AU2013100230A4 - Combination treatment for rheumatic disorders - Google Patents

Abstract

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 Abstract Provided herein are compositions and methods for the treatment of rheumatic disorders such as arthritis. Compositions disclosed herein comprise one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof. Methods for the treatment of rheumatic disorders disclosed herein comprise administration of such compositions to subjects in need of treatment.

Description

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 Combination treatment for rheumatic disorders Technical Field The present disclosure relates generally to the use of compositions comprising or consisting of a combination of one or more probiotic microorganisms and glucosamine or a salt thereof for the relief of joint pain and the treatment of rheumatic disorders such as arthritis, more particularly osteoarthritis. Background Rheumatic disorders are chronic conditions causing inflammation, pain and loss of function in joints, muscles, and related connective tissues. The most common rheumatic disorders are arthritic conditions. Arthritis affects hundreds of millions of individuals around the world resulting in burdens on economies and health systems as sufferers require ongoing medical treatment and their loss of function often results in lower productivity or an inability to work. As arthritic conditions typically increase in prevalence with age, the impacts of these conditions on societies, health systems and economies are becoming more severe with increasingly aged populations and with increased longevity of life. The two major forms of arthritis are inflammatory arthritis, such as rheumatoid arthritis, and osteoarthritis. Rheumatoid arthritis is a disease of the immune system targeting the synovium, resulting in pain, stiffness, swelling, joint damage, and loss of function of the joints. Inflammation most often affects joints of the hands and feet. Osteoarthritis, the most common form of arthritis, is a degenerative joint disease affecting cartilage and bone, characterized by a gradual degradation of cartilaginous tissue, together with the presence of inflammation and pain, typically arising secondary to mechanical stress, aging, dysplastic conditions and/or injury. Disability caused by osteoarthritis is common when the spine or weight bearing joints such as the hips or knees are affected. Inflammation and pain associated with rheumatoid arthritis, and osteoarthritis are typically treated using non-steroidal anti-inflammatory drugs (NSAIDs), steroid hormones or other immunosuppressive agents. However the use of such drugs is typically associated with some significant side effects including gastrointestinal and kidney problems.

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 2 Glucosamine and glucosamine derivatives such as N-acetylglucosamine have been proposed as treatments for joint pain, such as that associated with osteoarthritis. However the numerous studies and clinical trials conducted using glucosamine have yielded equivocal results, and in some cases conflicting results, on the efficacy of the treatment, with no feasible scientific explanations for the differences observed. A need remains in the art for improved methods and compositions suitable for the treatment of rheumatic disorders such as arthritis and the relief of joint pain associated with such disorders. Summary of the disclosure According to one aspect of the present disclosure there is provided a composition comprising one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof for the treatment of a rheumatic disorder. According to a further aspect of the present disclosure there is provided a composition consisting of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof for the treatment of a rheumatic disorder. According to a further aspect of the present disclosure there is provided a composition comprising one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof for the relief of joint pain in a subject. According to a further aspect of the present disclosure there is provided a composition consisting of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof for the relief of joint pain in a subject. According to a further aspect of the present disclosure there is provided a method for treating a rheumatic disorder in a subject, the method comprising administering to the subject an effective amount of a combination comprising one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof.

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 3 According to a further aspect of the present disclosure there is provided a method for treating a rheumatic disorder in a subject, the method comprising administering to the subject an effective amount of a combination consisting of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof. According to a further aspect of the present disclosure there is provided a method for relieving joint pain in a subject, the method comprising administering to the subject an effective amount of a combination comprising one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof According to a further aspect of the present disclosure there is provided a method for relieving joint pain in a subject, the method comprising administering to the subject an effective amount of a combination consisting of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof In accordance with the above aspects the rheumatic disorder may be arthritis. The arthritis may be selected from osteoarthritis, rheumatoid arthritis, traumatic arthritis, degenerative arthritis and dysplastic arthritis. In a particular embodiment the arthritis is osteoarthritis. In accordance with the above aspects the joint pain may be associated with a rheumatic disorder. Typically, the one or more probiotic microorganisms comprises strains of Lactobacillus and/or Bifidobacterium species. In an embodiment the Lactobacillus is a strain of Lactobacillus acidophilus. In an embodiment the Bifidobacterium is a strain of Bifidobacterium bifidum. The probiotic microorganisms may comprise a multi-strain combination of microorganisms. In particular embodiments the multi-strain combination comprises one or more strains of Lactobacillus acidophilus and one of more strains of Bifidobacterium bifidum. The probiotic microorganisms may be present in compositions disclosed herein in an amount from about 1 billion to about 50 billion cfu per unit dosage form. In one embodiment the one or more strains of Lactobacillus acidophilus are present in the C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 4 composition at about 1.25 billion cfu per unit dosage form. In one embodiment the one or more strains of Bifidobacterium bifidum are present in the composition at about 10 billion cfu per unit dosage form. The glucosamine may be administered in the form of glucosamine or a salt or derivative thereof Suitable glucosamine salts include, by way of example, glucosamine sulphate, glucosamine phosphate, glucosamine hydrochloride, glucosamine glucuronate, glucosamine ascorbate, glucosamine malate, glucosamine hydrogen malate, glucosamine citrate, glucosamine hydrogen citrate, and glucosamine dihydrogen citrate. In a particular embodiment the glucosamine salt is glucosamine sulphate. Suitable glucosamine derivatives include, by way of example, glucosamine-6-phosphate, N-acetyl-D glucosamine, N-acetyl-D-galactosamine, uridine diphosphate (UDP) glucose and UDP-N acetylglucosamine. In a particular embodiment the glucosamine is administered in the form of glucosamine sulphate. The glucosamine sulphate may be present in compositions disclosed herein in an amount of between about 250 mg and about 750 mg per unit dosage form, or at about 500 mg per unit dosage form. Compositions disclosed herein are typically in the form of dietary supplements. Compositions may be in solid or non-solid form, typically suitable for oral administration. In a particular embodiment the composition is in capsule form. In a particular embodiment, the composition is in the form of a capsule comprising about 675 mg glucosamine sulphate 2 KCL, about 1.25 billion cfu of two Lactobacillus acidophilus strains and about 10 billion cfu of Bifidobacterium bifidum. Typically in accordance with this embodiment administration of the capsules is three per day. Also provided herein is the use of a combination of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof, for the manufacture of a medicament for the treatment of rheumatic disorders or the relief of joint pain.

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 5 Definitions Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. The term "consisting of' will be understood to be exhaustive, excluding non-recited active components of the compositions. In the context of this specification, the terms "a" and "an" are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element. In the context of this specification, the term "about," is understood to refer to a range of numbers that a person of skill in the art would consider equivalent to the recited value in the context of achieving the same function or result. In the context of this specification, the term "probiotic" is to be given its broadest construction and is understood to refer to any live microorganism(s) which when administered in an effective amount improve the microbial balance in the gastrointestinal tract of the host and assist in promoting or providing a health benefit to the host. As used herein the terms "treating", "treatment" and variations thereof refer to any and all uses which remedy a rheumatic disorder or at least one symptom thereof, prevent the establishment of a rheumatic disorder, or otherwise prevent, hinder, retard, or reverse the progression of a rheumatic disorder or other undesirable symptom in any way whatsoever. Thus the terms "treating" and the like are to be considered in their broadest context. For example, treatment does not necessarily imply that a patient is treated until total recovery. In conditions which display or a characterized by multiple symptoms, the treatment need not necessarily remedy, prevent, hinder, retard, or reverse all of said symptoms, but may prevent, hinder, retard, or reverse one or more of said symptoms. As used herein, "relief' in the context of the relief of joint pain refers to the lessening of severity of pain, the duration of pain or the incidences of pain in one or more joints in a C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 6 subject, such as the toes, ankles, knees, hips, fingers, wrists, elbows or shoulders. The joint pain may or may not be associated with a rheumatic disorder. As used herein the term "associated with" means that the joint pain may result from, result in, be characteristic of, or otherwise associated with the rheumatic disorder. Thus, the association between the disorder and the pain may be direct or indirect and may be temporally and/or spatially separated. As used herein the term "effective amount" includes within its meaning a non-toxic but sufficient amount or dose of an agent or compound to provide the desired effect. The exact amount or dose required will vary from subject to subject depending on factors such as the species being treated, the age and general condition of the subject, the severity of the condition being treated, the particular agent being administered and the mode of administration and so forth. Thus, it is not possible to specify an exact "effective amount". However, for any given case, an appropriate "effective amount" may be determined by one of ordinary skill in the art using only routine experimentation. In the context of this specification, the term "subject" includes humans, primates, livestock animals (eg. sheep, pigs, cattle, horses, donkeys), laboratory test animals (eg. mice, rabbits, rats, guinea pigs), companion animals (eg. dogs, cats) and captive wild animals (eg. foxes, kangaroos, deer). Typically, the subject is a human or a laboratory test animal. Even more typically, the subject is a human. Detailed Description Embodiments of the present disclosure provide compositions comprising or consisting of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof, for the treatment of a rheumatic disorder and/or the relief of joint pain. Also provided are methods for treating rheumatic disorders and/or relieving joint pain in individuals, wherein individuals are administered a combination of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof Whilst not wishing to be bound by theory, as gut microflora influences host metabolic function and defence systems including immune responses, it is suggested that the administration of probiotic microorganisms to improve gastrointestinal tract function and C:\NRPortl\DCC\GRS\4953884 1.DOC-28/02/2013 7 integrity may influence the therapeutic efficacy of glucosamine. In some embodiments, compositions in accordance with the present disclosure may provide synergistic combinations of the glucosamine and the probiotic microorganisms. The compositions disclosed herein may comprise any one or more probiotic microorganisms. In particular embodiments the compositions comprise a multi-strain combination of probiotic microorganisms. The one or more probiotic microorganisms may include but are not limited to strains of Lactobacillus, Bifidobacterium, Streptococcus Saccharomyces, Bacillus, Enterococcus, Bacteroides or Propionibacterium. The Lactobacillus may be one or more of, but not limited to, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Lactobacillus salivarius, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus reuteri, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus gasseri or Lactobacillus sporogenes. In a particular embodiment the Lactobacillus is Lactobacillus acidophilus. The Bifidobacterium may be one or more of, but not limited to, Bifidobacterium bifidum, Bifidobacterium animalis, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium Lafti, Bifidobacterium breve or Bifidobacterium lactis. In one embodiment the Bifidobacterium is Bifidobacterium bifidum. The Streptococcus may be one or more of, but not limited to, Streptococcus thermophilus, streptococcus faecium, or Streptococcus salivarius. The Saccharomyces may be one or more of, but not limited to, Saccharomyces cerevisiae, Saccharomyces boulardii or Streptococcus Faecium. The Bacillus may be one or more of, but not limited to, Bacillus coagulans, Bacillus cereus, Bacillus clausii, or Bacillus pumilus. The Enterococcus may be, but not limited, to Enterococcusfaecium. In a particular embodiment, compositions of the present disclosure comprise a multi-strain probiotic combination including one or more strains of Lactobacillus acidophilus and one or more strains of Bifidobacterium bifidum.

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 8 In accordance with particular embodiments of the disclosure the amount of one or more probiotic microorganisms present in the compositions may be from about 0.5 billion to about 100 billion cfu per unit dosage form, or from about 1 billion to about 20 billion cfu per unit dosage form, or from about 1 billion to about 10 billion cfu per unit dosage form, depending on the strain. For example, in a particular embodiment one or more strains of Lactobacillus acidophilus may be present in the composition at about 1.25 billion cfu per unit dosage form and one or more strains of Bifidobacterium bifidum may be present in the composition at about 10 billion cfu per unit dosage form. The compositions disclosed herein also comprise glucosamine or a salt or derivative thereof Those skilled in the art will appreciate that any suitable salt or derivative or glucosamine may be employed. Salts include, by way of example only, glucosamine sulphate, glucosamine phosphate, glucosamine hydrochloride, glucosamine glucuronate, glucosamine ascorbate, glucosamine malate, glucosamine hydrogen malate, glucosamine citrate, glucosamine hydrogen citrate, and glucosamine dihydrogen citrate. Suitable glucosamine derivatives include, by way of example only, glucosamine-6-phosphate, N acetyl-D-glucosamine, N-acetyl-D-galactosamine, uridine diphosphate (UDP) glucose and UDP-N-acetylglucosamine. In accordance with particular embodiments of the disclosure the amount of glucosamine present in the composition may be between about 50 mg and about 1000 mg per unit dosage form, between about 100 mg an about 1000 mg per unit dosage form, between about 250 mg and about 750 mg per unit dosage form, or between about 500 mg and about 675 mg per unit dosage form. The amount of glucosamine present in the composition may be about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg or 1000 mg. The compositions of the present disclosure are typically provided as dietary supplements. The composition may be provided in, and administered in, any suitable form, including solid and non-solid forms. Typically the composition will be formulated to be suitable for oral administration. By way of example only, the composition may be in the form of a capsule, tablet, caplet, powder, solution, or emulsion. In particular embodiments the composition is in the form of a capsule. Alternatively, the composition may, for example, be provided in powder form, for example in sachets, for administration alone or by mixing C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 9 with a suitable liquid or foodstuff (such as water, fruit juice, milk or yoghurt). In a particular exemplary embodiment the composition of the present disclosure is in the form of a capsule to be administered about three times per day to a subject in need of treatment. However those skilled in the art will appreciate that the dosage to be administered may be varied depending on a variety of factors including for example, the exact composition employed, the severity of the rheumatic disorder or joint pain suffered by the subject, the age, body weight, general health and diet of the subject, the time of administration, rate of excretion, and combination with any other treatment or therapy. The number of administrations, the timing of administration and the duration of administration may be determined by the subject and/or a consulting health professional. The suitable dosage form of the composition may be prepared by any method well known in the art. The method may include the step of bringing the components of the composition into association with a carrier which constitutes one or more accessory ingredients. For example, oral compositions are prepared by uniformly and intimately bringing into association the components of the composition with a liquid carrier or finely divided solid carrier, or both and then, if necessary, shaping the product into the desired composition. Generally, compositions of the present disclosure are prepared in accordance with generally recognized pharmacopeia for use in animals and in humans. The compositions can include carriers such as a diluent, excipient, or vehicle. Such pharmaceutical carriers can be sterile liquids, such as water and oils. Compositions can contain a diluent such as lactose, sucrose, dicalcium phosphate, or carboxymethylcellulose; a lubricant, such as magnesium stearate, calcium stearate and talc; and a binder such as starch, natural gums, such as gum acacia gelatin, glucose, molasses, polvinylpyrrolidine, celluloses and derivatives thereof, povidone, crospovidones and other such binders known to those of skill in the art. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, and ethanol. A composition, if desired, also can contain minor amounts of wetting or emulsifying agents, or pH buffering agents, for example, acetate, sodium citrate, cyclodextrine derivatives, C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 10 sorbitan monolaurate, triethanolamine sodium acetate, triethanolamine oleate, and other such agents. Other examples of acceptable carriers or diluents are demineralised or distilled water; saline solution; vegetable based oils such as peanut oil, safflower oil, olive oil, cottonseed oil, maize oil, sesame oil, arachis oil or coconut oil; silicone oils, including polysiloxanes, such as methyl polysiloxane, phenyl polysiloxane and methylphenyl polysolpoxane; volatile silicones; mineral oils such as liquid paraffin, soft paraffin or squalane; cellulose derivatives such as methyl cellulose, ethyl cellulose, carboxymethylcellulose, sodium carboxymethylcellulose or hydroxypropylmethylcellulose; lower alkanols, for example ethanol or iso-propanol; lower aralkanols; lower polyalkylene glycols or lower alkylene glycols, for example polyethylene glycol, polypropylene glycol, ethylene glycol, propylene glycol, 1,3-butylene glycol or glycerin; fatty acid esters such as isopropyl palmitate, isopropyl myristate or ethyl oleate; polyvinylpyrridone; agar; carrageenan; gum tragacanth or gum acacia, and petroleum jelly. Typically, the carrier or carriers will form from 10% to 99.9% by weight of the compositions. The present disclosure also contemplates that compositions may be conveniently incorporated in a variety of food and/or beverage products, nutraceutical products, pharmaceuticals and over-the-counter formulations. The food may be a solid form such as a powder, or a liquid form. Specific examples of the types of beverages or foods include, but are not limited to water-based, milk-based, yoghurt-based, other dairy-based, milk substitute based such as soy milk or oat milk, or juice-based beverages, water, soft drinks, carbonated drinks, and nutritional beverages, (including a concentrated stock solution of a beverage and a dry powder for preparation of such a beverage); baked products such as crackers, breads, muffins, rolls, bagels, biscuits, cereals, bars such as muesli bars, health food bars and the like, dressings, sauces, custards, yoghurts, puddings, pre-packaged frozen meals, soups and confectioneries. The compositions of the disclosure may be used in conjunction with other therapies or supplements for the treatment of rheumatic disorders or the relief of joint pain. As such, the compositions of the disclosure may be used as part of a treatment regime or combination therapy. In accordance with such combination therapy, a composition of the C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02/2013 11 present disclosure may be coadministered with other suitable agents to facilitate the desired therapeutic or prophylactic outcome. By "coadministered" is meant simultaneous administration in the same formulation or in two different formulations via the same or different routes or sequential administration by the same or different routes. By "sequential" administration is meant a time difference of from seconds, minutes, hours, days, weeks, months or years between the administration of the two agents. These agents may be administered in any order. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. The present disclosure will now be described with reference to the following specific examples, which should not be construed as in any way limiting the scope of the disclosure.

C:\NRPortbl\DCC\GRS\4953884_1.DOC-28 02 2013 12 Examples Example 1 - Composition in capsule form By way of example only a suitable oral composition for use in accordance with the present disclosure is outlined below. The following is to be construed as merely an illustrative example of a composition and not as a limitation of the scope of the disclosure in any way. Dosage form Vegetarian Size 00 capsule, HPMC Ingredient details Glucosamine sulphate 2 KCL - 675 mg per capsule (equivalent to 500 mg glucosamine sulphate, 405 mg glucosamine per capsule) Lactobacillus acidophilus [Cul 60] - 1.25 billion cfu per capsule Lactobacillus acidophilus [Cul 21] - 1.25 billion cfu per capsule Bifidobacterium bifidum [Cul 73] - 10 billion cfu per capsule Vegetable magnesium stearate - 4 mg per capsule Silicon dioxide - 6 mg per capsule

Claims (5)

1. A composition comprising one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof for the treatment of a rheumatic disorder or for the relief of joint pain.

2. A composition according to claim 1 wherein the probiotic microorganisms comprise a multi-strain combination of Lactobacillus and Bifidobacterium species.

3. A composition according to claim 1 or 2, wherein the glucosamine is present as glucosamine sulphate, and the composition comprises about 675 mg comprising glucosamine sulphate 2 KCL, about 1.25 billion cfu of two Lactobacillus acidophilus strains and about 10 billion cfu of Bifidobacterium bifidum.

4. A composition according to any one of claims 1 to 3, wherein the rheumatic disorder is selected from osteoarthritis, rheumatoid arthritis, traumatic arthritis, degenerative arthritis and dysplastic arthritis.

5. A method for treating a rheumatic disorder or for relieving joint pain in a subject, the method comprising administering to the subject an effective amount of a combination of one or more probiotic microorganisms and glucosamine, or a salt or derivative thereof