CH712776A2 - Composition comprising antioxidants, glycosaminoglycans and pernacaniculus extract and uses thereof - Google Patents

Abstract

This invention relates to the use of at least one antioxidant and a glycosaminoglycan (GAG) in combination with at least one component derived from Perna Canaliculus for the manufacture of a preparation used for the maintenance, regeneration and repair of connective tissue in animals and humans.

Description

Description

BACKGROUND OF THE INVENTION [0001] One of the major health problems that physicians and veterinarians encounter more and more frequently is the chronic inflammation of connective tissues and joints. The connective tissues of animals and humans such as joints, tendons and ligaments are subject to degeneration usually caused by excessive stress, repetitive work, which can lead to diseases such as osteoarthritis. This chronic disease is characterized by degeneration and loss of cartilage in certain joints, which causes serious damage to the bones and overgrowth of the bone causing deformities on the affected limbs.

Its changes bring joint pain and inflammation, accompanied by stiffness and loss of mobility. Certain autoimmune diseases such as rheumatoid arthritis (RA), can also lead to the destruction of connective tissue. The prevention and treatment of his illnesses is a challenge because of the number of factors that affect joint diseases, as well as the difficulty in reaching areas of degeneration.

[0003] Today, most of the therapeutic treatments proposed have the sole purpose of reducing the symptoms (pain, inflammation, reduced mobility), rather than dealing with the underlying cause of the disease. Today, pharmaceutical treatments for osteoarthritis provide a partial reduction of pain and inflammation.

[0004] Drugs such as corticosteroids or non-steroidal anti-inflammatory drugs, such as ibuprofen and diclofenac, are frequently combined with non-pharmacological measures. Like weight loss and water exercises. Its products give fast results in terms of pain relief but have many long-term side effects (gastric problems, intestinal bleeding, myocardial infarction for NSAIDs and weight gain, sleep disorder, stomach pains, increased risks of infections and induces metabolic changes) and interfere with and block the natural mechanisms of the body to naturally rebuild healthy joints.

[0005] Oxygen-reactive species and free radicals are associated in an ignition process via numerous routes. During inflammation, oxidation damages DNA, proteins and lipids. In RA, the reactive oxygen species damage cartilage and extracellular matrix and inhibit collagen production and proteoglycan synthesis. One of the areas that can still be studied is the impact of free radicals on joint diseases. They play a significant role in the pathogenic reactions of osteoarthritis. Antioxidants have the properties of preventing the oxidation of other molecules by direct reactions or via more complex systems. They play an important role in the balance of oxidized states and control inflammation.

Glycosaminoglycans such as chondroitin and glucosamine or other kind of salts, are amino sugars present in the joints, connective tissues, basement membrane, membrane mucosa and synovial fluids. One of their roles is to increase joint lubrication and increase water levels inside the cartilage. A deficiency or acceleration of the destruction of its pillars can lead to a decrease in the synthesis of these macromolecules during periods of stress or following an injury.

[0007] Perna canaliculus (mussels green oranges) is a consumable mollusk, which is commonly found on the New Zealand coast. This type of mussel has long been used in arthritis treatments since the mid-seventies because of its many therapeutic properties to reduce the symptoms of arthritis in both humans and animals. Experimental studies have yielded diverse results but all indicate overall that some elements in the mold are potentially effective in reducing inflammation and pain due to arthritic problems.

DETAILED DESCRIPTION OF THE INVENTION AND ITS IMPLEMENTATION [0008] In accordance with this invention, it has been discovered that antioxidants and GAGs in combination with at least one of the components of Perna Caniculus (referenced herein as Perna extract). Canaliculus (EPC) is surprisingly helpful in the regeneration and repair of joint tissues for both animals and humans, particularly in the maintenance and support of joints and connective tissues. Stress-prone, prevent natural wear and cope with disease processes resulting from inflammatory conditions, autoimmune diseases and connective and connective tissue diseases The effects of synergy observed above in the treatment of diseases articular are considered.

This synergy modulates the immune and inflammatory response systems and encourages the regeneration of constituents that affect the joints and tissues. One of the objectives of this invention is to provide protection and repair of the connective tissues of animals as well as humans. The treatment as explained herein relates to the therapeutic treatment of the compounds of the invention for the prevention, amelioration or treatment of the disease.

The treatment of animals (and more specifically vertebrate animals and mammals such as dogs, cats, horses, cows, pigs as well as pets and farm animals) and humans has been envisaged.

The connective tissues as mentioned herein are not limited to joints, cartilage tendons, ligaments, synovial fluid, collagen and proteoglycans.

[0012] Conditions that can be treated in accordance with the present invention include, for example, connective tissue conditions or possible or already existing inflammatory conditions of the joints. These inflammatory conditions include, among others, autoimmune systemic diseases such as lupus erythematosus, rheumatoid arthritis, myasthenia gravis, Grave's disease, Hashimoto's thyroiditis, Crohn's disease, autoimmune haemolytic anemias, insulin-dependent diabetes mellitus, glomerulonephritis and rheumatic fever. Other diseases can be treated by the present invention. There are, for example, arthritic conditions such as osteoarthritis and gouty arthritis, or inflammatory diseases such as conjunctivitis, dermatitis, bronchitis or rhinitis, generally caused by allergies, infections, microorganisms, traumas or physical or chemical agents. Osteoarthritis as stipulated above refers to both the first form as well as the second observed form of this disease. The first form of the disease is related to trauma or joint disease and is associated with an alteration of the particular structure of the joints. The second type of osteoarthritis is much more common than the first form.

It may be due to trauma, such as a fracture or sprain, but also an inflammatory and / or metabolic, endocrine or drug-induced response.

Additionally, the inflammatory treatment of asthma is also envisaged. One aspect of this invention is a composition which comprises a combination of antioxidants, GAG or their salts and Perna caniculus. The extract of Perna caniculus is an active therapeutic component derived from the flesh of the mussel or one of its organs, provided that its use is possible in food supplement preparations or pharmaceutical preparations. This invention includes unrefined components of the mold, such as whole mold or other active extracts for therapeutic purposes. As previously stated, a therapeutically active extract in accordance with this invention is used to reduce inflammatory conditions and has immunomodulatory effects in animals and humans.

For example, several well-known studies carried out on animals suffering from arthritis have been used to determine the therapeutic effect of ECP. These studies include, among others, collagen-deficient arthritis in rats and mice, inflammatory edema in rats described by Miller et al., 1980, New Zealand Medical Journal 92: 667, and arthritis. in rats and mice by the injection of adjuvants prepared from dried tuberculosis Mycobacterium as described in Whitehouse, et al., 1997, Inflammopharmacology 5: 237-246.

The therapeutic activity of PCE can also be demonstrated by retaining that the PCE extract can reduce anti-nuclear antibodies, in particular anti-SSDNA antibodies or anti-DNA-DNA antibodies in humans with the SLE or in mice as in the study described in US Patent Application Serial No. 09 / 316,001 (Kendall and Lawson).

The PCE preparation may be a whole mussel preparation that has been freeze-dried and milled, available at Aroma NZ Ltd., Christchurch, New Zealand, or PCE from Essex Junction Laboratories, Vermont. In addition thereto, active extracts for therapeutic purposes of Perna Caniculus may also be used. Such active therapeutic extracts have been described as follows: Macrides and Kalafatis, PCT / AU95 / 00485, WO 96/05164 (purified lipid extract); Whitehouse et al., 1997, Inflammopharmacology 5: 237-246 (purified lipid extract); Kosuge and Sugiyama, U.S. Patent No. 4,801,453 (stabilized mussel extract); Couch et al., 1982, The New Zealand Medical Journal 95: 803 (a protein fraction); Miller et al., 1993, Agents Actions 38: 139 (an aqueous fraction).

GAGs may be combined with Glucosamine or an acceptable pharmacological salt, such as glucosamine sulfate or chondroitin. Antioxidant ingredients may come from a combination of vitamins C and E, or an acceptable pharmacological salt such as copper salts (in the form of citrate or gluconate), a pharmacologically acceptable zinc salt such as Zinc citrate or gluconate and a pharmacologically acceptable selenium salt such as selenomethionine. A composition that contains antioxidants, glucosamine, chondroitin and PCE can be formulated as a pharmaceutical preparation or as a dietary supplement using techniques known in the art. The formulation is prepared for oral administration.

Another aspect of this invention is the use of a combination of an antioxidant component, a GAG component and at least one PCE component for the manufacture of a remedy which is intended to treat conditions. potential or existing articular or connective tissue or inflammatory conditions. The antioxidant, GAG and PCE components can be administered by the same route or they can be administered via different routes. For example, antioxidants, GAG and PCE can all be administered orally, either simultaneously or at different times. One of the most preferable routes for the administration of PCE, particularly the whole mussel, is orally. One of the best ways for the administration of GAG is also through oral administration. Antioxidants, GAG and PCE can also be administered by intramuscular injection, intraperitoneal injection, parenteral administration, etc.

The antioxidant, GAG and PCE used in this invention can be used in admixture with conventional excipients, that is, pharmaceutically acceptable organic or inorganic carrier substances, suitable for parenteral, enteral application. and orally, which do not deliberately alter the active compounds. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, saline solutions, alcohols, gum arabic, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, carbohydrates such as lactose, amylose or starch, ester, magnesium stearate, talc, silicic acid, viscous paraffin, perfume oil, monoglycerides and diglycerides of fatty acids, esters of acids pentaerythritol, hydroxy methyl cellulose, polyvinylpyrrolidone, etc. The pharmaceutical preparations may be sterilized and, if desired, mixed with auxiliary agents such as, for example, lubricants, emulsifiers, salts which influence the osmotic pressure, buffers, coloring agents, flavoring agents and / or flavoring substances. or the like which do not harm the active compounds. Other pharmaceutically acceptable carriers include aqueous solutions, non-toxic excipients, including salts, preservatives, buffers and the like as described for example in Remington's Pharmaceutical.

The pharmaceutical compositions are preferably prepared and administered in dosage units. The solid dosage units are tablets, powders, capsules, granular forms and suppositories. For the treatment of a subject, depending on the activity of the compound, the modes of administration, the nature and severity of the disorder, the age and the body weight of the patient, different daily doses are required. In some circumstances, however, higher or lower daily doses may be appropriate. The average daily dose of the compounds of the present invention is typically as follows: for vitamin E, the average daily dose is generally about 0.1 to 1 mg / kg / day, more preferably about 0.3 to 0 , 6 mg / kg / day, more preferably about 0.4 to 0.5 mg / kg / day; For vitamin C, the average daily dose is generally about 1 to 40 mg / kg / day, more preferably about 5 to 20 mg / kg / day, more preferably about 8 to 13 mg / kg / day. ; For copper, the average daily dose is generally about 0.001 to 0.125 mg / kg / day, more preferably about 0.005 to 0.02 mg / kg / day, more preferably about 0.008 to 0.013 mg / kg / day. day; For zinc, the average daily dose is generally about 0.05 to 0.5 mg / kg / day, more preferably about 0.06 to 0.2 mg / kg / day, more preferably about 0 to 0.5 mg / kg / day. , 07 to 0.15 mg / kg / day; For selenium, the average daily dose is generally about 0.001 to 5 μg / kg / day, more preferably about 0.1 to 2 μg / kg / day, more preferably about 0.5 to 1 μg / kg / day. kg / day; For chondroitin, the average daily dose is generally from about 1 to about 400 mg / kg / day, preferably from about 10 to about 90 mg / kg / day, more preferably from about 20 to about 40 mg / kg. /day; For glucosamine or glucosamine sulfate, the average daily dose is generally from about 1 to about 400 mg / kg / day, preferably from about 10 to about 90 mg / kg / day, more preferably from about 20 to About 40 mg / kg / day; For ECP, when the ECP comprises ground whole mold, the average daily dose is generally from about 1 to about 500 mg / kg / day, preferably from about 10 to about 120 mg / kg / day, more preferably from about 20 to about 60 mg / kg / day. For components of ECP other than the whole mold, the average daily dose may vary but can be easily determined by an expert. The daily dosage may be administered in a single dose per day or in divided doses per day. The daily dosage may also be administered on a non-daily basis, such as, for example, every second or third day, provided that an average daily dose is as described above or obtained. The therapeutic administration of glucosamine is written in the following US patents: [0021] The combination of antioxidant, GAG and PCE can be administered simultaneously or alternatively with other therapeutic treatments conventionally used to treat the indicated diseases. For example, for the treatment of systemic lupus erythematosus, rheumatoid arthritis and osteoarthritis. Antioxidants, GAG and PCE can be administered together with anti-inflammatory agents, including corticosteroid agents such as, for example, prednisone or methylprednisolone and non-steroids.Anti-inflammatory agents such as, for example, salicylates, diclofenac, ketoprofen, piroxicam and celecoxib. For the treatment of systemic lupus erythematosus erythematosus, for example, the compounds of this invention may also be administered together with antimalarial drugs, including, for example, hydroxychloroquine or in conjunction with cytotoxic chemotherapies, including, for example, azathioprine and cyclophosphamide.

Another aspect of this invention is a kit containing a combination of anti-oxidant formulations, GAGs and PCE. The kit may contain the three components in separate formulations or one of the components combined in a single formulation. For example, a kit may contain a PCE formulation and a formulation comprising both antioxidant or glucosamine. The kit components may also be combined with other excipients or therapeutic agents. A kit would generally provide an average daily dose of antioxidant, GAG or PCE as described above.

[0022] One of the other aspects of this invention is the combination Perna canaliculus / GAG / antioxidants is used in conjunction with manganese supplementation. Manganese is an essential cofactor in cartilage production and manganese supplementation can improve the effectiveness of the invented combination, while protecting manganese deficiency.

Without further elaboration, it is believed that the chemistry specialists using the foregoing description can utilize the present invention to its greatest extent. The specific embodiments that are recommended should therefore be interpreted as merely illustrative and not limiting of the rest of the description.

Claims (10)

claims 1. Use of an antioxidant component, a glycosaminoglycan component and at least one Perna canaliculus component for the manufacture of a preparation for the treatment of an inflammatory disease. 2. Use according to claim 1, wherein the inflammatory disease is an autoimmune disease. 3. Use of an antioxidant component, a glycosaminoglycan component and at least one component of Perna canaliculus for the manufacture of a preparation for the treatment of an existing tissue or connective tissue. The use of claim 3, wherein the condition of the connective tissue is caused by osteoarthritis or rheumatoid arthritis. 5. A composition comprising an antioxidant component, a glycosaminoglycan component and at least one component of Perna canaliculus. The composition of claim 5 which is suitable for use as a dietary supplement. A set of preparations comprising an antioxidant formulation, a glycosaminoglycan formulation, and a Perna canaliculus formulation, wherein the Perna canaliculus formulation comprises at least one Perna canaliculus component. 8. Preparation set according to claim 7, wherein the formulation of antioxidants, glycosaminoglycan and Perna canaliculus are suitable for use as food supplements by oral administration. 9. Use according to claims 1 or 3 or 5 or 7, further comprising manganese. The use of claims 1 or 3, wherein the drug or dietary supplement is used for administration to a human or non-human mammal.