MX2007003947A

MX2007003947A - Pharmaceutical composition comprising the combination of an anti-arthritic agent, a chondro-protecting agent and an anti-inflammatory agent.

Info

Publication number: MX2007003947A
Application number: MX2007003947A
Authority: MX
Inventors: Victor Guillermo Alvarez Ochoa; Ma Elena Garcia Armenta; Josefina Santos Murillo
Original assignee: World Trade Imp Export Wtie Ag
Priority date: 2007-04-02
Filing date: 2007-04-02
Publication date: 2009-02-25
Also published as: CL2008000963A1; AR065916A1; WO2008120965A1

Abstract

The present invention is related to a pharmaceutical composition that comprises the synergistic combination of an anti-arthritic agent, such as Chondroitin sulfate as active principle; a chondroprotecting agent, such as Glucosamine as active principle, and an anti-inflammatory agent such as Meloximam as active principle, which are formulated in the form of an orally administered single dosage unit in a powder solution, available in monodose sachets useful for treating diseases such as: Osteoarthritis, rheumatoid arthritis, arthrosis and any other related rheumatic disease.

Description

PHARMACEUTICAL COMPOSITION COMPRISING THE COMBINATION AN ANTI-TRACT AGENT, A CONDROPROTECTOR AGENT AND AN ANTI-INFLAMMATORY AGENT.

FIELD OF THE INVENTION The present invention is applied in the pharmaceutical industry and describes a pharmaceutical composition composed of the synergistic combination of an anti-arthritic agent, such as: Chondroitin; a chondroprotective agent, such as: Glucosamine and an anti-inflammatory agent, being this: Meloxicam, which are formulated in a single dosage unit, which is indicated for the prevention and / or treatment of osteoarthritis, rheumatoid arthritis, osteoarthritis and other related rheumatic diseases. The combination of the active principles mentioned above produces a greater synergistic effect when they are administered together in a single dose unit unlike when they are administered independently, generating benefits such as: lower dosages, faster action and lower side effects . BACKGROUND OF THE INVENTION Currently, osteoarthritis is a disease that too often suffers a large part of the population of the western world, however, its distribution is universal, there are differences that are based on various factors such as: the geographical area, genetic patterns, environmental development and lifestyle. The impact of the disease from the economic and social point of view is enormous since osteoarthritis is the most important cause of functional disability in terms of processes related to the locomotor system and the second cause of permanent disability after cardiovascular diseases . People suffering from osteoarthritis are affected in their economic situation and their lifestyle, since the expenses invested in the treatment are very high and most likely the consequence of this disease is the loss of employment and salary, due to the disability that causes this disease. Among the effects related to lifestyle in people suffering from osteoarthritis are included: limitation in work performance, depression, despair, anxiety and loss of interest and motivation to perform activities of daily living.

Osteoarthritis is the most common type of arthritis and affects men and women of adulthood, especially the elderly, being frequent in men before they reach 45 years of age, while after 45 years, the disease is more common in women. However, osteoarthritis is not typical of people with advanced age, since there are young people who come to suffer from this disease, which is caused by an injury or a blow given in some joint. There are other causes that cause the appearance of osteoarthritis, among these may be: excess weight, muscle weakness; damage to the nerves that supply the area of the joints; synovial disease and even hereditary factors. Osteoarthritis is a disease of the joints that mainly affects cartilage. In osteoarthritis, the joints are damaged due to the deterioration of the cartilage, which is a firm, elastic and slippery tissue that covers the extreme parts of the bones. Under normal conditions, the cartilage provides a smooth and slippery surface that facilitates the mobility of the joints and allows the bones to move by sliding from one to the other, in addition to having the function of acting as a cushion between the bones. , absorbing the tension produced by everyday physical activities. In osteoarthritis, the surface of the cartilage that is present between the joints wears out and it breaks, causing the bones to move and cause friction against each other, causing symptoms such as pain, inflammation, deformity and difficulty to use the joint, bringing as a consequence, the loss of physical movement. It is important to mention that in the process of osteoarthritis, in addition to the wear suffered by the cartilage, another factor that plays a very important role for the onset of the disease, such as the liquid found in the joint called synovial fluid, intervenes. , which lubricates the joint and is mainly composed of a substance called hyaluronic acid. People suffering from osteoarthritis may have more hyaluronic acid than normal between the joints, however, this could be diluted, causing it to decrease its protective function. Osteoarthritis is a disease that affects only the joints, without causing any damage to other internal organs. When the body detects the damage that osteoarthritis causes in the cartilage, it responds by producing new cartilage; however, the construction of the new cartilage does not maintain the rhythm of production with respect to the speed with which it is destroyed, triggering the development of the final stage of osteoarthritis.

With regard to Rheumatoid Arthritis (RA), this is a chronic disease of common prevalence and worldwide distribution that most commonly affects people between 25 and 55 years of age, with women being more affected than men. It is characterized by severely affecting the survival, functional capacity and quality of life of the individual who suffers it, as well as the ability to maintain a satisfactory job. Rheumatoid arthritis commonly affects the joints on both sides of the body equally, with the wrists, fingers, knees, feet and ankles being the most frequently affected parts of the body. Rheumatoid arthritis (RA) is considered an autoimmune disease, the cause of which is unknown. The way this disease manifests is through the immune system, which in normal conditions fights foreign substances, such as viruses or bacteria, but in the case of this disease classified as autoimmune, the immune system takes the healthy tissue confusing it with foreign substances, causing the body to attack itself. Rheumatoid arthritis causes pain, stiffness, swelling and loss of function in the joints, and may also cause inflammation in other organs. The manifestation and severity of rheumatoid arthritis can vary considerably, and can be caused by: infection, inheritance (genes), hormonal activity, among others, these factors being those that can contribute to its development. Mortality from direct causes or complications derived from rheumatoid arthritis continues to be double that observed in the control population, without changing this trend in the last four decades. The economic impact derived from this pathology has been underestimated in Latin American countries. In the United States, rheumatoid arthritis is considered one of the main causes of disability pension and direct and indirect economic losses. Arthrosis is the most frequent joint disease and its prevalence increases with age. It is estimated that radiological signs of osteoarthritis are rare before 40 years of age (2%), appear in 30% of people between 45 and 65 years of age and in 68% of people over 65 years of age. age. The articular alterations typical of arthrosis begin in the second decade of life, affecting 90% of people over 40 years. Osteoarthritis affects the neck, lower back, knees, hips and joints of the fingers.

Approximately 70% of people over 70 show radiological evidence of the disease, but only half of them develop symptoms. Osteoarthritis can also affect joints that have been previously damaged by excessive and prolonged use, infection or previous rheumatic disease. Patients with osteoarthritis suffer from pain and functional deterioration. Nowadays there is a great variety of pharmaceutical products useful for the treatment of these diseases; However, the active ingredients included in the formulation of these medications are administered independently, causing the relief of the symptoms manifested by these conditions and properly by the presence of the disease itself, to be slower and less effective. The pharmacological treatments that are currently applied to treat osteoarthritis, rheumatoid arthritis, osteoarthritis and rheumatic diseases in general, consist mainly of the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), which treat the symptoms but do not slow the progression of these diseases, and may even cause the patient to get worse faster.

SUMMARY OF THE INVENTION In order to offer a pharmaceutical alternative that achieves a better quality of life in patients suffering from diseases such as: osteoarthritis, rheumatoid arthritis, osteoarthritis and other related rheumatic diseases, the development of the pharmaceutical composition that is described below was carried out. Currently, most of the medicines found in the market for the treatment of osteoarthritis, rheumatoid arthritis, osteoarthritis and other related rheumatic diseases, are composed of active ingredients that are formulated independently, which comply with a therapeutic activity specifies; However, these drugs only contemplate the treatment of the symptoms manifested by these diseases, but do not delay or stop the progression of them. For this reason, and in order to eliminate all the disadvantages that arise when the active ingredients are administered independently, is that the development of the pharmaceutical composition object of the present invention, which is composed of the synergistic combination of an antiarthritic agent, a chondroprotective agent and an anti-inflammatory agent, which produce a satisfactory therapeutic effect by being administered as a whole in a single oral dosage unit, unlike when they are administered independently, generating benefits such as: lower concentrations of the active ingredients formulated, lower doses administered, greater speed of action, greater effectiveness of the effect therapeutic and minor adverse effects. DETAILED DESCRIPTION OF THE INVENTION. Chondroitin is an antiarthritic with specific therapeutic activity. It consists of chains of repeated molecules called glycosaminoglycans (GAG), composed mainly of the combination of various sulphated and non-sulfated residues of glucuronic acid and n-acetyl-galactosamine, necessary for the formation of proteoglycans (which provides elasticity to the cartilage) , which are large macromolecules composed of a protein core to which multiple chains of glycosaminoglycans and oligosaccharides adhere found in the articular cartilage, which has a very important structural function, since it retains water and various nutrients useful for formation of a healthy joint matrix, besides allowing the passage of other molecules through it, this property being very important, since the cartilage does not receive blood supply. Its main function is It acts as an antiarthritic agent in patients suffering from rheumatic diseases. It was during the 60's that the extraction and purification of chondroitin was carried out for the first time, this being a substance that is naturally present in the body, as the main constituent of cartilage. Currently Chondroitin is obtained and manufactured from natural sources such as: shark cartilage and / or beef, as well as the cartilage of the trachea of bovines, which can also be obtained through synthetic processes. It is used to improve symptoms and prevent progressive damage during the degenerative process that manifests itself in patients suffering from osteoarthritis. For many years, experts in research stated that Chondroitin administered orally did not cause the desired effect, since the molecules that compose it are too large to question whether they could be absorbed through the digestive tract. However, in 1995, the researchers ruled out the aforementioned, on the basis that there was evidence that up to 15% of chondroitin administered orally is absorbed by the digestive tract intact. Chondroitin is widely used in Europe for the treatment of osteoarthritis, since in addition to treating The symptoms manifested by this disease, protects the joints from the damage caused by the progression of it. Glucosamine is characterized by having a specific therapeutic activity as a chondroprotective agent. It consists mainly of glucose, the type of sugar that the body transforms into energy and an amino acid called glutamine, which is the precursor of the generation of glycosaminoglycans and constitutes up to 50% of the composition of hyaluronic acid, which is the lubricant natural found in the synovial fluid, which has the function of being lubricant and buffer, to restore and maintain healthy functioning of the joints and / or joints. Glucosamine inhibits some cartilage-destroying enzymes, such as: collagenases and phospholipase A2 and the formation of other substances that damage tissues, such as: the superoxide radicals of macrophages. Glucosamine also fulfills several functions as a component of cartilage, among which are the following: • It is an essential part of proteoglycans and is essential for the production of glycosaminoglycans, which are cartilage proteins that accumulate water.

• Acts as a stimulant on chondrocytes that are cells that synthesize and secrete the organic components of the extracellular matrix, such as: collagen, hyaluronic acid, proteoglycans and glycoproteins. Glucosamine is the factor that determines the amount of proteoglycans that chondrocytes can synthesize. • Glucosamine sulfate provides significant amounts of sulfur, which is an essential nutrient in joints. In fact, individuals suffering from arthritis usually have deficiencies of that nutrient. • Glucosamine stimulates the mechanisms of self-repair of joint cartilages. The primary role of Glucosamine in the arrest or delay of joint degeneration seems to be due directly to its ability to act as an essential substrate and stimulate the synthesis of glycosaminoglycans and the structure of hyaluronic acid necessary for the formation of proteoglycans found in the structural matrix of the joints. Glucosamine is the fundamental block necessary for the biosynthesis of several types of compounds, among which are included: glycolipids, glycoproteins, glycosaminoglycans (which previously they were called: mucopolysaccharides), hyaluronate and proteoglycans. As a component of these macromolecules, glucosamine plays an essential role in the synthesis of cell membranes, connective tissue, articular surfaces, tendons, ligaments, synovial fluid, skin, nails, blood vessels, heart valves and bone matrix. Glucosamine is a very water soluble small molecule, which is easily absorbed by intestinal cells through active transport; and when administered orally as glucosamine sulfate, about 90% of its absorption is carried out rapidly in the gastrointestinal tract. Glucosamine is eliminated in the urine during the 48 hours following oral administration in a proportion of about 5% of the dose administered. The main amount of orally administered Glucosamine is metabolized in the joint tissues and is eliminated as C02 in the expired air. Glucosamine is rapidly incorporated into the articular cartilage, this being the tissue in which the highest concentrations of this compound are found. It is considered that the treatment with Glucosamine normalizes the biosynthesis of the substrates required to restore the functional capacities of the joints. Glucosamine does not show effects on the cardiocirculatory system, on function Respiratory and on the central or vegetative nervous system. A successful treatment for osteoarthritis must effectively control pain and slow or reverse the progression of the disease. Biochemical and pharmacological data together with studies in animals and humans show that Glucosamine can satisfy both criteria. Although Glucosamine treatment does not produce a dramatic reduction in pain, which is associated with the use of non-steroidal anti-inflammatory drugs, its ability to reduce pain is consistent and progressive, resulting in a long-term improvement in the disease and pain relief. Meloxicam is a non-steroidal anti-inflammatory that plays anti-inflammatory, analgesic and antipyretic functions. It is an enolcarboxamidic derivative that belongs to the group of enolic acid (related to oxicans: piroxicam, tenoxicam, sudoxicam). It has a potent inhibitory activity on cyclooxygenase-2 (COX-2), with a selectivity 75 times higher for COX-2 compared to COX-1, intervening as an inhibitor in the synthesis of prostaglandins that have the function of being responsible mediators of inflammatory processes. The selective and specific blockade carried out on the cyclooxygenase-2 gives Meloxicam a double therapeutic benefit by achieving, on the one hand, a remarkable anti-inflammatory and analgesic activity in patients suffering from rheumatic diseases (osteoarthritis, rheumatoid arthritis, arthrosis, osteoarthrosis), and on the other hand, it has a excellent tolerance with minimal adverse gastrointestinal or ulcerogenic effects, unlike those patients who are treated with other non-steroidal anti-inflammatory agents, such as indomethacin, naproxen or acetylsalicylic acid. The effective intracellular access of Meloxicam is determined by its lipophilic and amphiphilic properties. The low water solubility of Meloxicam at an acidic pH and its amphiphilic protonation behavior are responsible for the tissue kinetics that prevent the concentration of this active principle in certain tissues. Meloxicam has a good digestive absorption and an optimal bioavailability (89%), after having been administered a single dose orally. Some of the main pharmacokinetic characteristics are: prolonged absorption, sustained serum concentrations and long elimination half-life (20 hours), which allows a single daily dose to be administered. Once it has been absorbed in the digestive tract, the Meloxicam diffuses easily into blood and inflamed tissues, having a high adherence with plasma proteins (> 99%) and its metabolites are excreted both in the urine and feces. Meloxicam is indicated for the treatment of diseases such as: osteoarthritis, rheumatoid arthritis, gouty arthritis, muscular and traumatic affections, as well as inflammatory processes of soft tissues, airways and gynecological conditions. The antiarthritic agent used in the pharmaceutical composition object of the present invention is the active principle Chondroitin Sulfate, which is present in the formulation in a concentration range of 1.0 gr. up to 1.5 gr., a concentration of approximately 1.1 gr. being preferably used. to 1.3 gr. per unit dose. The chondroprotective agent that is formulated in the pharmaceutical composition object of the present invention is the active ingredient Glucosamine, which is present in a concentration range from 1.2 gr. up to 1.7 gr. , a concentration of about 1.4 g is preferably used. to 1.6 gr. per unit dose. The anti-inflammatory agent contained in the pharmaceutical composition object of the present invention is the active ingredient Meloxicam, being present in the formulation in a concentration range from 6.5 mg. to 17 mg., a concentration of about 7.0 mg, to 16.0 mg, is preferably used. per unit dose. The pharmaceutical composition protected by the present invention is formulated to be administered orally in a single dosage unit in powder form for solution with presentation in single-dose sachets, in which the synergistic combination of the active principles is contained: Chondroitin, Glucosamine and Meloxicam, as well as pharmaceutically acceptable excipients. Said pharmaceutical composition has been developed with the purpose of providing a pharmaceutical alternative for the treatment of diseases such as: osteoarthritis, rheumatoid arthritis, osteoarthritis and other related rheumatic diseases, which offers significant advantages such as: lower concentrations of Active ingredients contained in the formulation, effective control of pain suffered by patients suffering from these diseases, in addition to slowing or reversing the progression of them.

Claims

NOVELTY OF THE INVENTION Having described the present invention, it is considered as novelty and, therefore, the content of the following CLAIMS 1 is claimed as property. - Pharmaceutical composition composed of the synergistic combination of an antiarthritic agent, a chondroprotective agent and an anti-inflammatory agent, characterized because the antiarthritic agent is the active principle: Chondroitin Sulfate; the chondroprotective agent is the active principle: Glucosamine and the anti-inflammatory agent is the active ingredient: Meloxicam; as well as pharmaceutically acceptable excipients, formulated in a single dosage unit to be administered orally, indicated for the treatment of osteoarthritis, rheumatoid arthritis, osteoarthritis and other related rheumatic diseases. 2. - Pharmaceutical composition according to claim 1, characterized in that the anti-arthritic agent, as is the active principle: Chondroitin Sulfate is present in the formulation in a concentration range of 1.1 gr. to 1.3 gr., being preferably used in the formulation a concentration of 1.2 gr. per unit dose. 3. - Pharmaceutical composition according to claims 1 and 2, characterized in that the chondroprotective agent, as is the active ingredient: Glucosamine is present in the formulation in a concentration range of 1.4 gr. to 1.6 gr., a concentration of 1.5 gr. being preferably used in the formulation. per unit dose. 4. Pharmaceutical composition according to claims 1 to 3, characterized in that the anti-inflammatory agent, as is the active ingredient: Meloxicam is present in the formulation in a concentration range of 7.0 mg, to 16.0 mg. , a concentration of 7.5 and 15 mg being preferably used in the formulation. per unit dose. 5. Pharmaceutical composition according to claims 1 to 4, characterized in that it is formulated in a single dosage unit for oral administration in powder form for solution with presentation in single-dose sachets. 7. - The use of the pharmaceutical composition according to claims 1 to 5, characterized in that it is indicated for the treatment of diseases such as: osteoarthritis, rheumatoid arthritis, osteoarthritis and any other related rheumatic disease.