ES2468665A1 - Pharmaceutical composition of chondroitin sulfate and celecoxib (Machine-translation by Google Translate, not legally binding) - Google Patents
Pharmaceutical composition of chondroitin sulfate and celecoxib (Machine-translation by Google Translate, not legally binding) Download PDFInfo
- Publication number
- ES2468665A1 ES2468665A1 ES201201233A ES201201233A ES2468665A1 ES 2468665 A1 ES2468665 A1 ES 2468665A1 ES 201201233 A ES201201233 A ES 201201233A ES 201201233 A ES201201233 A ES 201201233A ES 2468665 A1 ES2468665 A1 ES 2468665A1
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- Prior art keywords
- chondroitin sulfate
- celecoxib
- composition
- weight
- osteoarthritis
- Prior art date
- Legal status (The legal status 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 status listed.)
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- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 title claims abstract description 51
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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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
COMPOSICi�N FARMACÉUTICA DE SULFATO DE CONDROITINA y CELECOXIB PHARMACEUTICAL COMPOSITION OF CONDROITINE SULPHATE and CELECOXIB
La presente invención se refiere a una composición farmacéutica para su administración oral que contiene como principios activos una combinación de sulfato de condroitina y celecoxib, que resulta especialmente efectiva para la regeneración del cartílago en pacientes afectados de artrosis. The present invention relates to a pharmaceutical composition for oral administration which contains as active ingredients a combination of chondroitin sulfate and celecoxib, which is especially effective for cartilage regeneration in patients suffering from osteoarthritis.
Las enfermedades osteoarticulares presentan una alta prevalencia entre la población de los países occidentales y constituyen un importante problema de salud, a la vez que tienen un notorio impacto socioeconómico, estimándose, por ejemplo, que son la primera causa de bajas laborales permanentes. Osteoarticular diseases have a high prevalence among the population of Western countries and constitute a major health problem, while having a noticeable socioeconomic impact, estimating, for example, that they are the leading cause of permanent work leave.
En particular, la artrosis es la enfermedad articular más frecuente, con una prevalencia que oscila entre el 6% y el 20% entre los mayores de 20 años, según se describe en el artículo Poley González y coL, 'Prevalencia de enfermedades osteoarticulares y consumo de recursos. Calidad de vida y dependencia en pacientes con artrosis", Semergen, 2011, 37 (9), 462-467. In particular, osteoarthritis is the most frequent joint disease, with a prevalence ranging from 6% to 20% among those over 20 years, as described in the article Poley González and coL, 'Prevalence of osteoarticular diseases and consumption of resources. Quality of life and dependence in patients with osteoarthritis ", Semergen, 2011, 37 (9), 462-467.
La artrosis es particularmente frecuente en la población de edad avanzada, siendo la mayor causa de dolor y de disfunción en pacientes mayores de 65 años. Se calcula que la prevalencia de la artrosis sintom�tica en España es de casi el 35% en los grupos de edad mayores de 65 años, tal como se describe en el artículo de Carmona y coL, 'Proyecto EPISER 2000: prevalencia de enfermedades reumáticas en la población española", Rev. Esp. ReumatoL, 2001, 28, 18-25. Osteoarthritis is particularly common in the elderly population, being the major cause of pain and dysfunction in patients over 65 years. It is estimated that the prevalence of symptomatic osteoarthritis in Spain is almost 35% in the age groups over 65 years, as described in the article by Carmona and coL, 'Project EPISER 2000: prevalence of rheumatic diseases in the Spanish population ", Rev. Esp. ReumatoL, 2001, 28, 18-25.
La artrosis es un trastorno crónico de las articulaciones, caracterizado por la degeneración y pérdida del cartílago, esclerosis del hueso subcondral adyacente e inflamación sinovial, y que habitualmente provoca dolor articulatorio y rigidez. Osteoarthritis is a chronic disorder of the joints, characterized by degeneration and loss of cartilage, sclerosis of the adjacent subchondral bone and synovial inflammation, and usually causes joint pain and stiffness.
La artrosis desencadena una creciente discapacidad física y deterioro de la calidad de vida de los sujetos afectados, a la vez que provoca un uso intenso de los recursos sanitarios. Osteoarthritis triggers a growing physical disability and deterioration of the quality of life of the affected subjects, while causing intense use of health resources.
La artrosis puede afectar a cualquier articulación, siendo más frecuente en manos, pies, columna vertebral, caderas y rodillas. Osteoarthritis can affect any joint, being more frequent in hands, feet, spine, hips and knees.
Se considera que la artrosis no tiene un tratamiento curativo definitivo, sino que el tratamiento farmacol�gico de la artrosis se focaliza en la disminución del dolor y en la mejoría de la capacidad funcional. It is considered that osteoarthritis does not have a definitive curative treatment, but that the pharmacological treatment of osteoarthritis focuses on the reduction of pain and on the improvement of functional capacity.
Existen en la actualidad dos aproximaciones en el tratamiento de la artrosis. Por un lado, existen los fármacos de acción sintom�tica rápida que se usan habitualmente para mejorar los síntomas dolorosos de forma rápida y potente. Dentro de este grupo se sitúan los analgésicos, los corticoides y los antiinflamatorios no esteroideos (AINEs), por ejemplo los inhibidores selectivos de la ciclooxigenasa 2 (COX-2). There are currently two approaches in the treatment of osteoarthritis. On the one hand, there are drugs of rapid symptomatic action that are usually used to improve painful symptoms quickly and potently. Within this group are analgesics, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), for example selective inhibitors of cyclooxygenase 2 (COX-2).
Dentro del grupo de los inhibidores selectivos de la COX-2, pueden mencionarse, por ejemplo, etoricoxib y celecoxib, cuyo uso est� autorizado en España para el alivio sintomático de la artrosis. Within the group of selective COX-2 inhibitors, for example, etoricoxib and celecoxib, whose use is authorized in Spain for the symptomatic relief of osteoarthritis, may be mentioned.
En particular, el celecoxib se ha demostrado eficaz en el tratamiento de la sintomatolog�a asociada a la artrosis, tal como se describe en el artículo P.L. McCormack, "Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarlhritis, rheumatoid arlhritis and ankylosing spondylitis'~ In particular, celecoxib has been proven effective in the treatment of osteoarthritis-associated symptoms, as described in article P.L. McCormack, "Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarlhritis, rheumatoid arlhritis and ankylosing spondylitis' ~
Drugs, 2011, 71 (18), 2457-89. Drugs, 2011, 71 (18), 2457-89.
Por otro lado, existen los fármacos denominados de acción sintom�tica lenta, habitualmente conocidos como SYSADOA (de las siglas en inglés, Symtomatic Slow Acting Drugs for Osteoarlhritis) que se caracterizan por presentar un inicio de acción lento, pero con un efecto que se prolonga durante más tiempo, y que, adicionalmente, se ha constatado que pueden actuar como modificadores de la enfermedad artr�sica debido a su efecto condroprotector, es decir, su capacidad de prevenir, retrasar, estabilizar, reparar y/o revertir las lesiones del hueso y cartílago, tal como se describe en el artículo S. Gim�nez Basallote, "Tratamiento de la artrosis en Atención Primaria: revisión de los fármacos de acción sintom�tica lenta (SYSADOA)", Semergen, 2008, 34 (8), 400-6. Entre los fármacos de este grupo se encuentran, por ejemplo, el sulfato de condroitina, el ácido hialur�nico y el sulfato de glucosamina. On the other hand, there are drugs called slow symptomatic action, usually known as SYSADOA (Symtomatic Slow Acting Drugs for Osteoarlhritis) that are characterized by presenting a slow onset of action, but with an effect that prolongs for a longer time, and that, additionally, it has been found that they can act as modifiers of arthritis due to their chondroprotective effect, that is, their ability to prevent, delay, stabilize, repair and / or reverse the lesions of the bone and cartilage, as described in article S. Gimnez Basallote, "Treatment of osteoarthritis in Primary Care: review of slow-acting symptomatic drugs (SYSADOA)", Semergen, 2008, 34 (8) , 400-6. Among the drugs in this group are, for example, chondroitin sulfate, hyaluronic acid and glucosamine sulfate.
En particular, el sulfato de condroitina est� aprobado en España para el tratamiento sintomático de la artrosis. In particular, chondroitin sulfate is approved in Spain for the symptomatic treatment of osteoarthritis.
En el estado de la técnica se han publicado algunos estudios acerca del efecto reparador del cartílago del sulfato de condroitina. As�, por ejemplo, en el artículo Wildi y col., "Chondraitin su/phate reduces both cartilage vo/ume /oss and bone marraw /esions in knee osteoarthritis patients starting as ear/y as 6 months after initiation of therapy: a randomised, doub/e-blind, p/acebo-contralled pi/ot study using MRI", Ann. Rheum. Dis., 2011, 70, 982-989, se describen los resultados de un estudio cl�nico realizado con pacientes afectados de artrosis de rodilla, a los que se les administr� 800 mg diarios de sulfato de condroitina, observándose que dicho tratamiento redujo de forma significativa la pérdida de volumen de cartílago, en comparación al tratamiento con placebo. Some studies have been published in the state of the art about the reparative effect of chondroitin sulfate cartilage. Thus, for example, in the article Wildi et al., "Chondraitin su / phate reduces both cartilage vo / ume / oss and bone marraw / esions in knee osteoarthritis patients starting as ear / and as 6 months after initiation of therapy: a randomized, doub / e-blind, for holly-contracted pi / ot study using MRI ", Ann. Rheum Dis., 2011, 70, 982-989, describe the results of a clinical study conducted with patients suffering from knee osteoarthritis, who were administered 800 mg daily of chondroitin sulfate, observing that such treatment reduced significantly the loss of cartilage volume, compared to placebo treatment.
As� mismo, recientemente algunos estudios realizados, tanto in vitra, como a nivel cl�nico, sugieren que el celecoxib, que se ha venido utilizando para el alivio del dolor e inflamación asociados a la osteoartritis, podría tener también algún efecto regenerador del cartílago, tal como se apunta en el artículo de Zweers y col., "Ce/ecoxib: considerations regarding its potentia/ disease-modifying praperties in osteoarthritis", Arthritis Res. Ther. 2011; 13 (5): 239. Likewise, recently some studies, both in vitro and clinically, suggest that celecoxib, which has been used for the relief of pain and inflammation associated with osteoarthritis, could also have some regenerating effect on cartilage. , as noted in the article by Zweers et al., "Ce / ecoxib: considerations regarding its potentia / disease-modifying praperties in osteoarthritis", Arthritis Res. Ther. 2011; 13 (5): 239.
Adicionalmente, la solicitud de patente internacional WO-A-03/015799 se refiere a composiciones basadas en la combinación de un inhibidor de la ciclooxigenasa 2 y sulfato de condroitina para el tratamiento del dolor, la inflamación o dolencias relacionadas con la inflamación, si bien no se refiere en particular al tratamiento de la artrosis, ni a la regeneración del cartílago articular. En concreto, en dicha patente se describe la preparación de cápsulas que contienen 1.200 mg de sulfato de condroitina y 200 mg de celecoxib. Additionally, international patent application WO-A-03/015799 refers to compositions based on the combination of a cyclooxygenase 2 inhibitor and chondroitin sulfate for the treatment of pain, inflammation or inflammation-related ailments, although It does not refer in particular to the treatment of osteoarthritis, nor to the regeneration of articular cartilage. Specifically, said patent describes the preparation of capsules containing 1,200 mg of chondroitin sulfate and 200 mg of celecoxib.
En general, es un hecho reconocido que la combinación de principios activos con distintos mecanismos de acción puede resultar favorable para el abordaje terapéutico de una determinada patología, de modo que dicha combinación puede producir un efecto terapéutico superior, a menudo con una menor cantidad de los principios activos, con la consiguiente reducción de los efectos adversos. Asimismo, la disponibilidad de dicha combinación de principios activos en una única forma farmacéutica resulta adicionalmente ventajosa de cara a conseguir un mejor cumplimiento terapéutico. In general, it is a recognized fact that the combination of active ingredients with different mechanisms of action may be favorable for the therapeutic approach of a certain pathology, so that such combination can produce a superior therapeutic effect, often with a smaller amount of active ingredients, with the consequent reduction of adverse effects. Likewise, the availability of said combination of active ingredients in a single pharmaceutical form is additionally advantageous in order to achieve a better therapeutic compliance.
Sin embargo, no resulta sencillo desarrollar una combinación que resulte efectiva y segura, puesto que existen múltiples factores impredecibles implicados en la combinación de fármacos, derivados de sus posibles interacciones. However, it is not easy to develop a combination that is effective and safe, since there are multiple unpredictable factors involved in the combination of drugs, derived from their possible interactions.
Pese a las diversas soluciones propuestas hasta la fecha en el estado de la técnica para el tratamiento de la artrosis, subsiste la necesidad de disponer de un tratamiento eficaz para aliviar los síntomas de dicha enfermedad y que a la vez que sea eficaz para el tratamiento de cartílagos dañados, para as� contribuir a disminuir la progresión de dicha patología. Despite the various solutions proposed to date in the state of the art for the treatment of osteoarthritis, there remains a need for effective treatment to alleviate the symptoms of said disease and that at the same time is effective for the treatment of Damaged cartilage, to help reduce the progression of this pathology.
El objeto de la presente invención es una composición farmacéutica para la administración oral que comprende sulfato de condroitina y celecoxib. The object of the present invention is a pharmaceutical composition for oral administration comprising chondroitin sulfate and celecoxib.
Tambi�n forma parte del objeto de la invención una forma farmacéutica de dosificación unitaria que comprende una cantidad terapéuticamente efectiva de dicha composición. A unit dosage pharmaceutical form comprising a therapeutically effective amount of said composition is also part of the object of the invention.
Forma parte también del objeto de la invención un comprimido que comprende una cantidad terapéuticamente efectiva de dicha composición. A tablet comprising a therapeutically effective amount of said composition is also part of the object of the invention.
Tambi�n forma parte del objeto de la invención una cápsula que comprende una cantidad terapéuticamente efectiva de dicha composición. A capsule comprising a therapeutically effective amount of said composition is also part of the object of the invention.
Forma parte también del objeto de la invención el uso de dicha composición para la preparación de un medicamento para el tratamiento de la artrosis. The use of said composition for the preparation of a medicament for the treatment of osteoarthritis is also part of the object of the invention.
El objeto de la presente invención es una composición farmacéutica para la administración oral que comprende sulfato de condroitina y celecoxib, donde la relación entre sulfato de condroitina y celecoxib est� comprendida entre 1,5:1 y 2,5:1, expresada en peso. The object of the present invention is a pharmaceutical composition for oral administration comprising chondroitin sulfate and celecoxib, where the ratio between chondroitin sulfate and celecoxib is comprised between 1.5: 1 and 2.5: 1, expressed by weight .
Los autores de la presente invención han desarrollado una composición farmacéutica para la administración oral que comprende la combinación de sulfato de condroitina y celecoxib en una proporción ponderal tal que, sorprendentemente, presenta una buena eficacia en el tratamiento sintomático y en la regeneración del cartílago dañado en pacientes con artrosis. The authors of the present invention have developed a pharmaceutical composition for oral administration comprising the combination of chondroitin sulfate and celecoxib in a weight ratio such that, surprisingly, it has a good efficacy in symptomatic treatment and in the regeneration of damaged cartilage in osteoarthritis patients
Sulfato de condroitina Chondroitin Sulfate
El sulfato de condroitina pertenece al grupo de los glicosaminoglicanos y constituye uno de los principales componentes estructurales del cartílago. Los glicosaminoglicanos son polisac�ridos constituidos por unidades repetitivas de disac�ridos formados por un amino azúcar (N-acetil galactosamina o N-acetil glucosamina) y un ácido ur�nico (glucur�nico o idur�nico). Chondroitin sulfate belongs to the group of glycosaminoglycans and is one of the main structural components of cartilage. Glycosaminoglycans are polysaccharides consisting of repetitive units of disaccharides formed by an amino sugar (N-acetyl galactosamine or N-acetyl glucosamine) and a uronic acid (glucuronic or iduronic).
El sulfato de condroitina es un glicosaminoglicano sulfatado, de peso molecular habitualmente comprendido entre 10.000 y 60.000 daltons, en función de la procedencia y el procedimiento de obtención. Chondroitin sulfate is a sulfated glycosaminoglycan, of molecular weight usually between 10,000 and 60,000 daltons, depending on the origin and the procedure for obtaining it.
El sulfato de condroitina est� constituido por unidades de disac�rido formadas por ácido D-glucur�nico y N-acetil-D-galactosamina, donde el residuo de Nacetil-D-galactosamina est� sulfatado, existiendo principalmente dos formas isom�ricas dependiendo de la posición del grupo sulfato: en la posición 4 (sulfato de condroitina A o 4-sulfato de condroitina) o en la posición 6 (sulfato de condroitina e o 6-sulfato de condroitina), según se muestra en la siguiente fórmula: Chondroitin sulfate is made up of disaccharide units formed by D-glucuric acid and N-acetyl-D-galactosamine, where the Nacethyl-D-galactosamine residue is sulfated, there are mainly two isomeric forms depending on the position of the sulfate group: in position 4 (chondroitin A sulfate or 4-chondroitin sulfate) or in position 6 (chondroitin sulfate eo 6-chondroitin sulfate), as shown in the following formula:
R =S03H R' =H R = S03H R '= H
R =H R' =S03H R = H R '= S03H
Adem�s de estas dos formas isom�ricas mayoritarias, el término "sulfato de condroitina" también incluye otras formas, como el "sulfato de condroitina B" (o In addition to these two major isomeric forms, the term "chondroitin sulfate" also includes other forms, such as "chondroitin B sulfate" (or
5 sulfato de dermatano, que est� sulfatado en la posición 4 del residuo de Nacetil-O-galactosamina, pero cuya unidad de disac�rido contiene un residuo de ácido L-idur�nico, en lugar de glucur�nico), o las formas disulfatadas "sulfato de condroitina O" (2,6-disulfato de condroitina), y "sulfato de condroitina E" (4,6disulfato de condroitina). 5 dermatan sulfate, which is sulfated at position 4 of the Nacethyl-O-galactosamine residue, but whose disaccharide unit contains a residue of L-iduronic acid, instead of glucuronic acid), or disulfated forms "chondroitin sulfate O" (2,6-chondroitin disulfate), and "chondroitin sulfate E" (4,6 chondroitin disulfate).
10 El sulfato de condroitina presenta grupos ácido en su estructura, tanto el grupo carbox�lico del ácido glucur�nico, como el grupo sulfato de la N-acetilgalactosamina, de manera que el sulfato de condroitina puede estar en forma de sal, con contraiones cati�nicos que pueden ser orgánicos o inorgánicos. Algunas sustancias orgánicas adecuadas que pueden formar sales con el sulfato de 10 Chondroitin sulfate has acidic groups in its structure, both the carboxylic group of glucuric acid, and the N-acetylgalactosamine sulfate group, so that chondroitin sulfate can be in salt form, with counterions cationics that can be organic or inorganic. Some suitable organic substances that can form salts with the sulfate of
15 condroitina son, por ejemplo, aminoaz�cares como O-glucosamina o 0galactosamina, as� como otras aminas como etanolamina o trietanolamina, entre otras. También pueden formarse sales con cationes inorgánicos, por ejemplo, con iones alcalinos o alcalinot�rreos, tales como sodio, potasio, magnesio o calcio, entre otros. Particularmente preferida es la sal sádica, que es la más Chondroitin are, for example, amino acids such as O-glucosamine or 0galactosamine, as well as other amines such as ethanolamine or triethanolamine, among others. Salts may also be formed with inorganic cations, for example, with alkali or alkaline earth ions, such as sodium, potassium, magnesium or calcium, among others. Particularly preferred is the sadistic salt, which is the most
20 frecuentemente disponible de forma comercial. 20 frequently available commercially.
En el marco de la presente invención, el término "sulfato de condroitina" se refiere indistintamente al sulfato de condroitina A, sulfato de condroitina B, sulfato de condroitina e, sulfato de condroitina O, sulfato de condroitina E, o sus sales farmac�uticamente aceptables, y sus mezclas. Within the framework of the present invention, the term "chondroitin sulfate" refers interchangeably to chondroitin A sulfate, chondroitin sulfate B, chondroitin sulfate e, chondroitin sulfate O, chondroitin sulfate E, or its pharmaceutically salts. acceptable, and mixtures thereof.
25 El sulfato de condroitina se puede obtener a partir de tejidos animales, por ejemplo a partir de tráqueas porcinas y bovinas, as� como del esqueleto cartilaginoso de tiburón, a través de procedimientos de extracción y purificación que son conocidos en el estado de la técnica, por ejemplo, según se describe en el artículo de Patat y col., "On fhe iso/afion and characferizafion of chondroifin sulfuric acid", Hoppe Seylers Z. Physiol. Chem., 1959,316, 1-6. Chondroitin sulfate can be obtained from animal tissues, for example from pig and bovine tracheas, as well as from the shark cartilaginous skeleton, through extraction and purification procedures that are known in the state of the art. , for example, as described in the article by Patat et al., "On fhe iso / afion and characferizafion of chondroifin sulfuric acid", Hoppe Seylers Z. Physiol. Chem., 1959,316, 1-6.
El sulfato de condroitina est� disponible de forma comercial a partir de diferentes suministradores, por ejemplo de la compa��a Sigma Chemical. Chondroitin sulfate is commercially available from different suppliers, for example from the company Sigma Chemical.
El sulfato de condroitina se obtiene habitualmente a partir de fuentes naturales, de manera que puede estar acompañado de impurezas constituidas por otras sustancias de origen natural presentes en los mismos tejidos, siendo adecuado Chondroitin sulfate is usually obtained from natural sources, so that it can be accompanied by impurities constituted by other naturally occurring substances present in the same tissues, being suitable
- para for
- su uso en las composiciones de la presente invención un sulfato de its use in the compositions from the Present invention a sulfate
- condroitina chondroitin
- de cualquier pureza y calidad, que sea farmac� uticamente from any purity Y quality, that be drug store only
- aceptable. acceptable.
Celecoxib Celecoxib
El término celecoxib corresponde a la Denominación Común Internacional (DCI) por la que se conoce habitualmente el producto 4-[5-(4-metilfenil)-3(trifluorometil)pirazol-1-il]bencenosulfonamida. The term celecoxib corresponds to the International Common Denomination (INN) by which the product 4- [5- (4-methylphenyl) -3 (trifluoromethyl) pyrazol-1-yl] benzenesulfonamide is commonly known.
El celecoxib es un antiinflamatorio no esteroideo (AINE), inhibidor selectivo de la ciclooxigenasa 2 (COX-2). Celecoxib is a non-steroidal anti-inflammatory drug (NSAID), a selective inhibitor of cyclooxygenase 2 (COX-2).
El celecoxib puede prepararse, por ejemplo, según el procedimiento descrito en la solicitud de patente internacional WO-A-95/15316. Celecoxib can be prepared, for example, according to the procedure described in international patent application WO-A-95/15316.
En el marco de la presente invención, el término celecoxib incluye también sus formas hidratadas, solvatos y formas polim�rficas. En el caso de utilizarse una forma hidratada o solvatada, el peso especificado a lo largo de la presente descripción se refiere siempre al peso equivalente de celecoxib. Within the framework of the present invention, the term celecoxib also includes its hydrated forms, solvates and polymorphic forms. In the case of using a hydrated or solvated form, the weight specified throughout the present description always refers to the equivalent weight of celecoxib.
La composición farmacéutica de la invención se caracteriza porque el sulfato de condroitina y el celecoxib est�n en una relación ponderal comprendida entre 1,5:1 y 2,5:1, es decir, que por cada unidad de peso de celecoxib, hay entre 1,5 Y 2,5 unidades de peso de sulfato de condroitina. The pharmaceutical composition of the invention is characterized in that chondroitin sulfate and celecoxib are in a weight ratio between 1.5: 1 and 2.5: 1, that is, for every unit of weight of celecoxib, there is between 1.5 and 2.5 weight units of chondroitin sulfate.
M�s preferiblemente, la relación entre sulfato de condroitina y celecoxib est� comprendida entre 1,8:1 y 2,2:1, expresada en peso. More preferably, the ratio between chondroitin sulfate and celecoxib is between 1.8: 1 and 2.2: 1, expressed by weight.
En una realización particularmente preferente, la relación entre sulfato de condroitina y celecoxib es 2:1, expresada en peso. In a particularly preferred embodiment, the ratio between chondroitin sulfate and celecoxib is 2: 1, expressed by weight.
La composición de la invención est� destinada a ser administrada por vía oral. Puede formularse tanto como una forma farmacéutica sólida (incluyendo comprimidos, cápsulas, granulados, polvos, grageas, etc.) o líquida (incluyendo soluciones, jarabes, suspensiones, etc.). The composition of the invention is intended to be administered orally. It can be formulated either as a solid pharmaceutical form (including tablets, capsules, granules, powders, dragees, etc.) or liquid (including solutions, syrups, suspensions, etc.).
La composición de la invención comprende habitualmente al menos un excipiente farmac�uticamente aceptable. Los excipientes que se emplean se seleccionan en función de la forma farmacéutica, y la misma se prepara de acuerdo con métodos bien conocidos, por ejemplo, como los que figuran en manuales de tecnología farmacéutica, por ejemplo el libro "Remington: The Science and Practice of Pharmacy", 20a edición, Lippincott, Williams & Wilkins, Filadelfia, 2000 [ISBN: 0-683-306472]. The composition of the invention usually comprises at least one pharmaceutically acceptable excipient. The excipients used are selected according to the pharmaceutical form, and it is prepared according to well known methods, for example, such as those contained in manuals of pharmaceutical technology, for example the book "Remington: The Science and Practice of Pharmacy ", 20th edition, Lippincott, Williams & Wilkins, Philadelphia, 2000 [ISBN: 0-683-306472].
Entre los excipientes farmac�uticamente aceptables que se pueden incluir en la composición farmacéutica de la invención se encuentran, por ejemplo, los siguientes: -agentes diluyentes como lactosa anhidra, latosa monohidrato, fosfato cálcico, Among the pharmaceutically acceptable excipients that may be included in the pharmaceutical composition of the invention are found, for example, the following: -Diluent agents such as anhydrous lactose, lactose monohydrate, calcium phosphate,
hidrogenofosfato de calcio anhidro, hidrogenofosfato de calcio dihidrato, sulfato cálcico, carbonato cálcico, carboximetilcelulosa cálcica, celulosa microcristalina o en polvo, acetato de celulosa, dextratos, dextrinas, dextrosa, fructosa, gliceril palmitoestearato, caolín, lactitol, carbonato magn�sico, óxido de magnesio, maltitol, maltodextrinas, maltosa, polimetacrilatos, almidón pregelatinizado, cloruro de sodio, almidón o sacarosa, entre otros, y sus mezclas; anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium sulfate, calcium carbonate, calcium carboxymethyl cellulose, microcrystalline or powdered cellulose, cellulose acetate, dextrates, dextrins, dextrose, fructose, glyceryl palmitostetate, kaolin, lactitol, lactitol, lactitol magnesium, maltitol, maltodextrins, maltose, polymethacrylates, pregelatinized starch, sodium chloride, starch or sucrose, among others, and mixtures thereof;
- --
- agentes tensioactivos como docusato de sodio, lauril sulfato de sodio, �teres alqu�licos etoxilados, aceite de ricino etoxilado, ácidos grasos etoxilados, esteres de sorbit�n etoxilados, entre otros, y sus mezclas; surfactants such as sodium docusate, sodium lauryl sulfate, ethoxylated alkyl ethers, ethoxylated castor oil, ethoxylated fatty acids, ethoxylated sorbitan esters, among others, and mixtures thereof;
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- agentes antiapelmazantes como sílice coloidal, fosfato cálcico trib�sico, silicato cálcico, silicato de magnesio, trisilicato de magnesio o talco, entre otros, y sus mezclas; agentes lubricantes como estearato de magnesio, estearato de calcio, palmitoestearato de glicerina, polox�meros, óxido de magnesio, benzoato de sodio, sílice coloidal, lauril sulfato de sodio, estearil fumarato de sodio, ácido esteárico, talco o behenato de glicerina, entre otros, y sus mezclas; anti-caking agents such as colloidal silica, calcium calcium phosphate, calcium silicate, magnesium silicate, magnesium trisilicate or talc, among others, and mixtures thereof; lubricating agents such as magnesium stearate, calcium stearate, glycerin palmostearate, poloxamers, magnesium oxide, sodium benzoate, colloidal silica, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc or glycerin behenate, among others, and their mixtures;
- --
- agentes suspensores como goma xantana, goma guar, ácido alg�nico, bentonita, carb�meros, carboximetilcelulosa sádica o cálcica, hidroxietilcelulosa, hidroxipropilcelulosa, hidroxipropilmetilcelulosa, hidroxipropilalginato, celulosa microcristalina o en polvo, sílice coloidal anhidra, dextrinas, gelatinas, caolín, silicato alum�nico-magn�sico, maltitol, povidona, ésteres de sorbit�n o tragacanto, entre otros, y sus mezclas; suspending agents such as xanthan gum, guar gum, alginic acid, bentonite, carbons, sadistic or calcium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropyl alginate, microcrystalline or powdered cellulose, colloidal anhydrous silica, dextrin, silica aluminum-magnesium, maltitol, povidone, sorbitan esters or tragacanth, among others, and mixtures thereof;
- --
- agentes aglutinantes como trisilicato de magnesio, celulosa, almidón, dextrina, dextrosa, polidextrosa, maltosa, matodextrina, etilcelulosa, metilcelulosa, polimetacrilatos, talco, povidona, ácido esteárico o sacarosa, entre otros, y sus mezclas; binding agents such as magnesium trisilicate, cellulose, starch, dextrin, dextrose, polydextrose, maltose, matodextrin, ethyl cellulose, methylcellulose, polymethacrylates, talc, povidone, stearic acid or sucrose, among others, and mixtures thereof;
- --
- agentes disgregantes como hidroxipropilcelulosa de bajo grado de sustitución, fosfato de calcio trib�sico, carboximetilcelulosa sádica o cálcica, croscarmelosa sádica, crospovidona o metilcelulosa, entre otros, y sus mezclas; disintegrating agents such as low-grade hydroxypropylcellulose, tribesic calcium phosphate, sadistic or calcium carboxymethylcellulose, sadic croscarmellose, crospovidone or methylcellulose, among others, and mixtures thereof;
- --
- agentes dispersantes como polox�meros o ésteres de sorbit�n, entre otros, y sus mezclas; dispersing agents such as poloxamers or sorbitan esters, among others, and mixtures thereof;
- --
- agentes edulcorantes como aspartamo, manitol, sorbitol, sacarina de sodio, ciclamato de sodio, sacarosa, dextrosa, fructosa, glucosa, inulina, isomaltosa, lactitol, maltosa, maltol, manitol, sucralosa, trehalosa, xilitol o taumatina, entre otros, y sus mezclas; sweetening agents such as aspartame, mannitol, sorbitol, sodium saccharin, sodium cyclamate, sucrose, dextrose, fructose, glucose, inulin, isomalt, lactitol, maltose, maltol, mannitol, sucralose, trehalose, xylitol or thaumatine, among others, and their mixtures;
- --
- agentes aromatizantes y saborizantes, y/o mezclas de los mismos. flavoring and flavoring agents, and / or mixtures thereof.
Las características físico-químicas de los excipientes, as� como el nombre de los productos comerciales bajo los que se comercializan se pueden encontrar en el libro de R.e. Rowe y col., "Handbook of Pharmaceutical Excipients", 4a edición, Pharmaceutical Press, Londres, 2003 [ISBN: 0-85369-472-9]. The physical-chemical characteristics of the excipients, as well as the name of the commercial products under which they are marketed, can be found in the book of R.e. Rowe et al., "Handbook of Pharmaceutical Excipients", 4th edition, Pharmaceutical Press, London, 2003 [ISBN: 0-85369-472-9].
La composición de la invención est� destinada a ser administrada por vía oral. Puede formularse tanto como una forma farmacéutica sólida (incluyendo comprimidos, cápsulas, granulados, polvos, grageas, etc.) o líquida (incluyendo soluciones, jarabes, suspensiones, etc.). The composition of the invention is intended to be administered orally. It can be formulated either as a solid pharmaceutical form (including tablets, capsules, granules, powders, dragees, etc.) or liquid (including solutions, syrups, suspensions, etc.).
En una realización preferente de la invención, la composición est� en forma sólida. In a preferred embodiment of the invention, the composition is in solid form.
En una realización especialmente preferente, la composición en forma sólida comprende los siguientes excipientes farmac�uticamente aceptables: In a particularly preferred embodiment, the solid form composition comprises the following pharmaceutically acceptable excipients:
- --
- entre el 1 % Y el 2,5% en peso de tensioactivo, y between 1% and 2.5% by weight of surfactant, and
- --
- entre el 5% yel 10% en peso de diluyente con respecto al peso total de la composición. between 5% and 10% by weight of diluent with respect to the total weight of the composition.
En una realización aún más preferente, la composición comprende adicionalmente los siguientes excipientes: In an even more preferred embodiment, the composition further comprises the following excipients:
- --
- entre el 0,1 % yel 1,5% en peso de lubricante; between 0.1% and 1.5% by weight of lubricant;
- --
- entre el 0,1% Y el 2% en peso de aglutinante; y between 0.1% and 2% by weight of binder; Y
- --
- entre el 0,1 % Y el 1,5% en peso de disgregante con respecto al peso total de la composición. between 0.1% and 1.5% by weight of disintegrant with respect to the total weight of the composition.
En una realización particularmente preferente de la invención, la composición comprende lauril sulfato sádico como tensioactivo; lactosa anhidra como diluyente; estearato magn�sico como lubricante, povidona como aglutinante y croscarmelosa sádica como disgregante. In a particularly preferred embodiment of the invention, the composition comprises sodium lauryl sulfate as a surfactant; anhydrous lactose as diluent; magnesium stearate as a lubricant, povidone as a binder and sadistic croscarmellose as a disintegrant.
Forma farmacéutica de dosificación unitaria Forma parte del objeto de la invención una forma farmacéutica de dosificación unitaria que comprende una dosis terapéuticamente efectiva de la composición farmacéutica de la invención. Pharmaceutical unit dosage form A pharmaceutical unit dosage form comprising a therapeutically effective dose of the pharmaceutical composition of the invention forms part of the object of the invention.
Cada forma de dosificación unitaria corresponde, por ejemplo, a un comprimido, una cápsula o un sobre monodosis de polvo o granulado para suspensión. Each unit dosage form corresponds, for example, to a tablet, a capsule or a single-dose powder or granules for suspension.
En una realización de la invención, forma farmacéutica de dosificación unitaria comprende entre 150 mg y 800 mg de sulfato de condroitina, más preferiblemente entre 300 mg y 500 mg de sulfato de condroitina y aún más preferiblemente comprende 400 mg de sulfato de condroitina, de manera que el celecoxib se incorpora a la misma en una cantidad de acuerdo con la relación ponderal sulfato de condroitina:celecoxib de la invención. In one embodiment of the invention, unit dosage pharmaceutical form comprises between 150 mg and 800 mg of chondroitin sulfate, more preferably between 300 mg and 500 mg of chondroitin sulfate and even more preferably comprises 400 mg of chondroitin sulfate, so that celecoxib is incorporated therein in an amount according to the weight ratio of chondroitin sulfate: celecoxib of the invention.
En otra realización de la invención, la forma farmacéutica de dosificación unitaria comprende entre 75 mg y 400 mg de celecoxib, más preferiblemente entre 150 mg y 250 mg de celecoxib y aún más preferiblemente comprende 200 mg de celecoxib, de manera el sulfato de condroitina se incorpora a la misma en una cantidad de acuerdo con la relación ponderal sulfato de condroitina:celecoxib de la invención. In another embodiment of the invention, the unit dosage pharmaceutical form comprises between 75 mg and 400 mg of celecoxib, more preferably between 150 mg and 250 mg of celecoxib and even more preferably comprises 200 mg of celecoxib, so that chondroitin sulfate is incorporates it in an amount according to the weight ratio of chondroitin sulfate: celecoxib of the invention.
En una realización particularmente preferente, la forma farmacéutica de dosificación unitaria comprende 400 mg de sulfato de condroitina y 200 mg de celecoxib. In a particularly preferred embodiment, the unit dosage pharmaceutical form comprises 400 mg of chondroitin sulfate and 200 mg of celecoxib.
En una realización preferente dicha forma de dosificación unitaria est� en forma de cápsula o comprimido. In a preferred embodiment said unit dosage form is in capsule or tablet form.
Forma parte del objeto de la invención un comprimido que comprende una cantidad terapéuticamente efectiva de la composición de la invención y al menos un agente auxiliar. A tablet comprising a therapeutically effective amount of the composition of the invention and at least one auxiliary agent forms part of the object of the invention.
Los comprimidos pueden ser comprimidos, opcionalmente recubiertos con película, grageas, comprimidos efervescentes y comprimidos dispersables, opcionalmente recubiertos. The tablets may be tablets, optionally coated with film, dragees, effervescent tablets and dispersible tablets, optionally coated.
Tambi�n forma parte del objeto de la invención una cápsula que comprende una cantidad terapéuticamente efectiva de la composición de la invención y al menos un agente auxiliar. Also part of the object of the invention is a capsule comprising a therapeutically effective amount of the composition of the invention and at least one auxiliary agent.
Las cápsulas incluyen cápsulas de gelatina dura y cápsulas de gelatina blanda. The capsules include hard gelatin capsules and soft gelatin capsules.
Se entiende por agente auxiliar un excipiente farmac�uticamente aceptable, tal como los descritos anteriormente. Auxiliary agent is understood as a pharmaceutically acceptable excipient, such as those described above.
En el contexto de la invención se entiende por "cantidad terapéuticamente efectiva" una cantidad de sulfato de condroitina comprendida entre 150 mg y 800 mg, o alternativamente una cantidad de celecoxib comprendida entre 75 mg y 400 mg de celecoxib. In the context of the invention, "therapeutically effective amount" means an amount of chondroitin sulfate between 150 mg and 800 mg, or alternatively an amount of celecoxib between 75 mg and 400 mg of celecoxib.
Los autores de la presente invención han desarrollado una composición que comprende sulfato de condroitina y celecoxib en una proporción tal que resulta muy eficaz para el tratamiento de la artrosis, en particular para el tratamiento de cartílagos articulares dañados. Por ello, también forma parte de la presente invención el uso de dicha composición para la preparación de un medicamento para el tratamiento de la artrosis, en particular para el tratamiento de cartílagos articulares dañados. The authors of the present invention have developed a composition comprising chondroitin sulfate and celecoxib in such a proportion that it is very effective for the treatment of osteoarthritis, in particular for the treatment of damaged articular cartilage. Therefore, the use of said composition for the preparation of a medicament for the treatment of osteoarthritis, in particular for the treatment of damaged articular cartilage, is also part of the present invention.
0, formulado de forma alternativa, forma también parte del objeto de la presente invención la composición de la invención para su uso en el tratamiento de la artrosis y en particular para el tratamiento de cartílagos articulares dañados. 0, alternatively formulated, the composition of the invention is also part of the object of the present invention for use in the treatment of osteoarthritis and in particular for the treatment of damaged articular cartilage.
Ejemplos Ejemplo 1: Cápsulas de sulfato de condroitina y celecoxib Examples Example 1: Chondroitin Sulfate Capsules and Celecoxib
Se prepararon cápsulas que comprendían la composición de la invención utilizando los componentes que se detallan en la siguiente tabla: Capsules comprising the composition of the invention were prepared using the components detailed in the following table:
- Componente Component
- Función Cantidad (mg) Porcentaje en peso (%) Function Amount (mg) Weight percentage (%)
- Celecoxib Celecoxib
- principio activo 200,0 29,75 active principle 200.0 29.75
- Sulfato de condroitina Chondroitin Sulfate
- principio activo 400,0 59,50 active principle 400.0 59.50
- Estearato magn�sico Magnesium stearate
- lubricante 5,0 0,74 lubricant 5.0 0.74
- Lauril sulfato sádico Sadistic Lauryl Sulfate
- tensioactivo 8,1 1,20 surfactant 8.1 1.20
- Povidona K30 Povidone K30
- aglutinante 6,7 1,00 binder 6.7 1.00
- Croscarmelosa sádica Sadistic Croscarmellose
- disgregante 2,7 0,40 disintegrating 2.7 0.40
- Lactosa anhidra Anhydrous lactose
- diluyente 49,8 7,41 thinner 49.8 7.41
- Total Total
- 672,3 100,0 672.3 100.0
En una granuladora se incorporaron el celecoxib, la lactosa anhidra y el lauril sulfato sádico, y se mezclaron estos tres ingredientes. Se disolvió la povidona en agua y con dicha solución se procedió a la granulación de la mezcla Celecoxib, anhydrous lactose and sadistic lauryl sulfate were incorporated into a granulator, and these three ingredients were mixed. The povidone was dissolved in water and with this solution the mixture was granulated
5 preparada anteriormente. 5 prepared above.
El granulado obtenido se secó en lecho fluido, se tamizó y se incorpor� al mezclador. Se a�adi� la croscarmelosa sádica, el sulfato de condroitina y el estearato magn�sico, y se mezcl� el conjunto hasta obtener una mezcla homogénea. The granulate obtained was dried in a fluid bed, screened and incorporated into the mixer. Sadistic croscarmellose, chondroitin sulfate and magnesium stearate were added, and the whole was mixed until a homogeneous mixture was obtained.
10 Se rellenaron las cápsulas de gelatina dura con la composición obtenida. Cada cápsula contenía 400 mg de sulfato de condroitina y 200 mg de celecoxib, de manera que la relación ponderal entre ambos era de 2: 1. 10 The hard gelatin capsules were filled with the composition obtained. Each capsule contained 400 mg of chondroitin sulfate and 200 mg of celecoxib, so that the weight ratio between the two was 2: 1.
15 Siguiendo sustancialmente el procedimiento del Ejemplo 1, se procedió a comprimir la mezcla final para obtener comprimidos. Following substantially the procedure of Example 1, the final mixture was compressed to obtain tablets.
Cada comprimido contenía 400 mg de sulfato de condroitina y 200 mg de celecoxib, de manera que la relación ponderal entre ambos era 2: 1. Each tablet contained 400 mg of chondroitin sulfate and 200 mg of celecoxib, so that the weight ratio between the two was 2: 1.
Claims (21)
- 1. one.
- Composici�n farmacéutica para administración oral que comprende sulfato de condroitina y celecoxib caracterizada porque la relación entre el sulfato de condroitina y el celecoxib est� comprendida entre 1,5: 1 y 2,5: 1, expresada en peso. Pharmaceutical composition for oral administration comprising chondroitin sulfate and celecoxib characterized in that the ratio between chondroitin sulfate and celecoxib is between 1.5: 1 and 2.5: 1, expressed by weight.
- 2. 2.
- Composici�n según la reivindicación 1, caracterizada porque la relación entre el sulfato de condroitina y el celecoxib est� comprendida entre 1,8:1 y 2,2:1, expresada en peso. Composition according to claim 1, characterized in that the ratio between chondroitin sulfate and celecoxib is between 1.8: 1 and 2.2: 1, expressed by weight.
- 3. 3.
- Composici�n según la reivindicación 2, caracterizada porque la relación entre el sulfato de condroitina y el celecoxib es de 2: 1, expresada en peso. Composition according to claim 2, characterized in that the ratio between chondroitin sulfate and celecoxib is 2: 1, expressed by weight.
- 4. Four.
- Composici�n según cualquiera de las reivindicaciones 1 a 3, caracterizada porque comprende al menos un excipiente farmac�uticamente aceptable. Composition according to any one of claims 1 to 3, characterized in that it comprises at least one pharmaceutically acceptable excipient.
- 5. 5.
- Composici�n según cualquiera de las reivindicaciones 1 a 4, caracterizada porque est� en forma sólida. Composition according to any one of claims 1 to 4, characterized in that it is in solid form.
- 6. 6.
- Composici�n según la reivindicación 5, caracterizada porque como excipientes farmac�uticamente aceptables comprende entre el 1 % Y el 2,5% en peso de tensioactivo y entre el 5% y el 10% en peso de diluyente, con respecto al peso total de la composición. Composition according to claim 5, characterized in that as pharmaceutically acceptable excipients it comprises between 1% and 2.5% by weight of surfactant and between 5% and 10% by weight of diluent, with respect to the total weight of the composition.
- 7. 7.
- Composici�n según la reivindicación 6, caracterizada porque comprende adicionalmente entre el 0,1% Y el 1,5% en peso de lubricante; entre el 0,1% Y el 2% en peso de aglutinante; y entre el 0,1% Y el 1,5% en peso de disgregante, con respecto al peso total de la composición. Composition according to claim 6, characterized in that it additionally comprises between 0.1% and 1.5% by weight of lubricant; between 0.1% and 2% by weight of binder; and between 0.1% and 1.5% by weight of disintegrant, with respect to the total weight of the composition.
- 8. 8.
- Forma farmacéutica de dosificación unitaria caracterizada porque comprende la composición según cualquiera de las reivindicaciones 1 a 7. Unit dosage pharmaceutical form characterized in that it comprises the composition according to any one of claims 1 to 7.
- 9. 9.
- Forma según la reivindicación 8, caracterizada porque comprende entre 150 mg y 800 mg de sulfato de condroitina. Form according to claim 8, characterized in that it comprises between 150 mg and 800 mg of chondroitin sulfate.
- 10. 10.
- Forma según la reivindicación 9, caracterizada porque comprende entre 300 mg y 500 mg de sulfato de condroitina. Form according to claim 9, characterized in that it comprises between 300 mg and 500 mg of chondroitin sulfate.
- 11. eleven.
- Forma según la reivindicación 10, caracterizada porque comprende 400 mg de sulfato de condroitina. Form according to claim 10, characterized in that it comprises 400 mg of chondroitin sulfate.
- 12. 12.
- Forma según la reivindicación 8, caracterizada porque comprende entre 75 mg y 400 mg de celecoxib. Form according to claim 8, characterized in that it comprises between 75 mg and 400 mg of celecoxib.
- 13. 13.
- Forma según la reivindicación 12, caracterizada porque comprende entre 150 mg y 250 mg de celecoxib. Form according to claim 12, characterized in that it comprises between 150 mg and 250 mg of celecoxib.
- 14. 14.
- Forma según la reivindicación 13, caracterizada porque comprende 200 mg de celecoxib. Form according to claim 13, characterized in that it comprises 200 mg of celecoxib.
- 15. fifteen.
- Forma según la reivindicación 14, caracterizada porque comprende 400 mg de sulfato de condroitina y 200 de celecoxib. Form according to claim 14, characterized in that it comprises 400 mg of chondroitin sulfate and 200 of celecoxib.
- 16. 16.
- Comprimido caracterizado porque comprende una cantidad terapéuticamente efectiva de la composición de cualquiera de las reivindicaciones 1 a 7 y al menos un agente auxiliar. Tablet characterized in that it comprises a therapeutically effective amount of the composition of any one of claims 1 to 7 and at least one auxiliary agent.
- 17. 17.
- Comprimido según la reivindicación 16, caracterizado porque comprende 400 mg de sulfato de condroitina y 200 de celecoxib. Tablet according to claim 16, characterized in that it comprises 400 mg of chondroitin sulfate and 200 of celecoxib.
- 18. 18.
- C�psula caracterizada porque comprende una cantidad terapéuticamente efectiva de la composición de cualquiera de las reivindicaciones 1 a 7 y al menos un agente auxiliar. Capsule characterized in that it comprises a therapeutically effective amount of the composition of any one of claims 1 to 7 and at least one auxiliary agent.
- 19. 19.
- C�psula según la reivindicación 18, caracterizada porque comprende 400 mg de sulfato de condroitina y 200 de celecoxib. Capsule according to claim 18, characterized in that it comprises 400 mg of chondroitin sulfate and 200 of celecoxib.
- 20. twenty.
- Uso de la composición según cualquiera de las reivindicaciones 1 a 7 para la preparación de un medicamento para el tratamiento de la artrosis. Use of the composition according to any of claims 1 to 7 for the preparation of a medicament for the treatment of osteoarthritis.
- 21. twenty-one.
- Uso según la reivindicación 20, para la preparación de un medicamento para el tratamiento de cartílagos articulares dañados. Use according to claim 20, for the preparation of a medicament for the treatment of damaged articular cartilage.
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