Universitéde Montreal

Kiadis Pharma Canada Inc.

Hopital Maisonneuve-rosemont

Theratechnologies Inc.

Celmed Biosciences Inc.

Luc Villeneuve

Denis Gravel

Abdelkrim Habi

Marc Vaillancourt

Hongsheng Su

Nestor Molfino

Denis-Claude Roy

Louis Gaboury

Richard Giasson

Tiechao Li

Martin Guimond

Ajay Kumar Gupta

Prabir Kumar Pal

Claude Laurendeau

Robert Bernier

Gerard Miller

Denis Claude Roy

Nestor A Molfino

Methods for treating an infection in a tissue sample are described. Tissue samples that are harvested from a patient may be infected with either bacteria or a virus. A rhodamine compound is mixed with the infected tissue sample to form a mixture. The mixture is then exposed to radiant energy to inhibit or kill the bacteria. The exposed mixture is then transplanted into the patient. The rhodamine compounds may be 2'-(6-dimethylamino-3-dimethylimino-3H-xanthen-9-yl) 4&#x2032;, 5&#x2032;-dichloro-benzoic acid methyl ester hydrochloride.

Halogenated rhodamine derivatives and applications thereof

Compositions and methods for reducing or preventing graft-versus-host disease associated with allogeneic stem cell transplantation are described. A method includes harvesting hematopoietic cells from a patient with an immunologic disorder and harvesting hematopoietic cells from a donor. The harvested hemaptopoietic cells from the patient and the donor are mixed ex vivo for a period of time sufficient to activate lymphocytes within the hematopoietic cells harvested from the donor such that an immune reaction occurs and an activated portion and an unactivated portion is produced. A rhodamine B derivative is then added to the mixture of cells and the mixture is irradiated at a suitable wavelength and intensity for the selective destruction and/or inactivation of the activated portion without substantially affecting the unactivated portion or causing systemic toxicity in said patient. The irradiated cells are then infused into the patient.

Rhodamine derivatives for photodynamic diagnosis and treatment

The present invention relates to the use of the photoactivable derivatives for the photodynamic treatment for the selective destruction and/or inactivation of immunologically reactive cells without affecting the normal cells and without causing systemic toxicity for the patient, wherein appropriate intracellular levels of said derivatives are achieved and irradiation of a suitable wavelength and intensity is applied.

Methods for treating a bacterial infection in a tissue sample are described. Tissue samples that are harvested from a patient may be infected with bacteria. A rhodamine compound is mixed with the infected tissue sample to form a mixture. The mixture is then exposed to radiant energy to inhibit or kill the bacteria. The exposed mixture is then transplanted into the patient. Examples of rhodamine compounds include 2'-(6-dimethylamino-3-dimethylimino-3H-xanthen-9-yl) 4&#x2032;,5&#x2032;-dichloro-benzoic acid methyl ester hydrochloride; 4,5-dibromorhodamine 110 2-(2-methoxy ethoxy)ethyl ester hydrobromide; acetate salt of 2,7-dibromorhodamine B hexyl ester; acetate salt of 2,7-dibromorhodamine B methyl ester; 4,5-dibromorhodamine 6G hydrobromide; rhodamine B 3-bromopropyl; acetate salt 2,7-dibromo-4&#x2032;-carboxytetramethylrosamine methyl ester; 4-bromo-5-phenyl rhodamine B methyl ester chloride; 2,7-dibromo-4,5-dimethyl rhodamine B methyl ester bromide; 2-bromo-7-ethynyl rhodamine B methyl ester bromide; and 4,5-dibromo-2,7-di-n-butyl rhodamine B methyl ester bromide.

Compounds of formula (I) wherein: one of R1, R2, R3, R4 and (R10)n represents halogen and each remaining R1, R2, R3, R4 and R10 group is independently selected from hydrogen, halogen, amino, acylamino, dialkylamino, cycloalkylamino, azacycloalkyl, alkylcycloalkylamino, aroylamino, diarylamino, arylalkylamino, aralkylamino, alkylaralkylamino, arylaralkylamino, hydroxy, alkoxy, aryloxy, aralkyloxy, mercapto, alkylthio, arylthio, aralkylthio, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, hydroxysulfonyl, amidosulfonyl, dialkylamidosulfonyl, arylalkylamidosulfonyl, formyl, acyl, aroyl, alkyl, alkylene, alkenyl, aryl, aralkyl, vinyl, alkynyl, and corresponding substituted groups; m=0-1; n=1-4, A is nil, O, or NH; R9 is alkylene; -Z is H, amino, dialkylamino, or a trialkylamino salt; X&#x2212; is an anion; R5, R6, R7 and R8 are independently H or C-Calkyl or R1 in combination with R5 or R6, or R2 in combination with R5 or R6, or R3 in combination with R7 or R8, or R4 in combination with R7 or R8 represents alkylene, are useful alone or with a pharmaceutically acceptable carrier, as intermediates and as bactericides, antiviral agents and in treatment of immunologic disorders.

An apparatus for irradiating a biological substance with a substantially uniform quantity of radiation energy comprises a radiation-generating device for producing radiation energy, a support structure for receiving the biological substance, and a motorized mechanism for reciprocating the radiation-generating device along a given path whereby the biological substance receives radiation energy from the radiation-generating device at each passage of the radiation-generating device. A series of sensors lie into a given plane and are subjected to radiation energy from the radiation-generating device upon each passage of that radiation-generating device for sensing and measuring the quantity of radiation energy by surface unit passing through the given plane and reaching the biological substance. Finally the radiation-generating device and the motorized mechanism are de-energized when the measured quantity of radiation energy by surface unit has reached a predetermined value.

Irradiating apparatus using a scanning light source for photodynamic

The present invention relates to novel photoactivable rhodamine derivatives for enhancing high quantum-yield production and singlet oxygen generation upon irradiation with light while maintaining desirable differential retention of rhodamine between normal and cancer cells. Representative derivatives are 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid methyl ester hydrochloride; 2-(4, 5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid ethyl ester hydrochloride; 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid octyl ester hydrochloride; 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride; 2-(6-ethyl amino-3-ethyl imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride; and photoactivable derivatives thereof. These derivatives are utilized in an amount to achieve appropriate intracellular levels of the derivative when irradiation of a suitable wavelength and intensity is applied to photoactivate the derivative and thereby induce cell killing.

Rhodamine derivatives for photodynamic therapy of cancer and in vitro

The present invention relates to novel photoactivable rhodamine derivatives for enhancing high quantum-yield production and singlet oxygen generation upon irradiation with light while maintaining desirable differential retention of rhodamine between normal and cancer cells, said derivatives are selected from the group consisting of 4,5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid methyl ester hydrochloride); 4, 5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid ethyl ester hydrochloride); 4, 5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid octhyl ester hydrochloride); 4,5-dibromorhodamine 110 n-butyl ester (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride); Rhodamine B n-butyl ester (2-(6-ethyl amino-3-ethyl imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride); and photoactivable derivatives thereof; whereby photoactivation of the derivatives induces cell killing while unactivated derivatives are substantially non-toxic to cells. Also, the present invention relates to the use of the photoactivable derivatives of the present invention for the photodynamic therapy of a cancer patient by destroying human cancer cells, wherein appropriate intracellular levels of the derivatives are achieved and irradiation with light of a suitable wavelength is applied. The present invention also relates to a method for the photodynamic therapy of a patient suffering from leukemias, disseminated multiple myelomas or lymphomas.

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Montreal, Canada

Luc Villeneuve