Synergistic nutraceutical composition controlling osteoarthritis through inhibition of its nociceptive and neuropathic pain components

Abstract

The present invention relates to a synergistic nutraceutical composition for the prevention and / or management of osteoarthritis. The composition comprises palmitoylethanolamide (PEA), undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically or nutraceutically acceptable excipient. The invention further relates to a process for the preparation of the said composition, which is formulated for oral administration. The synergistic combination of these bioactive ingredients supports joint health, maintains cartilage integrity, and improves joint comfort through complementary mechanisms of action.

Description

[0001] SYNERGISTIC NUTRACEUTICAL COMPOSITION CONTROLLING OSTEOARTHRITIS THROUGH INHIBITION OF ITS NOCICEPTIVE AND

[0002] NEUROPATHIC PAIN COMPONENTS

[0003] RELATED APPLICATION:

[0004] The present application claims benefit of the Indian Provisional Application No. IN202421061826 filed on, October 14th, 2024 the entire contents of which are hereby incorporated by reference.

[0005] FIELD OF THE INVENTION

[0006] The present invention relates to a synergistic nutraceutical composition for the prevention and / or management of osteoarthritis. More particularly, the invention pertains to a nutraceutical composition comprising palmitoylethanolamide (PEA), undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically or nutraceutically acceptable excipient. The present invention further relates to a process for the preparation of the said synergistic nutraceutical composition, which is formulated for oral administration and is adapted to support joint health, maintain cartilage integrity, and improve joint comfort through complementary and synergistic mechanisms of action, thereby providing a safe and effective formulation for long-term use in individuals requiring joint support or suffering from osteoarthritis.

[0007] BACKGROUND OF THE INVENTION

[0008] Osteoarthritis (OA) is one of the most prevalent degenerative joint disorders globally and represents a leading cause of disability among adults. This condition is characterized by the progressive degeneration of articular cartilage and the underlying subchondral bone, leading to pain, stiffness, inflammation and decreased joint mobility thereby adversely affecting the quality of life of affected individuals. The prevalence of OA increases progressively with advancing age, making it a significant health concern within the aging population. The societal and economic burden of OA includes both direct medical expenditures and indirect costs, including loss of productivity, work absenteeism, and disability-related expenses. OA primarily affects the articular cartilage, a smooth, resilient tissue that covers the ends of bones at synovial joints, facilitating low-friction movement and absorbing mechanical stress during physical activity. In osteoarthritis, the progressive degradation of articular cartilage results in bone-on-bone contact, leading pain, swelling, inflammation and restricted joint mobility. As the articular cartilage progressively deteriorates, the underlying subchondral bone undergoes structural and biochemical alterations, including sclerosis (hardening) and the formation of osteophytes (bone spurs), which collectively contribute to joint pain, reduced mobility and stiffness. The subchondral bone also becomes increasingly prone to microfractures, further intensifying the pain and inflammatory response associated with OA. Moreover, inflammation of the synovial membrane(synovitis), is a common pathological feature of OA. The synovium responsible for the production of synovial fluid that lubricates and nourishes the joint, becomes inflamed and hypertrophic, resulting in excessive synovial fluid accumulation, joint effusion and enhanced pain and swelling.

[0009] The nociceptive pain associated with OA primarily arises from mechanical stress and inflammatory processes within the affected joint. This form of pain results from the activation of nociceptors (pain receptors) located in the synovial membrane and subchondral bone and is typically perceived as a dull, aching sensation that may intensify into sharp pain during joint movement or weight-bearing activities. In contrast, neuropathic pain in OA is linked to nerve damage and sensitization and is often characterized by burning, tingling, or shooting sensations. It is postulated that chronic joint inflammation in OA induces sensitization of peripheral and central pain pathways, resulting in a persistent and amplified pain response. The limitations, side effects and long-term safety concerns associated with conventional pharmacological treatments for OA such as nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, and analgesics underscore the need for alternative therapeutic approaches. In this context, nutraceuticals - bioactive compounds derived from natural or food sources - offer a promising and safer alternative for the management and prevention of OA as they can modulate multiple pathological pathways while exhibiting a lower risk of adverse effects compared to synthetic drugs.

[0010] Current pharmacological interventions for osteoarthritis including non-steroidal antiinflammatory drugs (NSAIDs), corticosteroids, and disease-modifying agents are primarily directed toward providing symptomatic relief rather than addressing the underlying degenerative pathology of the disease. However, the prolonged use of such agents is frequently associated with adverse effects such as gastrointestinal irritation, cardiovascular complications, hepatic dysfunction and immunosuppression, thereby limiting their longterm applicability. Accordingly, there exists a growing need for safe and efficacious, nutraceutical-based compositions capable of supporting joint structure and function, reducing inflammation and alleviating pain while minimizing long-term safety concerns commonly associated with synthetic pharmacological therapies.

[0011] KR20220107698 discloses a composition for the prevention or treatment osteoarthritis, comprising at least one active ingredient selected from the group consisting of RSPO1 and RSPO2.

[0012] US 11622949 discloses a synergistic composition comprising agmatine in combination with one or more additional active ingredients exhibiting beneficial effects in the treatment of osteoarthritis and other osteo-articular disorders associated with neuropathy and related symptomatic manifestations.

[0013] US 10688144 discloses a pharmaceutical composition for the treatment of osteoarthritis comprising an extract of Angelica gigas Nakai, or a combined extract of Angelica gigas Nakai and Cnidium officinale as an active ingredient.

[0014] WO2023043297 discloses a pharmaceutical composition for the prevention or health functional food for the prevention or treatment of osteoarthritis comprising a selenium- containing material in combination with an antioxidant as active components.

[0015] While the aforementioned approaches demonstrate continued efforts to improve joint health through development of bioactive and functional compositions, many such formulations remain limited in efficacy due to their narrow mechanistic focus, restricted range of active ingredients or inconsistent clinical applicability. Most existing intervention primarily targets a single biochemical pathway or symptomatic aspect of osteoarthritis and therefore fails to comprehensively address the multifactorial pathophysiology of the disease which involves structural cartilage degeneration, inflammatory dysregulation, and oxidative stress acting in concert to drive disease onset and progression.

[0016] Accordingly, there remains a need for a synergistic nutraceutical composition capable of providing multi-component support for joint integrity and function, by effectively integrating chondroprotective, anti-inflammatory, and antioxidative mechanisms. Such composition should be formulated to ensure consistency, safety and efficacy during longterm administration thereby overcoming the limitations associated with existing therapeutic and nutraceutical approaches.

[0017] OBJECTIVE OF THE INVENTION

[0018] A primary object of the present invention is to provide a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract for use in the prevention and / or management of osteoarthritis.

[0019] Another object of the present invention is to provide a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, with at least one pharmaceutically or nutraceutically acceptable excipient, for use in the prevention and / or management of osteoarthritis.

[0020] Another object of the present invention is to provide a safe and effective composition for the long-term management of osteoarthritis, which serves as a nutraceutical alternative to conventional pharmacological therapies thereby minimizing the risk of adverse effects associated with prolonged use of conventional therapies.

[0021] A further object of the present invention is to provide a nutraceutical composition comprising defined ratios and concentrations of palmitoylethanolamide, undenatured collagen type II, and rosehip extract wherein the weight ratio of the components lies within the range of 1:0.0001:0.0333 to 1:0.4:5.3333 thereby ensuring synergistic efficacy and optimal therapeutic performance in the prevention or management of osteoarthritis.

[0022] Yet another object of the present invention is to provide a composition comprising: (a) palmitoylethanolamide, (b) undenatured collagen type II, and (c) rosehip extract, in the specific proportions, expressed either as percentages of the total composition or as quantitative per-dose amounts so as to achieve consistent synergistic efficacy and enhanced biofunctional outcomes in the prevention or management of osteoarthritis. It is an object of the present invention to provide the aforesaid synergistic composition in a pharmaceutically or nutraceutically acceptable oral dosage form, selected from but not limited to a tablet, capsule, pill, powder, hard or soft capsule, granule, pellet, caplet, minitablet, gummy, suspension, syrup, solution, emulsion, sachet, modified-release formulation, or any other oral delivery system suitable for ensuring effective bioavailability and patient compliance.

[0023] Another object of the present invention is to provide a composition comprising at least one pharmaceutically or nutraceutically acceptable excipient, selected from diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agents, solvents, and mixtures thereof to facilitate optimal formulation stability, manufacturability, and bioavailability of the active components.

[0024] A further object of the present invention is to provide a composition adapted to support joint cartilage regeneration, reduce inflammation and enhance joint mobility and flexibility in a subject suffering from osteoarthritis or other degenerative joint disorders, thereby contributing to overall joint health restoration and functional improvement.

[0025] Another object of the present invention is to provide a kit comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, optionally along with one or more pharmaceutically acceptable excipients wherein the kit is adapted for use in the prevention and / or management of osteoarthritis and is configured to allow convenient, accurate, and consistent administration of the active components.

[0026] It is an additional object of the invention to provide a composition formulated for oral administration that exhibits enhanced activity against osteoarthritis-associated cartilage degradation, wherein the enhancement is measured by various tests including biomarker tests.

[0027] It is a still further object of the present invention to provide a stable, safe, and well -tolerated composition suitable for long-term administration in humans, thereby improving overall quality of life and offering a sustained therapeutic benefit in individuals suffering from osteoarthritis or related degenerative joint conditions.

[0028] SUMMARY OF THE INVENTION

[0029] The present invention provides a synergistic nutraceutical composition developed for the prevention and / or management of osteoarthritis. The composition comprises palmitoylethanolamide, undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically or nutraceutically acceptable excipient. The invention further relates to a process for preparation of the said composition, which is formulated for oral administration in suitable nutraceutical dosage forms including but not limited to tablets, capsules, powders, granules, gummies, suspensions, or solutions.

[0030] The inventive composition represents a synergistic combination of three bioactive components that collectively provide multi-mechanistic support for joint health and function. The defined combination and relative proportions of palmitoylethanolamide, undenatured collagen type II, and rosehip extract result in complementary and interdependent mechanisms of action that contribute to the maintenance of cartilage integrity, enhancing joint mobility, and reduction of oxidative and inflammatory stress associated with osteoarthritis. The synergistic interaction among these components produces a therapeutic effect greater than the sum of their individual activities, thereby offering a clinically relevant advantage over existing monotherapy or additive formulations.

[0031] In one aspect, the present invention provides a synergistic nutraceutical composition wherein the weight ratio of palmitoylethanolamide: undenatured collagen type II : rosehip extract lies within the range of 1:0.0001:0.0333 to 1:0.4:5.3333. In another aspect, the composition comprises palmitoylethanolamide in an amount of 2 to 95% w / w, undenatured collagen type II in an amount of 0.01 to 15% w / w, and rosehip extract in an amount of 2 to 80 % w / w of the total composition, or corresponding quantitative amounts per unit dosage form. The composition can be formulated using conventional nutraceutical or pharmaceutical manufacturing techniques, employing excipients one or more pharmaceutically acceptable excipients selected from diluents, binders, lubricants, disintegrants, solubilizing agents, suspending agents, preservatives, or mixtures thereof, to ensure formulation stability, content uniformity, and enhanced bioavailability of the active ingredients.

[0032] In a preferred embodiment, the composition of the present invention is formulated for oral administration in a dosage form selected from but not limited to tablet, capsule, pill, powder, granule, pellet, gummy, suspension, syrup, solution, emulsion, sachet, or modified-release formulation or any other orally administrable form suitable for ensuring optimal stability, bioavailability, and patient compliance.

[0033] The invention thus provides a stable, safe, and well-tolerated nutraceutical composition suitable for long-term administration in humans. The composition offers a comprehensive and multi-mechanistic approach for maintenance of joint health and function, effectively addressing the structural, inflammatory and oxidative aspects of osteoarthritis. Furthermore, the invention serves as a scientifically substantiated nutraceutical alternative to conventional pharmacological agents thereby providing a safer and sustainable solution for the prevention and management of osteoarthritis.

[0034] BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 : Knee diameter study results

[0036] Figure 2: Effects on knee bend study results

[0037] Figure 3: Effect on Randall-Selitto test study results

[0038] Figure 4: Movement-evoked pain study results

[0039] Figure 5 : Hot plate study results

[0040] Figure 6: Spontaneous lifting behavior study results

[0041] Figure 7 : Grip strength study results

[0042] Figure 8: Serum IL-1 study results

[0043] Figure 9: Serum MMP-13 study results

[0044] Figure 10: Serum CTX-II study results

[0045] Figure 11 : Serum MMP-3 study results

[0046] Figure 12: Serum CP II study results

[0047] DETAILED DESCRIPTION OF THE INVENTION

[0048] The following detailed description sets forth the present invention and various embodiments thereof. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. It will be understood, however, that other embodiments and variations may be employed and modifications may be the described examples, without departing from the spirit or scope of the present as defined in the appended claims.

[0049] References to “an”, “one”, or “various” embodiments in the present disclosure are not necessarily directed to the same embodiment, and such references are intended to encompass one or more embodiments of the invention. Accordingly, the following detailed description should not be construed in a limiting sense, and the scope of the invention is to be determined solely by the appended claims, together with the full scope of legal equivalents to which such claims are entitled.

[0050] In one embodiment, the present invention provides a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically acceptable excipient.

[0051] In another embodiment, the present invention provides a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically acceptable excipient, the composition being formulated for use in the prevention or management of osteoarthritis.

[0052] The composition of the present invention is developed for the prevention or management of osteoarthritis and is formulated for oral administration. The synergistic combination of Palmitoylethanolamide, undenatured collagen type II, and rosehip extract act through complementary mechanisms to support and maintain joint health, preserve cartilage structure, and enhance joint comfort and mobility. The composition provides a multicomponent therapeutic approach that addresses the oxidative and inflammatory stress associated with osteoarthritis while minimizing or avoiding the adverse effects commonly observed with conventional pharmacological therapies.

[0053] As used herein, the term “synergistic” refers to the combined effect of palmitoylethanolamide, undenatured collagen type II, and rosehip extract wherein the resultant effect of their conjoint administration is greater than the sum of their individual effects. Each component performs a distinct and complementary biological function within the composition, palmitoylethanolamide contributes to the maintenance of normal inflammatory balance and physiological pain modulation; undenatured collagen type II supports immune tolerance toward joint cartilage and contributes to joint flexibility and mobility; and rosehip extract delivers natural antioxidants activity thereby protecting connective tissues from oxidative stress-induced damage. Collectively, these components act synergistic manner to support cartilage integrity, preserve joint structure and improve overall joint function in individuals susceptible to or suffering from osteoarthritis.

[0054] The composition according to the present invention comprises palmitoylethanolamide, undenatured collagen type II, and rosehip extract in a weight ratio of palmitoylethanolamide: undenatured collagen type II : rosehip extract within the range of 1:0.0001:0.0333 to 1:0.4:5.3333, 1:0.0001:0.0536 to 1:0.3667:5.1667, 1:0.0002:0.0769 to 1:0.3333:5, 1:0.0003:0.1042 to 1:0.30000:4.6667, 1:0.0005:0.15 to 1:0.2667:4.3333. This defined ratio ensures optimal synergistic interaction among the active ingredients resulting in enhanced efficacy in supporting joint structure, reducing inflammation and improving cartilage health compared to any single component or non-optimized combination thereof.

[0055] In another embodiment, the composition comprises palmitoylethanolamide in an amount ranging from 2% to 95% w / w, 2.5 % to 70 % w / w, 3.5 % to 70 % w / w, 4.5 % to 70 % w / w, 5.5 % to 70 % w / w, or 6 % to 70 % w / w of the total composition. The undenatured collagen type II in an amount ranging from 0.01 % to 15.0 % w / w, 0.01 % to 12.0 % w / w, 0.03 % to 10.0 % w / w, 0.10 % to 9.0 % w / w, 0.20 % to 9.0 % w / w, 0.30 % to 8.0 % w / w, 0.40 % to 7.0 % w / w, 0.50 % to 7 % w / w, or 0.55 % to 7 % w / w of the total composition. The rosehip extract in an amount ranging from 2 % to 80 % w / w, 2 % to 70 % w / w, 2 % to 60 % w / w, 2 % to 50 % w / w, 2 % to 45 % w / w, 3 % to 40 % w / w, 4 % to 40 % w / w, 5 % to 40 % w / w, 8 % to 40 % w / w, 10 % to 40 % w / w or 15 % to 40 % w / w of the total composition. These concentration ranges are selected to provide optimal bioactivity, synergistic efficacy and formulation stability while ensuring safety, palatability and patient compliance upon long-term administration.

[0056] In another embodiment, the present invention provides a composition comprising palmitoylethanolamide in an amount ranging from 150 mg to 1500 mg, 150 mg to 1400 mg, 150 mg to 1300 mg, 150 mg to 1200 mg, 150 mg to 1100 mg, or 150 mg to 1000 mg, undenatured collagen type II in an amount ranging from 0.15 mg to 60 mg, 0.2 mg to 55 mg, 0.3 mg to 50 mg, 0.4 mg to 45 mg or 0.5 mg to 40 mg and rosehip extract in an amount ranging from 50 mg to 800 mg, 75 mg to 775 mg, 100 mg to 750 mg 125 mg to 700 mg or 150 mg to 650 mg weight per unit dosage form. The specified quantitative ranges are selected to achieve an optimized synergistic interaction among the active ingredients, thereby providing enhanced efficacy in supporting and maintaining joint function, cartilage integrity, and musculoskeletal comfort upon oral administration as part of a daily regimen. The quantities of the active ingredients described herein are based on the effective daily dosage required to elicit the intended therapeutic and physiological benefits. The composition may be formulated to deliver proportionate amounts of the actives per unit dosage form such that the total daily intake corresponds to the predetermined effective dose. The composition may be administered once daily or in divided doses, such as twice daily, depending on individual requirements or formulation design considerations. Irrespective of the dosage regimen or frequency of administration, any composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract within the defined proportions or ranges shall be considered to fall within the scope of the present invention.

[0057] The composition of the present invention is formulated for oral administration and may be presented in a dosage form selected from but not limited to a tablet, capsule, pill, powder, hard or soft capsule filled with solids or liquids, granule, pellet, caplet, mini-tablet, gummy, suspension, syrup, solution, emulsion, sachet, or modified-re lease formulation, or any other pharmaceutically or nutraceutically acceptable oral dosage form. The oral dosage forms are designed to ensure formulation stability, enhanced bioavailability, and consumer acceptability while preserving the synergistic interaction and functional integrity of the active ingredients palmitoylethanolamide, undenatured collagen type II, and rosehip extract throughout the product’s shelf life and upon administration.

[0058] In another embodiment, the present invention provides a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, together with at least one pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient is selected from the group of diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agent, solvents, and mixtures thereof. The composition of the present invention may optionally include one or more additional pharmaceutically acceptable excipients to enhance formulation stability, palatability, flow characteristics or manufacturability .

[0059] These excipients may be used individually or in combination to facilitate content uniformity, ease of manufacture, enhanced formulation stability of the formulation and convenient administration of the final dosage form.

[0060] In certain embodiments, the pharmaceutically acceptable excipient is a diluent. The diluent but not limited to calcium carbonate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, calcium sulfate, magnesium oxide, microcrystalline cellulose, cellulose powder, maltodextrin, lactose anhydrous, lactose monohydrate, sucrose, mannitol, sorbitol, xylitol, starch, pregelatinized starch, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinylpyrrolidone, xanthan gum, or a mixture or equivalent thereof or like thereof. According to the present invention, the composition may comprise a diluent in an amount ranging from 1% to 98% by w / w of the total composition.

[0061] In certain embodiments, the pharmaceutically acceptable excipient is a binder. The binder includes, but are not limited to microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, Hypromellose, low-substituted hydroxypropyl cellulose, methylcellulose, pregelatinized starch, starch, povidone, Polyvinylpyrrolidone, copovidone, carbomer, sodium alginate, acacia, agar, guar gum, maltodextrin, pectin, tragacanth, or a mixture or equivalent thereof or like thereof. According to the present invention, the composition may comprise a binder in an amount ranging from 0.1% to 12% by w / w of the total composition.

[0062] In certain embodiments, the pharmaceutically acceptable excipient is a lubricant. The lubricant includes, but not limited to magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, or glyceryl behenate, zinc stearate or a mixture or equivalent thereof or like thereof. According to the present invention, the composition may comprise a lubricant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0063] In certain embodiments, the pharmaceutically acceptable excipient is a glidant. The glidant includes, but not limited to colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or a mixture or equivalent thereof or like thereof. According to the present invention, the composition may comprise a glidant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0064] In certain embodiments, the pharmaceutically acceptable excipient is a disintegrant. The disintegrant includes, but not limited to alginic acid, calcium alginate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, chitosan, com starch, pregelatinized starch, croscarmellose sodium, crospovidone, docusate sodium, low-substituted hydroxypropyl cellulose, methylcellulose, povidone, sodium alginate, sodium starch glycolate, cross-linked hydroxypropyl cellulose, or a mixture or equivalent thereof or like thereof. According to the present invention, the composition may comprise a disintegrant in an amount ranging from 0.4% to 15% by w / w of the total composition.

[0065] In certain embodiments, the pharmaceutically acceptable excipient is a surfactant or solubilizing agents. The surfactant or solubilizing agents includes, but not limited to polysorbates, sorbitan esters, polyethylene glycol esters, polyoxyethylene stearates, polyoxyethylene castor oil derivatives, poloxamers, sodium lauryl sulfate, sodium dodecyl sulfate, sodium stearate, sodium dioctyl sulfosuccinate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or a mixture or equivalent thereof or like thereof.

[0066] In certain embodiments, the pharmaceutically acceptable excipient is a suspending agent. Suitable suspending agents include, but are not limited to, natural gums such as acacia, tragacanth, xanthan gum, guar gum, locust bean gum, carrageenan, and alginates; cellulose derivatives such as sodium carboxymethylcellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and microcrystalline cellulose; clays and silicates such as bentonite, kaolin, and magnesium aluminum silicate; synthetic or semi-synthetic polymers such as carbomers, polyvinylpyrrolidone, polyacrylic acid derivatives, and poloxamers; as well as gelatin, starch, pregelatinized starch, pectin, sodium starch glycolate, or a mixture or equivalent thereof or like thereof.

[0067] In certain embodiments, the pharmaceutically acceptable excipient is a flavoring agent. Suitable flavoring agents include, but are not limited to, natural flavoring substances such as essential oils (e.g., peppermint, spearmint, clove, cinnamon, anise, fennel, cardamom, citrus oils, and ginger oil), fruit extracts and concentrates (e.g., apple, cherry, banana, strawberry, raspberry, pineapple, mango, peach, grape, blueberry, cranberry), cocoa, and vanilla; synthetic flavoring substances such as artificial fruit flavors, chocolate, caramel, butterscotch, coffee, and cola; sweetener-based flavoring agents such as aspartame, saccharin, acesulfame potassium, sucralose, stevia extract, xylitol, sorbitol, mannitol, and maltitol; and additional additives used for flavor modulation including flavor enhancers (e.g., glycyrrhizin, monosodium glutamate) and masking agents such as cyclodextrins, vanillin, and ethyl maltol or a mixture or equivalent thereof or like thereof.

[0068] In certain embodiments, the pharmaceutically acceptable excipient is a preservative. Suitable preservatives include, but are not limited to, parabens such as methylparaben, propylparaben, ethylparaben, butylparaben, and their sodium salts; benzoates such as benzoic acid, sodium benzoate, and potassium benzoate; sorbates such as sorbic acid, potassium sorbate, and calcium sorbate; alcohols and phenolic compounds such as ethanol, benzyl alcohol, phenol, cresol, and chlorocresol; quaternary ammonium compounds such as benzalkonium chloride and cetylpyridinium chloride; formaldehyde donors such as imidurea; chelating agents such as EDTA and its salts; sodium dehydroacetate; or a mixture or equivalent thereof or like thereof.

[0069] In certain embodiments, the pharmaceutically acceptable excipient is a buffering agent. Suitable buffers for suspensions include, but are not limited to, phosphate buffers such as sodium phosphate (monobasic, dibasic, and tribasic), potassium phosphate (monobasic and dibasic), sodium dihydrogen phosphate, and disodium hydrogen phosphate; citrate buffers such as citric acid, sodium citrate, and potassium citrate; acetate buffers such as acetic acid, sodium acetate, and potassium acetate; carbonate and bicarbonate buffers such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate; and other buffering agents such as lactic acid, sodium lactate, tromethamine (Tris), boric acid, sodium borate, glycine, or a mixture or equivalent thereof or like thereof.

[0070] In certain embodiments, the pharmaceutically acceptable excipient is a solvent. Suitable solvents for suspensions include, but are not limited to, aqueous solvents such as purified water, distilled water, and water for injection; alcohols such as ethanol and glycerol; polyols such as propylene glycol, polyethylene glycol, sorbitol solution, and mannitol solution; oils such as vegetable oils (e.g., soybean, sunflower, peanut, olive, sesame, com, cottonseed, and coconut oil), medium chain triglycerides, castor oil, and mineral oil; esters and other co-solvents such as triacetin and propylene carbonate; or a mixture or equivalent thereof or like thereof.

[0071] The composition of the present invention can be prepared employing conventional pharmaceutical or nutraceutical formulation methods known in the art for formulating oral dosage forms. In certain embodiments, the composition is prepared through direct compression, wherein the active pharmaceutical ingredients are intimately blended with suitable excipients such as fdlers, binders, disintegrants, and lubricants, followed by compression into tablets. In another embodiment, the composition may be prepared by granulation techniques, including wet or dry granulation, to enhance powder flowability, compressibility and content uniformity prior to compression or encapsulation. In further embodiment, the composition may be filled into sachets or capsules to facilitate ease of oral administration. Alternatively, the composition may be formulated as a powder or granule for reconstitution into an oral suspension. The method of preparation may further comprise mixing, blending, granulating, drying, sieving and compressing steps or combinations thereof, depending upon the intended dosage form. Other conventional pharmaceutical or nutraceutical processing techniques known as those skilled in the art may likewise be employed to obtain the desired stability, efficacy, bioavailability and patient compliance of the composition.

[0072] In another embodiment, the present invention provides a kit comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, wherein the kit is adapted for use in the prevention or management of osteoarthritis. In certain embodiments, the kit comprises the components in separate dosage units or combined within a single packaging system. In one embodiment, the palmitoylethanolamide is provided in the first container, the undenatured collagen type II is provided in the second container, and the rosehip extract is provided in a third container, wherein all containers are packaged together in a single kit. In other embodiments, the kit may comprise blister packs, sachets, bottles, or pouches, each containing one or more unit dosage forms of the composition. The dosage forms may be selected from tablets, capsules, powders, granules, suspensions, or solutions formulated for oral administrations. Optionally, the kit may include printed, electronic or digital instructions for use, describing the dosage regimen, mode of administration and intended synergistic benefits of co-administering the components. The instructions may specify the components are to be administered concurrently or sequentially to provide synergistic nutritional support for joint health, cartilage integrity, and mobility improvement in individuals at risk of or experiencing osteoarthritis.

[0073] In yet another embodiment, the present invention provides a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, wherein the composition comprises palmitoylethanolamide in an amount ranging from 150 mg to 1500 mg, undenatured collagen type II in an amount ranging from 0.15 mg to 60 mg, and rosehip extract in an amount ranging from 50 mg to 800 mg per unit dosage form. The weight ratio of palmitoylethanolamide : undenatured collagen type II : rosehip extract lies within the range of 1:0.0001:0.0333 to 1:0.4:5.3333. The composition is formulated for oral administration and is adapted to provide enhanced synergistic activity against osteoarthritis-associated cartilage degradation, wherein the enhancement in C- terminal cross-linked telopeptide of type II collagen (CTX-II) is at least 18.15 percent greater than the combined individual activities of the ingredients. This confirms the synergistic interaction among the three nutraceutical components, resulting in improved overall joint health and comfort when administered as part of a regular oral nutraceutical regimen.

[0074] Palmitoylethanolamide (PEA) is a fatty acid amid that may be obtained by standard synthesis or by extraction and purification from naturally occurring lipid sources. Undenatured collagen type II is derived from avian sternum cartilage, while rosehip extract is obtained from the fruits of Rosa canina L. For the purposes of the present invention, all active ingredients are sourced from established commercial suppliers and are not derived directly from biological resources by the applicant or inventors. Irrespective of the specific source or manufacturing method, or supplier, any composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract together falls within the scope of the present invention.

[0075] The synergistic nutraceutical composition of the present invention is safe, stable, and suitable for long-term administration in humans. It provides a scientifically validated, evidence -based formulation designed to maintain joint health, cartilage integrity, and overall mobility. The defined combination of palmitoylethanolamide, undenatured collagen type II, and rosehip extract, in conjunction with at least one pharmaceutically acceptable excipient, represents an innovative, consumer-safe and efficacious nutraceutical solution for the prevention or management of osteoarthritis. The composition further contributes to sustained joint comfort, improved flexibility and enhanced quality of life during prolonged use.

[0076] The present invention provides significant advantages over the prior art. The synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract demonstrates a synergistic effect that exceeds the additive effects of the individual effects of the components. This synergism results in enhanced efficacy in maintaining joint health, supporting cartilage structure and alleviating osteoarthritis- associated discomfort. The composition offers a safe, and scientifically substantiated alternative to conventional therapy for joint health support, thereby minimizing the limitations and adverse effects commonly associated with standard drug treatments. Furthermore, the formulation is versatile and suitable for various oral dosage forms, ensuring stability, reproducibility and patient compliance. Owing to its validated synergistic performance and multifunctional benefits, the invention represents a distinct technical advancement in the field of nutraceutical compositions for osteoarthritis management and demonstrates clear industrial applicability across the dietary supplement, functional food, and healthcare product sectors. EXAMPLES

[0077] The following examples are provided to further illustrate the present invention and its various embodiments. These examples are intended solely for the explanatory purpose and should not be construed as limiting the scope of the invention in any manner. It will be understood by those skilled in the art that modifications, substitutions, variations, and equivalents may be employed without departing from the spirit and scope of the invention as defined by the appended claims.

[0078] EXAMPLE-1: COMPOSITION Following is general composition formula as per the present invention:

[0079] Process for preparation of example 1 :

[0080] 1. Accurately weigh each ingredient in separate containers.

[0081] 2. Sift the previously weighed active ingredients and excipients through a sieve. 3. Combine the contents from step 2 to prepare suitable oral dosage form.

[0082] Example 2A - Sachet Example 2B - Sachet

[0083] Manufacturing process of Sachet:

[0084] 1. All the active ingredients and excipients were accurately weighed as per the batch

[0085] 5 formula and PEA, Undenatured collagen type II, Rosehip extract and MCC were passed through #40 mesh sieve and croscarmellose sodium maltodextrin, magnesium stearate and colloidal silicon dioxide were passed through #60 mesh sieve.

[0086] 2. PEA + Undenatured collagen type II + Rosehip extract + MCC were loaded into a 0 double-cone blender or bin blender.

[0087] 3. Citric acid, flavour, sweetener and colloidal silicon dioxide were added and blended for 5-7 minutes.

[0088] 4. Lubricants and glidants were added and mixed gently to improve flow properties without overmixing. 5 5. The blend underwent in-process checks including blend uniformity and flow properties.

[0089] 6. The blended powder was fdled into pre-formed sachets.

[0090] 7. Sachets were sealed and packed into suitable packs, labelled, and stored under recommended conditions. 0

[0091] Example 3A - Tablets

[0092] Example 3B - Tablets

[0093] Manufacturing process of Tablets:

[0094] 5 1. All the active ingredients and excipients were accurately weighed as per the batch formula and PEA, Undenatured collagen type II, Rosehip extract and MCC were passed through #40 mesh sieve and PVP K30 and Croscarmellose sodium were passed through #60 mesh sieve.

[0095] 2. PEA + Undenatured collagen type II + Rosehip extract + MCC (intragranular 0 portion) were loaded in a rapid mixer granulator (RMG) or planetary mixer.

[0096] 3. A binder solution was prepared and added to the blend while mixing to form uniform granules, which were passed through a suitable sieve and then dried using fluidized bed dryer (FBD) or tray dryer.

[0097] 4. The dried granules were passed through a 20# mesh sieve to break lumps. 5 5. The dries granules were transferred to a blender. Croscarmellose sodium (extra- granular portion), colloidal silicon dioxide were added and mixed for 5 minutes, magnesium stearate and talc, were added and blended for 2-3 minutes.

[0098] 6. The blend from Step 5 was compressed to form tablets and hypromellose-based film coating solution uniformly was applied over compressed tablets. 0 7. The finished products were packed into moisture-protective packaging, labelled, and stored under recommended conditions.

[0099] Example 4A - Capsules

[0100] 5 Example 4B - Capsules

[0101] Manufacturing process of Capsules:

[0102] 1. All the active ingredients and excipients were accurately weighed as per the batch formula and PEA, Undenatured collagen type II, Rosehip extract and MCC were 0 passed through #40 mesh sieve and croscarmellose sodium maltodextrin, magnesium stearate and colloidal silicon dioxide were passed through #60 mesh sieve.

[0103] 2. PEA + Undenatured collagen type II + Rosehip extract + MCC were loaded into a double-cone blender or bin blender. Croscarmellose sodium and colloidal silicon 5 dioxide were added and mixed for 5 minutes, magnesium stearate was added and blended for 2-3 minutes. 3. The blend from Step 2 the final blend into the capsule filling machine.

[0104] 4. The finished products were packed into moisture-protective packaging, labelled, and stored under recommended conditions. Example 5 - Suspension

[0105] Manufacturing process of Suspension:

[0106] 1. All the active ingredients and excipients were accurately weighed as per the batch formula and passed through an appropriate mesh sieve to remove lumps and ensure uniform particle size.

[0107] 2. -60-70% of purified water was added into a stainless-steel mixing vessel and slow agitation (200-300 rpm) was started. Glycerol was added and mixed until uniform.

[0108] 3. Preservatives (potassium sorbate / sodium benzoate) were dissolved in warm water (40-45 °C) separately, then add into main tank. Citric acid / sodium citrate buffer solution was added and mixed.

[0109] 4. Sweetener (sucralose or permitted one) and flavour was dissolved in a small volume of water and added to bulk. 5. Xanthan gum + Sodium CMC were pre-blended in a small amount of glycerol (to prevent lumping). Slurry was added slowly into the main tank under high shear mixing until fully hydrated (approx. 30-45 minutes).

[0110] 6. Palmitoylethanolamide (PEA) was pre-wetted with a small amount of polysorbate 80. Slurry was added into the main tank under continuous agitation. Disperse undenatured collagen type II and Rosehip extract were dispersed slowly into the bulk while mixing.

[0111] 7. Final volume was adjusted with the remaining purified water and mixed under slow stirring for 15-20 minutes.

[0112] 8. The final product of step-7 is filled in suitable containers and sealed;

[0113] 9. The containers were packed, labelled, and stored under recommended conditions.

[0114] EXAMPLE 3: Animal Study

[0115] Objective: To evaluate the synergistic anti-osteoarthritic effects of Palmitoyl ethanolamide, undenatured collagen type II and Rosehip extract in monosodium iodoacetate (MIA) induced osteoarthritis in rats.

[0116] Materials and Methods: Female Wistar rats aged 9-10 weeks and weighing 150-220 g at the start of experiment were divided into groups of 6 animals each.

[0117] All the animals were divided into the following groups: Normal control group, Disease control group, Standard group, Test group- 1 (Palmitoylethanolamide), Test group-2 (Undenatured collagen type II), Test group-3 (Rosehip extract) and Test group-4 (Palmitoylethanolamide + Undenatured collagen type II + Rosehip extract). These groups were denoted as N, D, S, Tl, T2, T3, and T4, respectively. Monosodium iodoacetate (2 mg in 25 pL) was injected intra-articularly into the right knee of pre-anesthetized (ether) rats in all groups except group N to induce osteoarthritis, followed by their respective treatments for 28 days. Blood samples were collected after 28 days of treatment using the retro-orbital plexus method.

[0118] All the animals in groups N, D, S, Tl, T2, T3, and T4 received treatments as per the table below, and efficacy was evaluated using the specified evaluation parameters.

[0119] *BID- Twice in a day

[0120] Evaluation parameters: 1. Knee diameter

[0121] 2. Knee bend score

[0122] 3. Randall-Selitto test

[0123] 4. Movement-evoked pain

[0124] 5. Hot plate study 6. Spontaneous lifting behavior

[0125] 7. Grip strength

[0126] 8. Serum IL- ip

[0127] 9. Serum MMP-13

[0128] 10. Serum CTX-II 11. Serum MMP-3

[0129] Statistical analysis: The statistical significance of the result was analyzed by two-way ANOVA followed by Tukey's multiple comparisons test. Animal study results: Knee diameter: Knee diameter, measured in mediolateral and anteroposterior dimensions, serves as an indicator of structural changes in osteoarthritis. An increase in knee diameter arises from osteophyte formation, synovial hypertrophy, and periarticular remodeling, and 5 directly reflects elevated inflammation and disease progression. The greater the knee diameter, the more advanced the osteoarthritis stage and associated functional impairment. Measurement of knee diameter therefore provides a reliable parameter for disease assessment, progression monitoring, and implant sizing in knee arthroplasty. Group T4 showed a 40.59% greater reduction in knee diameter than T1+T2+T3, indicating superior 10 efficacy in reducing inflammation and structural changes associated with osteoarthritis progression. The study results are provided in table 2 and figure 1.

[0130] Table 2:

[0131] 15 Knee bend score: The Knee Bend Score is a functional assessment parameter that quantifies the degree of difficulty, pain, or limitation experienced during knee flexion. The score is derived by evaluating the range of motion, ease of bending, and associated discomfort while performing a knee bend. In this scoring system, a higher score indicates greater stiffness, pain, and functional impairment, whereas a lower score denotes better

[0132] 20 flexibility, reduced symptoms, and clinical improvement. Thus, progressive reduction in the Knee Bend Score is indicative of therapeutic benefit and enhanced joint function. The parameter is non-invasive, reproducible, and clinically significant for monitoring osteoarthritis progression and evaluating treatment efficacy. Group T4 showed a 67.17% greater reduction in Knee Bend Score compared to T1+T2+T3, indicating markedly improved joint flexibility, reduced pain, and superior functional recovery in osteoarthritis. The study results are provided in table 3 and figure 2.

[0133] 5 Table 3:

[0134] Randall-Selitto test: The Randall - Selitto test measures nociceptive thresholds in osteoarthritis by applying progressive pressure to the affected joint or paw until a pain response is elicited. A lower pressure threshold indicates heightened pain sensitivity and 10 disease severity, while an increased threshold following treatment reflects analgesic efficacy. This method provides a reproducible and quantifiable parameter for evaluating therapeutic outcomes in osteoarthritis. Group T4 showed a 27.68% increase in Randall- Selitto threshold compared to T1+T2+T3, indicating a higher pain tolerance and stronger analgesic effect, demonstrating superior efficacy in reducing pain sensitivity associated 15 with osteoarthritis. The study results are provided in table 4 and figure 3.

[0135] Table 4:

[0136] Movement-evoked pain: Movement-evoked pain is an important clinical manifestation of osteoarthritis, typically occurring prior to the onset of pain at rest and contributing to functional impairment. In preclinical models of osteoarthritis, movement-evoked pain may 5 be quantitatively assessed by measuring hind limb compressive grip force, expressed in grams. A decrease in grip force is indicative of heightened nociception and reduced joint function. Administration of pharmacological agents that restore grip force toward baseline values demonstrates analgesic efficacy. An observed increase in grip force following treatment correlates with reduced pain sensitivity and improved locomotor activity.

[0137] 10 Accordingly, measurement of grip force provides a functional and translational biomarker for assessing the efficacy of therapeutic interventions targeting osteoarthritis-associated pain. Group T4 showed a 31.31% increase in pain threshold compared to T1+T2+T3, indicating a marked reduction in movement-evoked pain and improved joint function, demonstrating superior analgesic and functional efficacy in osteoarthritis management. The 15 study results are provided in table 5 and figure 4.

[0138] Table 5:

[0139] Hot plate assay: The hot plate assay provides a quantitative measure of thermal

[0140] 20 nociception in osteoarthritis models. In this method, rodents are placed on a heated surface (52-55 °C), and the latency to hind paw licking, shaking, or jumping is recorded in seconds. Decreased latency indicates enhanced nociception, whereas increased latency following administration of a therapeutic agent demonstrates analgesic efficacy. In osteoarthritis, this assay serves as a complementary biomarker to movement-evoked endpoints, reflecting both 5 peripheral and central sensitization, and is useful for evaluating the efficacy of candidate analgesic compounds. Group T4 showed a 23.44% increase in hot plate latency compared to T1+T2+T3, indicating enhanced pain threshold and stronger analgesic activity, thereby demonstrating superior efficacy of the T4 treatment in alleviating thermal nociception associated with osteoarthritis. The study results are provided in table 6 and figure 5.

[0141] 10

[0142] Table 6:

[0143] Spontaneous Lifting Behaviour: Spontaneous lifting behaviour is a non-evoked measure of nociception that reflects ongoing or resting pain associated with osteoarthritis. In rodent 15 models, animals with unilateral osteoarthritis show reduced frequency and duration of hind limb lifting when placed in an observation chamber. This reduction arises from joint discomfort and impaired weight distribution. Pharmacological interventions that alleviate osteoarthritis pain restore the frequency and duration of spontaneous hind limb lifting toward normal values. Quantification is typically performed by recording the number of 20 lifts within a defined observation period, providing a simple, reproducible, and translational biomarker of osteoarthritis pain. Increased lifting activity after treatment correlates with effective analgesic action and improved joint function. Group T4 showed a 21.43% increase in spontaneous lifting behaviour compared to T1+T2+T3, indicating effective pain relief and improved joint mobility, demonstrating superior analgesic and functional efficacy of the T4 treatment in osteoarthritis. The study results are provided in table 7 and figure 6.

[0144] Table 7:

[0145] 5

[0146] Grip strength: In rodent models, hind limb compressive grip force is quantified using a strain gauge system, with force expressed in grams. Osteoarthritis induction produces a marked reduction in grip strength, reflecting nociception and impaired joint function. Pharmacological agents that restore grip strength toward baseline levels demonstrate 10 analgesic efficacy. Increases in grip force following treatment correlate with reduced pain sensitivity and improved locomotor performance. Grip strength thus serves as a robust, quantitative, and translational biomarker for evaluating therapeutic interventions in osteoarthritis. Group T4 showed a 37.36% increase in grip strength compared to T1+T2+T3, reflecting enhanced neuromuscular performance, restored joint stability, and 15 greater overall functional recovery, signifying the superior therapeutic potential of the T4 treatment in osteoarthritis. The study results are provided in table 8 and figure 7.

[0147] Table 8:

[0148]

[0149] Serum IL-1 : Interleukin- 10 (IL- i ) is a pro-inflammatory cytokine that plays a central role in the pathogenesis of osteoarthritis. Elevated serum IL- 1 p levels are associated with cartilage degradation, synovial inflammation, and progression of joint damage. In 5 preclinical and clinical models, increased circulating IL- 1 p serves as a biomarker of disease activity and systemic inflammation. Pharmacological agents that reduce serum IL-ip concentrations demonstrate anti-inflammatory and disease-modifying potential. Measurement of IL-ip in serum, typically by ELISA, provides a quantitative and reproducible endpoint for evaluating the efficacy of candidate osteoarthritis therapies.

[0150] 10 Group T4 showed a 22.52% greater reduction in serum IL-ip levels compared to T1+T2+T3, indicating stronger suppression of systemic inflammation and enhanced disease-modifying activity, reflecting superior anti-inflammatory efficacy of the T4 treatment in osteoarthritis. The study results are provided in table 9 and figure 8.

[0151] 15 Table 9:

[0152] Serum MMP-13: Matrix metalloproteinase- 13 (MMP-13) is a collagenase that preferentially degrades type II collagen, a principal structural component of articular cartilage. In osteoarthritis, elevated serum MMP-13 levels correlate with cartilage breakdownjoint degeneration, and disease progression. Measurement of circulating MMP- 13, commonly by ELISA, provides a quantitative biomarker for monitoring osteoarthritic pathology. Therapeutic agents that lower serum MMP-13 concentrations demonstrate 5 potential chondroprotective and disease-modifying effects. Accordingly, serum MMP-13 serves as a translational endpoint for assessing efficacy of pharmacological interventions in osteoarthritis. Group T4 showed a 32.40% greater reduction in serum MMP-13 levels compared to T1+T2+T3, indicating pronounced inhibition of cartilage degradation and enhanced chondroprotective activity, demonstrating the superior disease-modifying 10 potential ofthe T4 treatment in osteoarthritis. The study results are provided in table 10 and figure 9.

[0153] Table 10:

[0154] 15 Serum CTX-II: C-terminal telopeptide of type II collagen (CTX-II) is a degradation product released during breakdown of articular cartilage. Elevated serum CTX-II levels are strongly associated with cartilage loss and progression of osteoarthritis. Quantification of CTX-II, typically by ELISA, provides a sensitive biomarker for monitoring structural joint damage. Pharmacological interventions that reduce serum CTX-II indicate inhibition of

[0155] 20 cartilage degradation and potential disease-modifying activity. Thus, serum CTX-II serves as a translational and quantitative endpoint for evaluating therapeutic efficacy in osteoarthritis models. A 22.15% greater reduction in serum CTX-II in Group-4 versus T1+T2+T3 indicates stronger inhibition of cartilage degradation and superior chondroprotective efficacy. The study results are provided in table 11 and figure 10.

[0156] Table 11:

[0157] 5 Serum MMP-3: Matrix metalloproteinase-3 (MMP-3), also known as stromelysin- 1, is an enzyme that degrades proteoglycans, laminin, and non-collagen matrix components in articular cartilage. Elevated serum MMP-3 levels are associated with synovial inflammation, cartilage degradation, and progression of osteoarthritis. Measurement of circulating MMP-3, typically by ELISA, provides a quantitative biomarker of joint tissue 10 remodelling and disease activity. Pharmacological agents that reduce serum MMP-3 concentrations demonstrate anti-inflammatory and chondroprotective potential. Accordingly, serum MMP-3 serves as a translational endpoint for evaluating therapeutic efficacy in osteoarthritis models. Group T4 showed a 32.52% greater reduction in serum MMP-3 levels compared to T1+T2+T3, indicating effective suppression of joint tissue 15 degradation and inflammation, thereby demonstrating superior chondroprotective and disease-modifying efficacy of the T4 treatment in osteoarthritis. The study results are provided in table 12 and figure 11.

[0158] Table 12:

[0159] Serum CP II: C-propeptide of type II procollagen (CP -II) is a biomarker of type II collagen synthesis and cartilage matrix turnover. In osteoarthritis, elevated serum CP-II reflects abnormal chondrocyte activation and dysregulated collagen metabolism in response to joint 5 damage. Persistently high CP-II levels are associated with progressive cartilage remodeling and disease severity. Reduction of serum CP-II following therapeutic intervention indicates suppression of pathological collagen turnover and restoration of cartilage homeostasis. Accordingly, a decrease in serum CP-II is considered beneficial and serves as a translational biomarker for evaluating disease-modifying efficacy of osteoarthritis treatments. Group T4 10 showed a 26.11% greater reduction in serum CP-II levels compared to T1+T2+T3, indicating improved regulation of cartilage matrix turnover and restoration of collagen homeostasis, thereby reflecting superior disease-modifying efficacy of the T4 treatment in osteoarthritis. The study results are provided in table 13 and figure 12.

[0160] 15 Table 13:

[0161] The results presented in the foregoing examples clearly demonstrate that the present invention provides a synergistic nutraceutical composition comprising palmitoylethanolamide, undenatured collagen type II, and rosehip extract, representing a significant technical advancement over existing nutraceutical and conventional pharmacological therapies for osteoarthritis. The defined combination produces an unexpected synergistic effect, delivering significantly greater improvement in cartilage protection, reduction of inflammatory markers, and enhancement of joint comfort compared to the individual ingredients administered separately. The composition integrates complementary mechanisms of action within a single standardized formulation, ensuring reproducibility, stability, and consistent efficacy across batches. Its ability to be formulated in multiple oral dosage forms such as tablets, capsules, granules, sachet and suspensions further enhances formulation versatility and long-term patient compliance.

[0162] The present invention possesses clear industrial and therapeutic applicability. By providing a safe, scientifically substantiated nutraceutical alternative to conventional pharmacological interventions, the composition effectively reduces long-term dependence on synthetic drugs and mitigates their associated adverse effects. The active component of the present invention exhibits favorable tolerability, safety and consumer acceptance, rendering the formulation suitable for routine and sustained use. The composition can be manufactured using standard nutraceutical processing techniques and equipments, thereby ensuring scalability, cost-effectiveness and compliance with applicable regulatory standards. Accordingly, the present invention integrates technical innovation with practical manufacturing and commercial viability, providing a safe, efficacious, and industrial applicable nutraceutical composition for the prevention and management of osteoarthritis and for promoting long-term joint health and mobility.

Claims

I / WE CLAIMS:

1. A synergistic nutraceutical composition comprising:(a) Palmitoylethanolamide;(b) Undenatured collagen type II; and(c) Rosehip extract; together with at least one pharmaceutically acceptable excipient.

2. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition is adapted for use in the prevention or management of osteoarthritis.

3. The synergistic nutraceutical composition as claimed in claim 1 , wherein the weight ratio of palmitoylethanolamide to undenatured collagen type II to rosehip extract is in the range of 1:0.0001:0.0333 to 1:0.4:5.3333.

4. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Palmitoylethanolamide in an amount ranging from 2 % to 95 % w / w of the total composition; and(b) Undenatured collagen type II in an amount ranging from 0.01 % to 15.0 % w / w of the total composition.(c) Rosehip extract in an amount ranging from 2 % to 80 % w / w of the total composition.

5. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Palmitoylethanolamide in an amount ranging from 150 mg to 1500 mg;(b) Undenatured collagen type II in an amount ranging from 0.15 mg to 60 mg; and(c) Rosehip extract in an amount ranging from 50 mg to 800 mg, by weight per unit dosage form.

6. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition is formulated for oral administration and wherein the composition isin a dosage form selected from tablet, capsule, pill, powder, hard capsule fdled with liquid or solids, soft capsule, granule, pellet, caplet, mini-tablet, gummy, suspension, syrup, solution, emulsion, sachet, modified-release formulation, or any other formulation intended for oral administration.

7. The synergistic nutraceutical composition as claimed in claim 1, wherein at least one pharmaceutically acceptable excipient is selected from the group comprising of diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agents, solvents, and mixtures thereof.

8. The synergistic nutraceutical composition as claimed in claim 1 or 2, wherein the composition is adapted to support joint cartilage regeneration, reduce inflammation, and improve joint mobility in a subject in need thereof.

9. A kit comprising:(a) Palmitoylethanolamide;(b) Undenatured collagen type II; and(c) Rosehip extract; wherein the kit is adapted for use in the prevention or management of osteoarthritis.

10. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Palmitoylethanolamide in an amount ranging from 150 mg to 1500 mg;(b) Undenatured collagen type II in an amount ranging from 0.15 mg to 60 mg; and(c) Rosehip extract in an amount ranging from 50 mg to 800 mg; wherein the weight ratio of palmitoylethanolamide: undenatured collagen type II : rosehip extract lies within the range of 1:0.0001:0.0333 to 1:0.4:5.3333; wherein the composition is formulated for oral administration; wherein the composition is adapted for use in the prevention or management of osteoarthritis.

Images