WO2009153200A1

WO2009153200A1 - Preparation containing glucosamine and/or chondroitin for prophylaxis and treatment of arthrosis and for supporting the immune system

Info

Publication number: WO2009153200A1
Application number: PCT/EP2009/057171
Authority: WO
Inventors: Gertrud Langhoff
Original assignee: Gertrud Langhoff
Priority date: 2008-06-18
Filing date: 2009-06-10
Publication date: 2009-12-23
Also published as: EP2303231A1; DE202008008059U1

Abstract

The present invention describes a liquid, aqueous formulation comprising: 1 to 60 wt.-% of a component (a) that consists of glucosamine and/or a physiologically acceptable derivative of glucosamine and/or chondroitin and/or a physiologically acceptable derivative of chondroitin, 0.1 to 30 wt.-% of a component (b) that consists of a phospholipid and/or a physiologically acceptable derivative of a phospholipid and 5 to 90 wt.-% of a component (c) consisting of a micelle stabilizer selected from the group consisting of (c1 ) carnitine and/or a physiologically compatible carnitine derivative, and (c2) one or more polyol(s) selected from the group consisting of: aldoses, ketoses, reduced aldoses and/or ketoses, physiologically acceptable glycosides of aldoses and/or ketoses, C₃-C₆- triols, C₃-C₆- tetraols, C₃-C₆- pentanols and C₃-C₆ hexanols, wherein each of the weight amounts relates to the total formulation.

Description

PREPARATION CONTAINING GLUCOSAMINE AND / OR CHONDROITIN TO THE PROPHYLAXIS AND THERAPY OF ARTHROSIS AS WELL AS TO SUPPORT THE IMMUNE SYSTEM

The invention relates to a liquid, aqueous formulation, a solid which is obtainable from the liquid formulation by drying and a pharmaceutical preparation comprising the formulation or the solid, in particular for the prophylaxis and / or treatment of osteoarthritis in humans and animals. Moreover, the invention relates to the use of the liquid formulation or of the solid as a dietary supplement, dietetic food or cosmetics.

The structure of the joints of the human body is principally characterized by three features:

a) both bones of the joint are separated by a joint gap, b) the two bone ends are covered with a cartilage layer, c) in the joint space is the synovial fluid.

The ends of each articular bone are covered with articular cartilage. The elastic articular cartilage allows in conjunction with the synovial fluid a balanced and low-friction movement.

Physiologically, the articular cartilage is also referred to as hyaline cartilage and is unique in its construction. Articular cartilage is characterized by its viscoelastic properties and is ideally adapted to the various biomechanical requirements placed on it. Due to these properties, it is able to provide sufficient support for the differentiated load patterns and weight distributions, while at the same time minimizing the frictional forces involved.

The main component of hyaline cartilage is the extracellular matrix, which consists of a network of different collagen fibrils, most notably collagen type II, and proteoglycans. While the collagen fibrils are largely responsible for the structural architecture and biomechanical elasticity of the cartilage and thus provide protection against shear forces, the proteoglycans are responsible for controlling water uptake and release due to their high water binding capacity. Functionally, they can thus adjust the cartilage to different static loads. With the constant intake and release of water, the diet of the chondrocytes in the non-perfused cartilage tissue is ensured at the same time. The cartilage and the synovial fluid form a functional unit. Synovial fluid is a substance that guarantees the metabolism of cartilage. Essential nutrients are supplied to him and degradation products removed. These metabolic processes mediated by the synovial fluid are stimulated by movement. Sufficient movement is thus of crucial importance for the health of the cartilage.

The synovial fluid has the special ability to adapt to the different requirements of the movements and thereby protect cartilage and bone. During slow movements (walking, turning, bending), the fluid behaves viscously, spreading evenly throughout the joint space, preventing the cartilaginous layers from rubbing against each other. In fast, jerky movements, such as running and jumping, however, the synovial fluid behaves like an elastic mass, which absorbs the enormous force effects similar to a shock absorber.

The cartilage is not perfused. Nevertheless, like any living tissue, it needs enough nutrients. These are supplied by the synovial fluid. In turn, the synovial fluid receives the nutrients from the peripherally perfused tissue. The better the perfusion of the peripheral tissue, the more efficiently nutrients can be delivered to the synovial fluid and thus to the cartilage.

It can be seen that in addition to a balanced diet, sufficient movement for the maintenance of healthy cartilage and joints is a prerequisite. If there is no movement, the synovial fluid loses its viscosity and elasticity. The cartilage will crack in succession and may eventually disappear completely leaving the bone ends exposed. This process is so painful that even simple movements are painful, it comes to joint arthrosis. This creates a circus vituosis, a self-reinforcing cycle. Due to the occurring pain, the joint is less moved and the lower movement of the metabolism in the joint is sustainably damaged.

Therefore, of prime importance are mechanisms that support the occurrence or the healing of joint arthrosis by prophylactic and therapeutic measures. To date, there is no causal pharmacological osteoarthritis therapy. However, there are substances that stop the loss of cartilage and sustainably improve the general joint function. These substances are glucosamine and chondroitin sulfate. Glucosamine is made by the healthy juvenile body itself from ingredients of the food. It is irreplaceable as a basic substance for cartilage, synovial fluid, tendons, bones but also for the connective tissue of arterial walls.

The same applies to chondroitin that is derived from glucosamine in the body. Glucosamine is much smaller than chondroitin. Because of this, glucosamine is usually better absorbed by the body than chondroitin. The absorption rates for glucosamine sulfate, for example, are above 90%, for chondroitin sulfate at about 5%. Studies have shown that orally ingested glucosamine sulfate is incorporated into the damaged cartilage matrix and the damaged cartilage can be restored.

With increasing age, the body loses more and more the ability to absorb condricin and glucosamine sulphate from food. Negative effects also have changing dietary habits. Cartilage and connective tissue are no longer on the menu for most people today. As a result of a lack of these two substances in the diet, there is a shortage of synovial fluid. In the further course erosions occur.

The object of the patent was to provide a nutrient formulation which rapidly supplies the nutrients glucosamine and chondroitin or their physiologically acceptable derivatives to the body and also improves the absorption. Another object of the invention is to enable the absorption of the substances mentioned after administration already through the skin and oral mucosa. At the same time, therapy should be based on orthomolecular medicine, i. that only substances that the body produces itself or is known to it as natural components come into play.

Surprisingly, it has now been found that with a formulation of phospholipids, glucosamine and / or chondroitin and a micellar stabilizer a very rapid onset of Arthrosephrophylaxe and therapy can already be achieved via mucous membranes, at the same time in an experimental study positive, subjective assessment of persons or animals provoked. In addition, the use of synthetic co-emulsifiers or surface-active substances can be completely dispensed with.

In addition, it has surprisingly been found that the nutrient formulations can be subjected to spray or freeze-drying, wherein powders are contained in which the vesicular structure is retained and thus rapid absorption is still ensured. That is, when dissolving the powder in water forms the original Emulsion off again. These powders can also be used directly or made into tablets without sacrificing the benefit of rapid resorption.

The present invention in a first embodiment is a liquid, aqueous formulation comprising:

1 to 60% by weight of a component (a) consisting of glucosamine and / or a physiologically acceptable derivative of glucosamine and / or chondroitin and / or a physiologically acceptable derivative of chondroitin,

0.1 to 30 wt .-% of a component (b), which consists of phospholipid and / or a physiologically acceptable derivative of a phospholipid, and

5 to 90 wt .-% of a component (c) consisting of a micelle stabilizer selected from the group consisting of

(c1) carnitine and / or a physiologically acceptable carnitine derivative, and (c2) one or more polyol (s) selected from the group consisting of: aldoses, ketoses, reduced aldoses and / or ketoses, physiologically acceptable glycosides of aldoses and / or ketoses, C ₃ -C ₆ -triols, C ₃ -C ₆ -tetraols, C ₃ -C ₆ -pentaols and C ₃ -C ₆ -hexaols, wherein the amounts by weight in each case relate to the entire formulation.

Component (a) consists of glucosamine and / or a physiologically acceptable derivative of glucosamine and / or chondroitin and / or a physiologically acceptable derivative of chondroitin.

Glucosamine (2-amino-2-deoxy-D-glucopyranose) is a derivative of D-glucose. Physiologically acceptable derivatives are, for example, glucosamine sulfate and / or glucosamine hydrochloride.

Chondroitin is a mucopolysaccharide consisting of a chain of alternating sugar derivatives (N-acetyl-D-galactosamine and D-glucuronic acid). It is usually used as its sulfuric acid derivative chondroitin sulfate.

A natural source of glucosamine and chondroitin or their physiologically acceptable derivatives are mussel extracts, for example extracts of the green-lipped mussel (Perna canaliculus). The extracts are extracted from the mussel meat and then freeze-dried. Mussel extracts are particularly preferred because they are rich in glucosaminoglycans. In a preferred embodiment of the present invention, therefore, a mussel extract is used as component (a).

In a further embodiment, the formulations according to the invention contain mussel extract in amounts of up to 40% by weight, preferably 2-30% by weight, particularly preferably 3-10% by weight.

In a preferred embodiment, the formulations according to the invention contain glucosamine sulfate and / or chondroitin sulfate. The formulations according to the invention particularly preferably contain glucosamine sulfate and chondroitin sulfate, preferably in a weight ratio of glucosamine sulfate: chondroitin sulfate of 100: 1 to 1: 1, more preferably 50: 1 to 2: 1, particularly preferably 20: 1 to 5: 1.

Component (a) is present in an amount of 1 to 60% by weight, preferably 3 to 50% by weight, more preferably 5 to 40% by weight, based in each case on the entire formulation.

Component (b) consists of a phospholipid and / or a physiologically acceptable derivative of the phospholipid. Particularly preferred is the use of phosphatidylcholine obtained from soy, rapeseed, milk, fish or egg lecithin. Also particularly preferred are mixtures of several phospholipids. Preferred phospholipids are phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid containing at least 50 to 95% by weight of phosphatidylcholine. Particularly preferred is the use of phospholipids obtained from soybean or egg lecithin. The lecithins may be either unsaturated, hydrogenated, hydrolyzed or hydroxylated. Also particularly preferred are phosphatidylcholines characterized by a chain length of the fatty acid of C ₆ to C ₂ o. In particular, those phospholipids are preferred which carry a Cs-fatty acid radical.

It has been found that the use of phospholipids, especially mixtures of phospholipids, plays an important role in the stabilization and emulsification of the aqueous formulation.

Component (b) is present in an amount of from 0.1 to 30% by weight, preferably from 1 to 15% by weight, particularly preferably from 3 to 8% by weight, based in each case on the entire formulation.

Component (c) consists of a micelle stabilizer selected from the group consisting of

(d) carnitine and / or a physiologically acceptable carnitine derivative, and (c2) one or more polyol (s) selected from the group consisting of: aldoses, ketoses, reduced aldoses and / or ketoses, physiologically acceptable glycosides of aldoses and / or ketoses, C ₃ -C ₆ -triols, C ₃ -C ₆ tetraols, C ₃ -C ₆ pentaols and C ₃ -C ₆ hexaols.

Component (c) is preferably selected from L-carnitine and / or physiologically acceptable derivatives such as carnitine tartrate and / or acyl-L-carnitine and from the group consisting of glycerol, pentitols, preferably glucose, fructose, maltodextrin, XyNt or hexitol, in particular sorbitol, mannitol, GuNt or inositol, as well as its physiologically acceptable derivatives such as inositol triphosphate and / or disodium inositol.

Particularly suitable micelle stabilizers are selected from the group consisting of L-ascorbic acid, sodium ascorbate, sucrose, glycerol and fructose.

Component (c) is present in an amount of 5-90% by weight, preferably 15-80% by weight, particularly preferably 25-70% by weight, based in each case on the entire formulation.

In a further preferred embodiment, the formulations according to the invention additionally contain hyaluronic acid or the physiologically acceptable derivatives, such as, for example, Sodium hyaluronate. Hyaluronic acid is a glucosaminoglycan and one of the major components of synovial fluid in the joints.

Hyaluronic acid and / or its physiologically acceptable derivatives may be present in an amount of 0.1-5% by weight, preferably 0.2-3% by weight, more preferably 0.3-2% by weight, based in each case on entire formulation.

In addition, the formulations according to the invention may additionally contain dermatan sulfate, and / or keratan sulfate and / or heparan sulfate. The substituents are preferably present in an amount of up to 10% by weight, preferably 1-8% by weight, more preferably 2-5% by weight, based in each case on the entire formulation.

In a further embodiment, the formulations according to the invention contain L-ascorbic acid and / or physiologically acceptable derivatives thereof. The physiologically acceptable derivatives include the alkali and / or alkaline earth metal salts, such as Na, - K, - Mg, - or calcium ascorbate. In addition, the physiologically acceptable derivatives include L-ascorbyl-6-palmitate. In a further embodiment, the formulations according to the invention additionally contain methylsulfonylmethane in amounts of up to 40% by weight, preferably 2 to 30% by weight, more preferably 3 to 20% by weight.

In a further embodiment of the present invention, the formulations additionally contain triglycerides containing saturated and / or monounsaturated fatty acids and / or polyunsaturated fatty acids and / or their ethyl esters. Preferably used are oils or fats comprising at least one fatty acid selected from linoleic acid, alpha-linolenic acid, di-homo-gamma-linolenic acid, gamma-linolenic acid, conjugated linoleic acid, eicosapentaenoic acid, docosahexaenoic acid. Particularly preferred is fish oil, krill oil or omega-3 fatty acid ethyl ester.

The oils or fats are characterized in that they contain the above fatty acids in an amount of 3 to 90 wt .-%, based on the oil or fat.

Furthermore, the formulations according to the invention preferably contain medium-chain triglycerides. Medium chain triglycerides (MCT for Medium-Chain Triglycerides) are an ester compound of medium chain fatty acids and glycerol. The medium-chain fatty acids consist of a carbon chain with 6 to 12 carbon atoms. The medium chain fatty acids are preferably saturated.

Fish oil and krill oil are distinguished by the fact that they contain 10 to 35% by weight of eicosapentaenoic acid and docosahexaenoic acid in the form of their triglycerides, based on the fish oil.

Omega-3-Fettsäureethylester characterized by the fact that they contain 10 to 90 wt .-% omega-3 fatty acids.

In addition, the formulation may additionally contain vegetable ingredients or plant extracts of red wine, Cistrus fruits, blueberry, acerola, elderberry, frankincense, red clover, ginseng or turmeric, for example flavonoids / anthocyanidins such as OPC (oligomeric procyanidins), quercetin, naringin, rutin, chrysin, ginsenoids or others, such as the trans-stilbene derivative resveratrol. The plant constituents are preferably present in an amount of up to 80% by weight, more preferably 1 to 60% by weight, in particular 5 to 30% by weight, based in each case on the entire formulation. Secondary plant substances such as OPC (oligomeric procyanidins), resveratrol or rutin, whose absorption is usually very poor, can be well absorbed with the formulations according to the invention. These substances are characterized by excellent radical scavenging properties and are therefore an ideal complement. In particular, in the nanoemulsions according to the invention, the plant extracts to be used according to the invention are absorbed much better by the body, and this also without the use of alcohol. Due to the greatly improved absorption of smaller amounts of these substances must be used to achieve a positive effect effect.

In addition, the formulations may additionally contain one or more ingredients selected from taurine, beta carotene, vitamin A, lycopene, zeaxanthin, astaxanthin, vitamin K, vitamin E, tocotrienols, vitamin K, biologically active selenide derivatives, or one or more water soluble vitamins , Furthermore, the formulations may comprise one or more elements in their physiologically acceptable form selected from the group consisting of boron, iron, copper, manganese, zinc, molybdenum and chromium.

By way of example only, it should be mentioned that the formulation according to the invention, based on 100 parts by weight of the formulation according to the invention, may furthermore contain independently of one another:

0.1 to 10 parts by weight, preferably 1 to 5 parts by weight of taurine;

0.1 to 1 part by weight, preferably 0.3 to 0.6 parts by weight of beta-carotene;

0.03 to 0.3 parts by weight, preferably, 0.07 to 0.2 parts by weight of vitamin A;

0.1 to 1 part by weight, preferably 0.3 to 0.6 parts by weight of lycopene

0.1 to 1 part by weight, preferably 0.3 to 0.6 parts by weight of zeaxanthin

0.1 to 1 part by weight, preferably 0.3 to 0.6 parts by weight of astaxanthin

0.1 to 5 parts by weight, preferably 0.3 to 2 parts by weight of vitamin E.

0.1 to 5 parts by weight, preferably 0.3 to 2 parts by weight tocotrienols

0.1 to 1 part by weight, preferably 0.3 to 0.6 parts by weight of vitamin K;

10 ^"5 to ^{3x10" 5} weight parts, preferably 1, 3x10 ^"4 to ^{2,7x10" 4} parts by weight biologically active selenium..;

one or more of the water-soluble vitamins and / or its physiologically acceptable derivatives, thiamine, riboflavin, niacin, NADH, NADPH, pyridoxine,

Pantothenic acid, biotin, folic acid and cobalamin in the following proportions by weight: Vitamin From To Preferred From Preferred To

Thiamine 10 ^"3 0.01 3x10 ^{" 3} 8x10 ^"3

Riboflavin 10 ^"3 0.01 3x10 ^{" 3} 8x10 ^"3

Niacin 2x10 ^"3 0.03 6x10 ^{" 3} 2x10 ^"2

NADH 2x10 ^"3 0.03 6x10 ^{" 3} 2x10 ^"2

Pyridoxine 10 ^"3 0.01 3x10 ^{" 3} 8x10 ^"3

Pantothenic acid 0.01 0.1 0.03 0.08

Biotin i o- ⁴ 10 ^"3 3x10 ^{" 4} 8x10 ^"4

Folic Acid 10 ^"4 10 ^{" 3} 3x10 ^"4 8x10 ^{" 4}

Cobalamin 10 ^"5 10 ^{" 4} 3x10 ^"5 8x10 ^{" 4}

One or more elements in their physiologically compatible form selected from the group consisting of boron, iron, copper, iodine, manganese, zinc, molybdenum and chromium.

Element From To Preferred From Preferred To

Boron 10 ⁴ 0.01 3x10 ^"4 8x10 ^{" 4}

Iron 0.01 0.05 0.02 0.03

Phosphorus 0.01 0.05 0.02 0.03

Copper 10 ^"3 5x10 ^{" 3} 2x10 ^"3 3x10 ^{" 3}

I od i o- ⁴ 5x10 ^"4 2x10 ^{" 4} 3x10 ^"4

Manganese 10 ^"3 5x10 ^{" 3} 2x10 ^"3 3x10 ^{" 3}

Molybdenum 2x10 ^"5 5x10 ^{" 4} 2x10 ^"4 3x10 ^{" 4}

Chrome 2x10 ^"5 5x10 ^{" 4} 2x10 ^"4 3x10 ^{" 4}

In a further embodiment, the formulations according to the invention may be present as a nutrient preparation and may additionally contain extracts of Stevia rebandiana.

In a further embodiment of the present invention, the formulations contain extracts of Stevia rebaudiana containing about 10-25% by weight of steviol glycosides, based on the dry extract, which have about 300 times more sweetening power than sugar. The formulations preferably contain 0.1 to 20% by weight, more preferably 0.2 to 10% by weight, in particular 0.3 to 2% by weight, based in each case on the entire formulation.

In a further preferred embodiment of the present inventive formulation, the formulation is substantially free of primary volatile alcohols (VOC) and / or ethoxylated or other synthetic surfactants, in particular substantially free of ethanol. In a further preferred embodiment of the formulation according to the invention, the formulation coenzyme Q10 also contains ubiquinone or its physiologically acceptable derivatives. Among the physiologically acceptable derivatives are coenzyme Q3, coenzyme Q4, coenzyme Q5, coenzyme Q6, coenzyme Q7, coenzyme Q8 or coenzyme Q9.

The formulation preferably contains coenzyme Q ₁₀ and / or its physiologically acceptable derivatives in an amount of 0.1-20% by weight, preferably 0.2-8% by weight, particularly preferably 0.3-4% by weight, in each case based on the entire formulation.

In addition, the formulations, preferably taurine and / or their physiologically acceptable derivatives such as e.g. Taurine chloramine and / or taurine bromine. The component is preferably present in an amount of 0.1-50% by weight, preferably 0.5-30% by weight, more preferably 1-10% by weight, based on the total formulation.

Furthermore, the formulations may comprise silicic acids, for example ortho or meta-silicic acids, in particular water-soluble silicic acids. The silicas may preferably be used in amounts of from 0.1 to 8% by weight, based on the formulation.

Furthermore, customary constituents, such as flavorings, dyes, thickeners and customary physiologically acceptable release agents may be present in the formulations according to the invention.

The liquid aqueous formulations according to the invention form vesicular structures. The formation of the vesicular structures also makes it possible to produce concentrated liquid formulations which, for example, have a water content of less than 40% by weight, based on the total formulation. In a preferred embodiment, the liquid aqueous formulations are present as an emulsion in the form of a micellar concentrate. The micelles in the liquid, aqueous formulations according to the invention preferably have an average diameter of less than 300 nm, preferably from 10 to 250 nm, more preferably from 50 to 230 nm and in particular from 130 to 210 nm or 50 to 130 nm. In a preferred embodiment, the liquid aqueous formulations according to the present invention are transparent to translucent.

The mean diameter of the vesicular structures can be determined by methods known to those skilled in the art, for example a Coulter Counter N24. For this purpose are at Room temperature (25 ° C) diluted a few drops of a sample with distilled water and placed in a cuvette. Subsequently, the average particle size is determined by means of light scattering. The preparation of the formulation according to the invention can be carried out by means of commercial high-pressure homogenizers with which the formulations according to the invention are homogenized. In particular, when the present formulations according to the invention are present as a nano-emulsion (average diameter of the micelles from 10 to 250 nm), the formulations can be rapidly absorbed by the body. It has surprisingly been found that the formulations according to the invention, in particular the micellar concentrates, lead to a significantly faster and increased absorption of both hydrophilic and lipophilic constituents. In particular, when the present aqueous liquid formulations are present as nano-emulsions, it is also possible to work without synthetic emulsifiers or co-emulsifiers and alcohols (ethanol).

The formulations according to the invention are preferably homogenized formulations, in particular homogenized emulsions.

The aqueous formulations according to the invention, in particular the nanoscale vesicular formulations, offer the following advantages over conventional crystalline or conventional administration forms of glucosamine, and / or chondroitin sulfate:

In the formulations of the invention, the active ingredient, ie the glucosamine, and / or chondroitin sulfate is present in vesicles. The vesicles have a very large surface, resulting in a large interaction area. In addition, the vesicles are stabilized by a phospholipid layer. The active substance vesicles have a modified particle surface which is hydrophilic and therefore allows the free mobility of the vesicles in an aqueous environment. Surprisingly, it was also found that the nanoscale vesicles have an increased solution pressure, which significantly improves the absorption capacity.

It has surprisingly been found that the nano-emulsions are particularly effective for the therapy and prophylaxis of osteoarthritis in humans and animals.

The formulations according to the invention can moreover be fed directly, ie unchanged and without further auxiliaries, to a suitable drying process, it being possible to obtain nanoscale vesicularly structured powders. The formulations according to the invention can also be dried.

Another object of the present invention is therefore a solid, obtainable from a formulation according to the invention by drying, preferably spray-drying or freeze-drying. It has surprisingly been found that the micellar structure is retained in the dried solids, so that the dissolution of the solid in water, the original micellar / vesicular emulsion structured can be recovered. This has considerable advantages since it allows the formulation according to the invention to be formulated simply as solid preparations.

In a preferred embodiment, the solids according to the invention are such that they additionally contain a polycarboxylic acid, preferably citric acid and / or polycarboxylic acid salt, preferably citric acid salt, in particular calcium and / or magnesium citrate or gluconic acid and / or gluconic acid salt, in particular Na, Mg or Ca. Gluconates have.

In a further preferred embodiment, the solids according to the invention are present in such a way that they additionally have bicarbonate, preferably sodium bicarbonate.

Another object is a granule, a chewable tablet, a tablet, dragee or capsule containing the solid according to the invention.

Another object of the present invention is a pharmaceutical preparation comprising a formulation according to the invention or a solid according to the invention.

Another object is a pharmaceutical preparation comprising a formulation according to the invention or a solid according to the invention for the therapy or prophylaxis of joint diseases, in particular arthritis in humans and animals.

The pharmaceutical preparation according to the invention is generally metered so that the amount of the amounts of component (a), preferably glucosamine sulphate, administered to the body is between 20 and 2000 mg / day, preferably 450 to 1500 mg / day, more preferably 200 to 1000 mg / Day (and individual with a body weight of 75 kg). The quantitative proportions of components (b) and (c) may be calculated based on the amount of component (c) based on their percentages mentioned above.

The preparation according to the invention can be administered in several single doses throughout the day. In addition, it is also possible to administer the components (a) to (c) individually.

Another object of the present invention is a kit of parts, comprising the components (a) to (c), wherein at least one of the components is spatially separated from the other. The kit of parts can be a container in which there are two or more compartments containing components (a) to (c). In the kit according to the invention, the individual components can be present independently of one another in the form of a micellar concentrate, a spray-dried or freeze-dried powder or tablets, dragees, capsules obtained therefrom. In a preferred embodiment, the kit according to the invention comprises at least one compartment and an additional container, two of the components selected from components (a) to (c) being contained in at least one of the compartments and / or in the container.

Another object of the present invention is a process for the preparation of a composition, characterized in that a liquid aqueous formulation of the emulsion-type, water-soluble, concentrate is spray-dried or freeze-dried such that micelles are retained in the resulting dried product.

The drying is preferably carried out at temperatures below 100 ⁰ C. The drying can also be such that partial components of the formulation according to the invention are converted into a solid and the remaining components are then applied to the already formed solids, preferably sprayed.

The emulsion-type, water-soluble concentrate may be used together with another aqueous formulation A containing a polycarboxylic acid, preferably citric acid and / or polycarboxylic acid salt, preferably citric acid salt, especially calcium and / or magnesium citrate or gluconic acid and / or gluconic acid salt, especially Na, Mg or Ca Gluconate, the spray or freeze-drying is fed, preferably such that micelles are retained in the dried material. Another object of the present invention is a gel comprising the liquid formulation of the invention or the solid according to the invention. The gels according to the invention are preferably obtainable in which a gelling agent, for example xanthan gum, is added to the aqueous formulation according to the invention. The gel is particularly suitable for topical applications.

It has surprisingly been found that the formulations or gels according to the invention can be topically applied to the bodies of the human and animal body which are affected by osteoarthritis.

It has surprisingly been found that the formulations or gels according to the invention also act transdermally. This applies in particular to the formulations with a mean vesicle size in the range from 10 to 250 nm. The pharmaceutical preparations can therefore also be used for the topical therapy and prophylaxis of joint diseases, in particular arthrosis in humans and animals.

Another object of the present invention is therefore the use of the formulation according to the invention for the prophylaxis and therapy of osteoarthritis. In addition, the nutrient preparation or the formulation according to the invention in a process for the preparation of nutrient preparations, preferably in a process for the preparation of a nutrient preparation for the prophylaxis and therapy of joint diseases, in particular arthritis in humans and animals.

Another object of the present invention is also the use of the formulation of the invention or the solid or gel according to the invention as a dietary supplement, dietetic food, pharmaceutical or cosmetic in humans and animals.

EXAMPLES

Example 1 :

Inventive formulation

The raw materials are dispersed in water and homogenized with soy phospholipid. Homogenizer: Panda 2K, NS 10012 from Niro Soavi .; Temp: 25 ° C; at 400bar.

Average particle size of the micelles of the micellar concentrate: 50 nm

Example 2:

Inventive formulation

Average particle size of the micelles of the micellar concentrate: 50 nm Example 3:

Inventive formulation

Average particle size of the micelles of the micellar concentrate: 150 nm

The emulsion of example 3 can be made into a gel with a content of 2% xanthan, based on the entire formulation. This gel can also be used for skin care or topical treatment of osteoarthritis on the affected joint.

Example 4:

Inventive formulation

The raw materials are dispersed in water and homogenized together with soy phospholipid. Homogenizer: Panda 2K, NS 10012 from Niro Soavi .; Temp: 25 ° C; at 400bar. Average particle size of the micelles of the micellar concentrate: 190 nm

To produce the solid according to the invention, the emulsion thus obtained is subsequently freeze-dried.

Example 5:

^* »Soluthin MD ex Phospholipid GmbH, Cologne.

The Soluthin MD ^® is sprayed at 70 ⁰ C in the dry space with a 5% aqueous solution of glucosamine sulphate.

Experimental studies

I. On the basis of the emulsion of Example 3, a human observational study was performed, the duration of which extended over 6 weeks. The two comparison groups each consisted of 5 subjects (all aged between 53 and 75 years). The subjects equally suffered from hip arthrosis. All patients took a non-steroidal anti-inflammatory drug at the beginning of the study, which had to be taken daily.

In each case 5 subjects 10 ml of the emulsion from Example 3 were administered orally over a period of 6 weeks.

As a comparison, capsules were administered orally in the comparison group with 5 subjects daily, in which the components glucosamine sulfate, chondroitin sulfate and coenzyme Q10 in powder form in appropriate amounts, as in Example 3, were present.

The critical parameters observed in the subjects were:

(a) duration of onset pain at morning stiffness,

(b) improving the stability and reduction of pain during exercise and

(c) administration of the analgesic.

The result of the last week (6th week) was listed.

The ratings were subjective according to: very good effect 1 good effect 2 moderate effect 3 hardly effect 4 no effect 5

With regard to the morning stiffness, which was determined in the morning by the subjects after getting up, "1" means that the morning stiffness has completely disappeared, i. the agent has a very good effect. The rating "5" means that for the subject the morning stiffness does not change over the experimental period, i. the agent has shown no effect.

Concerning the parameter "improvement of the stability and reduction of the pain with movement", shortened below "mobility", means "1", that the Action radius in the movement and the sensation of pain during movement has completely disappeared, ie, that the agent has a very good effect. The rating "5" means that there was no change for the subject over the experimental period, ie that the agent has no effect.

Agent used: formulation according to Example 3

Composition used: Capsules with powdery constituents (not according to the invention)

The success of the emulsion from Example 3 is already clearly noticeable after 6 weeks (in some cases a success was observed already after 10 days). In particular, the subjects were also able to significantly reduce the frequency of taking painkillers.

II. On the basis of the freeze-dried emulsion of Example 4, an observational study was carried out on dogs. On average, the dogs had a weight of 25 kg. The two comparison groups each consisted of 5 dogs. All dogs suffered equally from hip arthrosis and were treated daily with a nonsteroidal anti-inflammatory drug.

In each case 5 g of the solid according to the invention according to Example 4 were administered orally. The solid was fed once a day via the feed.

As a comparison, in the control group, a conventional powder formulation containing mussel extract was also orally administered by feeding it through the feed.

The amount of mussel extract supplied was identical in both experimental groups.

The critical parameters that were observed in the dogs:

a) agility in the morning, b) enjoyment of the movement, and c) it was checked whether the amount of analgesics used daily could be reduced.

Regarding morning mobility, the dogs were subjectively rated. A "1" means that the mobility of the dogs in the morning is comparable to that of non-diseased dogs, i.e. that the agent used has a very good effect. The rating "5" means that for the dog the mobility in the morning did not change over the experimental period, i.e. that the agent has no effect.

Regarding the joy of movement, the dogs were also rated subjectively. A "1" means that the mobility of the dogs is comparable to that of non-affected dogs. The rating "5" means that the dog's enjoyment of exercise has not changed over the experimental period, that is, the agent has no effect.

The result of the last week (6th week) was listed The evaluation was carried out subjectively according to: very good effect 1 good effect 2 moderate effect 3 hardly effect 4 no effect 5

Used active ingredient from Example 4:

Agent used: Conventional powder formulation (not according to the invention)

It can be seen that the solid according to the invention shows a significant improvement in the mobility in the morning, as well as in the joy of movement. It is noteworthy that an improvement was observed in part already after 1 week.

This shows that also the solids according to the invention can be successfully used for the treatment of osteoarthritis in animals.

Claims

claims:

1. A liquid, aqueous formulation comprising:

2. Formulation according to claim 1, characterized in that the component (b) lecithin, preferably soy and / or egg lecithin, more preferably phosphatidylcholines carrying a C _{6 to} C ₂ o-fatty acid residue, in particular C ₈ - fatty acid residue is.

3. A formulation according to any one of claims 1 or 2, characterized in that the component (c) is selected from L-carnitine and / or physiologically acceptable derivatives such as carnitine tartrate and / or acyl-L-carnitine and from the group consisting of Glycerol, pentite, preferably glucose, fructose, Maltodextrose, XyNt or hexitol, in particular sorbitol, mannitol, GuNt or inositol, and its physiologically acceptable derivatives such as inositol triphosphate and / or disodium inositol.

4. A formulation according to any one of claims 1 to 3, characterized in that the formulation additionally contains hyaluronic acid or the physiologically acceptable derivatives of hyaluronic acid, for example sodium hyaluronate.

5. A formulation according to any one of claims 1 to 4, characterized in that the formulation comprises a micelle stabilizer which is selected from the group consisting of L-ascorbic acid, sodium ascorbate, sucrose, glycerol and fructose.

6. A formulation according to any one of claims 1 to 5, characterized in that the formulation contains glucosamine sulfate and / or chondroitin sulfate.

7. A formulation according to any one of claims 1 to 6, characterized in that the formulation additionally contains medium-chain triglycerides.

8. A formulation according to any one of claims 1 to 7, characterized in that the formulation additionally contains triglycerides comprising saturated and / or monounsaturated fatty acid residues and / or polyunsaturated fatty acids and / or their ethyl esters, preferably oils or fats comprising at least one fatty acid residue selected from linoleic acid, alpha-linolenic acid, di-homo-gamma-linolenic acid, gamma-linolenic acid, conjugated linoleic acid, particularly preferably fish oil, krill oil, omega-3 fatty acid ethyl ester.

9. A formulation according to any one of claims 1 to 8, characterized in that the formulation additionally contain herbal ingredients or plant extracts, such as red wine, Cistrus fruits, blueberry, acerola, elderberry, frankincense or red clover, preferably, flavonoids / anthocyanidins, for example OPC ( Oligomeric procyanidins), quercetin, naringin, rutin, chrysin or resveratrol.

10. A formulation according to any one of claims 1 to 9, characterized in that the formulation additionally one or more of the water-soluble vitamins and / or its physiologically acceptable derivatives selected from the group of B vitamins consisting of pagamic acid, orotic acid, thiamine, riboflavin , Niacin, NADH, pyridoxine, pantothenic acid, biotin, cobalamin and folic acid.

1 1. A formulation according to any one of claims 1 to 10, characterized in that the formulation additionally one or more ingredients selected from taurine or its physiologically acceptable derivatives, beta Carotene, vitamin A, lycopene, zeaxanthin, astaxanthin, vitamin K, vitamin E, tocotrienols, vitamin K, coenzyme Q10 or its physiologically acceptable derivatives, biologically active selenium derivatives, one or more water soluble vitamins or one or more elements in their physiologically acceptable form selected from the group consisting of boron, iron, copper, phosphorus, manganese, zinc, molybdenum and chromium.

12. A formulation according to any one of claims 1 to 1 1, characterized in that the formulation is present as a nutrient preparation and additionally contains extracts of Stevia rebaudiana, preferably with a proportion of about 10-25% Steviolglykoside, based on the dry extract.

13. A formulation according to any one of claims 1 to 12, characterized in that the formulation is substantially free of primary volatile alcohols (VOC) and / or ethoxylated or other synthetic surfactants.

14. A formulation according to any one of claims 1 to 13, characterized in that the formulation contains coenzyme Q10 or its physiologically acceptable derivatives.

15. A formulation according to any one of claims 1 to 14, characterized in that the formulation coenzyme Q ₁₀ and / or their physiologically acceptable derivatives in an amount of 0.1 to 20 wt .-%, preferably 0.2 to 8 wt. -%, particularly preferably 0.3 to 4 wt .-% based on the total formulation contains.

16. A formulation according to any one of claims 1 to 15, characterized in that the formulation contains as component (a) at least one mussel extract.

17. A formulation according to any one of claims 1 to 16, characterized in that the emulsions are prepared by high-pressure homogenization and are preferably transparent to translucent.

18. A formulation according to any one of claims 1 to 17, characterized in that the formulation is present as an emulsion, the micelles with a average diameter of less than 300 nm, preferably from 10 to 250 nm, more preferably from 50 nm to 130 nm.

19. A solid obtainable from a formulation according to any one of claims 1 to 18 by drying, in particular spray drying or freeze drying.

20. A solid according to claim 19, characterized in that it additionally comprises a polycarboxylic acid, preferably citric acid and / or polycarboxylic acid salt, preferably citric acid salt, in particular calcium and / or magnesium citrate or gluconic acid and / or gluconic acid salt, in particular Na, Mg or Ca gluconates ,

21. A solid according to any one of claims 19 or 20, characterized in that it additionally contains bicarbonate, preferably sodium bicarbonate.

22. Gel comprising a formulation according to any one of claims 1 to 18 or a solid according to any one of claims 18 to 21.

23. A pharmaceutical preparation comprising a formulation according to one or more of claims 1 to 18 or a solid according to any one of claims 19 to 21 or a gel according to claim 22.

24. granules, chewable tablet, dragee or capsule containing the solid according to any one of claims 19 to 21.

25. Pharmaceutical preparation according to claim 23 for the prophylaxis and / or therapy of joint diseases, in particular arthrosis in humans and animals.

26. Use of a formulation according to any one of claims 1 to 18, a solid according to any one of claims 19 to 21 or a gel according to claim 22 as a dietary supplement, dietetic food or cosmetic.

27. Pharmaceutical preparation according to claim 23 and 25 for the topical treatment of osteoarthritis in humans and animals.