that said phlorin is encapsulated in a liposome.
Claim 9
Dependent Claim
31 words
A composition of matter in accordance with claim 6 characterized in that the molecules have the formula: in which Rl includes at least one atom with a valence greater than one.
Claim 10
Dependent Claim
18 words
A composition of matter according to claim 1 characterized in that the molecule includes at least one chlorin.
Claim 11
Dependent Claim
17 words
A composition of matter in accordance with claim 9 characterized in that said molecules has the formula:
Claim 12
Dependent Claim
64 words
A composition of matter accordinq to any of claims 1 - 10 characterized in that Rl includes at least one atom with a valence greater than one and in that Rl includes an ether linkage or a substituted ethyl ether function or a carbon-carbon linkage or a substituted alkyl function and R2-R15 are other covalently bound chemical groups with molecular weights less than 1,000.
Claim 13
Dependent Claim
50 words
A process for the in vivo destruction of tumors characterized in that the composition of matter of any of claims 1-11 is injected into a host having undesirable tissue, a predetermined period of time is permitted to elapse; and the undesirable tissue is illuminated with light at a predetermined intensity.
Claim 14
Dependent Claim
72 words
A process in accordance with claim 12 characterized in that said substance is used in a dosage of from about 1 to 4 mg/kg of body weight of the host, the time delay between the injection and illumination is within a range of about 3 hours to 7 days, and said intensity of illumination is at least 5mw/cm2 for an extended period of time, but no greater than 750mw/cm2 for twenty minutes.
Claim 15
Dependent Claim
51 words
A process according to either of claims 12 or 13 characterized in that 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.
Claim 16
Dependent Claim
43 words
A process according to any of claims 12 - 14 further characterized by the steps of transmitting radiation from the area being treated back to the source of radiation through a light conductor and using said radiation to control the dosage of radiation.
Claim 17
Dependent Claim
35 words
A process according to any of claims 12 - 15 characterized in that step of transmitting radiation through a diffuser includes the step of transmitting radiation through an air filled bulb whereby heat is dissipated.
Claim 18
Dependent Claim
33 words
A process in accordance with any of claims 12 - 16 characterized in that the intensity of illumination is between 0.5mw/square centimeters and one killowatt per square centimeter, whereby thermal effects are obtained.
Claim 19
Dependent Claim
25 words
A process according to any of claims 12 - 17 characterized in that the tumors are injected with phlorin, chlorin or DHE as the drug.
Claim 20
Dependent Claim
90 words
A process for the production of a photodynamic substance by forming compounds which have molecules with pyrrole or pyrrole-like parts, which compounds are photosensitizing, have the capability of localizing in and being retained in tumor cells for a longer time than in normal tissues; and of not being completely disaggregating in serum protein characterized by forming a mixture of compounds with at least one compound having molecules with pyrrole or pyrrole-like parts and separating at least some of the one compound from some of the remaining compounds of the mixture.
Claim 21
Dependent Claim
90 words
A process for the production of a photodynamic substance by forming compounds which have molecules with pyrrole or pyrrole-like parts, which compounds are photosensitizing, have the capability of localizing in and being retained in tumor cells for a longer time than in normal tissues; and of not being completely disaggregating in serum protein characterized by forming a mixture of compounds with at least one compound having molecules with pyrrole or pyrrole-like parts and separating at least some of the one compound from some of the remaining compounds of the mixture.
Claim 22
Dependent Claim
27 words
A process according to claim 19 characterized by forming from hematoporphyrin a compound having the formula: and separating at least some of the compound from other compounds.
Claim 23
Dependent Claim
45 words
A process according to claim 20 characterized in that Rl in the separated compound includes at least one atom with a valence greater than one, and includes an ether linkage, or a substituted ethyl ether function, or a carbon-carbon linkage, or a substituted alkyl function.
Claim 24
Dependent Claim
19 words
A process according to any of claims 19 - 21 characterized by dehydration of hematoporphyrin to form an ether.
Claim 25
Dependent Claim
25 words
A process according to any of claims 19 - 22 characterized in that the compound is separated according to the molecular weight of its aggregate.
Claim 26
Dependent Claim
41 words
A process according to any of claims 19 - 23 characterized in that the step of separating includes the step of selecting a range of molecular weights of the aggregates above 10,000 and separating according to this range of molecular weights.
Claim 27
Dependent Claim
44 words
A process according to any of claims 19 - 24 characterized in that the step of separating the compound includes the step of separating certain of the aggregates of the compound from compounds having a molecular weight greater than a preselected value above 10,000.
Claim 28
Dependent Claim
51 words
A process according to any of claims 21 - 25 characterized in that the step of separating the compound includes the steps of adjusting the pH of the solution to 9.5; and passing the resultant impure solution through a porous membrane system to exclude low molecular weight by-products thereby effecting purification.
Claim 29
Dependent Claim
68 words
A process according to any of claims 21 - 26 characterized by reacting hematoporphyrin with acetic/ sulfuric acids to form a solution, precipitating the crude product by neutralization in sodium acetate, dissolving the crude product with sodium hydroxide, adjusting the acidity of the solution to pH of 9.5 and passing the resultant impure solution through a porous membrane system to exclude low molecular weight by-products thereby effecting purification.
Claim 30
Dependent Claim
27 words
A process according to claim 19 characterized by forming a phlorin, by separating the phlorin and combining the phlorin with a material capable of entering neoplastic tissue.
Claim 31
Dependent Claim
27 words
A process according to claim 28 in which the step of combining is characterized by the step of combining the phlorin with a compound having the formula:
Claim 32
Dependent Claim
24 words
A process in accordance with claim 28 characterized in that the step of combining includes the step of encapsulating the phlorin in a liposome.
Claim 33
Dependent Claim
26 words
A process according to claim 19 characterized by forming a chlorin, separating the chlorin and combining the chlorin with a material capable of entering neoplastic tissue.
Claim 34
Dependent Claim
20 words
A process according to claim 31 characterized by the step of combining the chlorin with a compound having the formula:
Claim 35
Dependent Claim
18 words
A process in accordance with claim 31 characterized by the step of encapsulating the chlorin in a liposome.
Claim 36
Dependent Claim
14 words
A process in accordance with claim 31 characterized by encapsulating the chlorin in DHE.
Claim 37
Dependent Claim
113 words
Apparatus (12, 14; Fig. 8) for transmitting light from a light source (10, Fig. 8) for application to tissue containing the photosensitive substance produced by the process of claim 1 comprising: a transmitting light conductor (40; Fig. 2); and a light interface system (20A) for permitting radiation from a laser to enter said transmitting light conductor (40); characterized by a transmitting head (43; Figs. 8 - 11 and 82; Figs. 13, 14 and 92; Figs. 15 - 17) sealed against fluid and coupled to said transmitting light conductor (40); and said transmitting head having a control portion (62, 56; Fig. 10, 81, Fig. 14; 99; Fig. 17) for controlling radiation and transmitting it.
Claim 38
Dependent Claim
41 words
Apparatus according to claim 35 further including a receiving light path characterized by a receiving section (e.g. 37; 72, 74); said receiving section being adapted to receive reflected light and transmit it as a feedback signal through said receiving light path.
Claim 39
Dependent Claim
122 words
Apparatus (12; 14; Fig. 8) according to either claim 35 or claim 36 characterized in that said transmitting head (42) is made of a material (81; Figs. 13 and 14; and 92; Figs. 15 - 17) capable of passing radiation outwardly and backscattering radiation; said transmitting light conductor (40) having an end within said transmitting head (42; Figs. 8 - 11; and 82, Figs. 13 and 14 and 92 Figs. 15 - 17); said transmitting head being substantially cylindrical and having a diameter less than one inch; and the walls of said transmitting head being less than one-quarter the diameter of said head in thickness whereby no surface in contact with blood is heated to a temperature to cause coagulation of blood.
Claim 40
Dependent Claim
86 words
Apparatus according to any of claims 35 or 37 characterized in that said transmitting head (92) is cup-shaped, with a diffusing surface (99) closing said cup and the interior being reflective; the diameter of said cup being less than one-half inch; said transmitting conductor (90) entering said cup; and a tubular stem surrounding at least a portion of said transmitting light conductor and being connected to said transmitting head at an angle thereto to permit easy insertion near an eye for the application of radiation thereto.
Claim 41
Dependent Claim
36 words
Apparatus according to any of claims 35 - 38 characterized in that said receiving light path has a light sensor (28A; Fig. 9; 112, Fig. 19) at one end for converting radiation to an electrical signal.
Claim 42
Dependent Claim
44 words
Apparatus according to any of claims 35 or 39 characterized by at least one laser, a sensor (112, Fig. 9) for sensing radiation from said laser and means responsive to said sensor and said electrical signal for developing a signal related to radiation dosage.
References Cited (Backward Citations)
No citation records indexed.
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