Composition for treating osteoarthritis and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a composition for treating osteoarthritis and a preparation method thereof. The composition for treating osteoarthritis is prepared from the following raw materials in parts by weight: 1 to 3 parts of non-denatured type II collagen, 0.3 to 0.5 part of cowherb seed cyclic peptide A and 0.4 to 0.7 part of balanosine. According to the composition, through the synergistic effect of multiple active ingredients, the osteoarthritis symptom is jointly relieved, and joint tissue repair is promoted.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a composition for treating osteoarthritis and its preparation method. Background Technology

[0002] Osteoarthritis is a degenerative joint disease, commonly known as "wear-and-tear" arthritis, but its pathological mechanisms go far beyond simple mechanical wear and tear. Its main characteristic is the progressive destruction and loss of articular cartilage (the smooth tissue covering the ends of bones), accompanied by subchondral bone sclerosis, osteophyte formation, and periarticular hyperplasia. This process is usually triggered by a combination of factors, including aging, genetic factors, obesity, joint injury, or prolonged excessive weight-bearing, leading to a complex biological imbalance within the joint cavity, ultimately manifesting as pain, stiffness, limited mobility, and even loss of function. Osteoarthritis commonly affects weight-bearing joints, such as the knee and hip, as well as the spine and hands, causing severe and long-term negative impacts on patients' quality of life.

[0003] However, existing market solutions have significant functional limitations and safety concerns. Current mainstream products can be broadly divided into two categories: one is dietary supplements, such as chondroitin sulfate, glucosamine, and enzymatically hydrolyzed bone meal. These products have relatively simple ingredients, lack multi-target functional combinations, and are difficult to achieve synergistic effects in the complex pathological environment of joints. More importantly, their bioavailability is generally low, resulting in poor absorption rates, unstable and often very limited clinical efficacy, which damages consumer trust. The other category is chemical drugs, such as acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs). While these drugs can quickly relieve pain and inflammation, they only treat the symptoms and not the root cause, failing to slow disease progression or promote tissue repair. Long-term or high-dose use can lead to serious side effects such as gastrointestinal bleeding, cardiovascular risks, and liver and kidney toxicity, exposing patients, especially elderly patients requiring long-term medication, to extremely high medication risks.

[0004] Therefore, there is a clear, unmet clinical need in the treatment of osteoarthritis: an innovative approach that can simultaneously achieve the dual effects of "inflammation relief and pain control" and "promoting the repair of damaged tissues." An ideal treatment strategy should go beyond simple symptom management, delving into the joint microenvironment and achieving multi-target, synergistic intervention through the precise formulation of multiple active ingredients. This composition not only needs to effectively inhibit inflammatory factors and reduce pain, thereby rapidly improving the patient's quality of life, but also needs to provide the necessary nutritional and signaling support for chondrocyte regeneration and extracellular matrix synthesis, fundamentally repairing damaged joint tissue and delaying or even reversing disease progression. Based on this, the present invention provides a composition for treating osteoarthritis. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, the first objective of the present invention is to provide a composition for treating osteoarthritis, which, through the synergistic effect of multiple active ingredients, jointly relieves osteoarthritis symptoms and promotes joint tissue repair.

[0006] The second objective of this invention is to provide a method for preparing a composition for treating osteoarthritis, which has a simple process.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] A composition for treating osteoarthritis, comprising the following raw materials in parts by weight: 1-3 parts of non-denatured type II collagen, 0.3-0.5 parts of Wangbuliuxing cyclic peptide A, and 0.4-0.7 parts of Shegu Ning.

[0009] Furthermore, the ingredients include the following parts by weight: 2 parts of non-denatured type II collagen, 0.4 parts of Wangbuliuxing cyclic peptide A, and 0.6 parts of Shegu Ning.

[0010] Furthermore, it also includes the following ingredients in parts by weight: 0.8-1 parts sodium hyaluronate, 0.1-0.3 parts N-acetylglucosamine, 0.16-0.18 parts casein phosphopeptide, and 1-3 parts vitamin C.

[0011] Furthermore, it also includes the following ingredients in parts by weight: 0.9 parts sodium hyaluronate, 0.2 parts N-acetylglucosamine, 0.17 parts casein phosphopeptide, and 2 parts vitamin C.

[0012] In the above composition, the active ingredients work synergistically across multiple targets to improve the pathological process of osteoarthritis. Wangbuliuxing cyclic peptide A exerts its anti-inflammatory effect by regulating the NF-κB signaling pathway and inhibiting the release of inflammatory factors; when used in combination with non-denatured type II collagen, it can significantly reduce serum inflammatory factor levels, effectively relieving joint pain and inflammation. Shegu Ning can upregulate the expression of key cartilage repair genes Collagen II and Aggrecan, promoting cartilage tissue regeneration and repair. Furthermore, N-acetylglucosamine and sodium hyaluronate work synergistically to compensate for joint wear and bone spur formation caused by synovial fluid loss; while casein phosphopeptide and vitamin C work together to promote calcium absorption, increase bone density, prevent osteoporosis, and reduce fracture risk, thereby building a strong skeletal support system.

[0013] The method for preparing the above-mentioned composition for treating osteoarthritis includes the following steps:

[0014] Weigh each raw material according to the stated weight proportions, mix each raw material evenly, and then add pharmaceutically acceptable excipients to prepare the corresponding dosage form.

[0015] Furthermore, the dosage form is an oral preparation.

[0016] Furthermore, the oral preparation is a tablet, capsule, powder, oral liquid, powder, pill, or granule.

[0017] The beneficial technical effects of this invention are as follows:

[0018] The composition of this invention, through the synergistic effect of multiple active ingredients, alleviates osteoarthritis symptoms and promotes joint tissue repair. Animal experiments have shown that Wangbuliuxing cyclic peptide A can effectively inhibit the release of inflammatory factors by regulating the NF-κB signaling pathway, thus exerting an anti-inflammatory effect; when used in combination with non-denatured type II collagen, it can significantly reduce serum inflammatory factor levels and alleviate joint pain and inflammatory response. Simultaneously, Shegu Ning can upregulate the expression of cartilage repair-related genes Collagen II and Aggrecan, promoting cartilage tissue regeneration and repair. The components work together to exhibit a synergistic effect in anti-inflammation, analgesia, and cartilage repair, helping to restore joint function, improve the pathological process of osteoarthritis, and has promising clinical application prospects. Attached Figure Description

[0019] Figure 1 This shows the cytotoxicity results of Vaccaria segetalis cyclic peptide A; in the figure, A is the cytotoxicity result of the positive control group, B is the cytotoxicity result of the control group, and C is the cytotoxicity result of Vaccaria segetalis cyclic peptide A.

[0020] Figure 2 This shows the cytotoxicity results of sedge; in the figure, A is the cytotoxicity result of the positive control group, B is the cytotoxicity result of the control group, and C is the cytotoxicity result of sedge. Detailed Implementation

[0021] The following is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.

[0022] Example 1

[0023] A composition for treating osteoarthritis comprises the following raw materials in parts by weight: 2 parts of non-denatured type II collagen, 0.4 parts of Wangbuliuxing cyclic peptide A, 0.6 parts of Shegu Ning, 0.9 parts of sodium hyaluronate, 0.2 parts of N-acetylglucosamine, 0.17 parts of casein phosphopeptide, and 2 parts of vitamin C.

[0024] The method for preparing the above-mentioned composition for treating osteoarthritis includes the following steps:

[0025] Weigh each ingredient according to the stated weight proportions, mix non-denatured type II collagen, Wangbuliuxing cyclic peptide A, Shegu Ning, sodium hyaluronate, N-acetylglucosamine, casein phosphopeptide, and vitamin C evenly, add 1% maltodextrin of the total weight of the ingredients, and prepare capsules according to conventional methods.

[0026] Example 2

[0027] A composition for treating osteoarthritis comprises the following raw materials in parts by weight: 1 part non-denatured type II collagen, 0.3 parts Wangbuliuxing cyclic peptide A, 0.4 parts Shegu Ning, 0.8 parts sodium hyaluronate, 0.1 parts N-acetylglucosamine, 0.16 parts casein phosphopeptide, and 1 part vitamin C.

[0028] The method for preparing the above-mentioned composition for treating osteoarthritis includes the following steps:

[0029] Weigh each ingredient according to the stated weight proportions, mix non-denatured type II collagen, Wangbuliuxing cyclic peptide A, Shegu Ning, sodium hyaluronate, N-acetylglucosamine, casein phosphopeptide, and vitamin C evenly, then add starch at 1% of the total weight of the ingredients, and prepare the powder according to conventional methods.

[0030] Example 3

[0031] A composition for treating osteoarthritis comprises the following raw materials in parts by weight: 3 parts of non-denatured type II collagen, 0.5 parts of Wangbuliuxing cyclic peptide A, 0.7 parts of Shegu Ning, 1 part of sodium hyaluronate, 0.3 parts of N-acetylglucosamine, 0.18 parts of casein phosphopeptide, and 3 parts of vitamin C.

[0032] The method for preparing the above-mentioned composition for treating osteoarthritis includes the following steps:

[0033] Weigh each ingredient according to the stated weight proportions, mix non-denatured type II collagen, Wangbuliuxing cyclic peptide A, Shegu Ning, sodium hyaluronate, N-acetylglucosamine, casein phosphopeptide, and vitamin C evenly, add 2% lactose by weight of the total ingredients, and prepare granules according to conventional methods.

[0034] Comparative Example 1

[0035] A composition comprising the following raw materials in parts by weight: 2 parts of non-denatured type II collagen, 0.6 parts of strychnine, 0.9 parts of sodium hyaluronate, 0.2 parts of N-acetylglucosamine, 0.17 parts of casein phosphopeptide, and 2 parts of vitamin C.

[0036] Comparative Example 2

[0037] A composition comprising the following raw materials in parts by weight: 2 parts of non-denatured type II collagen, 0.4 parts of Wangbuliuxing cyclic peptide A, 0.9 parts of sodium hyaluronate, 0.2 parts of N-acetylglucosamine, 0.17 parts of casein phosphopeptide, and 2 parts of vitamin C.

[0038] Experimental Example 1

[0039] Experiment 1 investigated the cytotoxicity of the raw materials Wangbuliuxing cyclic peptide A and Shegu Ning involved in Example 1 using L929 fibroblasts. The specific experimental steps are as follows:

[0040] L929 fibroblasts in the logarithmic growth phase were resuspended in DMEM complete medium to obtain a concentration of 1×10⁻⁶ cells. 5 Cell suspension at a concentration of [number] cells / mL was used. 100 μL of the cell suspension was added to each well of a 96-well plate, and the plates were incubated at 37°C with 5% CO2 for 12 hours. After discarding the culture medium in each well, 100 μL of DMEM complete medium containing 50 μg / mL of Wangbuliuxing cyclic peptide A or Shegu Ning from Example 1 was added, and the plates were incubated for another day. Cell morphology in each well was observed under a microscope. The normal group was treated with serum-free DMEM medium, and the positive group was treated with DMEM complete medium supplemented with 5% phenol. Results are shown below. Figure 1-2 .

[0041] Figure 1 This shows the cytotoxicity results of Vaccaria segetalis cyclic peptide A. In the figure, A represents the cytotoxicity results of the positive control group, B represents the cytotoxicity results of the control group, and C represents the cytotoxicity results of Vaccaria segetalis cyclic peptide A. Figure 2 This shows the cytotoxicity results of strychnine. In the figure, A represents the cytotoxicity results of the positive control group, B represents the cytotoxicity results of the control group, and C represents the cytotoxicity results of strychnine. Observation Figure 1-2 It is known that neither Wangbuliuxing cyclic peptide A nor Shegu Ning of the present invention has obvious cytotoxicity.

[0042] Experiment Example 2

[0043] Experiment 2 investigated the efficacy of the compositions from Examples 1-3 and Comparative Examples 1-2. The specific experimental steps are as follows:

[0044] 2.1 Laboratory Animals

[0045] Seventy SPF-grade male SD rats, weighing 180-200g, were selected and acclimatized for one week.

[0046] 2.2 Establishing a knee osteoarthritis model

[0047] Ten rats were randomly selected as the sham surgery group, in which only the skin was incised, without severing the anterior cruciate ligament. The remaining rats underwent a transection of the anterior cruciate ligament in the right posterior knee joint, a positive "drawer test," and were kept unstable for 6 weeks to establish a rat model of knee osteoarthritis.

[0048] 2.3 Grouping and Administration

[0049] The rat model of knee osteoarthritis was randomly divided into the following six groups, with 10 rats in each group: Example 1-3 groups, Comparative Example 1-2 groups, and Model group.

[0050] Model group and sham surgery group: administered an equal volume of normal saline by gavage for 8 consecutive weeks;

[0051] Examples 1-3: The compositions of Examples 1-3 were administered by gavage at a dose of 1.2 g / kg once daily for 8 consecutive weeks;

[0052] Comparative Examples 1-2: The compositions of Comparative Examples 1-2 were administered by gavage at a dose of 1.2 g / kg once daily for 8 consecutive weeks.

[0053] 2.4 Detection Indicators

[0054] 2.4.1 Thermal pain threshold time

[0055] Each group of rats was placed in a smart hot plate apparatus. The time when the rats began to lick their paws was observed, and they were quickly removed. The time to the heat pain threshold was recorded. The results are shown in Table 1.

[0056] 2.4.2 Serum biochemical indicators

[0057] After the thermal pain threshold time test, the rats in each group were sacrificed, blood was collected from the abdominal aorta, and the supernatant was collected by centrifugation. The serum levels of IL-1β, TNF-α, and MMP-3 in each group of rats were detected using a kit. The results are shown in Table 2.

[0058] 2.4.3 Expression of Repair Proteins

[0059] The muscle tissue around the right posterior knee joint of rats was dissected to obtain an intact right knee joint. The collected knee joint tissue was fixed in formaldehyde for 30 hours, dehydrated with alcohol, soaked in naphtha for 2 hours, and then paraffin-embedded for 4 hours before being sectioned. The sections were incubated overnight in an incubation solution containing 1:1000 diluted anti-Collagen II and anti-Aggrecan antibodies. Detection was then performed using 1:500 diluted fluorescently labeled secondary antibody, with incubation at room temperature for 1 hour. The expression levels of Collagen II and Aggrecan were quantitatively analyzed using ImageJ software; the results are shown in Table 3.

[0060] Table 1

[0061] Table 2

[0062] Table 3

[0063] As shown in Table 1, the thermal pain threshold time was significantly reduced in the model group compared to the sham surgery group. Compared to the model group, the thermal pain threshold time was significantly increased in Examples 1-3 and Comparative Examples 1-2. Compared to Example 1, the thermal pain threshold time was reduced in Comparative Example 1. These results indicate that Wangbuliuxing cyclic peptide A can relieve pain.

[0064] As shown in Table 2, compared with the sham-operated group, the serum levels of IL-1β, TNF-α, and MMP-3 in the model group were significantly increased. Compared with the model group, the serum levels of IL-1β, TNF-α, and MMP-3 in Examples 1-3 and Comparative Examples 1-2 were significantly decreased. Compared with Example 1, the serum levels of IL-1β, TNF-α, and MMP-3 in Comparative Example 1 were significantly decreased. These results indicate that Vaccaria segetalis cyclic peptide A can affect the NF-κB signaling pathway to exert an anti-inflammatory effect, thereby inhibiting the release of inflammatory factors and reducing the content of inflammatory factors in serum.

[0065] As shown in Table 3, compared with the sham surgery group, the expression levels of Collagen II and Aggrecan in the model group were significantly reduced. Compared with the model group, the expression levels of Collagen II and Aggrecan in Examples 1-3 and Comparative Examples 1-2 were significantly increased. Compared with Example 1, the expression levels of Collagen II and Aggrecan in Comparative Example 2 were significantly reduced. These results indicate that *Smilax china* can promote the expression of cartilage repair-related genes Collagen II and Aggrecan, which is beneficial to the repair of damaged tissues.

[0066] In summary, the composition of this invention, through the synergistic effect of multiple active ingredients, alleviates osteoarthritis symptoms and promotes joint tissue repair. Animal experiments show that Wangbuliuxing cyclic peptide A can effectively inhibit the release of inflammatory factors by regulating the NF-κB signaling pathway, thus exerting an anti-inflammatory effect; when used in combination with non-denatured type II collagen, it can significantly reduce serum inflammatory factor levels and alleviate joint pain and inflammatory response. Simultaneously, Shegu Ning can upregulate the expression of cartilage repair-related genes Collagen II and Aggrecan, promoting cartilage tissue regeneration and repair. The components work together to exhibit a synergistic effect in anti-inflammation, analgesia, and cartilage repair, helping to restore joint function, improve the pathological process of osteoarthritis, and has promising clinical application prospects.

[0067] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.

Claims

1. A composition for treating osteoarthritis, characterized in that, The ingredients include the following parts by weight: 1-3 parts of non-denatured type II collagen, 0.3-0.5 parts of Wangbuliuxing cyclic peptide A, and 0.4-0.7 parts of Shegu Ning.

2. The composition for treating osteoarthritis according to claim 1, characterized in that, The ingredients include the following parts by weight: 2 parts of non-denatured type II collagen, 0.4 parts of Wangbuliuxing cyclic peptide A, and 0.6 parts of Shegu Ning.

3. The composition for treating osteoarthritis according to claim 1 or 2, characterized in that, It also includes the following ingredients in parts by weight: sodium hyaluronate 0.8-1 parts, N-acetylglucosamine 0.1-0.3 parts, casein phosphopeptide 0.16-0.18 parts, and vitamin C 1-3 parts.

4. The composition for treating osteoarthritis according to claim 3, characterized in that, It also includes the following ingredients in parts by weight: 0.9 parts sodium hyaluronate, 0.2 parts N-acetylglucosamine, 0.17 parts casein phosphopeptide, and 2 parts vitamin C.

5. A method for preparing the composition for treating osteoarthritis according to any one of claims 1-4, characterized in that, Includes the following steps: Weigh each raw material according to the stated weight proportions, mix each raw material evenly, and then add pharmaceutically acceptable excipients to prepare the corresponding dosage form.

6. The method for preparing the composition for treating osteoarthritis according to claim 5, characterized in that, The dosage form is an oral preparation.

7. The method for preparing the composition for treating osteoarthritis according to claim 6, characterized in that, The oral preparations are tablets, capsules, powders, oral liquids, granules, pills, or granules.

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