The present invention is directed to a pharmaceutical composition and method for treating a subj ect diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and/or TDP-43 aggregation- inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5 - or 6 -membered aromatic ring, or a 5, 6 - or 6, 6 - fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subj ect no longer needs it.
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
The present invention is directed to a pharmaceutical composition and method for treating a subject diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and/or TDP-43 aggregation-inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subject no longer needs it.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
3.
USES OF HALOGENATED XANTHENES IN ONCOLOGY AND VIROLOGY
A method for treating a viral infection of a mammalian subject that comprises administering a virus- inhibiting amount of a halogenated xanthene, a pharmaceutically acceptable salt, an alkyl ester or amide or aromatic ester or amide derivative thereof as disclosed within, to that mammalian subject. A method of inducing a type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene as discussed above, and an immunogen to which that response is to be enhanced.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 31/683 - Diesters d'acide du phosphore avec deux composés hydroxyle, p. ex. phosphatidylinositols
A61K 39/42 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire viraux
A61P 31/14 - Antiviraux pour le traitement des virus ARN
4.
Micromolar Halogenated Fluorescein Assists in Full Skin-Thickness Wound Healing
Board of Regents, The University of Texas System (USA)
Inventeur(s)
El Ayadi, Amina
Jay, Jayson Walter
Wachter, Eric A.
Rodrigues, Dominic
Pershing, Edward V.
Abrégé
The present invention contemplates a method of treating a mammalian skin wound that extends at least into the epidermal layer of the skin of a subject mammal that comprises treating the wound in the substantial absence of actinic light by topical application of an aqueous pharmaceutical composition containing a wound closure-assisting amount of rose bengal, a lactone, salt, ester or amide hereof dissolved or dispersed therein as well as gel-inducing amount of a thickening agent (gellant) that causes the aqueous pharmaceutical composition to gel at a temperature of about 33° to about 40° C. The treated wound is thereafter covered with a dressing that is opaque to actinic light at least in the area over the wound. This treatment method is repeated a plurality of times over the following up to about fifteen days or until the wound is closed, whichever time of time is shorter.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/353 - 3,4-Dihydrobenzopyranes, p. ex. chromane, catéchine
A61K 47/34 - Composés macromoléculaires obtenus par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyesters, acides polyaminés, polysiloxanes, polyphosphazines, copolymères de polyalkylène glycol ou de poloxamères
A61P 17/02 - Médicaments pour le traitement des troubles dermatologiques pour traiter les blessures, les ulcères, les brûlures, les cicatrices, les cheloïdes, ou similaires
5.
MICROMOLAR HALOGENATED FLUORESCEIN ASSISTS IN FULL SKIN-THICKNESS WOUND HEALING
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (USA)
Inventeur(s)
El Ayadi, Amina
Jay, Jayson, Walter
Wachter, Eric, A.
Rodrigues, Dominic
Pershing, Edward, V.
Abrégé
The present invention contemplates a method of treating a mammalian skin wound that extends at least into the epidermal layer of the skin of a subj ect mammal that comprises treating the wound in the substantial absence of actinic light by topical application of an aqueous pharmaceutical composition containing a wound closure-assisting amount of rose bengal, a lactone, salt, ester or amide hereof dissolved or dispersed therein as well as gel-inducing amount of a thickening agent (gellant ) that causes the aqueous pharmaceutical composition to gel at a temperature of about 33° to about 40° C. The treated wound is thereafter covered with a dressing that is opaque to actinic light at least in the area over the wound. This treatment method is repeated a plurality of times over the following up to about fifteen days or until the wound is closed, whichever time of time is shorter.
A61L 26/00 - Aspects chimiques des bandages liquides ou utilisation de matériaux pour les bandages liquides
A61P 17/02 - Médicaments pour le traitement des troubles dermatologiques pour traiter les blessures, les ulcères, les brûlures, les cicatrices, les cheloïdes, ou similaires
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 47/69 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament le conjugué étant caractérisé par sa forme physique ou sa forme galénique, p. ex. émulsion, particule, complexe d’inclusion, stent ou kit
6.
PHOTODYNAMIC ANTI-GRAM-POSITIVE BACTERIAL ACTIVITY OF PHARMACEUTICAL-GRADE ROSE BENGAL
This invention contemplates combined use of a rose bengal (RB ) derivative with irradiation of bacteria with light to treat and kill the irradiated bacteria. In one aspect, Gram-positive bacteria are treated in a method in which the bacteria are contacted with an aqueous pharmaceutical composition containing a rose bengal (RB ) compound of Formula I. discussed within, dissolved or dispersed therein at about 0. 2 to about 3. 1 µg/mL. Those contacted bacteria are contacted with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 0. 7 to about 7. 2 J/cm2 . A similar method is contemplated for treating Gram-negative bacteria that are one or more of Burkholderia, Salmonella, and Proteus using an aqueous pharmaceutical composition containing about 2 to about 15 µM concentration of the RB compound.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
of treating Gram-negative bacteria that also exhibit resistance to the anti-bacterial compound colistin (MIC≥50 mg/mL) except for Burkholderia, Proteus, and Serratia that comprises contacting the bacteria with an aqueous pharmaceutical composition containing a rose bengal (RB) compound of Formula I, below, dissolved or dispersed therein at a concentration of about 0.01 to about 15 mg/mL and irradiating those contacted bacteria with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 16 to about 160 J/cm2, treat and kill the irradiated bacteria
of treating Gram-negative bacteria that also exhibit resistance to the anti-bacterial compound colistin (MIC≥50 mg/mL) except for Burkholderia, Proteus, and Serratia that comprises contacting the bacteria with an aqueous pharmaceutical composition containing a rose bengal (RB) compound of Formula I, below, dissolved or dispersed therein at a concentration of about 0.01 to about 15 mg/mL and irradiating those contacted bacteria with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 16 to about 160 J/cm2, treat and kill the irradiated bacteria
of treating Gram-negative bacteria that also exhibit resistance to the anti-bacterial compound colistin (MIC≥50 mg/mL) except for Burkholderia, Proteus, and Serratia that comprises contacting the bacteria with an aqueous pharmaceutical composition containing a rose bengal (RB) compound of Formula I, below, dissolved or dispersed therein at a concentration of about 0.01 to about 15 mg/mL and irradiating those contacted bacteria with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 16 to about 160 J/cm2, treat and kill the irradiated bacteria
wherein X, R1, R2 and M+ are defined within.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A01N 43/16 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés hétérocycliques comportant des cycles avec un ou plusieurs atomes d'oxygène ou de soufre comme uniques hétéro-atomes du cycle avec un hétéro-atome des cycles à six chaînons avec l'oxygène comme hétéro-atome du cycle
A01P 1/00 - DésinfectantsComposés antimicrobiens ou leurs mélanges
A61N 5/06 - Thérapie par radiations utilisant un rayonnement lumineux
The present invention contemplates a method of treating Gram-negative bacteria that also exhibit resistance to the anti-bacterial compound colistin (MIC > 50 mg/mL ) except for Burkholderia, Proteus, and Serra tia that comprises contacting the bacteria with an aqueous pharmaceutical composition containing a rose bengal (RB ) compound of Formula I, below, dissolved or dispersed therein at a concentration of about 0. 01 to about 15 mg/mL and irradiating those contacted bacteria with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 16 to about 160 J/cm2, treat and kill the irradiated bacteria wherein X, R1, R2 and M+ are defined within.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A method of inducing a Type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the Type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene, and an immunogen to which that response is to be enhanced. A mammalian HX compound-adjuvanted vaccine composition that contains an immunogen present in a vaccine-effective amount along with an adjuvant-effective amount of a halogenated xanthene (HX) compound and one or more excipients present at about 0.001% by weight to 10% by weight of the vaccine composition dissolved or dispersed in a pharmaceutically acceptable diluent.
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
11.
In vitro and xenograft anti-tumor activity of a halogenated-xanthene against refractory pediatric solid tumors
A method of treating a pediatric cancerous solid tumor in a mammalian subject is disclosed that comprises intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor. Another contemplated method comprises the steps of intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor and systemically administering a tumor-inhibiting effective amount of a systemic anti-cancer medication that provides synergistic cytotoxicity with the halogenated xanthene. The two administrations can occur concurrently, or one prior to the other.
A61K 31/343 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide condensés avec un carbocycle, p. ex. coumarane, bufaralol, béfunolol, clobenfurol, amiodarone
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
12.
Halogenated xanthene composition and method for treating hematologic cancers
4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/21 - Esters, p. ex. nitroglycérine, sélénocyanates
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
13.
Halogenated Xanthene-Containing Topical Anti-Gram-Positive Bacterial Ophthalmic Composition and Method
The present invention contemplates a topical ophthalmic system for treating a Gram-positive bacterially-infected mammalian eye. The system comprises an ophthalmic composition containing a halogenated fluorescein or a pharmaceutically acceptable salt or ester thereof dissolved or dispersed in an aqueous ophthalmic carrier and present in an anti-bacterial keratitis-treating effective concentration of about 0.2 µg/mL to about 50 µg/mL. The ophthalmic composition has a pH value of about 6.5 to about 7.6, a viscosity of about 10 to about 300 cps and an osmolality of about 270 mOsm/kg to about 340 mOsm/kg. The ophthalmic composition is present in a vessel opaque to actinic light. Also contemplated is a method of treating a mammal having a Gram-positive bacterial infection of an eye by administering the ophthalmic composition to the infected eye and maintaining the treated eye in the substantial absence of actinic light for about 3 hours to about 12 hours.
A61K 8/81 - Cosmétiques ou préparations similaires pour la toilette caractérisés par la composition contenant des composés organiques macromoléculaires obtenus par des réactions faisant intervenir uniquement des liaisons insaturées carbone-carbone
C08F 220/58 - Amides contenant de l'oxygène en plus de l'oxygène de la fonction carbonamide
14.
PHOTODYNAMIC ANTI-GRAM-POSITIVE BACTERIAL ACTIVITY OF PHARMACEUTICAL-GRADE ROSE BENGAL
This invention contemplates combined use of a rose bengal (RB) derivative with irradiation of bacteria with light to treat and kill the irradiated bacteria. In one aspect, Gram-positive bacteria are treated in a method in which the bacteria are contacted with an aqueous pharmaceutical composition containing a rose bengal (RB) compound of Formula I, discussed within, dissolved or dispersed therein at about 0.2 to about 3.1 µg/mL. Those contacted bacteria are contacted with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 0.7 to about 7.2 J/cm2. A similar method is contemplated for treating Gram-negative bacteria that are one or more of Burkholderia, Salmonella, and Proteus using an aqueous pharmaceutical composition containing about 2 to about 15 µM concentration of the RB compound.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
This invention contemplates combined use of a rose bengal (RB ) derivative with irradiation of bacteria with light to treat and kill the irradiated bacteria. In one aspect, Gram-positive bacteria are treated in a method in which the bacteria are contacted with an aqueous pharmaceutical composition containing a rose bengal (RB ) compound of Formula I, discussed within, dissolved or dispersed therein at about 0. 2 to about 3. 1 μg/mL. Those contacted bacteria are contacted with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 0. 7 to about 7. 2 J/cm2. A similar method is contemplated for treating Gram-negative bacteria that are one or more of Burkholderia, Salmonella, and Proteus using an aqueous pharmaceutical composition containing about 2 to about 15 μM concentration of the RB compound.
The present invention contemplates a topical ophthalmic system for treating a Gram-positive bacterially-infected mammalian eye. The system comprises an ophthalmic composition containing a halogenated fluorescein or a pharmaceutically acceptable salt or ester thereof dissolved or dispersed in an aqueous ophthalmic carrier and present in an anti-bacterial keratitis-treating effective concentration of about 0.2 μg/mL to about 50 μg/mL. The ophthalmic composition has a pH value of about 6.5 to about 7.6, a viscosity of about 10 to about 300 cps and an osmolality of about 270 mOsm/ kg to about 340 mOsm/ kg. The ophthalmic composition is present in a vessel opaque to actinic light. Also contemplated is a method of treating a mammal having a Gram-positive bacterial infection of an eye by administering the ophthalmic composition to the infected eye and maintaining the treated eye in the substantial absence of actinic light for about 3 hours to about 12 hours.
The present invention contemplates a topical ophthalmic system for treating a Gram-positive bacterially-infected mammalian eye. The system comprises an ophthalmic composition containing a halogenated fluorescein or a pharmaceutically acceptable salt or ester thereof dissolved or dispersed in an aqueous ophthalmic carrier and present in an anti-bacterial keratitis-treating effective concentration of about 0.2 µg/mL to about 50 µg/mL. The ophthalmic composition has a pH value of about 6.5 to about 7.6, a viscosity of about 10 to about 300 cps and an osmolality of about 270 mOsm/ kg to about 340 mOsm/ kg. The ophthalmic composition is present in a vessel opaque to actinic light. Also contemplated is a method of treating a mammal having a Gram-positive bacterial infection of an eye by administering the ophthalmic composition to the infected eye and maintaining the treated eye in the substantial absence of actinic light for about 3 hours to about 12 hours.
A method of inducing a Type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the Type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene, and an immunogen to which that response is to be enhanced. A mammalian HX compound-adjuvanted vaccine composition that contains an immunogen present in a vaccine-effective amount along with an adjuvant-effective amount of a halogenated xanthene (HX) compound and one or more excipients present at about 0.001% by weight to 10% by weight of the vaccine composition dissolved or dispersed in a pharmaceutically acceptable diluent.
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C1-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61P 35/02 - Agents anticancéreux spécifiques pour le traitement de la leucémie
20.
COMPOSITION AND METHOD FOR ORAL TREATMENT OF LEUKEMIA
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C1-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Diagnostic reagents for in virology, microbiology and ophthalmology Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of tumors; Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of solid tumors, namely, melanoma, breast cancer, basal cell carcinoma, prostate cancer, and small cell and non-small cell lung cancer, squamous cell carcinoma and primary and metastatic liver cancers; Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of pediatric solid tumors, namely, Ewing sarcoma, neuroblastoma, osteosarcoma, neuroepithelioma, and rhabdomyosarcoma; Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of leukemia; Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of leukemia, namely, acute B-cell lymphoblastic leukemia, T-cell lymphoblastic leukemia, acute myeloid leukemia; Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of psoriasis; Preparations for pharmaceutical skin care; Diagnostic preparations for medical use, namely, for use in virology, microbiology, ophthalmology; Diagnostic mediums for use in virology, microbiology, ophthalmology; Pharmaceutical preparations and substances for use as vaccine adjuvants, immune system stimulators or suppressors, and immune system modulators
A method of inducing a Type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the Type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene, and an immunogen to which that response is to be enhanced. A mammalian HX compound-adjuvanted vaccine composition that contains an immunogen present in a vaccine-effective amount along with an adjuvant-effective amount of a halogenated xanthene (HX) compound and one or more excipients present at about 0.001% by weight to 10% by weight of the vaccine composition dissolved or dispersed in a pharmaceutically acceptable diluent.
A method of inducing a Type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the Type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene, and an immunogen to which that response is to be enhanced. A mammalian HX compound-adjuvanted vaccine composition that contains an immunogen present in a vaccine-effective amount along with an adjuvant-effective amount of a halogenated xanthene (HX) compound and one or more excipients present at about 0.001% by weight to 10% by weight of the vaccine composition dissolved or dispersed in a pharmaceutically acceptable diluent.
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
24.
Combination Of Local And Systemic Immunomodulative Therapies For Enhanced Treatment of Cancer
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 39/245 - Herpetoviridae, p. ex. virus de l'Herpès simplex
A method of treating a pediatric cancerous solid tumor in a mammalian subject is disclosed that comprises intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor. Another contemplated method comprises the steps of intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor and systemically administering a tumor-inhibiting effective amount of a systemic anti-cancer medication that provides synergistic cytotoxicity with the halogenated xanthene. The two administrations can occur concurrently, or one prior to the other.
A61K 31/343 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide condensés avec un carbocycle, p. ex. coumarane, bufaralol, béfunolol, clobenfurol, amiodarone
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
26.
USES OF HALOGENATED XANTHENES IN ONCOLOGY AND VIROLOGY
A method for treating a viral infection of a mammalian subject that comprises administering a virus- inhibiting amount of a halogenated xanthene, a pharmaceutically acceptable salt, an alkyl ester or amide or aromatic ester or amide derivative thereof as disclosed within, to that mammalian subject. A method of inducing a type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene as discussed above, and an immunogen to which that response is to be enhanced.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 31/683 - Diesters d'acide du phosphore avec deux composés hydroxyle, p. ex. phosphatidylinositols
A61K 39/42 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire viraux
A61P 31/14 - Antiviraux pour le traitement des virus ARN
27.
TREATMENT OF SOLID CANCEROUS TUMORS BY ORAL ADMINISTRATION OF A HALOGENATED XANTHENE
The present invention contemplates a method of treating a solid cancerous tumor in a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of a halogenated xanthene (HX), the lactone thereof, a pharmaceutically acceptable salt, or a C1-C4 alkyl or aromatic ester thereof (collectively an HX compound) to that mammalian subject, and liquid and solid pharmaceutical compositions for administering the HX compound. In addition, a method of inhibiting the growth of a GI tract carcinoma of a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of an HX compound, as well as solid and liquid pharmaceutical compositions therefor.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
28.
Treatment of Solid Cancerous Tumors by Oral Administration of a Halogenated Xanthene
The present invention contemplates a method of treating a solid cancerous tumor in a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of a halogenated xanthene (HX), the lactone thereof, a pharmaceutically acceptable salt, or a C1-C4 alkyl or aromatic ester thereof (collectively an HX compound) to that mammalian subject, and liquid and solid pharmaceutical compositions for administering the HX compound. In addition, a method of inhibiting the growth of a GI tract carcinoma of a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of an HX compound, as well as solid and liquid pharmaceutical compositions therefor.
A61K 9/28 - DragéesPilules ou comprimés avec revêtements
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 47/14 - Esters d’acides carboxyliques, p. ex. acides gras monoglycérides, triglycérides à chaine moyenne, parabènes ou esters d’acide gras de PEG
in vivo in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene as discussed above, and an immunogen to which that response is to be enhanced.
C07D 413/10 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne carbonée contenant des cycles aromatiques
30.
TREATMENT OF SOLID CANCEROUS TUMORS BY ORAL ADMINISTRATION OF A HALOGENATED XANTHENE
The present invention contemplates a method of treating a solid cancerous tumor in a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of a halogenated xanthene (HX), the lactone thereof, a pharmaceutically acceptable salt, or a C1-C4 alkyl or aromatic ester thereof (collectively an HX compound) to that mammalian subject, and liquid and solid pharmaceutical compositions for administering the HX compound. In addition, a method of inhibiting the growth of a GI tract carcinoma of a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of an HX compound, as well as solid and liquid pharmaceutical compositions therefor.
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
31.
Uses of halogenated xanthenes in oncology and virology
A method for treating a viral infection of a mammalian subject that comprises administering a virus-inhibiting amount of a halogenated xanthene, a pharmaceutically acceptable salt, an alkyl ester or amide or aromatic ester or amide derivative thereof as disclosed within, to that mammalian subject. A method of inducing a type I interferon response in a mammalian subject that presents with a microbial infection, cancerous tumor or hematological malignancy that comprises administering an amount of a halogenated xanthene as discussed above, effective to induce the type I interferon response. A method of enhancing a mammalian immunogen-specific immune response that comprises contacting mammalian cells, in vivo or present in a mammalian cell growth supporting medium, with an adjuvant-effective amount of a halogenated xanthene as discussed above, and an immunogen to which that response is to be enhanced.
A61K 9/28 - DragéesPilules ou comprimés avec revêtements
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 31/706 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 47/14 - Esters d’acides carboxyliques, p. ex. acides gras monoglycérides, triglycérides à chaine moyenne, parabènes ou esters d’acide gras de PEG
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C1-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61P 35/02 - Agents anticancéreux spécifiques pour le traitement de la leucémie
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
33.
COMPOSITION AND METHOD FOR TREATING HEMATOLOGIC CANCERS
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C2-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated, A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium, The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
THE GOVERNORS OF THE UNIVERSITY OF CALGARY (Canada)
Inventeur(s)
Wachter, Eric, A.
Abrégé
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C2-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated, A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium, The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
A61N 5/10 - RadiothérapieTraitement aux rayons gammaTraitement par irradiation de particules
35.
Halogenated xanthene composition and method for treating hematologic cancers
4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
36.
Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
A method of treating a pediatric cancerous solid tumor in a mammalian subject is disclosed that comprises intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor. Another contemplated method comprises the steps of intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor and systemically administering a tumor-inhibiting effective amount of a systemic anti-cancer medication that provides synergistic cytotoxicity with the halogenated xanthene. The two administrations can occur concurrently, or one prior to the other.
A61K 31/343 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide condensés avec un carbocycle, p. ex. coumarane, bufaralol, béfunolol, clobenfurol, amiodarone
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
38.
IN VITRO AND XENOGRAFT ANTI-TUMOR ACTIVITY OF A HALOGENATED-XANTHENE AGAINST REFRACTORY PEDIATRIC SOLID TUMORS
THE GOVERNORS OF THE UNIVERSITY OF CALGARY (Canada)
PROVECTUS PHARMATECH, INC. (USA)
Inventeur(s)
Singer, Jamie
Wachter, Eric A.
Swift, Lucy
Zhang, Chunfen
Trippett, Tanya
Narendran, Aru
Abrégé
A method of treating a pediatric cancerous solid tumor in a mammalian subject is disclosed that comprises intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor. Another contemplated method comprises the steps of intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor and systemically administering a tumor-inhibiting effective amount of a systemic anti-cancer medication that provides synergistic cytotoxicity with the halogenated xanthene. The two administrations can occur concurrently, or one prior to the other.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A method of treating a pediatric cancerous solid tumor in a mammalian subject is disclosed that comprises intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor. Another contemplated method comprises the steps of intralesionally administering an amount of a halogenated xanthene or a pharmaceutically acceptable salt thereof, preferably Rose Bengal disodium, that elicits ablation of tumor cells of the administered tumor and systemically administering a tumor-inhibiting effective amount of a systemic anti-cancer medication that provides synergistic cytotoxicity with the halogenated xanthene. The two administrations can occur concurrently, or one prior to the other.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A treatment for inflammatory dermatoses, such as psoriasis and atopic dermatitis (eczema), is disclosed that utilizes topical administration of a halogenated xanthene, such as rose bengal, together with administration of one or more complementary targeted systemic dermatology therapies, preferably a therapy that addresses the inflammatory pathway and is other than an NSAID that is a COX-1 and/or COX-2 inhibitor. Examples of complementary targeted systemic therapeutic ingredients include: corticosteroids, including betamethasone dipropionate and fluocinonide; dithranol; vitamin D analogs, including calcipotriol; and retinoids, non-biologics including methotrexate, ciclosporin, hydroxycarbamide, and fumarates including dimethyl fumarate; as well as one or more biologies, including antibodies or paratope-containing antibody portions to TNF-a, antibodies to pro-inflammatory cytokines interleukin-12, interleukin-23 and interleukin-17, and TNF inhibitors. Treatment of other epithelial tissue, such as the lining of the gut, is also disclosed.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
41.
COMBINATION OF LOCAL AND SYSTEMIC THERAPIES FOR ENHANCED TREATMENT OF DERMATOLOGIC CONDITIONS
A treatment for inflammatory dermatoses, such as psoriasis and atopic dermatitis (eczema), is disclosed that utilizes topical administration of a halogenated xanthene, such as rose bengal, together with administration of one or more complementary targeted systemic dermatology therapies, preferably a therapy that addresses the inflammatory pathway and is other than an NSAID that is a COX-1 and/or COX-2 inhibitor. Examples of complementary targeted systemic therapeutic ingredients include: corticosteroids, including betamethasone dipropionate and fluocinonide; dithranol; vitamin D analogs, including calcipotriol; and retinoids, non-biologics including methotrexate, ciclosporin, hydroxycarbamide, and fumarates including dimethyl fumarate; as well as one or more biologies, including antibodies or paratope-containing antibody portions to TNF-a, antibodies to pro-inflammatory cytokines interleukin-12, interleukin-23 and interleukin-17, and TNF inhibitors. Treatment of other epithelial tissue, such as the lining of the gut, is also disclosed.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
42.
Combination of local and systemic therapies for enhanced treatment of dermatologic conditions
A treatment for inflammatory dermatoses, such as psoriasis and atopic dermatitis (eczema), is disclosed that utilizes topical administration of a halogenated xanthene, such as rose bengal, together with administration of one or more complementary targeted systemic dermatology therapies, preferably a therapy that addresses the inflammatory pathway and is other than an NSAID that is a COX-1 and/or COX-2 inhibitor. Examples of complementary targeted systemic therapeutic ingredients include: corticosteroids, including betamethasone dipropionate and fluocinonide; dithranol; vitamin D analogs, including calcipotriol; and retinoids, non-biologics including methotrexate, ciclosporin, hydroxycarbamide, and fumarates including dimethyl fumarate; as well as one or more biologics, including antibodies or paratope-containing antibody portions to TNF-α, antibodies to pro-inflammatory cytokines interleukin-12, interleukin-23 and interleukin-17, and TNF inhibitors. Treatment of other epithelial tissue, such as the lining of the gut, is also disclosed.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/245 - Herpetoviridae, p. ex. virus de l'Herpès simplex
C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
44.
METHOD OF EX VIVO ENHANCEMENT OF IMMUNE CELL ACTIVITY FOR CANCER IMMUNOTHERAPY WITH A SMALL MOLECULE ABLATIVE COMPOUND
H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC. (USA)
PROVECTUS PHARMATECH, INC. (USA)
Inventeur(s)
Singer, Jamie
Wachter, Eric A.
Sarnaik, Amod
Philon-Thomas, Shari
Liu, Hao
Abrégé
A cancer immunotherapy method is disclosed in which "induced immune anticancer agents" are isolated after being induced in an animal host by intralesional (IL) administration of a halogenated xanthene tumor-ablative compound into a solid cancerous tumor of that host animal. A sample of the induced immune anticancer agents is removed (collected) from the tumor-bearing host, banked if desired, cultured and preferentially expanded to form an immunologically-effective enriched tumor-specific immune anticancer agent composition. That composition is reintroduced in to the host from which the predecessor induced immune anticancer agents were taken, or into another immunologically suitable host in need.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
45.
Method of ex vivo enhancement of immune cell activity for cancer immunotherapy with a small molecule ablative compound
H. Lee Moffitt Cancer Center and Research Institute, Inc. (USA)
Inventeur(s)
Singer, Jamie
Wachter, Eric
Sarnaik, Amod
Pilon-Thomas, Shari
Liu, Hao
Abrégé
A cancer immunotherapy method is disclosed in which “induced immune anticancer agents” are isolated after being induced in an animal host by intralesional (IL) administration of a halogenated xanthene tumor-ablative compound into a solid cancerous tumor of that host animal. A sample of the induced immune anticancer agents is removed (collected) from the tumor-bearing host, banked if desired, cultured and preferentially expanded to form an immunologically-effective enriched tumor-specific immune anticancer agent composition. That composition is reintroduced in to the host from which the predecessor induced immune anticancer agents were taken, or into another immunologically suitable host in need.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 35/17 - LymphocytesLymphocytes BLymphocytes TCellules tueuses naturellesLymphocytes activés par un interféron ou une cytokine
A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C12P 21/00 - Préparation de peptides ou de protéines
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
C12P 21/02 - Préparation de peptides ou de protéines comportant une séquence connue de plusieurs amino-acides, p. ex. glutathion
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
46.
METHOD OF EX VIVO ENHANCEMENT OF IMMUNE CELL ACTIVITY FOR CANCER IMMUNOTHERAPY WITH A SMALL MOLECULE ABLATIVE COMPOUND
H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC. (USA)
Inventeur(s)
Singer, Jamie
Wachter, Eric, A.
Sarnaik, Amod
Philon-Thomas, Shari
Liu, Hao
Abrégé
A cancer immunotherapy method is disclosed in which "induced immune anticancer agents" are isolated after being induced in an animal host by intralesional (IL) administration of a halogenated xanthene tumor-ablative compound into a solid cancerous tumor of that host animal. A sample of the induced immune anticancer agents is removed (collected) from the tumor-bearing host, banked if desired, cultured and preferentially expanded to form an immunologically-effective enriched tumor-specific immune anticancer agent composition. That composition is reintroduced in to the host from which the predecessor induced immune anticancer agents were taken, or into another immunologically suitable host in need.
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
47.
Combination of rose bengal and systemic immunomodulative therapies for enhanced treatment of cancer
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 31/35 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
48.
Combination of local and systemic immunomodulative therapies for melanoma and liver cancer
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 47/60 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique macromoléculaire, p. ex. une molécule oligomérique, polymérique ou dendrimérique obtenu par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyurées ou polyuréthanes le composé organique macromoléculaire étant un oligomère, un polymère ou un dendrimère de polyoxyalkylène, p. ex. PEG, PPG, PEO ou polyglycérol
C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Medicinal and pharmaceutical preparations, namely, pharmaceutical medications for the treatment and prevention of cancers, melanoma, breast cancer, basal cell carcinoma, squamous cell carcinoma and cancers of the liver
50.
Process for the synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′, 4′, 5′7′-tetraiodo-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (Rose Bengal) and related xanthenes
A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100° C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.
Process for the synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one(Rose Bengal) and related xanthenes
A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100° C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.
A61K 31/35 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
C07K 16/18 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
53.
COMBINATION OF LOCAL AND SYSTEMIC IMMUNOMODULATIVE THERAPIES FOR ENHANCED TREATMENT OF CANCER
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
A61K 31/352 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle condensés avec des carbocycles, p. ex. cannabinols, méthanthéline
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
54.
PROCESS FOR THE SYNTHESIS OF 4,5,6,7-TETRACHLORO-3',6'-DIHYDROXY-2',4',5',7'-TETRAIODO-3H-SPIRO[ISOBENZOFURAN-1,9'-XANTHEN]-3-ONE (ROSE BENGAL) AND RELATED XANTHENES
A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100°C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.
Process for the synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (rose bengal) and related xanthenes
A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100° C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.
