WO2002028400A1

WO2002028400A1 - A therapeutic formulation containing glucosamine, methylsulfonymethane and eventually ascorbic acid and manganese

Info

Publication number: WO2002028400A1
Application number: PCT/IE2000/000116
Authority: WO
Inventors: Clare Hughes; Louise Grubb
Original assignee: Nutraceutics Limited
Priority date: 2000-10-03
Filing date: 2000-10-03
Publication date: 2002-04-11
Also published as: AU2000275502A1

Abstract

A therapeutic formulation for the treatment of osteoarthritis and the maintenance of joint function in animals comprises from 10 to 25% w/v of glucosamine and from 6 to 20% w/v methylsulfonylmethane.

Description

A THERAPEUTIC FORMULATION CONTAINING GLUCOSAMINE, METHELSULFONYMETHANE AN_D EVENTUALLY ASCORBIC ACID AND MANGANESE

Introduction

The present invention relates to a therapeutic formulation for the treatment of arthritis. In particular it relates to a therapeutic composition for the treatment of osteoarthritis and the maintenance of joint function in animals.

Arthritis, formerly called degenerative joint disease, is the number one cause of movement limitation and probably the leading cause of disability in animals and humans. Arthritis is not one disease, but a group of diseases whose common features are that they can cause pain, inflammation, and limited movement of the joints. There are more than 100 diseases that so affect the joints, the most common of which is osteoarthritis.

In a joint afflicted with osteoarthritis, the cartilage that covers and cushions the ends of the bones degenerates, allowing bones to rub together. The major symptom of osteoarthritis is pain resulting from the joint inflammation.

The connective tissues of humans and animals are constantly subjected to stresses and strains from mechanical forces that can result in afflictions, such as arthritis, joint inflammation and stiffness. Such afflictions are especially acute in joints, such as the neck, back, arms, hips, ankles and feet. Indeed, connective tissue afflictions are quite common. Further, such afflictions can not only be painful but, in their extreme, can also be debilitatory.

The connective tissues are naturally equipped to repair themselves by manufacturing and remodelling prodigious amounts of collagen (a chief component of connective tissues) and proteoglycans (PGs) - the other major component of connective tissues. This ongoing process is placed under stress when an injury occurs to connective tissues. In such cases, the production of connective tissue (along with collagen and proteoglycans) can double or triple over normal amounts, thereby increasing the demand for the building blocks of both collagens and proteoglycans.

The building blocks for collagen are amino acids, especially proline, glycine and lysine. Proteoglycans (PGs) are large and complex macromolecules comprised mainly of long chains of modified sugars called glycosaminoglycans (GAGs) or mucopolysaccharides. PGs provide the framework for collagen to follow. They also hold water to give the connective tissues, especially cartilage flexibility, resiliency and resistance to compression.

In the production of PGs, the rate-limiting step is the conversion of glucose to glucosamine for the production of GAGs. Glucosamine, an aminosugar, is the key precursor to all the various modified sugars found in GAGs such as glucosamine sulfate, galactosamine or N-acetylglucosamine. Glucosamine also makes up 50% of hyaluronic acid - the backbone of PGs - on which other GAGs like chondroitin sulfates are added. GAGs are then used to build PGs and eventually, connective tissue. Once glucosamine is formed, there is no turning away from the synthesis of GAG polymers and the synthesis of proteoglycan.

There are several disclosures wherein it has been suggested to bypass the rate- limiting step of the conversion of glucose to glucosamine in those pathways that produce proteoglycans by the provision of exogenous quantities of glucosamine. For example, the intravenous administration of glucosamine and derivations thereof have been disclosed in US Pat. No. 3,232,836 for assisting in the healing of wounds on the surface of the body. In US Pat. No. 3,682,076 the use of glucosamine and salts thereof are disclosed for the treatment of arthritic conditions. The use of glucosamine salts has also been disclosed for the treatment of inflammatory diseases of the gastrointestinal tract in US Pat. No. 4,006,224. US Pat. No. 5,587,363 describes a method for the treatment and repair of connective tissue in humans and animals by administering glucosamine in combination with chondroitin.

It is clear that any improved therapeutic composition which includes an analgesic and anti-inflammatory component as well as components that provide the building blocks for the production of connective tissue, is of benefit to both humans and animals alike.

The present invention is directed toward a therapeutic formulation for more effective or alternative treatment of osteoarthritis and/ or the maintenance of joint function in animals , especially non-humans .

Statements of Invention

According to the invention there is provided a therapeutic formulation comprising glucosamine and methylsulfonylmethane.

The invention also provides a therapeutic formulation for the treatment of osteoarthritis and the maintenance of joint function in animals comprising glucosamine and methylsulfonylmethane.

Preferably the glucosamine is present at a concentration of from 10 to 25%w/v of the formulation and the metiiylsulfonylmethane present in a concentration from 6 to 20%w/v of the formulation. Preferably the concentration ratio of glucosamine to methylsulfonylmethane is from 1:1 to 3:1, most preferably from 3:2 to 2:1.

In one embodiment of the invention the formulation includes ascorbic acid preferably at a concentration of from 0.05 to 2%w/v.

In another embodiment of the invention the formulation includes manganese preferably at a concentration of from 0.025 to l%w/v.

The formulation of the invention may further comprise an excipient selected from any one or more of sodium benzoate, potassium sorbate, microcrystalline cellulose, carboxymethyl cellulose sodium, flavouring agents, colouring agents, dextrose, sorbitol, xanthan gum or water. Especially preferred is a formulation including caramel flavouring and caramel colouring.

In one embodiment of the invention the formulation is in the form of a liquid.

The formulation may also be in the form of a powder, paste, tablet or capsule.

The invention also provides a method for the treatment of osteoarthritis and/ or for maintenance of joint function in animals comprising the step of administering a therapeutic amount of a formulation comprising glucosamine and methylsulfonylmethane.

The invention further provides a method for reducing inflammation of connective tissue in animals comprising the step of administering a therapeutic amount of a formulation comprising glucosamine and methylsulfonylmethane.

In this case the therapeutic formulation includes a therapeutic amount of manganese and/ or a therapeutic amount of ascorbic acid. Preferably the formulation is administered orally. Alternatively the formulation may be administered in a foodstuff.

In one embodiment of the invention the formulation is administered in a plurality of daily dosages .

Detailed Description

The invention provides a therapeutic formulation which combines glucosamine with methylsulfonylmethane (MSM). Co-factors such as ascorbic acid (vitamin

C) and manganese may also be included.

Throughout the description and claims of the specification the term glucosamine is taken to include glucosamine salts and/ or mixtures thereof.

In particular glucosamine HC1 is used as it has been found to supply more free glucosamine than glucosamine sulphate or acetyl glucosamine.

Studies have indicated that orally administered salts of glucosamine show better bioavailability levels then glucosamine administered parenterally (Setnikar L. et al, Pharmacokinetics of Glucosamine in Man, Arzneim Forsch (Germany) 43:1109-13;1993). These studies indicate that the salts of glucosamine may act as prodrugs allowing good absorption of glucosamine, the glucosamine diffusing into several tissues including bone and articular tissue.

Large amounts of glucosamine are required to repair and treat connective tissue. As orally administered formulations comprising glucosamine salts have been found to have high bioavailability, higher concentrations of glucosamine are available for the repair and formation of connective tissue. The presence of the natural analgesic MSM provides an anti-inflammatory effect. MSM is commonly used as a dietary supplement, to improve the overall state of health and resistance to disease, without any side effects. Research has shown that MSM is helpful in improving joint flexibility, reducing stiflhess, improving circulation and cell vitality, reducing pain and scar tissue and in breaking up calcium deposits. MSM is also thought to make cells more permeable, enabling the body to flush out undesirable foreign particles. MSM sustains cell flow-through allowing harmful substances to flow out while permitting nutrients to flow in thereby preventing pressure build-up in cells which causes inflammation in the joints and elsewhere and translates to pain.

MSM is a natural form of organic sulphur found in the fluid of all living organisms. It is present in a variety of foods, including most fresh raw fruits and vegetables, milk, meat, seafood and some grains. However, MSM is volatile and is easily lost during even moderate processing. Cooking, drying, smoking, pickling, and long term storage can deplete the MSM content of food. Unless the diet is composed primarily of raw foods, it is unlikely that sufficient MSM will be ingested to significantly contribute to the nutritional sulphur requirement.

MSM also has a synergistic effect with glucosamine. The sulphur donated by MSM is a building block of glucosaminoglycans which forms the matrix for regeneration of joint cartilage.

US patent No. 4,296,130 describes the use of cosmetic preparations containing

MSM. US Patent No.s 4,514,421 and 4,616,039 describe the dietary and pharmaceutical uses of MSM. US Patent No. 4,973,605 describes the use of MSM to relieve pain and nocturnal cramps and to reduce stress-induced deaths in animals. Nutritional supplements containing this patented, licensed form of MSM have been available commercially from Advanced Medical Nutrition Inc (SMN-Q since 1986.

To date there has been no disclosure of a formulation comprising both glucosamine and MSM in the treatment of osteoarthritis .

In addition to glucosamine and MSM the formulation of the present invention also contains manganese and vitamin C. Manganese is an essential co factor for the synthesis of GAGs from glucosamine and vitamin C (ascorbic acid) is a necessary cofactor in the synthesis of collagen. Glucosamine, MSM, manganese and vitamin C therefore provide a beneficial combination in the treatment of osteoarthritis and the maintenance of joint function in animals.

Manganese plays a role in the synthesis of glycosaminoglycans and glycoproteins, which are important constituents of cartilage and bone. Many reproductive problems in horses and skeletal abnormalities in foals have been ascribed to manganese deficiency. [Current Therapy in Equine Medicine, 2 (1987) pp 402-403].

Vitamin C (ascorbic acid) is needed for the production of collagen. Vitamin C also enhances manganese uptake by the body.

In the present invention it was found that preparing a therapeutic formulation in liquid form has significant advantages.

MSM has a high bioavailability especially when the formulation is administered in a liquid form. Other known compositions only show an anti-inflammatory effect after several days. However the liquid formulation of the present invention was found to provide maximum absorption of all the components. Administration in liquid form also maximises the assimilation, absorption and bioavailability of glucosamine.

Liquids are more easily administered. Foodstuffs may be either coated with the liquid formulation or mixed with the liquid formulation. Alternatively the liquid formulation may be administered orally on its own.

In preparing the formulations for oral dosage any pharmaceutical medium may be employed, media containing for example water, oils, alcohols, preservatives, colouring agents and other commercial excipients may be used. Flavouring agents such as caramel may be added to make the formulation more palatable to animals. The formulation may also include an ingestable carrier in which case the formulation is in the form of a tablet, capsule, syrup or powder.

Glucosamine and MSM may be administered sequentially rather than concurrently however for ease of administration to animals concurrent use is preferred.

The invention will be more clearly understood from the following examples.

Example 1

Dosage formulations for oral administration to equine or canine animals were prepared. In a preferred embodiment each dosage contains the following:

10ml Dosage 5ml Dosage

Compound Equine Canine

Glucosamine 10,000mg 600mg

MSM 5,000mg 400mg MSM under the trade name Alavis™ is available from Carolwood Corporation. Glucosamine is isolated from chitin of shellfish and is available for example from Buckston Scott, UK.

Example 2

The formulation of example 1 may be supplemented with manganese and ascorbic acid as follows.

10ml Dosage 5ml Dosage

Compound Equine Canine

Glucoasmine 10,000mg 600mg

MSM 5,000mg 400mg

Manganese lOOmg 2.5mg

Ascorbic acid 700mg 50mg

Example 3

The formulation of examples 1 and 2 may be further supplemented with standard excipients as follows.

50ml Dosage 5ml Dosage

Compound Equine Canine

Glucoasmine 10,000mg 600mg

MSM 5,000mg 400mg

Manganese lOOmg 2.5mg

Ascorbic acid 700mg 50mg

The invention is not limited to the embodiments hereinbefore described which may be varied in detail.

Claims

1. A therapeutic formulation comprising glucosamine and methylsulfonylmethane .

2. A therapeutic formulation for the treatment of osteoarthritis and the maintenance of joint function in animals comprising glucosamine and methylsulfonylmethane .

3. A therapeutic formulation as claimed in claim 1 or 2 wherein the glucosamine is present at a concentration of from 10 to 25%w/v of the formulation.

4. A therapeutic formulation as claimed in any preceding claim wherein the methylsulfonylmethane is present at a concentration of from 6 to

20%w/v of the formulation.

5. A therapeutic formulation as claimed in any preceding claim wherein the concentration ratio of glucosamine to methylsulfonylmethane is from 1:1 to 3:1, preferably from 3:2 to 2:1.

6. A formulation as claimed in any preceding claim including ascorbic acid.

7. A formulation as claimed in claim 6 wherein the ascorbic acid is present at a concentration of from 0.05 to 2%w/v.

8. A formulation as claimed in any preceding claim including manganese.

9. A formulation as claimed in claim 8 wherein the manganese is present at a concentration of from 0.025 to l%w/v.

10. A formulation as claimed in any preceding claim further comprising an excipient selected from any one or more of sodium benzoate, potassium sorbate, microcrystalline cellulose, carboxymethyl cellulose sodium, flavouring agents, colouring agents, dextrose, sorbitol, xanthan gum or water.

11. A formulation as claimed in any preceding claim in the form of a liquid.

12. A formulation as claimed in any preceding claim in the form of a powder, paste, tablet or capsule.

13. A method for the treatment of osteoarthritis and/or for maintenance of joint function in animals comprising the step of administering a therapeutic amount of a formulation comprising glucosamine and methylsulfonylmethane .

14. A method for reducing inflammation of connective tissue in animals comprising the step of administering a therapeutic amount of a formulation comprising glucosamine and methylsulfonylmethane.

15. A method as claimed in claim 13 or 14 wherein the therapeutic formulation includes a therapeutic amount of manganese.

16. A method as claimed in claim 13 or 14 wherein the therapeutic formulation includes a therapeutic amount of ascorbic acid.

17. A method as claimed in any of claims 13 to 16 wherein the formulation is administered orally.

18. A method as claimed in any of claims 13 to 17 wherein the formulation is administered in a foodstuff.

19. A method as claimed in any of claims 13 to 16 wherein the formulation is administered in a plurality of daily dosages.