Pharmaceutical composition for preventing and treating joint inflammation / relieving pain and method for preparing the same.

Abstract

To provide a pharmaceutical composition that functions and is used for the prevention and treatment of arthritis, as well as the relief of joint pain, and a preparation method thereof. 【Solution】The present composition comprises the following components, and can be developed into tablets, capsules, dispersible tablets, chewable tablets, effervescent tablets, lozenges, and other oral preparations. 1. 99% glucosamine sulfate 2KCL, 2. chondroitin sulfate, 3. methylsulfonylmethane (MSM), 4. type II collagen, 5. Morinda root P.E. extract, 6. Epimedium grandiflorum extract, 7. Sambucus williamsii Hance extract, 8. Drynaria fortunei (Kunze) J.Sm. extract, 9. turmeric root extract, 10. hyaluronic acid, and 11. chitosan

Description

TECHNICAL FIELD

[0001] BACKGROUND ART A. Technical Field The present invention relates to a pharmaceutical composition for preventing and treating joint pain, and a method for preparing the present composition. Specifically, the present invention includes a composition for treating joint pain comprising herbs and the corresponding preparation method.

[0002] B. Description of the Related Art The pandemic has increased people's awareness of participating in various sports and exercises. However, the risk of sports injuries during exercise has also increased. This is because many people have blind spots or are ignorant about exercise and fitness, leading to many misunderstandings and errors. Depending on the degree of impact and torque on the joints resulting from various sports and exercises, their intensity can be classified into three categories: Low intensity: recreational swimming, static boating or skiing, aerobics, golf, walking, ballroom dancing, water aerobics. Moderate intensity: bowling, fencing, cycling, rowing, ice skating, rock climbing, tennis doubles, jazz and ballet dancing, aerobic exercise, weightlifting, sailing, brisk walking, cross-country skiing, table tennis, kayaking, hiking, horseback riding, inline skating, alpine skiing. High intensity: baseball, softball, basketball, volleyball, soccer, rugby, handball, squash, tennis singles, running, lacrosse, water skiing, karate. For this reason, sports that involve jumping movements, in particular, have a high incidence of sports injuries. However, the likelihood of such serious injuries is low if you are not experiencing accidental trauma or bruising to your joints during general exercise (such as from a fall or collision). The general attitude is to not seek medical attention unless absolutely necessary. For example, in skydiving, many skydivers suffer injuries from "hard landings," but often they don't take it seriously, assuming the pain will subside in a few days. Similarly, after a knee injury (such as falling on your knee or twisting your knee), many people do not seek medical attention as long as they can continue to walk (or limp). These injured or bruised areas can develop inflammation and, with age, can lead to long-term complications. Synovial inflammation can affect the structure of the joint cartilage and bone, resulting in permanent joint instability and painful injuries.

[0003] Joint inflammation, while not life-threatening, almost always affects daily life and quality of life. Often, symptoms are initially hidden and not apparent, but gradually accumulate over years, leading to recurring pain, knee swelling, muscle weakness, and decreased flexibility. While osteoarthritis cannot be completely prevented, simple measures can be taken to slow its progression. To manage the pain, it is necessary to first address the joint inflammation to prevent the condition from worsening. Especially in middle-aged and older adults, inflammation of the knee joint can gradually worsen, accompanied by pain, swelling, and fluid accumulation within the joint. Certain occupational work, strenuous exercise, and injuries can create excessive pressure on the joint, accelerating degenerative changes in chondrocytes. Degenerated cells, in turn, reduce matrix synthesis, further exacerbating chondrocyte destruction, creating a vicious cycle. Without preparation, even seemingly minor injuries, such as missteps, can be pathogenic factors for osteoarthritis, of which there are over 100 types.

[0004] Osteoarthritis (OA) is a chronic degenerative disease of bones and joints that endangers the health of middle-aged and older adults. It is characterized by slow cartilage breakdown over several years. In normal cartilage, there is a delicate balance between matrix synthesis and breakdown, but in osteoarthritis, cartilage breakdown exceeds synthesis. This balance between synthesis and breakdown is influenced by age and regulated by several factors produced by synovial and chondrocytes. There are no significant racial or geographical differences, and it is a common and prevalent disease characterized by degeneration and destruction of articular cartilage as well as bone hyperplasia. The disease typically begins at age 20, but most cases are asymptomatic and generally difficult to detect. Clinically, osteoarthritis of the knee is the most common. With the increasing elderly population worldwide, the incidence of OA is on the rise year by year, seriously impacting the quality of life for middle-aged and older adults. The clinical presentation includes joint pain, swelling, and functional impairment. The main pathological changes are degeneration of articular cartilage, subchondral bone lesions, and synovial changes, ultimately leading to degradation of the cartilage matrix, chondrocyte death, and destruction of the structural integrity of the joint. The etiology of OA is multifaceted, and the clinical and pathological features can be summarized into three aspects: 1. functional degeneration, 2. cartilage damage, and 3. neobone formation on and around the articular surface. Mechanical and biological factors that interact to alter intraosseous pressure are important causes of its development. These include aging, wear and tear, obesity, and biochemical and genetic factors that inhibit the synthesis of cartilage matrix proteoglycans and promote the degradation of proteoglycans, hyaluronic acid, and collagen.

[0005] The main treatments for knee joint pain include oral therapy, physical therapy, Western medicine, and traditional Chinese medicine. Physical therapy is only suitable as an adjunct treatment because it does not cure the condition and can only alleviate the patient's pain. Western medicine is generally not recommended because it can easily irritate the gastrointestinal tract and be significantly harmful to the patient's body. Traditional Chinese medicine has drawbacks such as a long treatment period, slow effectiveness, and unclear results, and for these reasons, it is not well-received by patients. However, oral therapy remains the main method of treating osteoarthritis because it is effective and easy to maintain.

[0006] Methods for preventing and treating arthritis: To enhance the formulation of the compound for arthritis, hyaluronic acid and chitosan are added to the compound. This compound reduces inflammation and pain, improves joint lubrication, prevents and treats arthritis early, reduces joint friction and wear, and better protects articular cartilage.

[0007] Brief summary of the invention The main object of the present invention is to provide a pharmaceutical composition for preventing and treating joint inflammation / relieving knee pain, comprising the following components in weight percent: (i) Glucosamine sulfate 2KCl (99% glucosamine sulfate) 10-50%; (ii) Chondroitin sulfate 10-40%; (iii) Methylsulfonyl methane (MSM) 1-40%; (iv) Type II collagen 1-40%; (v) Morinda root PE extract 1-40%; (vi) Epimedium grandiflorum extract 1-40%; (vii) Sambucus williamsii Hanc extract 1-40%; (viii) Drynaria (ix) Curcuma longa (Kunze) J. Sm. extract 1-40%; (x) Turmeric root extract 1-40%; (x) Hyaluronic acid 1-20%; and (xi) Chitosan 1-40%; these components are sieved, mixed, granulated, and filled to obtain the composition, or compressed into tablets, sugar-coated tablets, film-coated tablets, hard capsules, soft capsules, enteric-coated capsules, granules, enteric-coated preparations, pills, or powders.

[0008] Another object of the present invention is to provide a pharmaceutical composition that functions and is used for the prevention, treatment, and relief of arthritis and joint pain. The pharmaceutical composition repairs the cartilage matrix, improves arthritis and pain caused by sports or occupational injuries, and reduces inflammation, pain, stiffness, and swelling in the joints. This pharmaceutical composition relieves dull pain in the back and lower back, repairs joint damage, reduces arthritis and pain, and minimizes cartilage destruction. This pharmaceutical composition is effective in relieving conditions such as frozen shoulder, tennis elbow, golfer's elbow, and sprains. In the case of gouty arthritis, this pharmaceutical composition counteracts uric acid-induced inflammation and exhibits remarkable anti-inflammatory, analgesic, and anti-gout effects. Another main objective of the present invention is the following steps: (i) A step of screening the components of the composition; (ii) A step of mixing the constituent components to obtain a homogeneous mixture; (iii) A method for preparing a pharmaceutical composition for preventing, treating, and relieving joint pain, comprising the step of filling a mixture into hollow capsules to obtain capsules weighing 500 mg each.

[0009] A further object of the present invention is to provide a pharmaceutical composition which is formulated as an oral dosage form selected from the group consisting of tablets, capsules, dispersible tablets, chewable tablets, effervescent tablets, and lozenges, and which is formulated as a capsule containing 500 mg of the composition. The pharmaceutical composition is used to prevent and treat osteoarthritis in joints selected from the group consisting of knee, hip, wrist, spinal, wrist, shoulder, and ankle joints, and its components are present in amounts effective for preventing and treating arthritis while minimizing side effects.

[0010] A further object of the present invention is to provide a pharmaceutical composition in which the glucosamine sulfate 2KCl has a purity of 99% and the turmeric root extract is standardized to contain 95% by weight of curcuminoids.

[0011] These features, embodiments, and advantages of the present invention, as well as other features, embodiments, and advantages, will be better understood by referring to the following drawings, description, and claims.

[0012] A more complete understanding of the nature and purpose of the present invention will become apparent by examining the following detailed description in conjunction with the accompanying drawings. [Brief explanation of the drawing]

[0013] [Figure 1] This shows normal cells (a brief explanation of normal cells). [Figure 2] The results for prostaglandin E2 at a dose of 100 μg / mL are shown. Detailed description of the invention

[0014] The following detailed description relates to the best mode currently intended for carrying out exemplary embodiments of the present invention. Since the scope of the present invention is best defined by the appended claims, this description should not be construed as restrictive, but is provided solely for the purpose of illustrating the general principles of the present invention.

[0015] According to preferred embodiments of the present invention, the disclosure of the present invention provides a method for formulating and preparing a composition for preventing arthritis and reducing joint pain. This composition exhibits excellent therapeutic effects against inflammation and pain in the knee joint region. The main objectives are to improve the quality of life by reducing pain and inflammation in patients, and to slow or prevent the progression of permanent damage in the early stages, thereby achieving the dual benefits of maintaining health and treating the condition.

[0016] The main formulation of the present invention contains glucosamine sulfate 2KCl, chondroitin sulfate, methylsulfonylmethane (MSM), bone collagen (type II collagen protein), Morinda officinalis (Ba Ji Tian), Epimedium (Yin Yang Huo), elderberry, Drynaria (Gu Sui Bu), and turmeric, with hyaluronic acid and chitosan added as main components.

[0017] Supplementing with glucosamine can stimulate damaged cartilage tissue to initiate regeneration and promote cartilage tissue metabolism to prevent degeneration. By reconstructing stiff and worn joint tissue, it can reduce the degree of pain, similar to taking moderate-strength anti-inflammatory analgesics, and by reducing inflammation, it can alleviate joint pain and swelling, making the joint more flexible and resilient. These experiments have confirmed that when glucosamine is combined with chondroitin to treat early or moderate arthritis, this composition produces a complementary effect without significant side effects. Glucosamine can significantly improve symptoms of mobility problems, joint pain, synovial fluid accumulation, and morning stiffness in patients.

[0018] Chondroitin sulfate is a type of sulfated glycosaminoglycan (GAG) that possesses anti-inflammatory, antiviral, and anti-allergic properties and accelerates wound healing. Chondroitin sulfate is a major component of the intercellular matrix and plays a crucial role in maintaining the relative stability and normal function of the cellular environment. Due to its high concentration in articular cartilage, chondrocytes can retain sufficient moisture and achieve buffering, lubrication, and support functions. By building the collagen protein necessary for cartilage, it promotes the proliferation of osteoblasts, encourages new bone formation, and accelerates the bone healing process. This helps regenerate gradually depleted cartilage. Therefore, using glucosamine and chondroitin sulfate together not only alleviates symptoms of bone and joint pain, but also helps normalize joint metabolism, improve joint mobility, and increase bone density and hardness. It also lowers serum uric acid levels, treats gout, prevents gout attacks, and reduces symptoms.

[0019] MSM, commonly known as organosulfur, is a natural analgesic with anti-inflammatory and analgesic properties, and is relatively safe. It can alleviate arthritis and protect joints from damage. Collagen protein is the main component of cartilage tissue between joints, and MSM functions as an essential material in collagen synthesis. Two clinical trials have shown that MSM can improve the quality of life for patients with osteoarthritis and alleviate several symptoms, including joint pain and stiffness.

[0020] Type II Collagen: Type II collagen can be used to relieve muscle and joint pain and inflammation. Type II collagen is the main component of human articular cartilage, epiphyseal cartilage, and trabeculae. Collagen makes up 70-86% of the organic matter in bone. Bone collagen is also an important component of human muscles and skin, and plays a significant role in maintaining bone flexibility, coordination of body movements, and skin elasticity. Only type II collagen can inhibit the cause of joint inflammation; this means that collagen-specific immune T cells (collagen-specific T cells, C-ST cells) are not activated, and therefore, the inflammatory response is not induced, eliminating pain. Unlike analgesics that merely block pain sensation while inflammation persists and the condition worsens, this pain relief addresses the root cause. It is 2-3 times more effective in reducing arthritis pain compared to commonly used glucosamine and chondroitin preparations.

[0021] The capsule formulation of this invention contains five beneficial herbal preparations: Morinda officinalis, Epimedium elderberry, Drynaria, and turmeric. By combining these ingredients, their effects work synergistically, producing favorable results. Furthermore, the addition of hyaluronic acid and chitosan further enhances anti-inflammatory and analgesic effects.

[0022] Morinda officinalis (Ba Ji Tian): In traditional medicine, Morinda officinalis is used to strengthen bones and kidneys, reduce swelling, relieve pain, and treat orthopedic diseases such as osteoporosis and femoral head necrosis. Morinda officinalis has remarkable anti-inflammatory and analgesic effects and can treat arthritis, promote bone synthesis, reduce osteolysis, and prevent fractures after osteoporosis. The active ingredient, Morinda officinalis polysaccharide, can inhibit apoptosis of osteoblasts, thereby slowing the degeneration of articular cartilage and improving knee joint function. Morinda officinalis can inhibit the expression of nitric oxide synthase in serum, synovial membrane, and articular cartilage, lower NO levels, inhibit inflammatory responses, and slow the histological progression of osteoarthritis of the knee.

[0023] Epimedium (Yin Yang Huo): Epimedium has the effects of "tonifying the kidney, strengthening yang, benefiting essence, and strengthening bones". Epimedium has active ingredients that can promote the proliferation and differentiation of osteoblasts, promote bone growth, prevent calcium loss, protect gonadal tissues and maintain hormone levels. Epimedium has preventive and therapeutic effects on gouty arthritis, including both acute gouty arthritis and chronic gouty arthritis. Epimedium has a wide range of functions such as acting on the cardiovascular system, central nervous system, blood system, immune system, as well as anti-inflammatory, anti-osteoporosis, anti-aging, and osteoporosis prevention effects. These effects can be explained either through the traditional Chinese medicine theory of "tonifying the kidney and strengthening yang" or through modern medical dynamic observations in bone biology, all of which indicate that this herb has good preventive and therapeutic effects on osteoporosis.

[0024] Elderberry: Elderberry has analgesic and anti-inflammatory effects, and can also be used as a single medicament or a combined medicament for treating osteoarthritis. It is mainly used to treat rheumatoid arthritis, trauma, fractures, gout, Kaschin-Beck disease, and edema. Elderberry contains a large amount of proanthocyanidins and purple pigments, both of which may benefit the human body through multiple pathways. Elderberry proanthocyanidins improve immune function by promoting the production of cytokines, these cytokines act as messengers of the immune system and help regulate immune responses to protect the body and improve disease resistance. In European folk remedies, it has been used to treat polycythemia associated with arthritis, asthma, colds, and constipation.

[0025] Drynariae Rhizoma (Gu Sui Bu): Generally, Drynariae Rhizoma is used in orthopedics, and has effects such as tonifying the kidney, strengthening bones, healing trauma, and alleviating pain. Drynariae Rhizoma is often used in the treatment of kidney deficiency, low back pain, tinnitus and hearing loss, loose teeth, contusions and subcutaneous hemorrhage, as well as tendon and bone injuries. Drynariae Rhizoma plays an important role in alleviating postprandial hyperglycemia and hyperuricemia, and treating complications such as impaired glucose tolerance, diabetes, obesity, hyperuricemia, and osteoporosis. Modern research has proven that Drynariae Rhizoma has an anti-inflammatory effect to prevent osteoarthritis, thereby reducing the damage of inflammatory factors to the cartilage matrix, and protecting and repairing articular cartilage. This makes it possible to promote proteoglycan synthesis, promote bone calcium absorption, increase blood calcium and phosphorus levels, facilitate bone calcification and fracture healing, and delay degenerative changes in bone cells.

[0026] Turmeric: Traditional Chinese medicine uses turmeric for chest and hypochondriac pain, rheumatic shoulder and arm pain, joint swelling and pain caused by injuries, etc. Curcumin is the main active ingredient of turmeric. Curcumin and its derivatives can delay the pathological progression of osteoarthritis. Its mechanisms include blocking inflammation-related signaling pathways, reducing the production of inflammatory factors and lowering their activity, thereby alleviating inflammatory reactions; enhancing antioxidant enzyme activity through regulating immune functions via interaction with immune cells and immune molecules, inhibiting oxidative stress and chondrocyte apoptosis, and promoting cartilage protection. Since amino acids are essential constituents of bacterial cell walls, and acetic acid and pipecolic acid are food components, the phenolic hydroxyl group of curcumin forms esters with acetic acid, amino acids, and pipecolic acid, which facilitates the penetration into bacterial cell walls, achieves systemic drug delivery, and improves therapeutic effects. Studies have shown that turmeric has effects of lowering blood pressure, anticoagulation, lipid lowering, anti-inflammation, antioxidation, anti-gout, and α-glucosidase inhibition. Turmeric reduces serum uric acid through two pathways that inhibit uric acid production and promote uric acid excretion.

[0027] Hyaluronic acid is one of the components of the natural lubricant in the human knee joint. In the body, over 50% of hyaluronic acid is found in the skin, lungs, and intestines. It is also present in synovial fluid, cartilage, umbilical cord, blood vessel walls, and other interstitial tissues. It is the only acidic mucopolysaccharide found in almost all living organisms, from bacteria to humans and all animals. Due to its high viscoelasticity, plasticity, permeability, and excellent biocompatibility, it is widely used in the pharmaceutical, cosmetic, and food industries and is currently the best moisturizing substance found in nature.

[0028] Hyaluronic acid (HA) is a major component of articular cartilage and synovial fluid, and its high viscoelasticity plays a crucial role in joint protection. In low-impact activities such as walking, hyaluronic acid acts as a viscous fluid, reducing friction between tissues. In high-impact activities such as running, it acts as an elastic fluid, buffering impact stress. When supporting body weight, it acts as a gel-like elastomer, functioning as a cushion to reduce pressure on the joint. As we age, the concentration and molecular weight of HA in bones and joints decrease, leading to cartilage deterioration and damage. This results in physiological dysfunction of the joint, and therefore affects the joint's function of shock absorption and lubrication. Consequently, osteoarthritis, rheumatoid arthritis, and other infectious and non-infectious arthritis occur. Therefore, in the treatment of joint diseases, supplementing with hyaluronic acid can restore the lubricating function of synovial fluid and promote joint repair, with high molecular weight hyaluronic acid being more effective than low molecular weight hyaluronic acid. The important proteoglycan in articular cartilage is aggrecan, which binds to hyaluronic acid, giving the cartilage compressibility and elasticity, helping to alleviate pain in mild to moderate osteoarthritis, reduce friction, and improve knee joint function.

[0029] Hyaluronic acid (HA) imparts viscoelasticity to synovial fluid, acting as a lubricant and shock absorber. In synovial fluid, hyaluronic acid covers the surface of articular cartilage, sharing deep spaces within the cartilage with collagen fibers and sulfated proteoglycans. This protects the cartilage and prevents proteoglycans from leaking from the cartilage matrix into the synovial fluid, thus maintaining a normal cartilage matrix. In synovial fluid of the knee associated with osteoarthritis, the concentrations of hyaluronic acid, glycosaminoglycans, and sulfated keratin are lower than in synovial fluid of a normal knee.

[0030] Supplementing with exogenous hyaluronic acid (HA) is beneficial for the production of newly synthesized hyaluronic acid. It also plays a role in promoting tissue wound healing, increasing the hyaluronic acid content in synovial fluid, and accumulating on the surface of cartilage and synovial membrane to form a viscoelastic protective film, repairing damaged barriers and preventing further destruction and bone matrix loss. This reduces friction caused by joint movement and tissue sliding, increasing the range of motion of the joint. It has a strong inhibitory effect on the excitability of pain receptors and sensory fibers located within and beneath the synovial membrane, which can alleviate joint pain.

[0031] While the viscoelastic properties of hyaluronic acid (HA) itself provide physical protection to pain receptors, hyaluronic acid as a molecular barrier can effectively prevent the release and diffusion of inflammatory mediators. Simultaneously, it promotes synovial fluid reflux, removes locally accumulated inflammatory mediators and tissue metabolites, improves the intra-articular environment, and reduces and breaks the vicious cycle of localized joint lesions, thereby inhibiting local inflammation, by reducing joint pain and increasing joint mobility. It is a key compound recognized in this process, playing a crucial role in activating and regulating the immune response, promoting angiogenesis, and in cell proliferation and migration. During the inflammatory phase, high molecular weight hyaluronic acid increases, absorbing water and swelling, which creates a porous scaffold suitable for cell migration, inhibiting neutrophil migration and reducing the inflammatory response. During the proliferative phase, hyaluronic acid oligosaccharides promote angiogenesis, facilitating the migration of fibroblasts to injured tissue and constructing a new extracellular matrix. In the remodeling phase, hyaluronic acid regulates scar formation and improves joint function. Studies have shown that free radicals, particularly hydroxyl free radicals, can cause cleavage of hyaluronic acid molecular chains. Hyaluronic acid can then remove free radicals from the body through this reaction. Some researchers also believe that the rapid metabolism of hyaluronic acid in joints can help remove cellular debris (which can be embedded in high molecular weight network structures and removed along with their metabolism) and assist in the removal of chondrocyte metabolites and waste products. This suggests that hyaluronic acid plays a crucial role in cartilage nutrition and metabolism.

[0032] Hyaluronic acid and its derivatives have been used as therapeutic adjuvants in the treatment of osteoarthritis to enhance the lubrication of joint surfaces and thereby reduce joint pain. Culture studies have also shown that hyaluronic acid has beneficial effects by inhibiting fibronectin fragment-mediated cartilage dissolution. Hyaluronic acid also inhibits neutrophil migration and phagocytosis, reducing the inflammatory response and thereby promoting the body's repair processes. It also has inhibitory effects on prostaglandin synthesis and proteoglycan release and degradation, which may reduce pain perception. Intra-articular injections of high molecular weight (HA) hyaluronic acid can effectively relieve pain in patients with osteoarthritis and rheumatoid arthritis, thereby providing a certain therapeutic effect. In addition to its lubricating effect, HA may also improve the inflammatory response by reducing macrophage phagocytosis.

[0033] Chitosan is a linear polysaccharide and the most important derivative of chitin. Chitosan is a product derived from chitin with a degree of deacetylation exceeding 70%. For the multiple translations of chitin, such as chitin or chitin polysaccharides, chitosan, prepared from chitin via deacetylation, has multiple translations, including chitin polysaccharides, chitinamine sugars, chitosan, deacetylated chitin polysaccharides, deacetylated chitin, and polyglucosamine. Chitosan is composed of randomly distributed glucosamine (deacetylation units) and N-acetylglucosamine (acetylation units), linked by β-(1-4) glycosidic bonds. Chitosan exhibits excellent biocompatibility, biodegradability, and bioactivity, making it suitable for use as a bone repair material. Chitin possesses high hydrophilicity and strong adsorption capacity to chondrocytes, promoting their normal function. Therefore, it is a valuable scaffold material. Chitosan contains natural calcium and can be incorporated into three-dimensional growth scaffolds for bone tissue engineering. It can function as a biocarrier material for seed cells or active growth factors.

[0034] Chitosan inhibits fibroblast activity in vitro, thereby preventing the formation of fibrous tissue within the joint cavity. Furthermore, its viscoelastic and lubricating properties allow it to form a colloidal network on the cartilage surface, functioning as a biological barrier. It also enhances the secretory function of synovial cells, thereby relieving pain and improving joint function. Chitin, a precursor of chitosan, can prevent nerve cell death and promote the regeneration of damaged nerves. It possesses film-forming and spinnable properties, aids in wound healing and bone formation, and is absorbable by the human body. These characteristics suggest that chitosan is beneficial for the healing of articular cartilage injuries, the prevention of joint adhesions, and the protection of articular cartilage.

[0035] Chitosan is known for its antibacterial, anti-inflammatory, biocompatible, osteoconductive, biodegradable, and adsorbent properties. In addition to its low toxicity, its combination of multiple bioactive functions—including antimicrobial, antifungal, hemostatic, low immunogenicity, scar prevention, and drug release from the matrix—offers ample opportunities for further development. Chitosan is a hydrophilic, high-molecular-weight cationic polysaccharide, and its biocompatibility and safety make it an ideal material for treating bone defects. Its excellent water-retention capacity, comparable to hyaluronic acid, contributes to sustained hydration, pain relief, protection of articular cartilage, and prevention of joint adhesions. It also promotes rapid skin regeneration and accelerates wound healing. By increasing synovial fluid secretion, it provides lubrication, cushioning, and nourishment to the knee joint, thereby reducing pain and improving joint function. Considering their safety, biodegradability, biocompatibility, and unique biological activity, chitin and its derivatives have promising applications in the treatment of bone and joint diseases, are ideal ligands for preparing trace element supplements, and certainly require widespread attention and utilization in the medical field.

[0036] In the treatment of joint diseases, chitosan and its degradation products are involved in the synthesis of synovial fluid components, including chondroitin, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid, all of which are essential for the nutrition of articular cartilage. Adding chitosan not only improves the anti-degradation ability of hyaluronic acid but also enhances the therapeutic effect. Therefore, chitosan and its degradation products can play an important role in the treatment and prevention of joint diseases such as osteoarthritis, joint adhesions, articular cartilage degeneration, cartilage defects, fractures, and bone defects.

[0037] The pathogenesis of osteoarthritis (OA) is due to a combination of factors including trauma, metabolism, and genetic factors, and at the local joint level, it is primarily an inflammatory response involving various inflammatory factors. Chitosan exhibits similar effects to hyaluronic acid (HA), but its unique ability to inhibit fibroblast proliferation may actively contribute to the onset and progression of OA, and this needs to be confirmed in clinical trials. In summary, intra-articular injection of chitosan overcomes the limitations of conventional conservative treatment, not only alleviating symptoms but also promoting the repair of articular cartilage, providing a comprehensive, simple, and effective treatment approach.

[0038] According to the present invention, the dosage for preventing and treating joint inflammation / relieving knee pain is two capsules twice a day with warm water.

[0039] This invention discloses a composition for preventing and treating arthritis and alleviating joint pain, and suitable target populations thereof. The composition is suitable for individuals with gouty arthritis, joint pain and swelling, arthritis, joint stiffness, limited mobility, and joint noise. It is also effective in cases of high physical activity levels where joint wear and tear are likely to occur, when maintaining a fixed posture for long periods and experiencing stress on specific joints (e.g., mouse hands, cervical dysplasia), in middle-aged and elderly individuals with degenerative bone conditions, and when it is necessary to increase bone density and improve bone flexibility. In particular, it is useful for individuals with joint and bone-related diseases such as osteophytes, osteoporosis, arthritis, rheumatoid arthritis, gout, joint sprains, herniated discs, and frozen shoulder.

[0040] This invention discloses the use and effects of a composition for preventing and treating arthritis and alleviating joint pain. 1. Accelerates the regeneration and repair of cartilage cells. 2. To provide essential materials for constructing and repairing cartilage tissue, tendons, and ligaments. 3. Reduce damage to articular cartilage, bone, and adjacent structures, thereby aiding in the reconstruction of joint tissue. 4. Stimulates the repair and regeneration of elastic cartilage tissue and prevents loss of cartilage elasticity. 5. To relieve pain, stiffness, redness, warmth, swelling, and discomfort around the joints caused by inflammation of the cartilage tissue in the fingers, knees, and hips. 6. Prevents morning joint stiffness, tenderness, and catching sensations due to inactivity, and improves mobility. 7. Maintain a balance in synovial fluid secretion to prevent arthritis. 8. Reduces inflammation, loss of tension, and extensibility of the ligaments and muscles of the joints. 9. Relieves inflammation, pain, swelling, and discomfort caused by osteoarthritis and rheumatoid arthritis. 10. Counteract and slow down joint destruction, deformation, and calcification.

[0041] This invention discloses the function and use of a composition for preventing and treating joint inflammation and alleviating joint pain. This composition is used to repair cartilage matrix and to improve joint inflammation and pain caused by sports or occupational injuries, relieving joint inflammation, pain, stiffness, and swelling. It also relieves dull back and lower back pain, repairs joint damage, reduces joint inflammation and pain, and minimizes cartilage destruction. It is effective in alleviating symptoms of conditions such as frozen shoulder, tennis elbow, golfer's elbow, and sprains. For gouty arthritis, it counteracts uric acid-induced inflammation and exhibits significant anti-inflammatory, analgesic, and anti-gout effects.

[0042] The test reports for Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement both include pharmaceutical compositions in accordance with the present invention.

[0043] the purpose We will develop an osteoarthritis model using human chondrocytes and evaluate the effectiveness of Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement in alleviating joint pain and discomfort. Furthermore, we will conduct tests on prostaglandin E2 biomarker levels to determine whether the osteoarthritis condition improves after administration of 100 μg / mL of each supplement.

[0044] The pro-inflammatory cytokines used to induce inflammation in cells are recombinant human tumor necrosis factor α (TNF-α) and recombinant human IL-1β protein (IL-1-β).

[0045] Sample Information Two samples, namely Quan Wei Active Joint Supplement capsules and Quan Wei Ultra Joint Supplement capsules, were provided by the customer, The Beauty Nation Pte Ltd, through Temasek Polytechnic - Centre of Innovation for Complementary Health Products. The Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement were provided in the manufacturer's commercial packages, containing 100 and 90 capsules respectively. Each capsule of Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement contains 500 mg of the supplement in powder form.

[0046] The ingredients in Quan Wei Active Joint Supplement include glucosamine sulfate 2KCl (175mg), chondroitin sulfate (100mg), methylsulfonyl methane (MSM-50mg), type II collagen (50mg), Morinda root extract (25mg), Epimedium grandiflorum extract (25mg), Sambucus williamsii Hance extract (25mg), Drynaria fortune (Kunze) J.Sm (25mg), and turmeric root extract (25mg).

[0047] The ingredients in Quan Wei Ultra Joint Supplement include glucosamine sulfate (145 mg), chondroitin sulfate (90 mg), MSM (45 mg), type II collagen (45 mg), Morinda (25 mg), Epimedium (25 mg), Sambucus (25 mg), Drynaria (25 mg), Turmeric (25 mg), Hyaluronic acid (25 mg), and Chitosan (25 mg).

[0048] All supplements were stored at room temperature in a cool, dry place, following the manufacturer's packaging instructions.

[0049] Experimental Design 1.Material 1.1 Cell lines

[0050] The following cell lines were purchased from Promocell.

[0051] [Table 1]

[0052] 1.2. Pro-inflammatory cytokines I purchased the following pro-inflammatory cytokines from Sigma-Aldrich.

[0053] [Table 2]

[0054] I purchased the following pro-inflammatory cytokines from Cell Signaling Technology.

[0055] [Table 3]

[0056] 1.3. Cell culture medium I purchased the following cell culture media from Promocell.

[0057] [Table 4]

[0058] 1.4. ELISA kit The following ELISA kits were purchased from Abcam.

[0059] [Table 5]

[0060] The following ELISA kits were purchased from Thermofisher.

[0061] [Table 6]

[0062] 2. Method 2.1. Sample Preparation The Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement, both in capsule form, were opened to expose the powder contents. The capsules were prepared using 10% ethanol as the solvent at a concentration of 500 μg / mL.

[0063] Both supplements were further diluted to 100 μg / mL using chondrocyte growth medium as the solvent. These were considered "high-dose supplements."

[0064] 2.2. Preparation of pro-inflammatory cytokines TNF-α was reconstituted in water to a concentration of 0.1 mg / mL according to the supplier's instructions. The TNF-α was further diluted with chondrocyte growth medium to a concentration of 10 ng / mL and used to induce inflammation in human chondrocytes.

[0065] IL1-β was reconstituted in water according to the supplier's instructions to a concentration of 0.2 mg / mL. IL1-β was further diluted in chondrocyte growth medium to a concentration of 5 ng / mL and used to induce inflammation in human chondrocytes.

[0066] 2.3. Preparation of culture medium The chondrocyte growth medium supplement mix was added to 500 mL of chondrocyte growth medium according to the supplier's recommendations. As a result, a "complete basal medium for the mid-stage growth" was obtained. 5 mL of penicillin-streptomycin was added to the chondrocyte growth medium.

[0067] 2.4. Reinitialization of cryopreserved culture The cryopreserved HCH cells were thawed in a 37°C warm water bath, with minimal ice remaining. The vials were sterilized with 70% ethanol and handled in a biosafety cabinet. 1 mL of cells were dispensed into a T25 flask, and 5 mL of chondrocyte growth medium was added. The T25 flask was gently shaken to ensure even distribution for chondrocyte growth. The flask was incubated in a humidified incubator with 5% CO2, and the cells were monitored daily. The growth medium was replaced every 3–4 days until the flask reached a confluence of 80–90%.

[0068] 2.5. Passaging of HCH cells The growth medium was removed from the T25 flask and washed with 2.5 mL of sterile HEPES buffered equilibrium salt solution (HEPEBSS). After washing, 2.5 mL of trypsin / EDTA solution in a 0.04% / 0.03% ratio was added to the T25 flask. The flask was incubated at room temperature for 2–4 minutes, or until 90% of the cells detached from the flask surface. Next, 2.5 mL of trypsin neutralizing solution (TNS) was added to the T25 flask to neutralize it. The cell suspension was placed in a 15 mL centrifuge tube and centrifuged at 200 x g for 5 minutes, and the supernatant was discarded. The cell pellet was resuspended in 5 mL of chondrocyte growth medium. These cells were transferred to a new T25 flask and gently shaken to ensure uniform distribution for chondrocyte growth. The flask was incubated in a humidified incubator with 5% CO2, and the cells were monitored daily. The growth medium was changed every 3-4 days until the flask reached 80-90% confluence. Passaging was repeated as needed to maintain cell growth, and the cells were maintained for up to 7 passages.

[0069] 2.6.Quantum quantification 2.6.1. Seeding HCH Cells were removed from the incubator and visually observed using a phase-contrast inverted microscope to detect any morphological abnormalities shown in Figure 1. With healthy cell activity, the cells were removed from the culture flask by trypsin treatment and centrifuged at 200xg for 5 minutes. The cell palette was approximately 5x10⁶. 4 The cells were then resuspended to a cell density of 2x10⁻¹⁰ cells / mL. 4 Cells were seeded in a 48-well plate at a rate of 400 μL / well.

[0070] 2.7. Sample Analysis 2.7.1. Pre-treatment Chondrocyte growth medium was removed from four of the wells in the 48-well plate. 400 μL each of Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement were added to the individual wells at a dose of 100 μg / mL. This step was performed to simulate prophylactic administration before any inflammation of the cells. Each supplement was added redundantly to the wells of the 48-well plate. The cells were pre-treated for 24 hours in a 37°C incubator with 5% CO2.

[0071] 2.7.2. Disease Modeling and Treatment All culture medium was removed from the wells, and 200 μL of Quan Wei Active Joint Supplement and Quan Wei Ultra Joint Supplement were added to each individual well at a dose of 100 μg / mL. Each supplement was added redundantly to the wells of the 48-well plate. 100 μL of TNF-α (concentration 5 ng / mL) and 100 μL of iL1-β (concentration 10 ng / mL) were also added to the same wells of individual cells.

[0072] Disease models (DM) were created by adding 200 μL of 10% ethanol at a concentration of 100 μg / mL, 100 μL of TNF-α at concentrations of 5 ng / mL and 10 ng / mL, and 100 μL of iL1-β at concentrations of 5 ng / mL and 10 ng / mL, respectively, to 48-well plates.

[0073] Two wells of healthy cells (HC) were kept as a control, and 400 μL of 10% ethanol at concentrations of 100 μg / mL or 25 μg / mL was added. TNF-α and iL1-β were not added.

[0074] Cells were kept in an incubator containing 5% CO2 at 37°C for 48 hours, and the culture medium was collected and analyzed for five types of biomarkers.

[0075] result 1. Prostaglandin E2 Prostaglandin E2 is involved in the physiology of normal joints and is a major mediator of the inflammatory response to tissue damage. A decrease in its levels from disease models would suggest an indicator of reduced inflammation.

[0076] In three runs of the experiment, as shown in Figure 2, the prostaglandin E2 marker levels were reduced with Quan Wei Ultra Joint Supplement compared to the disease model (DM). Quan Wei Ultra Joint Supplement showed statistically significant (*p<0.05) downregulation. This indicates that Quan Wei Ultra Joint Supplement is effective in reducing cellular inflammation at a dose of 100 μg / mL.

[0077] Healthy cells (HC) show downregulation and statistically significant differences between disease models (DM). *** This showed p<0.001. This indicates the establishment of a control model for conducting the experiment.

[0078] 2. Data Overview

[0079] (Table 7) Average results for prostaglandin E2 (dosage 100 μg / mL) JPEG2026169110000008.jpg3591* shows p<0.05, and *** shows p<0.001, with a statistically significant difference between the two.

[0080] Restrictions It is important to be aware of the limitations of in vitro tests conducted in a laboratory environment. The product is intended for ingestion into the human body, and the results of this study were obtained in a closed, clean, biosafety laboratory handled by laboratory staff. This experiment does not take into account the human digestive cycle. Because only specific cell lines were used in this experiment, it does not consider the different cell lines present in humans. This in vitro test serves as an indicator of whether or not the product is effective.

[0081] conclusion Quan Wei Ultra Joint Supplement was found to exhibit superior efficacy against prostaglandin E2 at a dose of 100 μg / mL compared to Quan Wei Active Joint Supplement.

[0082] The foregoing is illustrative of the present invention and should not be construed as a limitation. While exemplary embodiments of the present invention are described, those skilled in the art will readily understand that many modifications are possible in the exemplary embodiments without substantially departing from the novel teachings and advantages of the present invention. Accordingly, all such modifications are intended to fall within the scope of the present invention as defined in the claims. The present invention is defined by claims corresponding to those described in the following claims.

Claims

1. A pharmaceutical composition for preventing and treating arthritis / relieving knee pain, wherein the pharmaceutical composition comprises: (i) 10-50% by weight of glucosamine sulfate 2KCl (99% by weight glucosamine sulfate); (ii) 10-40% by weight of chondroitin sulfate; (iii) 1-40% by weight of methyl-sulfonyl-methane (MSM); (iv) 1-40% by weight of type II collagen; (v) 1-40% by weight of Morinda root PE extract; (vi) 1-40% by weight of Epimedium grandiflorum extract; (vii) 1-40% by weight of Sambucus illiamsii Hanc extract; (viiii) 1-40% by weight of Drynaria fortunei (Kunze) J. Sm. A pharmaceutical composition comprising 1 to 40% by weight of an extract; (ix) 1 to 40% by weight of turmeric root extract; (x) 1 to 20% by weight of hyaluronic acid; and (xi) 1 to 40% by weight of chitosan, wherein the composition is obtained by sieving, mixing, granulating, filling or compressing the components, and then forming it into tablets, sugar-coated tablets, film-coated tablets, hard capsules, soft capsules, enteric-coated capsules, granules, enteric-coated preparations, pills, or powders.

2. The pharmaceutical composition according to claim 1, wherein the composition is formulated as an oral dosage form selected from the group consisting of tablets, capsules, dispersible tablets, chewable tablets, effervescent tablets, and lozenges.

3. The pharmaceutical composition according to claim 2, which is formulated as a capsule containing 500 mg of the composition.

4. The pharmaceutical composition according to claim 1, used to prevent and treat osteoarthritis in a joint selected from the group consisting of the knee joint, hip joint, wrist joint, spinal joint, wrist joint, shoulder joint, and ankle joint.

5. A pharmaceutical composition according to claim 1, used for preventing and treating gouty arthritis.

6. The pharmaceutical composition according to claim 1, wherein the purity of the glucosamine sulfate 2KCl is 99%.

7. The pharmaceutical composition according to claim 1, wherein the constituent components are present in an amount effective for preventing and treating joint inflammation with minimal side effects.

8. The pharmaceutical composition according to claim 1 or 2, wherein the turmeric root extract is standardized to contain 95% by weight of curcuminoids.

9. The pharmaceutical composition according to claim 1 or 2, wherein the preparation is formulated as an enteric-coated capsule designed to be released in the small intestine to maximize the absorption of the active ingredient.

10. The pharmaceutical composition according to claim 1 or 2, wherein the type II collagen is derived from avian cartilage and has a molecular weight of 250 to 300 kDa.

11. The pharmaceutical composition according to claim 1 or 2, particularly for the treatment of osteoarthritis of the knee, wherein the recommended dosage is two capsules twice a day.

12. The pharmaceutical composition according to claim 1 or 2, wherein the hyaluronic acid has a molecular weight of 0.5 to 1.5 million daltons for optimal bioavailability.

13. The pharmaceutical composition according to claim 1 or 2, wherein the particle size of all active ingredients is less than 100 microns, thereby improving dissolution and absorption.

14. The pharmaceutical composition according to claim 1 or 2, wherein the Epimedium grandiflorum extract is standardized to contain 10 to 20% by weight of icariin.

15. The pharmaceutical composition according to claim 7, wherein the arthritis relates to a condition selected from the group consisting of osteoarthritis and gouty arthritis.

16. A method for preparing the pharmaceutical composition described in claim 1, (i) A step of screening the components described in claim 1; (ii) A step of mixing the constituent components to obtain a homogeneous mixture; (iii) A method comprising the step of filling the above mixture into hollow capsules to obtain capsules weighing 500 mg each.

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