Compositions and methods for treating conditions associated with extracellular matrix dysfunction by administering micronutrient compositions

Abstract

The micronutrient compositions are highly effective in the treatment of joint-related inflammation and in the reduction of ECM-disrupting enzymes in the joint, preferably in the treatment of (chronic) arthritis. The micronutrient composition preferably comprises: vitamin C, vitamin E (D-alpha tocopherol), vitamin B6, vitamin D3, folic acid, L-proline, L-lysine, copper, betaine HCl, chondroitin sulfate, N-acetyl-glucosamine, Pycnogenin, SAMe, radix ranunculi ternati, Boswellia serrata, nettle, and glutamine.

Description

Technical Field

[0001] The present application discloses methods of treating chronic arthritis and maintaining joint health by administering a micronutrient composition in a mammal. Background Art

[0002] Pathological symptoms associated with extracellular matrix dysfunction include chronic arthritis, a common disease that affects the physical ability and quality of life of millions of people worldwide. Arthritis often develops with aging and also develops due to accumulated trauma and injury events. The pathological changes in the affected joints are characterized by dramatic changes in the composition of the synovial cartilage and synovial fluid. The pathological process of arthritis development involves chronic inflammation, which aggravates extracellular matrix dysfunction and arthritic manifestations. Sustained long-term effective treatment options are needed to alleviate chronic diseases such as arthritis. Summary of the invention

[0003] The purpose of the micronutrient composition of the present invention is to prevent, treat and delay damage and dysfunction of connective tissue, such as in arthritis. The present inventors discovered the micronutrient composition of the present invention by using an experimental model of human chondrocytes and synovial fibroblasts cultured in mammalian cells.

[0004] The object is achieved by a micronutrient composition comprising or consisting of 10 to 17 ingredients, preferably 12 to 17 ingredients, such as the first 12 ingredients in the following list, more preferably 15 to 17 ingredients, most preferably all 17 ingredients selected from the group consisting of Vitamin C, Vitamin E (D-alpha tocopherol), Vitamin B6, Vitamin D3, Folic acid, L-proline, L-lysine, Copper, Betaine HCl, Chondroitin sulfate, N-acetyl-glucosamine, Pycnogenol, SAMe, Cat's claw, Boswellia serrata, Nettle and Glutamine, optionally comprising a formulation adjuvant for formulating the micronutrient composition in a dosage form for administration to a mammal. Preferably, the micronutrient composition comprises or consists of the ingredients of mixture A or B as determined in Table 1 below.

[0005] Preferably, the micronutrient composition contains the following amounts of micronutrients: Vitamin C 10mg-50000mg, Vitamin E (D-alpha tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0006] Preferably, for the micronutrient composition, the dosage form is selected from the group consisting of capsules, cachets, pills, tablets, lozenges, powders, granules, solutions and / or suspensions in aqueous or non-aqueous liquids, oil-in-water or water-in-oil liquid emulsions, elixirs, syrups, pastilles, suppositories, electuaries or pastes, each containing predetermined amounts of the ingredients of the micronutrient composition.

[0007] Preferably, the dosage form is one oral capsule taken once a day, twice a day or three times a day.

[0008] Preferably, the formulation adjuvant is selected from the group consisting of a binder, a disintegrant, a lubricant, a colorant, a sweetener, a flavoring agent, and a mixture thereof.

[0009] Said objects are achieved by the use of a micronutrient composition in a pharmaceutical composition and by a pharmaceutical composition containing the micronutrient composition and optionally a pharmaceutically acceptable carrier.

[0010] The pharmaceutical composition is preferably used for preventing or treating arthritis or inflammation.

[0011] The pharmaceutical composition is preferably used for preventing or treating chronic arthritis, or for preventing or treating joint-related inflammation.

[0012] The object is achieved by a method for preparing a micronutrient composition or a pharmaceutical composition by mixing the ingredients of the micronutrient composition or the pharmaceutical composition and optionally bringing the mixture into a desired dosage form, preferably comprising mixing:

[0013] As a specific dosage, vitamin C 10mg-50000mg, vitamin E (D-alpha tocopherol) 1mcg-3000mcg, vitamin B6 0.1mg-1000mg, vitamin D3 10IU-10000IU, folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, copper 0.1mg-15mg, betaine HCl 10mg-2000mg, chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0014] In one embodiment, in each figure, the combination refers to a micronutrient composition and comprises: Vitamin C, Vitamin E (D-alpha tocopherol), Vitamin B6, Vitamin D3, Folic Acid, L-Proline, L-Lysine, Copper, Betaine HCl, Chondroitin Sulfate, N-Acetyl-Glucosamine, Pycnogenol, SAMe, Cat's Claw, Boswellia serrata, Urtica dioica, and Glutamine. The individual components of the micronutrient mixture (shown as a combination in the attached figure) are in the following ranges: Vitamin C 10mg-50000mg, Vitamin E (D-alpha tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic Acid 10-5,000mcg, L-Proline 1mg-20,000mg, L-Lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin Sulfate 10mg-10000mg, N-Acetyl-Glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0015] In one embodiment, a mammal is treated with a micronutrient composition to reduce pro-inflammatory IL-6, and to reduce secretion of MMP13, an ECM destroying enzyme in joints. As an example, one of the diseases is osteoarthritis. The micronutrient composition comprises vitamin C, vitamin E (D-alpha tocopherol), vitamin B6, vitamin D3, folic acid, L-proline, L-lysine, copper, betaine HCl, chondroitin sulfate, N-acetyl-glucosamine, pycnogenol, SAMe, cat's claw, boswellia serrata, nettle and glutamine, and is specifically within the following ranges: vitamin C 10mg-50000mg, vitamin E (D-alpha tocopherol) 1mcg-3000mcg, vitamin B6 0.1mg-1000mg, vitamin D3 10IU-10000IU, folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, copper 0.1mg-15mg, betaine HCl 10mg-2000mg, chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, Cat's Claw 1mg-10000mg, Boswellia serrata 1mg-10000mg, Urtica dioica 1mg-20000mg, and Glutamine 1mg-10000mg. The micronutrient composition described throughout the disclosure refers to Mixture A. Finally, the present invention is further described in the detailed description to further illustrate various aspects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Exemplary embodiments are illustrated by way of example only and not limitation, with reference to the figures of the accompanying drawings in which like reference numerals represent similar elements, and in which:

[0017] Figure 1 The effect of micronutrient compositions on type II collagen accumulation in cultured human chondrocytes (HC) is shown.

[0018] Figure 2 Shown is the effect of a micronutrient composition on aggrecan accumulation in ECM produced by human chondrocytes (HC).

[0019] Figure 3 The effect of a micronutrient composition on hyaluronan synthesis in cultured human chondrocytes (HC) is shown.

[0020] Figure 4A The effect of a micronutrient composition on type II collagen accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0021] Figure 4BThe effect of a micronutrient composition on type II collagen accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0022] Figure 5A The effect of a micronutrient composition on aggrecan accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0023] Figure 5B The effect of a micronutrient composition on aggrecan accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0024] Fig. 6A The effect of a micronutrient composition on hyaluronic acid accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0025] Figure 6B The effect of a micronutrient composition on hyaluronic acid accumulation in cultured human synovial fibroblasts (HSF) is shown.

[0026] Figure 7 Shown is the effect of a micronutrient composition on interleukin 6 (IL6) secretion in cultured human chondrocytes (HC).

[0027] Figure 8 The effect of a micronutrient composition on matrix metalloproteinase 13 (MMP13) secretion in cultured human chondrocytes (HC) is shown.

[0028] Other features of the present disclosure will be apparent from the accompanying drawings and from the detailed description of the embodiments that follows. DETAILED DESCRIPTION

[0029] Various combinations of micronutrients have been used to treat and reduce highly chronic arthritis in mammals. However, in the present invention, the specific combination of micronutrients in the composition forms a good combination that shows unexpected results and effects. The ranges shown in the table are optimal for 1 dose. However, the range of concentrations can be wider or narrower than described. The combination of micronutrients can be used as 1 dose or multiple doses. (Chronic) arthritis is a common disease that affects the physical ability and quality of life of millions of people around the world. Arthritis often accompanies aging, but also develops due to accumulated trauma and injury events.

[0030] The pathological changes in the affected joints are characterized by dramatic changes in the composition of the synovial cartilage and synovial fluid. The pathological process of arthritis development involves chronic inflammation, which exacerbates the arthritic manifestations.

[0031] The object of the present invention is to study the effects of some naturally occurring compounds, formulated in a form suitable for administration to mammals suffering from arthritic processes, using experimental models of cultured human chondrocytes and synovial fibroblasts. (Chronic) arthritis is a common disease that affects the physical abilities and quality of life of millions of people worldwide. Arthritis usually develops with aging and also due to accumulated trauma and injury events.

[0032] The pathological changes in the affected joints are characterized by drastic changes in the composition of the synovial cartilage and the synovial fluid.The pathological process of arthritis development involves (chronic) inflammation, which exacerbates the arthritic manifestations.

[0033] The inflammatory process is initiated by adding bacterial lipopolysaccharide (LPS) to the cell culture medium. The parameters tested include the cell release of interleukin 6 (IL6) as an indicator of induced inflammation, the cell culture accumulation of specific extracellular matrix (ECM) components such as type II collagen II (Col2), aggrecan (Aggr) and hyaluronic acid (HA), and the release of matrix metalloproteinase 13 (MMP13) as an indicator of cartilage digestion process. The addition of LPS to the cell culture causes an inflammatory process characterized by a sharp increase in the cell release of IL6 and MMP13 and a decrease in the cell culture content of Col2, Aggr and HA.

[0034] These arthritic processes were reversed to varying degrees by cell culture medium addition of Cat's Claw extract, Boswellia serrata extract, Nettle Leaf extract, nutrient mixture Mix A, L-glutamine, S-adenosylmethionine, alpha-keto-glutarate and iron (II) fumarate. All combinations of tested compounds had anti-arthritic effects that were far superior to the use of the individual components in all aspects tested in this study, resulting in the present invention demonstrating pleiotropic effects.

[0035] We conclude that specific combinations of naturally occurring compounds can reduce arthritic processes in cultured human synoviocytes. These findings support the use of the tested compound combinations in the prevention and treatment of (chronic) arthritis in humans.

[0036] Table 1: Compositions of two micronutrient combinations, Mixture A and Mixture B, and their concentration ranges:

[0037] Individual components Mixture A Mixture B Vitamin C 10mg-50,000mg 10mg-50,000mg Vitamin E (D-alpha Tocopherol) 1mcg-3,000mcg 1mcg-3,000mcg Vitamin B6 0.1mg-1,000mg 0.1mg-1,000mg Vitamin D3 10IU-10,000IU 10IU-10,000IU Folic acid 10mcg-5,000mcg 10mcg-5,000mcg L-Proline 1mg-20,000 mg 1mg-20,000mg L-Lysine 1mg-20,000 mg 1mg-20,000mg copper 0.1mg-15mg 0.1mg-15mg Betaine HCl 10mg-2,000mg 10mg-2,000mg Chondroitin Sulfate 10mg-10,000mg 10mg-10,000mg N-acetyl-glucosamine 10mg-50,000mg 10mg-50,000mg Pycnogenol 5mg-2,000 mg 5mg-2,000mg SAMe N / A 10mg-10,000mg Cat's Claw N / A 1mg-10,000mg Boswellia serrata N / A 1mg-10,000mg nettle N / A 1mg-20,000mg Glutamine N / A 1mg-10,000mg

[0038] Physiological dosage ranges for mammals (e.g., humans) have been calculated as follows: Vitamin C 10 mg-50000 mg, Vitamin E (D-alpha tocopherol) 1 mcg-3000 mcg, Vitamin B6 0.1 mg-1000 mg, Vitamin D3 10 IU-10000 IU, Folic acid 10-5,000 mcg, L-proline 1 mg-20,000 mg, L-lysine 1 mcg-20000 mg, Copper 0.1 mg-15 mg, Betaine HCl 10 mg-2000 mg, Chondroitin sulfate 10 mg-10000 mg, N-acetyl-glucosamine 10 mg-50000 mg, Pycnogenol 5 mg-2,000 mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, Boswellia serrata 1mg-10000mg, Urtica dioica 1mg-20000mg, and glutamine 1mg-10000mg. The physiological dose is shown within the range calculated after in vivo studies, which is suitable for various delivery or administration methods. Due to the different delivery modes of micronutrient compositions, it depends on many factors, such as different absorption, severity, individual differences, absorption, but not limited to these.

[0039] A method of treating a mammal (such as a human) for treating (chronic) arthritis joint inflammation using a micronutrient composition comprising the following ranges: Vitamin C 10mg-50000mg, Vitamin E (D-alpha tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic Acid 10-5,000mcg, L-Proline 1mg-20,000mg, L-Lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin Sulfate 10mg-10000mg, N-Acetyl-Glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, Boswellia serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg. The micronutrient composition can be used alone or in combination.

[0040] Materials and methods: Unless otherwise stated, all reagents were purchased from Sigma-Aldrich. Cat's claw and Boswellia serrata extracts were supplied by Bulk Supplements. Urtica dioica leaf powder was obtained from Monterey Bay Spice Company. Arteriforte was supplied by Dr Rath Health program, BV. Bacterial lipopolysaccharide (LPS) was obtained from Sigma-Aldrich. Stock solutions of the above supplements were prepared in dimethyl sulfoxide (DMSO) at 100 mg / ml (LPS at 25 mg / ml). Stock solutions of L-glutamine, S-adenosylmethionine (SAMe), α-ketoglutarate (AKG), and iron (II) fumarate (Fe) (all from Sigma-Aldrich) were prepared in deionized water at 10 mg / ml (Fe at 1 mg / ml). All stock solutions were aliquoted and stored at -20°C prior to use. The final DMSO concentration in the cell culture medium did not exceed 0.5%.

[0041] All compounds were tested individually and as Mixture 1 and Mixture 2. Compositions were made by combining 40 mcl of each of the following: Cat's Claw Extract, Boswellia (Boswalia) Extract, Urtica Leaf Extract and Mixture 1 (100 mg / ml DMSO), with SAMe, Glutamine and AKG (10 mg / ml H2O) and Fe (1 mg / ml H2O). The combined stock solution concentration was considered to be 100 mg / ml and was used accordingly in the experiments.

[0042] Cell culture experiments were conducted to investigate the effects of micronutrient compositions on the production of synovial cartilage components in cultured human synoviocytes.

[0043] Cell culture: Human synovial fibroblasts (HSF) (supplied by ScienCell) were subcultured in synoviocyte medium (ScienCell) supplemented with 2% fetal bovine serum (FBS) and synoviocyte growth supplement (ScienCell) at 37°C in a 5% CO2 atmosphere. Human chondrocytes (HC) (supplied by Sigma-Aldrich) were subcultured in chondrocyte growth medium supplemented with chondrocyte growth medium supplement mix (Sigma-Aldrich) at 37°C in a 5% CO2 atmosphere. The cell culture medium was refreshed every 2-3 days.

[0044] Experimental: For the experiments, cells were seeded in 96-well plastic cell culture plates covered with fibronectin (Greiner Bio-One) and grown to confluence in the corresponding cell culture medium at 37°C and 5% CO2. 3mcg / ml bacterial lipopolysaccharide (LPS, inflammation-inducing treatment) was added to the cells, and the micronutrient composition was applied in the growth medium for the indicated period of time, as indicated in the corresponding legend. At the end of the incubation, the cultured cell layer was washed twice with phosphate-buffered saline (PBS) and treated in two ways: for exposure to the extracellular matrix (ECM), the cells were lysed by incubation with 0.5% Triton X100 / PBS for 3 minutes, followed by incubation with 25mM NH4OH / PBS for 3 minutes at room temperature, or by fixing the cells at 4°C for one hour using 3% formaldehyde / PBS. The treated cell layer was washed four times with PBS and then incubated with 1% bovine serum albumin (BSA) in PBS at RT for one hour.

[0045] By standard sandwich immunoassay (ELISA, all reagents derive from Sigma-Aldrich), respectively use rabbit polyclonal anti-aggregant, rabbit polyclonal anti-II collagen antibody or biotinylated hyaluronic acid binding protein as main processing, and as secondary processing with horseradish peroxidase (HRP) putative goat anti-rabbit IgG antibody or HRP putative high density streptavidin, measure aggrecan, II collagen and hyaluronic acid content (it is exposed ECM or in fixed cells) in 96 orifice plates prepared as described above.The color change reaction of HRP substrate (TMB substrate solution, Sigma-Aldrich) recorded as 450nm optical density by using microplate optical density reader (Molecular Devices) is estimated the component content analyzed.The experiment is repeated at least three times, and the result provides (mean + / -SD) with the percentage ratio of not adding control.

[0046] Effect of micronutrient composition on the release of inflammatory markers in cultured human synoviocytes: As described above, the inflammatory process was induced in human chondrocytes cultured in 96-well plates using LPS. LPS and micronutrient compositions were added to the cells as indicated in the corresponding legends. At the end of the indicated incubation period, interleukin 6 (IL6) and matrix metalloproteinase 13 (MMP13) levels in the conditioned cell culture medium were measured by ELISA using an analytical kit (R&D Systems) according to the manufacturer's protocol. The experiment was repeated at least three times, and the results are provided as a percentage of the unsupplemented control (mean + / - SD).

[0047] The figures provide results of representative experiments from at least three independent experiments with similar designs. Figure 1 The effect of micronutrient composition on type II collagen accumulation in cultured human chondrocytes (HC) is shown. HC was seeded into 96-well plates covered with fibronectin at the 5th generation and grown in chondrocyte growth medium. 3mcg / ml LPS and test compounds were added to the fused HC cultures for 14 days. After incubation, the extracellular matrix (ECM) produced by the cells was exposed by sequential treatment with 0.5% Triton X100 and 25mM NH4OH in PBS. The type II collagen content in the ECM produced by HC was determined by immunoassay. The results are provided as a percentage of the unsupplemented control (mean + / - SD, n = 4). Compared with individual components and mixture 1, the combination of all ingredients as micronutrient compositions (i.e., mixture 2) at a concentration of 100mcg / ml and 200mcg / ml was the most effective. Compared with the control, the combination of 200mcg / ml resulted in an increase of more than 1700% in extracellular type II collagen deposition. The combination of all ingredients at concentrations of 100mcg / ml and 200mcg / ml (i.e. Mixture 2) was most effective compared to the individual ingredients and Mixture 1. The micronutrient composition comprising 200mcg / ml of the ingredients resulted in an increase in extracellular type II collagen deposition of more than 1700% compared to the control. These are compelling and unprecedented results.

[0048] Figure 2 The effect of a micronutrient composition on the accumulation of aggrecan in cultured human chondrocytes (HC) is shown. HC were seeded into 96-well plates covered with fibronectin at the 5th generation and grown in chondrocyte growth medium. 3mcg / ml LPS and a micronutrient composition as shown were added to the confluent HC cultures and incubated for 14 days. After incubation, the extracellular matrix (ECM) produced by the cells was exposed by sequential treatment with 0.5% Triton X100 and 25mM NH4OH in PBS. The aggrecan content in the ECM produced by HC was determined by immunoassay. The results are provided as a percentage of the unsupplemented control (mean + / - SD, n = 4). Compared with the other tested components, the micronutrient composition mixture 1, which is a combination of all components at a concentration of 200mcg / ml, is significantly more effective and results in an increase of more than 320% in extracellular aggrecan deposition compared to the control.

[0049] Figure 3The effect of micronutrient composition on hyaluronic acid accumulation in cultured human chondrocytes (HC) is shown. HC was inoculated into 96-well plates covered with fibronectin at the 5th generation and grown in chondrocyte growth medium. 3mcg / ml LPS and micronutrient composition as shown in the figure were added to the fused HC culture for 14 days. After incubation, the cell layer was fixed with 3% formaldehyde / PBS, and the HC HA content was measured as described in the materials and methods. The results are provided as a percentage of the unsupplemented control (mean + / - SD, n = 4). Compared with the control, the combination of all ingredients of the micronutrient composition as a concentration of 200mcg / ml caused the hyaluronic acid synthesis in the chondrocytes to increase by more than 200%. This is not only unexpected, but also shows the effectiveness of the micronutrient composition.

[0050] Figure 4A and Figure 4B The effect of a micronutrient composition on type II collagen accumulation in cultured human synovial fibroblasts (HSF) is shown. HSF were seeded into 96-well plates covered with fibronectin at passage 5 and grown in synoviocyte growth medium. Confluent HSF cultures were supplemented with 3mcg / ml LPS and micronutrient compositions as shown and incubated for 7 days. After incubation, the cell layers were fixed with 3% formaldehyde in PBS ( Figure 4B ), or by sequential treatment with 0.5% Triton X100 and 25 mM NH4OH in PBS to expose the extracellular matrix (ECM) produced by the cells ( Figure 4A ). Type II collagen content in HSF (B) and HSF-produced ECM (A) was determined by immunoassay. Results are presented as a percentage of unsupplemented controls (mean + / - SD, n = 4). Unprecedented results were shown, where all combinations of ingredients were more effective than individual compounds and mixture A at both tested concentrations. At a concentration of 100 mcg / ml, collagen deposition in the ECM of synovial fibroblasts was increased by 338% compared to unsupplemented controls. Figure 4B It was shown that in the presence of 50 mcg / ml of the combination of all ingredients, type II collagen production in synovial fibroblasts was increased by 130%.

[0051] Figure 5A and Figure 5BThe effects of micronutrient compositions alone and as micronutrient compositions on aggrecan accumulation in cultured human synovial fibroblasts (HSF) are shown. HSF were seeded into 96-well plates covered with fibronectin at passage 5 and grown in synoviocyte growth medium. Confluent HSF cultures were supplemented with 3mcg / ml LPS and micronutrient compositions as indicated and incubated for 7 days. After incubation, the cell layers were fixed with 3% formaldehyde in PBS ( Figure 5B ), or by sequential treatment with 0.5% Triton X100 and 25 mM NH4OH in PBS to expose the extracellular matrix (ECM) produced by the cells ( Figure 5A ). Aggrecan content in HSF (B) and HSF-produced ECM (A) was determined by immunoassay. Results are presented as a percentage of unsupplemented controls (mean + / - SD, n = 4). Figure 5A The micronutrient combination in was shown to result in an increase in aggrecan extracellular deposition by more than 10,500% at 100 mcg / ml. Boswellia serrata applied alone was more effective than the combination (more than 14,700% increase) with respect to aggrecan deposition in the ECM at the same concentration.

[0052] However, the micronutrient composition appears to have more diverse beneficial effects than Boswellia (based on its efficacy on other ECM components and anti-inflammatory effects seen in other data). Figure 5B It was shown that the maximum aggrecan production in synovial fibroblasts was observed in the presence of 50 mcg / ml of the micronutrient composition (130% increase).

[0053] Fig. 6A and 6B The effect of a micronutrient composition on hyaluronic acid accumulation in cultured human synovial fibroblasts (HSF) is shown. HSF were seeded into 96-well plates covered with fibronectin at passage 5 and grown in synoviocyte growth medium. Confluent HSF cultures were supplemented with 3mcg / ml LPS and micronutrient compositions as shown and incubated for 7 days. After incubation, the cell layers were fixed with 3% formaldehyde in PBS ( Figure 6B ), or by sequential treatment with 0.5% Triton X100 and 25 mM NH4OH in PBS to expose the extracellular matrix (ECM) produced by the cells ( Fig. 6A HSF ( Figure 6B ) and ECM produced by HSF ( Fig. 6A). The results are presented as a percentage of the unsupplemented control (mean + / - SD, n = 4). Fig. 6A The micronutrient composition was shown to be most effective at concentrations of 50 and 100 mcg / ml. At 200 mcg / ml, it resulted in an increase in extracellular deposition of hyaluronic acid by more than 1200%, Figure 6B It was shown that the maximum hyaluronic acid accumulation in synovial fibroblasts was observed in the presence of 50 mcg / ml of the micronutrient composition (over 370% increase).

[0054] Figure 7 The effect of a micronutrient composition on interleukin 6 (IL6) production in cultured human chondrocytes (HC) is shown. HC were seeded into fibronectin-coated 96-well plates at passage 5 and grown in chondrocyte growth medium. Confluent HC cultures were supplemented with 3 ng / ml LPS and micronutrient compositions as indicated for 2 hours. After incubation, IL6 content in cell culture conditioned medium was determined by ELISA as described in Materials and Methods. Results are provided as a percentage relative to unsupplemented controls (mean + / - SD, n = 4). Figure 7 It was shown that the greatest reduction in IL-6 secretion was observed in the presence of 50 and 100 mcg / ml of the combination of all ingredients compared to the other micronutrient compositions. IL6 secretion in chondrocytes was reduced from 244% in the presence of LPS to 80% in the presence of LPS plus micronutrient composition.

[0055] Figure 8 The effect of a micronutrient composition on the secretion of matrix metalloproteinase 13 (MMP13) in cultured human chondrocytes (HC) is shown. HC were seeded into 96-well plates covered with fibronectin at passage 5 and grown in chondrocyte growth medium. 3 ng / ml LPS and micronutrient compositions were supplemented to confluent HC cultures as shown and incubated for 2 hours. Subsequently, the MMP13 content in the cell culture conditioned medium was determined by ELISA as described in Materials and Methods. Results are provided as a percentage of unsupplemented controls (mean + / - SD, n = 4). Figure 8The maximum reduction in MMP13 secretion (an enzyme that destroys the ECM) in chondrocytes by a micronutrient composition of 100 mcg / ml was shown. It was reduced from 2484% in the LPS control to 93% in the presence of LPS plus a micronutrient composition. In summary, the final micronutrient composition (referred to as a combination in this application) consists of Mixture A with other micronutrients. The micronutrient composition contains: Vitamin C, Vitamin E (D-alpha tocopherol), Vitamin B6, Vitamin D3, Folic Acid, L-Proline, L-Lysine, Copper, Betaine HCl, Chondroitin Sulfate, N-Acetyl-Glucosamine, Pycnogenol, SAMe, Cat's Claw, Boswellia Serrata, Urtica and Glutamine. The components of the micronutrient mixture (shown as a combination in the attached figure) are in the following ranges: Vitamin C 10mg-50,000mg, Vitamin E (D-alpha tocopherol) 1-3,000mcg, Vitamin B6 0.1-1,000mg, Vitamin D3 10IU-10,000IU, Folic Acid 10-5,000mcg, L-Proline 1-20,000mg, L-Lysine 1-20,000mg, Copper 0.1-15mg, Betaine HCl 10-2,000mg, Chondroitin Sulfate 10-10,000mg, N-Acetyl-Glucosamine 10-50,000mg, Pycnogenol 5-2,000mg, SAMe 10-10,000 mg, cat's claw 1-10,000 mg, Boswellia serrata 1-10,000 mg, Urtica dioica 1-20,000 mg, and glutamine 1-10,000 mg. In another embodiment, the micronutrient composition consists of: vitamin C, vitamin E (D-alpha tocopherol), vitamin B6, vitamin D3, folic acid, L-proline, L-lysine, copper, betaine HCl, chondroitin sulfate, N-acetyl-glucosamine, pycnogenol, SAMe, cat's claw, Boswellia serrata, Urtica dioica and glutamine. The components of the micronutrient mixture (shown as a combination in the attached figure) are in the following ranges: Vitamin C 10mg-50,000mg, Vitamin E (D-alpha tocopherol) 1-3,000mcg, Vitamin B6 0.1-1,000mg, Vitamin D3 10IU-10,000IU, Folic Acid 10-5,000mcg, L-Proline 1-20,000mg, L-Lysine 1-20,000mg, Copper 0.1-15mg, Betaine HCl 10-2,000mg, Chondroitin Sulfate 10-10,000mg, N-Acetyl-Glucosamine 10-50,000mg, Pycnogenol 5-2,000mg, SAMe 10-10,000mg, cat's claw 1-10,000mg, boswellia serrata 1-10,000mg, nettle 1-20,000mg, and glutamine 1-10,000mg.Compared to other ingredients, it demonstrates the highest efficacy in simultaneously supporting key extracellular mechanisms important for healthy joints.

[0056] The combination increased the production and extracellular deposition of key important ECM components (type II collagen, aggrecan and hyaluronic acid) by synoviocytes and chondrocytes under pro-inflammatory conditions (in the presence of LPS):

[0057] Reduced pro-inflammatory IL-6

[0058] Reduced secretion of MMP13 (ECM-destroying enzyme in joints)

[0059] Some formulations are prepared so that the micronutrient composition is administered to mammals. Physiological doses are calculated and each dose is administered to relieve arthritis patients or any joint pain or patients with arthritis associated with inflammation, enzyme-damaged joints, and to increase the deposition of key important ECM components, thereby treating, preventing and repairing joints, and if the formulation is oral, a specific dose is given in the form of an oral capsule once a day, twice a day or three times a day. Formulations suitable for oral administration can be in the form of capsules, cachets, pills, tablets, lozenges (using a flavoring matrix, usually sucrose and gum arabic or tragacanth), powders, granules, or solutions or suspensions in aqueous or non-aqueous liquids, or oil-in-water or water-in-oil liquid emulsions, or elixirs or syrups, or lozenges (using an inert matrix, such as gelatin and glycerin or sucrose and gum arabic), each containing a predetermined amount of the subject composition as an active ingredient. The subject composition can also be administered as a suppository, ointment or paste.

[0060] When preparing oral solid pharmaceutical products, the micronutrient composition is mixed with an excipient (and, if necessary, one or more additives, such as a binder, a disintegrant, a lubricant, a colorant, a sweetener and a flavoring agent), and the resulting mixture is processed by conventional methods to produce an oral solid pharmaceutical product, such as a tablet, a coated tablet, a granule, a powder or a capsule. The additive can be those commonly used in the art. Examples of excipients include lactate, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose and silicic acid. Binders include water, ethanol, propanol, simple syrup, glucose solution, starch solution, liquefied gelatin, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl starch, methyl cellulose, ethyl cellulose, shellac, calcium phosphate and polyvinyl pyrrolidone. Disintegrants include dry starch, rice flour, L-leucine, sodium arginine, powdered agar, sodium bicarbonate (sodium hydroxy carbonate), calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride and lactose. Lubricants include refined talc, stearates, borax and polyethylene glycol. Sweeteners include sucrose, orange peel, citric acid and tartaric acid.

[0061] When preparing a liquid drug product for oral administration, the micronutrient composition is mixed with an additive (such as a sweetener, a buffer, a stabilizer or a flavoring agent), and the resulting mixture is processed by a conventional method to produce a liquid drug product for oral administration, such as an internal solution, a syrup or an elixir. Examples of sweeteners include vanillin; examples of buffers include sodium citrate; and examples of stabilizers include tragacanth, gum arabic and gelatin.

[0062] For transdermal (eg, topical) administration, dilute sterile aqueous or partially aqueous solutions (generally about 0.1% to 5% concentration) may be prepared with the micronutrient compositions, otherwise similar to the parenteral solutions described above.

[0063] Formulations containing the micronutrient composition for rectal or vaginal administration can be provided as suppositories, which can be prepared by mixing the subject composition with one or more suitable non-irritating carriers (including, for example, cocoa butter, polyethylene glycol, suppository wax or salicylate), which are solid at room temperature but liquid at body temperature, and thus melt in a suitable body cavity and release the encapsulated one or more compounds and one or more compositions. Formulations suitable for vaginal administration also include vaginal suppositories, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art.

[0064] The targeted release portion for capsules containing the micronutrient composition can be incorporated into the delayed release system by applying an immediate release layer over the delayed release core; using a coating or compression process, or in a multi-unit system, such as a capsule containing delayed release beads and immediate release beads.

[0065] When used in relation to micronutrient compositions, the term "slow release" is art-recognized. For example, a therapeutic composition that releases a substance over time may exhibit a slow release profile compared to a bolus administration in which the entire amount of the substance is made bioavailable at once. In specific embodiments, upon contact with body fluids (including blood, cerebrospinal fluid, mucous secretions, lymph, etc.), one or more pharmaceutically acceptable excipients may undergo gradual or delayed degradation (e.g., by hydrolysis), thereby concomitantly releasing any material incorporated therein, such as therapeutic and / or biologically active salts and / or compositions, over a sustained or extended period of time (compared to release from a suppository). This release may result in extended delivery of a therapeutically effective amount of any therapeutic agent disclosed herein.

[0066] Current efforts in the field of drug delivery include developing targeted delivery, in which the drug is active only in target areas of the body (e.g., mucous membranes, such as in the nasal cavity), and sustained-release formulations, in which the micronutrient composition is released from the formulation in a controlled manner over a period of time. Types of sustained-release formulations include liposomes, drug-loaded biodegradable microspheres, and micronutrient composition polymer conjugates.

[0067] Delayed release dosing formulations are produced by coating solid dosage forms with a film of a polymer, which is insoluble in the acidic environment of the stomach, but soluble in the neutral environment of the small intestine. Delayed release dosage units can be prepared, for example, by coating micronutrient compositions with selected coating materials. Micronutrient compositions can be tablets for incorporation into capsules, tablets for use as kernels in "coated core" dosage forms, or multiple drug-containing beads, particles or granules for incorporation into tablets or capsules. Preferred coating materials include bioerodible, gradually hydrolyzable, gradually water-soluble and / or enzymatically degradable polymers, and can be conventional "enteric" polymers. As will be appreciated by those skilled in the art, enteric polymers become soluble in the higher pH environment of the lower gastrointestinal tract, or slowly erode when the dosage form passes through the gastrointestinal tract, and enzymatically degradable polymers are degraded by bacterial enzymes present in the lower gastrointestinal tract, particularly in the colon. Alternatively, delayed release tablets can be prepared by dispersing the drug in a matrix of a suitable material (such as a hydrophilic polymer or a fatty compound). Suitable hydrophilic polymers include, but are not limited to, cellulosic polymers or copolymers, cellulose esters, acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate and vinyl or enzyme-degradable polymers or copolymers as described above. These hydrophilic polymers are particularly useful for providing a delayed release matrix. The fatty compound used as matrix material includes, but is not limited to, wax (e.g., carnauba wax) and tristearin. Once the active ingredient is mixed with the matrix material, the mixture can be compressed into tablets.

[0068] Pulsatile release dosage forms are dosage forms that simulate multiple dosing profiles without the need for repeated dosing and typically allow for at least a two-fold reduction in dosing frequency compared to drugs provided as conventional dosage forms (e.g., as solutions or conventional solid dosage forms for immediate drug release). Pulsatile release profiles are characterized by periods of no release (lag time) or reduced release followed by rapid drug release. These can be formulated for critically ill patients using the micronutrient compositions of the present invention.

[0069] As used herein, the phrases "parenteral administration" and "administered parenterally" refer to modes of administration other than enteral and topical, such as injection, and include, but are not limited to, intravenous, intramuscular, intrapleural, intravascular, intrapericardial, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, and intrastemal injection and infusion.

[0070] Certain micronutrient compositions suitable for parenteral administration disclosed herein comprise a combination of one or more of the subject compositions with one or more pharmaceutically acceptable sterile, isotonic, aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, or sterile powders, which may be reconstituted into a sterile injectable solution or dispersion just prior to use, and which may contain antioxidants, buffers, bacteriostats, solutes that render the formulation isotonic in the blood of the intended recipient, or suspending or thickening agents.

[0071] When preparing an injection product, the micronutrient composition is mixed with an additive (such as a pH adjuster, a buffer, a stabilizer, an isotonic agent or a local anesthetic), and the resulting mixture is treated by a conventional method, thereby producing an injection for subcutaneous injection, intramuscular injection or intravenous injection. Examples of pH adjusters or buffers include sodium citrate, sodium acetate and sodium phosphate; examples of stabilizers include sodium pyrosulfite, EDTA, thioglycolic acid and thiolactic acid; examples of local anesthetics include procaine hydrochloride and lidocaine hydrochloride; and examples of isotonic agents include sodium chloride and glucose.

[0072] The phrase "pharmaceutically acceptable" is recognized in the art. In some embodiments, the term includes compositions, polymers and other materials and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of mammals (both humans and animals) without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit-risk ratio.

[0073] The phrase "pharmaceutically acceptable carrier" is art-recognized and includes, for example, a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material, which is involved in carrying or transporting any subject composition from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the subject composition and not injurious to the patient. In some embodiments, a pharmaceutically acceptable carrier is non-pyrogenic. Some examples of materials that can be used as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution solution); (19) ethanol; (20) phosphate buffer solution; and (21) other non-toxic compatible substances used in pharmaceutical preparations.

[0074] In certain embodiments, the micronutrient compositions described herein are formulated such that the compositions will be delivered to a mammal in a therapeutically effective amount as part of a prophylactic or therapeutic treatment to promote joint repair.

[0075] In certain embodiments, the dosage of a micronutrient composition (which may be referred to as a therapeutic composition provided herein) may be determined by reference to the plasma concentration of the therapeutic composition or other encapsulated material.

[0076] The therapeutic micronutrient compositions provided herein can be administered to a subject in need of treatment by various conventional routes of administration, including oral, topical, parenteral, such as intravenous, subcutaneous or intramedullary. In addition, the therapeutic compositions can be administered intranasally, as rectal suppositories, or using a "flash" formulation (i.e., dissolving the drug in the mouth without the use of water). In addition, the compositions can be administered to a subject in need of treatment by controlled release formulations, site-specific drug delivery, transdermal drug delivery, patch-mediated drug delivery (active / passive), by stereotactic injection, or in nanoparticles.

[0077] The active ingredient may be present in the therapeutic compositions of the present invention in concentrations intended for topical administration to the skin, intranasally, pharynx, bronchially, intravaginally, rectally or to the eye.

[0078] For use as an aerosol, the active ingredient can be packaged in a pressurized aerosol container together with a gaseous or liquefied propellant (e.g., dichlorodifluoromethane, carbon dioxide, nitrogen, propane, etc.) and conventional adjuvants (e.g., co-solvents and wetting agents) as may be desired or required. The most commonly used routes of administration also include preferred transmucosal (nasal, oral / sublingual, vaginal, ocular and rectal) and inhalation routes.

[0079] In addition, in certain embodiments, the subject micronutrient composition of the present application can be lyophilized or subjected to other suitable drying techniques such as spray drying. The subject composition can be administered once, or can be divided into multiple smaller doses to be administered at different time intervals, which depends in part on the release rate of the composition and the desired dosage.

[0080] The preparations that can be used for the method provided herein include those that are suitable for oral, nasal, local (including oral and sublingual), rectal, vaginal, aerosol and / or parenteral administration. The preparation can be conveniently provided in unit dosage form, and can be prepared by any method known in the pharmaceutical field. The amount of the subject micronutrient composition that can be combined with a carrier material to produce a single dose can vary according to the treated experimenter and a specific mode of administration.

[0081] The acceptable amount of treatment described herein can be administered in an inhalation or aerosol formulation. An inhalation or aerosol formulation can include one or more agents, such as adjuvants, diagnostic agents, imaging agents, or therapeutic agents that can be used for inhalation therapy. Relative to the gross weight of the formulation, the final aerosol formulation can, for example, contain 0.005-90% w / w, such as 0.005-50%, 0.005-5% w / w, or 0.01-1.0% w / w of the drug.

[0082] Examples of suitable aqueous and non-aqueous carriers that can be used in the micronutrient compositions include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters (such as ethyl oleate). Proper fluidity can be maintained, for example, by the use of coating materials (such as lecithin), by maintaining the required particle size in the case of dispersions, and by the use of surfactants.

[0083] Industrial use

[0084] Thus, in this study, we demonstrated that micronutrient composition plays a decisive role in regulating joint mechanisms by enhancing ECM-related components in individuals. Prevention and treatment of arthritis patients using optimal combinations of natural ingredients and micronutrients formulated in various forms suitable for administration are described.

[0085] Implementation

[0086] The following are preferred embodiments of the invention. The individual features may be freely combined with each other and with the claims without departing from the invention.

[0087] 1. A micronutrient composition for reducing chronic arthritis, the micronutrient composition comprising:

[0088] Vitamin C 10mg-50000mg, Vitamin E (D-alpha Tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic Acid 10-5,000mcg, L-Proline 1mg-20,000mg, L-Lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin Sulfate 10mg-10000mg, N-Acetyl-Glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, boswellia serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg, which is formulated into a specific form for mammalian administration.

[0089] 2. The micronutrient composition according to embodiment 1, which is composed of the following items: Vitamin C 10mg-50000mg, Vitamin E (D-α-tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0090] 3. A method for treating a mammal suffering from chronic arthritis, the method comprising:

[0091] Administering a micronutrient composition containing, as specific doses, Vitamin C 10mg-50000mg, Vitamin E (D-alpha tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic Acid 10-5,000mcg, L-Proline 1mg-20,000mg, L-Lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin Sulfate 10mg-10000mg, N-Acetyl-Glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0092] 4. The method according to embodiment 8, comprising:

[0093] The micronutrient composition is administered for treating joint-related inflammation and reducing ECM-destroying enzymes in the joints.

[0094] 5. The micronutrient composition according to embodiment 4, wherein the joint-related inflammation is due to increased IL-6.

[0095] 6. The method according to embodiment 4, wherein the ECM-destroying enzyme is matrix metalloproteinase 13.

[0096] 7. The method according to embodiment 3, wherein the specific dose is one oral capsule once a day, twice a day or three times a day.

[0097] 8. A method of treating a mammal, the method comprising:

[0098] For specific diseases, specific functions and specific dosages, a micronutrient composition is administered, which contains: Vitamin C 10mg-50000mg, Vitamin E (D-alpha tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

[0099] 9. The method according to embodiment 8, wherein the specific disease is chronic arthritis.

[0100] 10. The method according to embodiment 8, wherein the specific function of the micronutrient composition is to reduce the secretion of pro-inflammatory IL-6 and matrix metalloproteinase 13, an ECM-destroying enzyme in the joints.

[0101] 11. The micronutrient composition according to embodiment 8, wherein the specific dose is one oral capsule once a day, twice a day or three times a day.

[0102] 12. The method of embodiment 8, wherein the micronutrient composition increases the production and deposition of important ECM components by synoviocytes and chondrocytes in the joints of mammals suffering from chronic arthritis.

Claims

1. A micronutrient composition comprising or consisting of: 10 to 17 ingredients, preferably 12 to 17 ingredients, such as the first 12 ingredients in the following list, more preferably 15 to 17 ingredients, most preferably all 17 ingredients selected from the group consisting of: Vitamin C, Vitamin E (D-alpha tocopherol), Vitamin B6, Vitamin D3, folic acid, L-proline, L-lysine, copper, betaine HCl, chondroitin sulfate, N-acetyl-glucosamine, Pycnogenol, SAMe, Cat's Claw, Boswellia serrata, Nettle and Glutamine, and Optionally, a formulation adjuvant is included for formulating the micronutrient composition in a dosage form for administration to a mammal.

2. The micronutrient composition according to claim 1, comprising the following amounts of micronutrients: Vitamin C 10mg-50000mg, Vitamin E (D-α-tocopherol) 1mcg-3000mcg, Vitamin B6 0.1mg-1000mg, Vitamin D3 10IU-10000IU, Folic Acid 10-5,000mcg, L-Proline 1mg-20,000mg, L-Lysine 1mcg-20000mg, Copper 0.1mg-15mg, Betaine HCl 10mg-2000mg, Chondroitin Sulfate 10mg-10000mg, N-Acetyl-Glucosamine 10mg-50000mg, Pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

3. The micronutrient composition of claim 1, wherein the dosage form is selected from the group consisting of capsules, cachets, pills, tablets, lozenges, powders, granules, solutions and / or suspensions in aqueous or non-aqueous liquids, oil-in-water or water-in-oil liquid emulsions, elixirs, syrups, lozenges, suppositories, ointments or pastes, each containing predetermined amounts of the ingredients of the micronutrient composition.

4. The micronutrient composition according to one of claims 1 to 3, wherein the dosage form is one oral capsule taken once a day, twice a day or three times a day.

5. The micronutrient composition according to one of claims 1 to 3, wherein the formulation adjuvant is selected from the group consisting of binders, disintegrants, lubricants, colorants, sweeteners, flavoring agents and mixtures thereof.

6. Use of the micronutrient composition according to one of claims 1 to 3 in a pharmaceutical composition.

7. A pharmaceutical composition comprising the micronutrient composition according to one of claims 1 to 3 and optionally a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, which is used for preventing or treating arthritis or inflammation.

9. The pharmaceutical composition according to claim 8, which is used for preventing or treating chronic arthritis.

10. The pharmaceutical composition according to claim 8, which is used for preventing or treating joint-related inflammation.

11. A process for preparing a micronutrient composition according to one of claims 1 to 3 by mixing the ingredients of the micronutrient composition according to one of claims 1 to 3 and optionally bringing the mixture into the desired dosage form.

12. The method of claim 11, comprising mixing: As a specific dosage, vitamin C 10mg-50000mg, vitamin E (D-α-tocopherol) 1mcg-3000mcg, vitamin B6 0.1mg-1000mg, vitamin D3 10IU-10000IU, folic acid 10-5,000mcg, L-proline 1mg-20,000mg, L-lysine 1mcg-20000mg, copper 0.1mg-15mg, betaine HCl 10mg-2000mg, chondroitin sulfate 10mg-10000mg, N-acetyl-glucosamine 10mg-50000mg, pycnogenol 5mg-2,000mg, SAMe 10mg-10000mg, cat's claw 1mg-10000mg, frankincense serrata 1mg-10000mg, nettle 1mg-20000mg, and glutamine 1mg-10000mg.

13. A method for preparing the pharmaceutical composition according to claim 7, said method being carried out by mixing the ingredients of the pharmaceutical composition according to claim 7, and optionally bringing the mixture into a desired dosage form.

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