AR084940A1 - A CROFELEMER WITH A POLIDISPERSITY INDEX WITHIN A RANGE BETWEEN 0.9 AND 1.2 - Google Patents

A CROFELEMER WITH A POLIDISPERSITY INDEX WITHIN A RANGE BETWEEN 0.9 AND 1.2

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Publication number
AR084940A1
AR084940A1 ARP120100277A ARP120100277A AR084940A1 AR 084940 A1 AR084940 A1 AR 084940A1 AR P120100277 A ARP120100277 A AR P120100277A AR P120100277 A ARP120100277 A AR P120100277A AR 084940 A1 AR084940 A1 AR 084940A1
Authority
AR
Argentina
Prior art keywords
crofelemer
range
water
sepharose
partially purified
Prior art date
Application number
ARP120100277A
Other languages
Spanish (es)
Inventor
Vikas Parashar
Mubeen Ahmad Khan
Snehal Shah
Sukumar Sinha
Vipin Kumar Pandey
Original Assignee
Glenmark Pharmaceuticals Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glenmark Pharmaceuticals Ltd filed Critical Glenmark Pharmaceuticals Ltd
Publication of AR084940A1 publication Critical patent/AR084940A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/47—Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps

Abstract

Un proceso para aislar y purificar una composición de proantocianidina polimérica, donde la composición tiene una alta pureza y es apropiada para utilizar en formulaciones farmacéuticamente efectivas. En particular, se refiere a un proceso para producir un crofelemer apropiado para formulaciones farmacéuticas y con un nivel de pureza y una concentración que permite utilizarlo de manera terapéuticamente efectiva.Reivindicación 1: Un crofelemer con un índice de polidispersidad dentro del rango entre 0,9 y 1,2 caracterizado porque se puede obtener por un método que comprende los pasos de: A) aislar crofelemer purificado parcialmente agitando una mezcla de látex vegetal crudo o polvo de látex vegetal liofilizado y agua o solvente(s) miscible(s) en agua a una temperatura dentro del rango entre 15ºC y 60ºC; y B) purificar el crofelemer purificado parcialmente usando una técnica de cromatografía en columna. Reivindicación 12: El método de acuerdo con la reivindicación 11, caracterizado porque el proceso de aislar crofelemer purificado parcialmente en el paso (A) comprende los pasos de: (a) agitar la mezcla de látex vegetal crudo o polvo de látex vegetal liofilizado y agua o solvente(s) miscible(s) en agua a una temperatura dentro del rango entre 15ºC y 60ºC; (b) separar la fase líquida; (c) opcionalmente, concentrar la fase líquida para obtener un jarabe sólido, líquido o concentrado; y (d) opcionalmente, agregar agua o solvente(s) miscible(s) en agua al jarabe sólido, líquido o concentrado. Reivindicación 14: El método de acuerdo con la reivindicación 12, caracterizado porque el paso (b) se lleva a cabo usando filtración, sedimentación, centrifugación y/o decantación o combinaciones de los mismos. Reivindicación 23: El método de acuerdo con la reivindicación 12, caracterizado porque el paso (c) se lleva a cabo usando ultrafiltración y/o usando un evaporador rotativo o una combinación de los mismos. Reivindicación 28: El método de acuerdo con la reivindicación 27, caracterizado porque la cromatografía de intercambio iónico se lleva a cabo usando una agarosa modificada por carboximetilación. Reivindicación 29: El método de acuerdo con la reivindicación 28, caracterizado porque la agarosa modificada por carboximetilación es CM-Sepharose. Reivindicación 68: Un crofelemer amorfo caracterizado porque a) tiene un índice de polidispersidad dentro del rango entre 0,9 y 1,2; b) contiene taspina en una cantidad menor de 500 ppm; c) tiene un valor del ensayo de pureza mayor del 85%; d) tiene menos del 0,15% de una impureza, que preferiblemente se mide con un Tiempo de Retención Relativo de 0,07; e) tiene un contenido de agua dentro del rango entre 7% y 17% (% en peso), que preferiblemente se analiza por un método de KF; que se puede obtener por un método que comprende los pasos de: A) aislar crofelemer purificado parcialmente agitando una mezcla de látex vegetal crudo o polvo de látex vegetal liofilizado y agua o solvente(s) miscible(s) en agua a una temperatura dentro del rango entre 15ºC y 60ºC; y B) purificar crofelemer purificado parcialmente usando una única columna de CM-Sepharose, donde, la proporción entre la CM-Sepharose y la alimentación de la columna de CM-Sepharose se encuentra dentro del rango entre aproximadamente 3,5:1 y 11:1 o un conjunto de dos columnas de CM-Sepharose y Sephadex LH-20, donde, la proporción entre la CM-Sepharose y la alimentación de la columna de CM-Sepharose se encuentra dentro del rango entre aproximadamente 3,5:1 y 11:1 y la proporción entre el Sephadex LH-20 y la alimentación de la columna de Sephadex LH-20 se encuentra dentro del rango entre aproximadamente 8:1 y 90:1. Reivindicación 70: Un crofelemer amorfo caracterizado porque tiene la fórmula (1) donde R = H (procianidina) y/o R = OH (prodelfinidina), Promedio n ~ 5 (7 unidades) donde, las estructuras de las unidades monoméricas son de fórmulas (2) ó (3). Reivindicación 74: Una composición farmacéutica caracterizada porque comprende crofelemer de acuerdo con cualquiera de las reivindicaciones 1 - 10 y 65 a 73, o que comprende el crofelemer que se puede obtener por un método de acuerdo con cualquiera de las reivindicaciones 11 a 64, y uno o más excipientes, vehículos, diluyentes o mezclas de los mismos farmacéuticamente aceptables. Reivindicación 76: Una composición farmacéutica de acuerdo con la reivindicación 74, caracterizada porque es para el tratamiento de la diarrea asociada con VIH/SIDA, Síndrome de Intestino Irritable, infección aguda y diarrea pediátrica.A process for isolating and purifying a polymeric proanthocyanidin composition, where the composition has a high purity and is suitable for use in pharmaceutically effective formulations. In particular, it refers to a process for producing an appropriate crofelemer for pharmaceutical formulations and with a level of purity and a concentration that allows it to be used therapeutically effectively. Claim 1: A crofelemer with a polydispersity index within the range between 0.9 and 1.2 characterized in that it can be obtained by a method comprising the steps of: A) isolating partially purified crofelemer by stirring a mixture of raw vegetable latex or lyophilized vegetable latex powder and water or water-miscible solvent (s) at a temperature within the range between 15 ° C and 60 ° C; and B) purify the partially purified crofelemer using a column chromatography technique. Claim 12: The method according to claim 11, characterized in that the process of isolating partially purified crofelemer in step (A) comprises the steps of: (a) stirring the mixture of raw vegetable latex or lyophilized vegetable latex powder and water or solvent (s) miscible in water at a temperature within the range between 15 ° C and 60 ° C; (b) separate the liquid phase; (c) optionally, concentrate the liquid phase to obtain a solid, liquid or concentrated syrup; and (d) optionally, add water or solvent (s) miscible in water to solid, liquid or concentrated syrup. Claim 14: The method according to claim 12, characterized in that step (b) is carried out using filtration, sedimentation, centrifugation and / or decantation or combinations thereof. Claim 23: The method according to claim 12, characterized in that step (c) is carried out using ultrafiltration and / or using a rotary evaporator or a combination thereof. Claim 28: The method according to claim 27, characterized in that the ion exchange chromatography is carried out using a carboxymethylation modified agarose. Claim 29: The method according to claim 28, characterized in that the carboxymethylation modified agarose is CM-Sepharose. Claim 68: An amorphous crofelemer characterized in that a) has a polydispersity index within the range between 0.9 and 1.2; b) contains taspine in an amount less than 500 ppm; c) has a purity test value greater than 85%; d) has less than 0.15% of an impurity, which is preferably measured with a Relative Retention Time of 0.07; e) has a water content within the range between 7% and 17% (% by weight), which is preferably analyzed by a KF method; which can be obtained by a method comprising the steps of: A) isolating partially purified crofelemer by stirring a mixture of raw vegetable latex or lyophilized vegetable latex powder and water or solvent (s) miscible in water at a temperature within range between 15ºC and 60ºC; and B) purify partially purified crofelemer using a single CM-Sepharose column, where, the ratio between the CM-Sepharose and the feeding of the CM-Sepharose column is within the range between about 3.5: 1 and 11: 1 or a set of two columns of CM-Sepharose and Sephadex LH-20, where, the ratio between CM-Sepharose and the feeding of the CM-Sepharose column is within the range between approximately 3.5: 1 and 11 : 1 and the ratio between the Sephadex LH-20 and the feed of the Sephadex LH-20 column is in the range between approximately 8: 1 and 90: 1. Claim 70: An amorphous crofelemer characterized in that it has the formula (1) wherein R = H (procyanidin) and / or R = OH (prodelfinidine), Average n ~ 5 (7 units) where, the structures of the monomer units are of formulas (2 or 3). Claim 74: A pharmaceutical composition characterized in that it comprises crofelemer according to any one of claims 1-10 and 65 to 73, or comprising the crofelemer that can be obtained by a method according to any of claims 11 to 64, and one or more pharmaceutically acceptable carriers, diluents or mixtures thereof. Claim 76: A pharmaceutical composition according to claim 74, characterized in that it is for the treatment of diarrhea associated with HIV / AIDS, Irritable Bowel Syndrome, acute infection and pediatric diarrhea.

ARP120100277A 2011-01-27 2012-01-27 A CROFELEMER WITH A POLIDISPERSITY INDEX WITHIN A RANGE BETWEEN 0.9 AND 1.2 AR084940A1 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
IN233MU2011 2011-01-27
IN245MU2011 2011-01-28
US201161444803P 2011-02-21 2011-02-21
US201161445046P 2011-02-22 2011-02-22
IN569MU2011 2011-03-01
US201161452730P 2011-03-15 2011-03-15

Publications (1)

Publication Number Publication Date
AR084940A1 true AR084940A1 (en) 2013-07-10

Family

ID=45562974

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP120100277A AR084940A1 (en) 2011-01-27 2012-01-27 A CROFELEMER WITH A POLIDISPERSITY INDEX WITHIN A RANGE BETWEEN 0.9 AND 1.2

Country Status (4)

Country Link
AR (1) AR084940A1 (en)
BR (1) BR112013018688B1 (en)
RU (1) RU2593014C2 (en)
WO (1) WO2012101008A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8962680B2 (en) 2010-10-31 2015-02-24 Salix Pharmaceuticals, Ltd. Methods and compositions for treating HIV-associated diarrhea
US20220143119A1 (en) * 2019-03-20 2022-05-12 Alphyn Biologics, Llc Croton lechleri compositions for use in the treatment of skin cancer
US20220110992A1 (en) * 2020-09-22 2022-04-14 Alphyn Biologics, Llc Topical croton lechleri compositions and their use in the treatment of a bacterial colonization or primary or secondary bacterial infection of an underlying skin disorder
WO2022066812A1 (en) * 2020-09-22 2022-03-31 Alphyn Biologics, Llc Croton lechleri compositions and their use in the treatment of cystic fibrosis

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5211944A (en) 1990-10-12 1993-05-18 Shaman Pharmaceuticals, Inc. Proanthocyanidin polymers having antiviral activity and methods of obtaining same
IN179200B (en) * 1994-02-21 1997-09-13 Werner Dr Med Nawrocki
EP0935417B1 (en) 1996-10-16 2009-05-06 Napo Pharmaceuticals, Inc. Enteric formulations of proanthocyanidin polymer antidiarrheal compositions
US7325195B1 (en) 1998-10-20 2008-01-29 Arant Gene W Adjustable-speed electronic method of composing information
WO2000047062A2 (en) * 1999-02-01 2000-08-17 Shaman Pharmaceuticals, Inc. Enteric formulations of proanthocyanidin polymer dietary supplements and methods for preparing same
RU2381245C1 (en) * 2008-07-10 2010-02-10 Государственное образовательное учреждение высшего профессионального образования "Белгородский государственный университет" Method of production of concentrated colouring agent
WO2011024049A2 (en) * 2009-08-26 2011-03-03 Glenmark Pharmaceuticals Ltd Method for producing proanthocyanidin polymer compositions for pharmaceutical formulations

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RU2013134704A (en) 2015-03-10
RU2593014C2 (en) 2016-07-27
BR112013018688B1 (en) 2021-08-24
WO2012101008A1 (en) 2012-08-02
BR112013018688A2 (en) 2016-10-18

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