WO2013093164A1 - Tranexamic acid gel - Google Patents
Tranexamic acid gel Download PDFInfo
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- WO2013093164A1 WO2013093164A1 PCT/ES2012/070892 ES2012070892W WO2013093164A1 WO 2013093164 A1 WO2013093164 A1 WO 2013093164A1 ES 2012070892 W ES2012070892 W ES 2012070892W WO 2013093164 A1 WO2013093164 A1 WO 2013093164A1
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- tranexamic acid
- methylparaben
- acid
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Definitions
- the invention relates to a tranexamic acid gel.
- tranexamic acid is administered as tablets orally, or parenterally. It is rapidly absorbed orally through the intestinal tract and the duration of the action is 4 to 6 hours through this route (after administration of 500 mg).
- a field of application is in interventions in the oral cavity.
- it is used to control possible bleeding after dental interventions in hemophiliacs.
- its use is limited, being its main use in tooth extraction.
- Document ES 2,272,064 describes an aqueous pharmaceutical composition for application in the mucosa comprising one or more water-insoluble and / or water-soluble substances, and one or more medications, and having an osmotic pressure of less than 150 mOsm
- These compositions may comprise tranexamic acid (0.1%).
- These compositions are liquid compositions and have very low electrolyte concentrations, that is, they are hypotonic solutions.
- a tranexamic acid gel characterized in that it comprises between 1% and 14% by weight of tranexamic acid, and between 0.1 and 10% by weight of at least one carbomer.
- Carbomers are high molecular weight synthetic polymers of acrylic acid, preferably with allylsucrose or pentaerythritol allyl ethers. Also included within the carbomers are the salts and derivatives of these compounds. Indeed, this composition forms a gel which facilitates topical application. In addition this composition has a clearly hypertonic osmolarity. The gel can be applied directly to the wound site caused by tooth extraction.
- the gel is bioadhesive and stable. It has been found that, surprisingly, with stable tranexamic acid concentrations below 14%, a stable bioadhesive gel is formed, while with higher concentrations a precipitate is formed more or less randomly over time. Being bioadhesive, the gel remains in the place of application even if it is an area of difficult permanence. In this way, the hemostatic effect causes the formation of the necessary clot to prevent bleeding, effectively plugging the wound.
- the gel comprises at least one preservative and / or antifungal of the group formed by parahydroxybenzoic acid, derivatives of parahydroxybenzoic acid, and mixtures of the above (also called parabens), and most preferably of the group formed by methyl parahydroxybenzoate (also called methylparaben, and marketed , for example, under the name of Nipagin®), propylparahydroxybenzoate (also called propylparaben, and marketed, for example, under the name of Nipasol®) and mixtures thereof.
- parahydroxybenzoic acid also called parahydroxybenzoic acid
- derivatives of parahydroxybenzoic acid also called parabens
- mixtures of the above also called parabens
- most preferably of the group formed by methyl parahydroxybenzoate also called methylparaben, and marketed , for example, under the name of Nipagin®
- propylparahydroxybenzoate also called propylparaben, and marketed, for example, under the name of Nipa
- the gel comprises a solvent of the group consisting of propylene glycol, isopropyl alcohol, ethyl alcohol, polyethylene glycol, polyethylene glycol stearate and polyethylene glycol derivatives.
- the gel comprises between 5% by weight and 50% by weight of the solvent.
- the gel comprises between 6% and 10% by weight of tranexamic acid, since with these concentrations it is particularly effective and, nevertheless, remains totally stable.
- the gel comprises between 0.5% and 5% by weight of at least one carbomer.
- Carbomers can have different molecular weights. They preferably have a molecular weight between 7x10 5 and 4x10 9 . They are marketed, for example, under the name Carbopol®.
- Carbopol® 934 has a molecular weight of 3,000,000 and has a high relative viscosity in topical applications [(29,400 - 39,400 cP (0.5% weight at pH 7.5)]. Chemically it is a water-soluble acrylic acid polymer crosslinked with a sucrose or pentaerythritol allyter.
- Carbopol® 940 with a molecular weight of 4,000,000, consists of polymers of cross-linked acrylic acid with pentaerythritol allyl ether. Its gels have a very high relative viscosity [(40,000 - 60,000 cP (0.5% weight at pH 7.5)].
- Carbopol® 974 (like 934) is also a high molecular weight polymer of acrylic acid crosslinked with sucrose or pentaerythritol allyl ethers. It has the ability to sustain the transfer of the active ingredients dispersed in the matrix, so it is considered very suitable for oral application. Topical products of high relative viscosity are obtained [(29,400 - 39,400 cP (0.5% by weight at pH 7.5)]. Carbopol® 1342, with a high molecular weight, is also ideal in the formation of creams and gels. It is a copolymer of acrylic acid and a long chain alkyl methacrylate crosslinked with pentaerythritol allyl ethers. Topical applications formulated with this carbomer show a medium relative viscosity [(9,500 - 26,500 cP (0.5% weight at pH 7.5)].
- tranexamic acid between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 35% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06 % propylparaben (Nipasol®).
- tranexamic acid between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 30% and 35% by weight of ethanol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06 % propylparaben (Nipasol®).
- tranexamic acid between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 40% by weight of polyethylene glycol 200, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
- tranexamic acid between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 40% by weight of polyethylene glycol 400, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
- a water-soluble acrylic acid polymer crosslinked with a sucrose or pentaerythritol allyl ether of molecular weight between 7x10 5 and 4x10 9 (preferably Carbopol® 934), between 10% and 30% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
- tranexamic acid between 0.5% and 4% by weight of a polymer of the acrylic acid crosslinked with allyl ether of pentaerythritol, of molecular weight between 7x10 5 and 4x10 9 ( preferably Carbopol® 940), between 10% and 40% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06% of propylparaben ( Nipasol®).
- a polymer of the acrylic acid crosslinked with allyl ether of pentaerythritol of molecular weight between 7x10 5 and 4x10 9 (preferably Carbopol® 940)
- propylene glycol between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06% of propylparaben ( Nipasol®).
- tranexamic acid between 2% and 6% by weight of an acrylic acid copolymer and a long chain alkyl methacrylate crosslinked with pentaerythritol allyl ethers, of molecular weight between 7x10 5 and 4x10 9 (preferably Carbopol® 1342), between 10% and 45% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
- the gel comprises 8% by weight of tranexamic acid.
- the gel comprises 0.3% by weight of methylparaben (Nipagin®) and / or 0.05% by weight of propylparaben (Nipasol®).
- the pH of the gel is between 6.5 and 7.5.
- tranexamic acid is dissolved in water, stirred until completely dissolved
- Nipagin® and Nipasol® are dissolved in propylene glycol while stirring until completely dissolved.
- PHASE 3 The Nipagin® and Nipasol® are dissolved in propylene glycol while stirring until completely dissolved.
- Carbopol 974 is added to the solution obtained in phase 1 and stirred (anchor stirrer) until a transparent gel is formed.
- An alkalizing agent is added to the gel to obtain a final pH between 6.5-7.5.
- Carbopol ® 974 0.5 to 4%
- Carbopol ® 934 0.5 to 5%
Abstract
Tranexamic acid gel that comprises between 1% and 14% by weight tranexamic acid and between 0.1 and 10% by weight of at least one carbomer. The gel may also comprise preservatives and a solvent and have a pH of between 6.5 and 7.5.
Description
GEL DE ÁCIDO TRANEXAMICO TRANEXAMIC ACID GEL
DESCRIPCIÓN DESCRIPTION
Campo de la invención Field of the Invention
La invención se refiere a un gel de ácido tranexámico. The invention relates to a tranexamic acid gel.
Estado de la técnica State of the art
Actualmente el ácido tranexámico se administra en forma de comprimidos por vía oral, o bien por vía parenteral. Por vía oral se absorbe rápidamente a través del tracto intestinal y la duración de la acción, por esta vía es de 4 a 6 horas (tras la administración de 500 mg). Currently, tranexamic acid is administered as tablets orally, or parenterally. It is rapidly absorbed orally through the intestinal tract and the duration of the action is 4 to 6 hours through this route (after administration of 500 mg).
Un campo de aplicación es en intervenciones en la cavidad bucal. Así, por ejemplo, se emplea para controlar posibles hemorragias después de intervenciones dentales en hemofílicos. En el caso de niños, su uso es limitado, siendo su principal utilización en extracción dental. A field of application is in interventions in the oral cavity. Thus, for example, it is used to control possible bleeding after dental interventions in hemophiliacs. In the case of children, its use is limited, being its main use in tooth extraction.
En el documento ES 2.272.064 se describe una composición farmacéutica acuosa para aplicar en la mucosa que comprende una o más substancias insolubles en agua y/o poco solubles en agua, y una o más medicamentos, y que tiene una presión osmótica de menos de 150 mOsm. Estas composiciones pueden comprender ácido tranexámico (0,1 %). Estas composiciones son composiciones líquidas y tienen unas concentraciones de electrolitos muy bajas, es decir son soluciones hipotónicas. Document ES 2,272,064 describes an aqueous pharmaceutical composition for application in the mucosa comprising one or more water-insoluble and / or water-soluble substances, and one or more medications, and having an osmotic pressure of less than 150 mOsm These compositions may comprise tranexamic acid (0.1%). These compositions are liquid compositions and have very low electrolyte concentrations, that is, they are hypotonic solutions.
Existe sin embargo la necesidad de composiciones que comprendan ácido tranexámico con las que se obtenga un mejor resultado terapéutico.
Sumario de la invención There is however a need for compositions comprising tranexamic acid with which a better therapeutic result is obtained. Summary of the invention
Esta finalidad se consigue mediante un gel de ácido tranexámico caracterizado porque comprende entre un 1 % y un 14% en peso de ácido tranexámico, y entre un 0,1 y un 10% en peso de por lo menos un carbómero. Los carbómeros son polímeros sintéticos de alto peso molecular de ácido acrílico, preferentemente con alilsucrosa o aliléteres de pentaeritritol. También se incluyen dentro de los carbómeros las sales y los derivados de estos compuestos. Efectivamente, esta composición forma un gel lo que facilita la aplicación tópica. Además esta composición tiene una osmolaridad claramente hipertónica. El gel se puede aplicar directamente en el lugar de la herida provocada por una extracción dental. De esta forma se disminuyen o evitan los efectos secundarios provocados por otras formas farmacéuticas, como son los trastornos gastrointestinales (que pueden ser producidos por los comprimidos administrados por vía oral) o los efectos hipotensivos (descritos en casos de administración intravenosa rápida). Adicionalmente, el gel es bioadhesivo y es estable. Se ha descubierto que, sorprendentemente, con concentraciones de ácido tranexámico inferiores al 14% se forma un gel bioadhesivo estable, mientras que con concentraciones superiores se forma un precipitado de una forma más o menos aleatoria en el tiempo. Al ser bioadhesivo, el gel permanece en el lugar de aplicación aunque sea una zona de difícil permanencia. De esta manera, el efecto hemostático hace que se favorezca la formación del coágulo necesario para evitar el sangrado, taponando de forma eficaz la herida. This purpose is achieved by a tranexamic acid gel characterized in that it comprises between 1% and 14% by weight of tranexamic acid, and between 0.1 and 10% by weight of at least one carbomer. Carbomers are high molecular weight synthetic polymers of acrylic acid, preferably with allylsucrose or pentaerythritol allyl ethers. Also included within the carbomers are the salts and derivatives of these compounds. Indeed, this composition forms a gel which facilitates topical application. In addition this composition has a clearly hypertonic osmolarity. The gel can be applied directly to the wound site caused by tooth extraction. This reduces or avoids the side effects caused by other pharmaceutical forms, such as gastrointestinal disorders (which can be produced by orally administered tablets) or hypotensive effects (described in cases of rapid intravenous administration). Additionally, the gel is bioadhesive and stable. It has been found that, surprisingly, with stable tranexamic acid concentrations below 14%, a stable bioadhesive gel is formed, while with higher concentrations a precipitate is formed more or less randomly over time. Being bioadhesive, the gel remains in the place of application even if it is an area of difficult permanence. In this way, the hemostatic effect causes the formation of the necessary clot to prevent bleeding, effectively plugging the wound.
Preferentemente el gel comprende al menos un conservante y/o antifúngico del grupo formado por ácido parahidroxibenzóico, derivados de ácido parahidroxibenzóico, y mezclas de los anteriores (también denominados parabenes), y muy preferentemente del grupo formado por metilparahidroxibenzoato (también denominado metilparaben, y comercializado, por ejemplo, bajo el nombre de Nipagin®), propilparahidroxibenzoato (también denominado propilparaben, y comercializado, por ejemplo, bajo el nombre de Nipasol®) y mezclas de los anteriores.
Ventajosamente el gel comprende un disolvente del grupo formado por propilenglicol, alcohol isopropílico, alcohol etílico, polietilenglicol, estearato de polietilenglicol y derivados de polietilenglicol. Preferentemente el gel comprende entre un 5% en peso y un 50% en peso del disolvente. Preferably the gel comprises at least one preservative and / or antifungal of the group formed by parahydroxybenzoic acid, derivatives of parahydroxybenzoic acid, and mixtures of the above (also called parabens), and most preferably of the group formed by methyl parahydroxybenzoate (also called methylparaben, and marketed , for example, under the name of Nipagin®), propylparahydroxybenzoate (also called propylparaben, and marketed, for example, under the name of Nipasol®) and mixtures thereof. Advantageously, the gel comprises a solvent of the group consisting of propylene glycol, isopropyl alcohol, ethyl alcohol, polyethylene glycol, polyethylene glycol stearate and polyethylene glycol derivatives. Preferably the gel comprises between 5% by weight and 50% by weight of the solvent.
Preferentemente el gel comprende entre un 6% y un 10% en peso de ácido tranexámico, ya que con estas concentraciones es particularmente eficaz y, sin embargo, sigue siendo totalmente estable. Preferably the gel comprises between 6% and 10% by weight of tranexamic acid, since with these concentrations it is particularly effective and, nevertheless, remains totally stable.
Ventajosamente el gel comprende entre un 0,5% y un 5% en peso de por lo menos un carbómero. Advantageously, the gel comprises between 0.5% and 5% by weight of at least one carbomer.
Los carbómeros pueden tener diversos pesos moleculares. Preferentemente tienen un peso molecular comprendido entre 7x105 y 4x109. Son comercializados, por ejemplo, bajo el nombre Carbopol®. Carbomers can have different molecular weights. They preferably have a molecular weight between 7x10 5 and 4x10 9 . They are marketed, for example, under the name Carbopol®.
El Carbopol® 934 tiene un peso molecular de 3.000.000 y presenta una alta viscosidad relativa en las aplicaciones tópicas [(29.400 - 39.400 cP (0.5% de peso en pH 7.5)]. Químicamente es un polímero hidrosoluble del ácido acrílico entrecruzado con un aliléter de sacarosa o de pentaeritritol. Carbopol® 934 has a molecular weight of 3,000,000 and has a high relative viscosity in topical applications [(29,400 - 39,400 cP (0.5% weight at pH 7.5)]. Chemically it is a water-soluble acrylic acid polymer crosslinked with a sucrose or pentaerythritol allyter.
El Carbopol® 940, con un peso molecular de 4.000.000, está constituido por polímeros de ácido acrílico reticulado con aliléter de pentaeritritol. Sus geles presentan una muy alta viscosidad relativa [(40.000 - 60.000 cP (0.5% de peso en pH 7.5)]. Carbopol® 940, with a molecular weight of 4,000,000, consists of polymers of cross-linked acrylic acid with pentaerythritol allyl ether. Its gels have a very high relative viscosity [(40,000 - 60,000 cP (0.5% weight at pH 7.5)].
El Carbopol® 974 (como el 934) es también un polímero de alto peso molecular del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol. Posee la capacidad de sostener la cesión de los ingredientes activos dispersos en la matriz, por lo que se considera muy apto para su aplicación oral. Se obtienen productos de uso tópico de alta viscosidad relativa [(29.400 - 39.400 cP (0.5% de peso en pH 7.5)].
El Carbopol® 1342, con un elevado peso molecular, resulta también idóneo en la formación de cremas y geles. Es un copolímero de ácido acrílico y un alquilmetacrilato de cadena larga entrecruzado con aliléteres de pentaeritritol. Las aplicaciones tópicas formuladas con este carbómero muestran una mediana viscosidad relativa [(9.500 - 26.500 cP (0.5% de peso en pH 7.5)]. Carbopol® 974 (like 934) is also a high molecular weight polymer of acrylic acid crosslinked with sucrose or pentaerythritol allyl ethers. It has the ability to sustain the transfer of the active ingredients dispersed in the matrix, so it is considered very suitable for oral application. Topical products of high relative viscosity are obtained [(29,400 - 39,400 cP (0.5% by weight at pH 7.5)]. Carbopol® 1342, with a high molecular weight, is also ideal in the formation of creams and gels. It is a copolymer of acrylic acid and a long chain alkyl methacrylate crosslinked with pentaerythritol allyl ethers. Topical applications formulated with this carbomer show a medium relative viscosity [(9,500 - 26,500 cP (0.5% weight at pH 7.5)].
Todos ellos resultan adecuados y válidos para formar geles de aplicación oral. Hay diversas composiciones del gel que son particularmente ventajosas, como son las siguientes: All of them are suitable and valid to form gels for oral application. There are various gel compositions that are particularly advantageous, such as the following:
- entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol (preferentemente Carbopol® 974), entre un 10% y un 35% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol (preferentemente Carbopol® 974), entre un 30% y un 35% en peso de etanol, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 35% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06 % propylparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 30% and 35% by weight of ethanol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06 % propylparaben (Nipasol®).
- entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol (preferentemente Carbopol® 974), entre un 10% y un 40% en peso de polietilenglicol 200, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®).
- entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol (preferentemente Carbopol® 974), entre un 10% y un 40% en peso de polietilenglicol 400, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 40% by weight of polyethylene glycol 200, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose allyl ethers or of pentaerythritol (preferably Carbopol® 974), between 10% and 40% by weight of polyethylene glycol 400, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
- entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero hidrosoluble del ácido acrílico entrecruzado con un aliléter de sacarosa o de pentaeritritol, de peso molecular comprendido entre 7x105 y 4x109 (preferentemente Carbopol® 934), entre un 10% y un 30% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero del ácido acrílico reticulado con aliléter de pentaeritritol, de peso molecular comprendido entre 7x105 y 4x109 (preferentemente Carbopol® 940), entre un 10% y un 40% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a water-soluble acrylic acid polymer crosslinked with a sucrose or pentaerythritol allyl ether, of molecular weight between 7x10 5 and 4x10 9 (preferably Carbopol® 934), between 10% and 30% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer of the acrylic acid crosslinked with allyl ether of pentaerythritol, of molecular weight between 7x10 5 and 4x10 9 ( preferably Carbopol® 940), between 10% and 40% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0.06% of propylparaben ( Nipasol®).
- entre un 6% y un 10% en peso de ácido tranexámico, entre un 2% y un 6% en peso de un copolímero de ácido acrílico y un alquilmetacrilato de cadena larga entrecruzado con aliléteres de pentaeritritol, , de peso molecular comprendido entre 7x105 y 4x109 (preferentemente Carbopol® 1342), entre un 10% y un 45% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben (Nipagin®) y entre un 0,015 y un 0,06% de propilparaben (Nipasol®). - between 6% and 10% by weight of tranexamic acid, between 2% and 6% by weight of an acrylic acid copolymer and a long chain alkyl methacrylate crosslinked with pentaerythritol allyl ethers, of molecular weight between 7x10 5 and 4x10 9 (preferably Carbopol® 1342), between 10% and 45% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben (Nipagin®) and between 0.015 and 0, 06% propylparaben (Nipasol®).
Preferentemente el gel comprende un 8% en peso de ácido tranexámico. Preferably the gel comprises 8% by weight of tranexamic acid.
Ventajosamente el gel comprende un 0,3% en peso de metilparaben (Nipagin®) y/o un 0,05% en peso de propilparaben (Nipasol®).
Preferentemente el pH del gel está comprendido entre 6,5 y 7,5. Ejemplos Ejemplo 1 : Composición: Advantageously, the gel comprises 0.3% by weight of methylparaben (Nipagin®) and / or 0.05% by weight of propylparaben (Nipasol®). Preferably the pH of the gel is between 6.5 and 7.5. Examples Example 1: Composition:
Se disuelve el ácido tranexámico en agua, se agita hasta total disolución The tranexamic acid is dissolved in water, stirred until completely dissolved
2a FASE: PHASE 2:
Se disuelven el Nipagin® y Nipasol® en propilenglicol agitando hasta disolución total.
3a FASE: The Nipagin® and Nipasol® are dissolved in propylene glycol while stirring until completely dissolved. PHASE 3:
Se añade a la solución obtenida en la fase 1 el Carbopol 974 y se agita (agitador de ancla) hasta formación de un gel transparente. Carbopol 974 is added to the solution obtained in phase 1 and stirred (anchor stirrer) until a transparent gel is formed.
4a FASE: 4 to PHASE:
Se incorpora al gel obtenido en la 3a fase la solución obtenida en la 2a fase. Se agita (agitador de ancla) hasta incorporación homogénea, obteniéndose un gel transparente dotado de propiedades bioadhesivas. It is incorporated into the gel obtained in stage 3 to the solution obtained in the 2nd phase. Stir (anchor agitator) until homogeneous incorporation, obtaining a transparent gel with bioadhesive properties.
5a FASE: PHASE 5:
Se añade al gel un agente alcalinizante para obtener un pH final comprendido entre 6,5- 7,5. An alkalizing agent is added to the gel to obtain a final pH between 6.5-7.5.
Control galénico - Caracterización del gel Galenic Control - Gel Characterization
Se ponen 5 g de gel en tubo de centrifugación. En otro tubo igual se colocan 5 g de agua desionizada. Se centrifuga a 5000 rpm durante 15 minutos y no se observa separación de fases. Procedimiento de fabricación: el mismo del ejemplo 1 .
Eiemplo 2: 5 g of gel is placed in a centrifuge tube. In another equal tube, 5 g of deionized water are placed. It is centrifuged at 5000 rpm for 15 minutes and no phase separation is observed. Manufacturing procedure: the same as in example 1. Example 2:
Procedimiento de fabricación: el mismo del ejemplo 1 . Manufacturing procedure: the same as in example 1.
Ejemplo 3: Example 3:
Ácido tranexámico 8 %Tranexamic acid 8%
Carbopol® 974 0,5 a 4 %Carbopol ® 974 0.5 to 4%
Alcohol 96e 30 a 35 %Alcohol 96 and 30 to 35%
Nipagin® 0,30 %Nipagin® 0.30%
Nipasol® 0,05 %Nipasol® 0.05%
Agua desionizada c.s.p. 100 gDeionized water c.s.p. 100g
NaOH c.s.p. pH 6,5 a 7,5
Procedimiento de fabricación: el mismo del ejemplo 1 , pero utilizando un disolvente distinto: alcohol 96e. Ejemplo 4: NaOH csp pH 6.5 to 7.5 Manufacturing procedure: the same as in example 1, but using a different solvent: alcohol 96 e . Example 4:
Procedimiento de fabricación: el mismo del ejemplo 1 , pero utilizando un disolvente distinto: polietilenglicol 200.
Manufacturing process: the same as in example 1, but using a different solvent: polyethylene glycol 200.
Eiemplo 5: Example 5:
Procedimiento de fabricación: el mismo del ejemplo 1 , pero utilizando un disolvente distinto: polietilenglicol 400. Manufacturing process: the same as in example 1, but using a different solvent: polyethylene glycol 400.
Ejemplo 6: Example 6:
Ácido tranexámico 8 % Tranexamic acid 8%
Carbopol® 934 0,5 a 5 % Carbopol ® 934 0.5 to 5%
Propilenglicol 10 a 30 % Propylene Glycol 10 to 30%
Nipagin® 0,30 % Nipagin® 0.30%
Nipasol® 0,05 % Nipasol® 0.05%
Agua desionizada c.s.p. 100 g Deionized water c.s.p. 100g
NaOH c.s.p. pH 6,5 a 7,5
Procedimiento de fabricación: el mismo del ejemplo 1 , pero sustituyendo el Carbopol® 974 por otro tipo de distinta polimerización (Carbopol® 934). NaOH csp pH 6.5 to 7.5 Manufacturing procedure: the same as in example 1, but replacing Carbopol ® 974 with another type of different polymerization (Carbopol ® 934).
Ejemplo 7: Example 7:
Procedimiento de fabricación: el mismo del ejemplo 1 , pero sustituyendo el Carbopol® 974 por otro tipo de distinta polimerización (Carbopol® 940).
Manufacturing procedure: the same as in Example 1, but replacing Carbopol ® 974 with another type of different polymerization (Carbopol ® 940).
Ejemplo 8: Example 8:
Procedimiento de fabricación: el mismo del ejemplo 1 , pero sustituyendo el Carbopol® 974 por otro tipo de distinta polimerización (Carbopol® 1342).
Manufacturing procedure: the same as in example 1, but replacing Carbopol ® 974 with another type of different polymerization (Carbopol ® 1342).
Claims
REIVINDICACIONES
1 - Gel de ácido tranexámico caracterizado porque comprende entre un 1 % y un 14% en peso de ácido tranexámico, y entre un 0,1 y un 10% en peso de por lo menos un carbómero. 1 - Tranexamic acid gel characterized in that it comprises between 1% and 14% by weight of tranexamic acid, and between 0.1 and 10% by weight of at least one carbomer.
2 - Gel según la reivindicación 1 , caracterizado porque comprende un conservante del grupo formado por ácido parahidroxibenzóico, derivados de ácido parahidroxibenzóico, y mezclas de los anteriores, preferentemente del grupo formado por metilparahidroxibenzoato, propilparahidroxibenzoato y mezclas de los anteriores. 2 - Gel according to claim 1, characterized in that it comprises a preservative of the group consisting of parahydroxybenzoic acid, derivatives of parahydroxybenzoic acid, and mixtures of the foregoing, preferably of the group consisting of methyl parahydroxybenzoate, propyl parahydroxybenzoate and mixtures of the foregoing.
3 - Gel según una de las reivindicaciones 1 ó 2, caracterizado porque comprende un disolvente del grupo formado por propilenglicol, alcohol isopropílico, alcohol etílico, polietilenglicol, estearato de polietilenglicol y derivados de polietilenglicol. 3 - Gel according to one of claims 1 or 2, characterized in that it comprises a solvent of the group consisting of propylene glycol, isopropyl alcohol, ethyl alcohol, polyethylene glycol, polyethylene glycol stearate and polyethylene glycol derivatives.
4 - Gel según cualquiera de las reivindicaciones 1 a 3, caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico. 5 - Gel según cualquiera de las reivindicaciones 1 a 4, caracterizado porque comprende entre un 0,5% y un 5% en peso de por lo menos un carbómero. 4 - Gel according to any of claims 1 to 3, characterized in that it comprises between 6% and 10% by weight of tranexamic acid. 5 - Gel according to any of claims 1 to 4, characterized in that it comprises between 0.5% and 5% by weight of at least one carbomer.
6 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 5% en peso y un 50% en peso de dicho disolvente. 6 - Gel according to claim 1, characterized in that it comprises between 5% by weight and 50% by weight of said solvent.
7 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol, entre un 10% y un 35% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben.
8 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol, entre un 30% y un 35% en peso de etanol, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 7 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of cross-linked acrylic acid with sucrose or pentaerythritol allyl ethers, between 10% and 35% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0.06 % of propilparaben. 8 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of cross-linked acrylic acid with sucrose or pentaerythritol allyl ethers, between 30% and 35% by weight of ethanol, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0.06 % of propilparaben.
9 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol, entre un 10% y un 40% en peso de polietilenglicol 200, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 10 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero, de peso molecular comprendido entre 7x105 y 4x109, del ácido acrílico reticulado con aliléteres de sacarosa o de pentaeritritol, entre un 10% y un 40% en peso de polietilenglicol 400, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 9 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose or pentaerythritol allyl ethers, between 10% and 40% by weight of polyethylene glycol 200, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0, 06% propilparaben. 10 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a polymer, of molecular weight between 7x10 5 and 4x10 9 , of the acrylic acid crosslinked with sucrose or pentaerythritol allyl ethers, between 10% and 40% by weight of polyethylene glycol 400, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0, 06% propilparaben.
1 1 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 5% en peso de un polímero hidrosoluble del ácido acrílico entrecruzado con un aliléter de sacarosa o de pentaeritritol, de peso molecular comprendido entre 7x105 y 4x109, entre un 10% y un 30% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 1 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 5% by weight of a water-soluble acrylic acid polymer crosslinked with an allyl ether of sucrose or pentaerythritol, of molecular weight between 7x10 5 and 4x10 9 , between 10% and 30% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0 , 06% propilparaben.
12 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 0,5% y un 4% en peso de un polímero del ácido acrílico reticulado con aliléter de pentaeritritol, de peso molecular comprendido entre 7x105 y 4x109, entre un 10% y un 40% en peso de propilenglicol,
entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 12 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 0.5% and 4% by weight of a polymer of the cross-linked acrylic acid with pentaerythritol allylter, of molecular weight between 7x10 5 and 4x10 9 , between 10% and 40% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0.06% of propylparaben.
13 - Gel según la reivindicación 1 , caracterizado porque comprende entre un 6% y un 10% en peso de ácido tranexámico, entre un 2% y un 6% en peso de un copolímero de ácido acrílico y un alquilmetacrilato de cadena larga entrecruzado con aliléteres de pentaeritritol, de peso molecular comprendido entre 7x105 y 4x109, entre un 10% y un 45% en peso de propilenglicol, entre un 0,15 y un 0,65 en peso de metilparaben y entre un 0,015 y un 0,06% de propilparaben. 13 - Gel according to claim 1, characterized in that it comprises between 6% and 10% by weight of tranexamic acid, between 2% and 6% by weight of an acrylic acid copolymer and a long chain alkyl methacrylate crosslinked with allyl ethers of pentaerythritol, of molecular weight between 7x10 5 and 4x10 9 , between 10% and 45% by weight of propylene glycol, between 0.15 and 0.65 by weight of methylparaben and between 0.015 and 0.06 % of propilparaben.
14 - Gel según cualquiera de las reivindicaciones 1 a 13, caracterizado porque comprende un 8% en peso de ácido tranexámico. 14 - Gel according to any of claims 1 to 13, characterized in that it comprises 8% by weight of tranexamic acid.
15 - Gel según cualquiera de las reivindicaciones 1 a 14, caracterizado porque comprende un 0,3% en peso de metilparaben. 15 - Gel according to any of claims 1 to 14, characterized in that it comprises 0.3% by weight of methylparaben.
16 - Gel según cualquiera de las reivindicaciones 1 a 15, caracterizado porque comprende un 0,05% en peso de propilparaben. 17 - Gel según cualquiera de las reivindicaciones 1 a 16, caracterizado porque su pH está comprendido entre 6,5 y 7,5.
16 - Gel according to any of claims 1 to 15, characterized in that it comprises 0.05% by weight of propylparaben. 17 - Gel according to any of claims 1 to 16, characterized in that its pH is between 6.5 and 7.5.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ESP201132073 | 2011-12-22 | ||
| ES201132073A ES2375784B1 (en) | 2011-12-22 | 2011-12-22 | Tranexamic acid gel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013093164A1 true WO2013093164A1 (en) | 2013-06-27 |
Family
ID=45607510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/ES2012/070892 WO2013093164A1 (en) | 2011-12-22 | 2012-12-20 | Tranexamic acid gel |
Country Status (2)
| Country | Link |
|---|---|
| ES (1) | ES2375784B1 (en) |
| WO (1) | WO2013093164A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9775821B2 (en) | 2014-03-25 | 2017-10-03 | Leading BioSciences, Inc. | Compositions for the treatment of autodigestion |
| US10772861B2 (en) | 2010-09-23 | 2020-09-15 | Leading Biosciences, LLC | Administration of serine protease inhibitors to the stomach |
| US11202768B2 (en) | 2016-01-11 | 2021-12-21 | Leading BioSciences, Inc. | Compositions and methods for treating and preventing adhesions and ileus |
| US11642324B1 (en) | 2022-03-01 | 2023-05-09 | Bio 54, Llc | Topical tranexamic acid compositions and methods of use thereof |
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| CA2161652A1 (en) * | 1993-04-30 | 1994-11-10 | Patricia B. Williams | Topical compositions for re-epitheliazation of persistent epithelial defects |
| JPH09124878A (en) * | 1995-10-31 | 1997-05-13 | Shiseido Co Ltd | Gel composition |
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| WO2011078700A1 (en) * | 2009-12-17 | 2011-06-30 | Don Macalister | Topical oral gel formulations for dental use |
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| JP3447177B2 (en) * | 1996-05-17 | 2003-09-16 | 株式会社資生堂 | Gel composition |
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2011
- 2011-12-22 ES ES201132073A patent/ES2375784B1/en active Active
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| WO1992009307A1 (en) * | 1990-11-22 | 1992-06-11 | Kabi Pharmacia Ab | A gel-forming liquid carrier composition |
| CA2161652A1 (en) * | 1993-04-30 | 1994-11-10 | Patricia B. Williams | Topical compositions for re-epitheliazation of persistent epithelial defects |
| JPH09124878A (en) * | 1995-10-31 | 1997-05-13 | Shiseido Co Ltd | Gel composition |
| WO1998017252A1 (en) * | 1996-10-18 | 1998-04-30 | Virotex Corporation | Pharmaceutical gel preparation applicable to mucosal surfaces and body tissues |
| ES2272064T3 (en) | 1998-04-21 | 2007-04-16 | Teijin Limited | MEDICINAL COMPOSITIONS TO APPLY IN THE MUCOSA. |
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| US10772861B2 (en) | 2010-09-23 | 2020-09-15 | Leading Biosciences, LLC | Administration of serine protease inhibitors to the stomach |
| US11439611B2 (en) | 2010-09-23 | 2022-09-13 | Leading BioSciences, Inc. | Administration of serine protease inhibitors to the stomach |
| US9775821B2 (en) | 2014-03-25 | 2017-10-03 | Leading BioSciences, Inc. | Compositions for the treatment of autodigestion |
| US11123317B2 (en) | 2014-03-25 | 2021-09-21 | Leading BioSciences, Inc. | Compositions for the treatment of autodigestion |
| US11202768B2 (en) | 2016-01-11 | 2021-12-21 | Leading BioSciences, Inc. | Compositions and methods for treating and preventing adhesions and ileus |
| US11642324B1 (en) | 2022-03-01 | 2023-05-09 | Bio 54, Llc | Topical tranexamic acid compositions and methods of use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2375784A1 (en) | 2012-03-06 |
| ES2375784B1 (en) | 2013-01-24 |
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