Preparation method and application of traditional Chinese medicine compound preparation with anti-infection and bone repair functions

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a preparation method and application of a traditional Chinese medicine compound preparation with anti-infection and bone repair functions. The traditional Chinese medicine compound preparation is prepared from the following raw materials in parts by mass: 10 to 30 parts of flos lonicerae, 10 to 20 parts of flos chrysanthemi indici, 5 to 20 parts of herba taraxaci, 5 to 15 parts of radix astragali seu hedysari, 5 to 20 parts of cortex eucommiae, 1 to 10 parts of herba violae, 1 to 10 parts of radix semiaquilegiae, 1 to 5 parts of gelatin, 1 to 5 parts of collagen, 1 to 2 parts of trehalose, 1 to 3 parts of chitosan, 1 to 2 parts of emulsifier and 100 to 200 parts of soluble calcium salt aqueous solution. The traditional Chinese medicine compound preparation has the dual requirements of infection resistance and bone repair, meanwhile, the stability is remarkably improved through dosage form improvement, the preparation method is simple, and a potential traditional Chinese medicine compound preparation choice is provided for clinical treatment of chronic osteomyelitis.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and in particular to the preparation method and application of traditional Chinese medicine compound preparations that take into account both anti-infection and bone repair. Background Technology

[0002] Osteomyelitis, an infectious disease of the bones caused by pyogenic bacteria, typically presents with acute onset, such as high fever, chills, persistent and severe pain at the site of infection, local swelling, elevated skin temperature, and limited mobility.

[0003] Currently, Western medicine primarily treats osteomyelitis with high-dose antibiotics, followed by lesion debridement combined with Billroth irrigation after acute symptoms are controlled. However, early symptoms are easily confused with post-fracture infections, purulent soft tissue infections, and other diseases, often leading to misdiagnosis or delayed treatment, and subsequently developing into chronic osteomyelitis. Furthermore, the pathogens easily develop drug resistance, making clinical symptoms difficult to control and significantly increasing the difficulty of nursing care. If the disease progresses further and leads to loss of spinal cord nerve function, patients may experience serious complications such as below-paraplegia motor dysfunction, sensory loss, urinary and fecal incontinence, and malnutrition.

[0004] Traditional Chinese medicine (TCM) clinical practice, based on a holistic approach, primarily employs acupuncture, massage, and medication to treat osteomyelitis, adhering to the principle of treating both internal and external factors through syndrome differentiation and prescription. TCM treatment focuses on nourishing Yin and Qi, warming the kidneys and strengthening the spleen, and promoting detoxification. It improves blood supply to bones and soft tissues by regulating Qi and replenishing blood, promotes marrow production by tonifying the kidneys, and addresses local meridian blockages by invigorating blood circulation and removing blood stasis. These combined efforts promote blood circulation, reduce toxicity in the affected area, and enhance the body's defense mechanisms, thereby achieving the goal of curing osteomyelitis. Compared to Western medicine, TCM treatment is more targeted, has better efficacy, and is less likely to induce drug resistance.

[0005] However, although traditional Chinese medicine preparations are less likely to induce drug resistance in the treatment of osteomyelitis, they are currently highly susceptible to environmental influences and deterioration, eventually losing their biological activity. This greatly limits their application in the field of osteomyelitis. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing technologies by proposing a method for preparing traditional Chinese medicine compound preparations that combines anti-infection and bone repair, and its application.

[0007] This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following raw materials by weight: 10-30 parts honeysuckle, 10-20 parts wild chrysanthemum, 5-20 parts dandelion, 5-15 parts astragalus, 5-20 parts eucommia, 1-10 parts violet, 1-10 parts purple-backed dandelion, 1-5 parts gelatin, 1-5 parts collagen, 1-2 parts trehalose, 1-3 parts chitosan, 1-2 parts emulsifier, and 100-200 parts soluble calcium salt aqueous solution.

[0008] Honeysuckle is harvested in early summer when the flowers are still in bud and not yet open, then dried in the shade. It can be used raw, stir-fried, or made into a syrup. It has a sweet taste and cold properties. It enters the lung, heart, and stomach meridians. It clears heat and detoxifies, and disperses wind-heat. It is mainly used to treat early-stage carbuncles and boils with redness, swelling, heat, and pain; external wind-heat; early-stage febrile diseases; dysentery due to heat toxicity; summer heat with thirst; and sore throat. This herb has broad-spectrum antibacterial activity, with strong inhibitory effects on pathogenic bacteria such as Staphylococcus aureus and Shigella dysenteriae; it also has significant anti-inflammatory and antipyretic effects.

[0009] Wild chrysanthemums are harvested in autumn and winter when the flowers first open, and then dried in the sun or steamed and then dried. They have a pungent and bitter taste; are slightly cold in nature; and enter the lung and liver meridians. They clear heat and detoxify; dispel wind and calm the liver. They are used to treat boils, carbuncles, erysipelas, eczema, dermatitis, wind-heat colds, sore throat, and hypertension.

[0010] Dandelion, sweet and slightly bitter in taste, cold in nature. It clears heat and detoxifies, reduces swelling and dissipates nodules. It is mainly used to treat upper respiratory tract infections, conjunctivitis, mumps, mastitis, gastritis, dysentery, hepatitis, cholecystitis, acute appendicitis, urinary tract infections, pelvic inflammatory disease, boils and carbuncles, pharyngitis, acute mastitis, lymphadenitis, scrofula, boils and carbuncles, acute conjunctivitis, fever from colds, acute tonsillitis, acute bronchitis, and urinary tract infections.

[0011] Astragalus membranaceus (Huang Qi) is sweet in taste and slightly warm in nature. It enters the lung, spleen, liver, and kidney meridians. It has the effects of tonifying qi and strengthening the exterior, astringing sweat and preventing prolapse, promoting tissue regeneration and relieving sores, and promoting diuresis and reducing swelling. It is used to treat qi deficiency and fatigue, sinking of middle qi, chronic diarrhea and rectal prolapse, hematochezia and metrorrhagia, spontaneous sweating due to exterior deficiency, carbuncles that are difficult to heal, chronic ulcers that do not heal, anemia and chlorosis, internal heat and thirst, chronic nephritis, proteinuria, and diabetes. Prepared astragalus membranaceus tonifies qi and strengthens the middle jiao, while raw astragalus membranaceus strengthens the exterior and promotes tissue regeneration.

[0012] Eucommia ulmoides is a plant belonging to the Eucommiaceae family. Eucommia ulmoides Oliv. The bark of the tree. Sweet in taste and warm in nature. It enters the liver and kidney meridians. It can nourish the liver and kidneys, strengthen muscles and bones, and calm the fetus. It is used to treat lower back pain, weakness in the legs and knees, dribbling urination, itching in the genital area, threatened miscarriage, fetal restlessness, and high blood pressure.

[0013] Viola yedoensis, dried whole herb. Harvested in spring and autumn, impurities removed, washed, and sun-dried. Bitter and pungent in taste, cold in nature; enters the heart and liver meridians. Clears heat and detoxifies, cools the blood and reduces swelling. Mainly used to treat jaundice, dysentery, mastitis, red and swollen eyes, and pharyngitis; externally applied to treat traumatic injuries, carbuncles, and snake bites.

[0014] Purple-backed amaranth has a pungent, bitter, and sweet taste, and is neutral or cold in nature. It can reduce swelling, detoxify, and promote urination. It is mainly used to treat scrofula, hernia, and difficulty urinating.

[0015] Preferably, the emulsifier is Tween 80.

[0016] Preferably, the soluble calcium salt is calcium chloride.

[0017] Preferably, the calcium ion concentration in the aqueous solution of the soluble calcium salt is 0.1-1 mol / L.

[0018] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth. Reflux extract twice with ethanol-water solution, each reflux extraction time being 1-2 hours. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and emulsifier to the acetic acid solution, homogenize for 1-3 min, lower to -20 to -40℃, keep warm for 10-30 min, raise to 40-50℃, keep warm for 5-10 min, lower again to -50 to -60℃, keep warm for 10-20 min, raise to room temperature, add dropwise to calcium chloride solution, let stand for 1-2 h, filter, and freeze dry.

[0019] Preferably, in S1, the mass fraction of the ethanol aqueous solution is 50-70%.

[0020] Preferably, in S1, during the reflux extraction process, the material-to-liquid ratio is 1:5-8.

[0021] Preferably, in S2, the mass fraction of the acetic acid solution is 1-2%.

[0022] Preferably, in step S2, the homogenization rate is 5000-10000 r / min.

[0023] The above-mentioned traditional Chinese medicine compound preparations that combine anti-infection and bone repair are used in the preparation of drugs for treating osteomyelitis.

[0024] Compared with existing technologies, the present invention has the following advantages: Based on the concept of holistic regulation in traditional Chinese medicine, this invention effectively addresses the problems of difficult infection control, slow bone repair, and poor formulation stability in the treatment of chronic osteomyelitis through compound formulation and preparation process.

[0025] This invention utilizes the combined use of Astragalus membranaceus and Eucommia ulmoides, which is beneficial for improving blood circulation in the affected area, tonifying the liver and kidneys, and strengthening muscles and bones, thus providing a foundation for tissue repair. Combined with the effects of honeysuckle, wild chrysanthemum, dandelion, Viola yedoensis, and Amaranthus purpurea, it can effectively promote osteoblast activity, showing significant efficacy in the treatment of osteomyelitis. Furthermore, the combination of honeysuckle, wild chrysanthemum, dandelion, Viola yedoensis, and Amaranthus purpurea, with their active ingredients, may exert a synergistic antibacterial effect through a multi-target approach. This not only effectively interferes with bacterial growth but also regulates local immune responses, promotes the release of endogenous antibacterial substances, thereby comprehensively clearing pathogens within the lesion and reducing the development of drug resistance. Compared with single-antibiotic targeted therapy, it has a significant advantage in reducing the risk of drug resistance.

[0026] This invention uses a composite carrier of gelatin, collagen and chitosan, and adds trehalose as a protective agent. By combining the components through freeze-thaw cycles and freeze-drying processes, a relatively complete coating structure can be formed on the surface of the extract, significantly reducing the impact of environmental factors on the active ingredients. Furthermore, by combining it with calcium chloride for solidification, the physical stability and shelf life of the preparation can be effectively improved, thus enhancing the therapeutic effect.

[0027] This invention addresses the dual needs of anti-infection and bone repair, while significantly improving stability through dosage form improvements. Moreover, the preparation method is simple, providing a promising traditional Chinese medicine compound preparation option for the clinical treatment of chronic osteomyelitis. Attached Figure Description

[0028] Figure 1 The graph shows the cumulative release rate of the traditional Chinese medicine compound preparations obtained in Example 5 and Comparative Examples 1-2 during 60 days of constant temperature storage at 25°C.

[0029] Figure 2 The cumulative release curves of the traditional Chinese medicine compound preparations obtained in Example 5 and Comparative Examples 1-2 in the digestive system are shown.

[0030] Figure 3 Comparison of bone volume fraction of tibia in mice from the normal group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group.

[0031] Figure 4 This is a comparison of bacterial colony counts in the tibial bone marrow tissues of mice in the model group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group. Detailed Implementation

[0032] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0033] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0034] Example 1: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 10g honeysuckle, 10g wild chrysanthemum, 5g dandelion, 5g astragalus, 5g eucommia, 1g violet, 1g purple-backed safflower, 1g gelatin, 1g collagen, 1g trehalose, 1g chitosan, 1g Tween 80, and 100g of a 0.1mol / L calcium chloride aqueous solution.

[0035] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 50% ethanol aqueous solution, with a material-to-liquid ratio of 1:5. The first reflux extraction is carried out for 1 hour, and the second reflux extraction is carried out for 1 hour. Combine the filtrates, concentrate and vacuum dry, and pulverize and pass through a 100-mesh sieve to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 20g of 1% acetic acid solution, homogenize for 1min at a homogenization speed of 5000r / min, cool to -20℃ and hold for 10min, heat to 40℃ and hold for 5min, cool again to -50℃ and hold for 10min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 1h, filter, and freeze dry.

[0036] Example 2: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 30g honeysuckle, 20g wild chrysanthemum, 20g dandelion, 15g astragalus, 20g eucommia, 10g violet, 10g purple-backed sage, 5g gelatin, 5g collagen, 2g trehalose, 3g chitosan, 2g Tween 80, and 200g of calcium chloride aqueous solution with a concentration of 1mol / L.

[0037] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 70% ethanol aqueous solution at a material-to-liquid ratio of 1:8. The first reflux extraction lasts for 2 hours, and the second reflux extraction lasts for 2 hours. Combine the filtrates, concentrate, vacuum dry, and pulverize to pass through a 100-mesh sieve to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 40g of 2% acetic acid solution, homogenize for 3min at a homogenization speed of 10000r / min, cool to -40℃ and hold for 30min, heat to 50℃ and hold for 10min, cool again to -60℃ and hold for 20min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 2h, filter, and freeze dry.

[0038] Example 3: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 15g honeysuckle, 18g wild chrysanthemum, 8g dandelion, 12g astragalus, 8g eucommia, 7g violet, 3g purple-backed dandelion, 4g gelatin, 2g collagen, 1.5g trehalose, 2.5g chitosan, 1.5g Tween 80, and 120g of a 0.5mol / L calcium chloride aqueous solution.

[0039] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice with a 65% ethanol aqueous solution at a material-to-liquid ratio of 1:6. The first extraction was carried out for 100 minutes and the second extraction for 80 minutes. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 35g of 1.5% acetic acid solution, homogenize for 2min at a homogenization speed of 7000r / min, cool to -35℃ and hold for 15min, heat to 48℃ and hold for 7min, cool again to -58℃ and hold for 12min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 100min, filter, and freeze dry.

[0040] Example 4: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 25g honeysuckle, 12g wild chrysanthemum, 16g dandelion, 8g astragalus, 16g eucommia, 3g violet, 7g purple-backed dandelion, 2g gelatin, 4g collagen, 1.5g trehalose, 1.5g chitosan, 1.5g Tween 80, and 180g of a 0.5mol / L calcium chloride aqueous solution.

[0041] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 55% ethanol aqueous solution at a material-to-liquid ratio of 1:7. The first reflux extraction is carried out for 80 minutes, and the second reflux extraction is carried out for 100 minutes. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 25g of 1.5% acetic acid solution, homogenize for 2min at a homogenization speed of 9000r / min, cool to -25℃ and hold for 25min, heat to 42℃ and hold for 9min, cool again to -52℃ and hold for 18min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 80min, filter, and freeze dry.

[0042] Example 5: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 20g honeysuckle, 15g wild chrysanthemum, 12g dandelion, 10g astragalus, 12g eucommia, 5g violet, 5g purple-backed dandelion, 3g gelatin, 3g collagen, 1.5g trehalose, 2g chitosan, 1.5g Tween 80, and 150g of a 0.5mol / L calcium chloride aqueous solution.

[0043] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 60% ethanol aqueous solution at a material-to-liquid ratio of 1:6.5. The first reflux extraction lasts for 90 minutes, and the second reflux extraction lasts for 90 minutes. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 30g of 1.5% acetic acid solution, homogenize for 2min at a homogenization speed of 8000r / min, cool to -30℃ and hold for 20min, heat to 45℃ and hold for 8min, cool again to -55℃ and hold for 15min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 90min, filter, and freeze dry.

[0044] Comparative Example 1: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 25g honeysuckle, 20g wild chrysanthemum, 18g dandelion, 8g violet, 8g purple-backed amaranth, 3g gelatin, 3g collagen, 1.5g trehalose, 2g chitosan, 1.5g Tween 80, and 150g of a 0.5mol / L calcium chloride aqueous solution.

[0045] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 60% ethanol aqueous solution at a material-to-liquid ratio of 1:6.5. The first reflux extraction is performed for 90 minutes, and the second reflux extraction is performed for 90 minutes. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and Tween 80 to 30g of 1.5% acetic acid solution, homogenize for 2min at a homogenization speed of 8000r / min, cool to -30℃ and hold for 20min, heat to 45℃ and hold for 8min, cool again to -55℃ and hold for 15min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 90min, filter, and freeze dry.

[0046] Comparative Example 2: This traditional Chinese medicine compound preparation, which combines anti-infection and bone repair, contains the following ingredients: 20g honeysuckle, 15g wild chrysanthemum, 12g dandelion, 10g astragalus, 12g eucommia, 5g violet, 5g purple-backed sage, 6g gelatin, 1.5g trehalose, 2g chitosan, 1.5g Tween 80, and 150g of a 0.5mol / L calcium chloride aqueous solution.

[0047] The preparation method of the above-mentioned traditional Chinese medicine compound preparation that combines anti-infection and bone repair includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth, pass through a 100-mesh sieve, and extract twice by reflux with a 60% ethanol aqueous solution at a material-to-liquid ratio of 1:6.5. The first reflux extraction lasts for 90 minutes, and the second reflux extraction lasts for 90 minutes. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, trehalose, chitosan, and Tween 80 to 30g of 1.5% acetic acid solution, homogenize for 2min at a homogenization speed of 8000r / min, cool to -30℃ and hold for 20min, heat to 45℃ and hold for 8min, cool again to -55℃ and hold for 15min, heat to room temperature, add dropwise to calcium chloride solution, let stand for 90min, filter, and freeze dry.

[0048] Accurately weigh 1.0g of each of the traditional Chinese medicine compound preparations obtained in Example 5 and Comparative Examples 1-2, and then store them at a constant temperature of 25℃. They were taken out on the 5th, 10th, 15th, 20th, 25th, 30th and 60th days, respectively, and measured by UPLC. The peak area was recorded and the cumulative release rate was calculated.

[0049] like Figure 1 As shown, with the extension of storage time, the cumulative release rate of each group gradually increases and the release rate gradually slows down; while the cumulative release rate of Example 5 is always lower than that of the comparative example under the same conditions.

[0050] The traditional Chinese medicine compound preparations obtained in Example 5 and Comparative Examples 1-2 were first placed in simulated gastric fluid and allowed to stand at 36°C for 2 hours. After filtration, the filter cake was placed in simulated intestinal fluid and allowed to stand at 36°C for 4 hours. During the experiment, 2 mL of supernatant was taken every hour, and 2 mL of fresh simulated gastric fluid or fresh simulated intestinal fluid was added. The supernatant was filtered through a 0.22 μm filter membrane, and UPLC was performed to determine the peak area and calculate the cumulative release rate. Figure 2 As shown, Example 5 exhibits the best release effect, significantly superior to the comparative example.

[0051] A comparative experiment was conducted using the traditional Chinese medicine compound preparations obtained in Example 5 and Comparative Examples 1-2, as follows: Sixty male SD rats (210±10g) were randomly divided into 5 groups (normal group, model group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group). Rats in the model group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group underwent osteomyelitis modeling treatment (SD rats were fed for 1 week and fasted for 12 hours before the procedure). After anesthesia with sodium pentobarbital, the skin was prepared and disinfected, the knee joint was flexed, and an 8-gauge needle was used to drill into the medullary cavity of the tibia from the anterior middle 1 / 3 of the tibial plateau, slightly posterior to the vertical line of the tibia. A breakthrough or loss of momentum was felt during drilling. The needle (8-gauge) was then inserted into the medullary cavity of the tibia through the anterior hole, and 100μL of Staphylococcus aureus suspension (1×10⁻⁶) was injected. 8 cfu / mL). Withdraw the needle and apply slight pressure to the puncture site.

[0052] After modeling, local reactions were observed, including redness and swelling of the affected limb, reduced movement, and flexion. Four weeks later, local redness, sinus tract formation, and purulent discharge were observed. Imaging examination revealed periosteal hyperplasia, thickening and increased density of cortical bone, and the presence of sequestra and osteolytic cavities, indicating successful experimental modeling.

[0053] After the model was successfully constructed, rats in Example 5, Comparative Example 1, and Comparative Example 2 were administered the traditional Chinese medicine compound preparations obtained in Example 5, Comparative Example 1, and Comparative Example 2 by gavage for 4 weeks (once a day), at a dose of 1 g / kg body weight. At the same time, the normal group and the model group were given the same dose of physiological saline by gavage.

[0054] After sacrificing rats, the bone volume fraction (BV / TV) of the tibia was measured in the normal group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group to characterize the microstructure of bone trabeculae. Bone marrow tissue from the tibia of the model group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group was weighed, homogenized, plated, and the colony count was calculated.

[0055] like Figure 3 and Figure 4 As shown, the tibia of mice in Example 5 group had the highest bone volume fraction, significantly better than the control group; while the bone marrow of mice in Example 5 group had the lowest bacterial colony count, significantly better than the control group. This confirms that the traditional Chinese medicine compound preparation obtained in Example 5 can effectively promote the recovery of bone trabeculae in patients with osteomyelitis and can penetrate deep into the bone marrow tissue to exert a bactericidal effect.

[0056] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. A traditional Chinese medicine compound preparation that combines anti-infection and bone repair, characterized in that, The raw materials, by weight, include: 10-30 parts honeysuckle, 10-20 parts wild chrysanthemum, 5-20 parts dandelion, 5-15 parts astragalus, 5-20 parts eucommia, 1-10 parts violet, 1-10 parts purple-backed gentian, 1-5 parts gelatin, 1-5 parts collagen, 1-2 parts trehalose, 1-3 parts chitosan, 1-2 parts emulsifier, and 100-200 parts soluble calcium salt aqueous solution.

2. The traditional Chinese medicine compound preparation that combines anti-infection and bone repair according to claim 1, characterized in that, The emulsifier is Tween 80.

3. The traditional Chinese medicine compound preparation according to claim 1, which combines anti-infection and bone repair, is characterized in that, The soluble calcium salt is calcium chloride.

4. The traditional Chinese medicine compound preparation according to claim 1, which combines anti-infection and bone repair, is characterized in that, The calcium ion concentration in the aqueous solution of soluble calcium salts is 0.1-1 mol / L.

5. The method for preparing a traditional Chinese medicine compound preparation that combines anti-infection and bone repair as described in any one of claims 1-4, characterized in that, Includes the following steps: S1. Mix and grind honeysuckle, wild chrysanthemum, dandelion, astragalus, eucommia, violet, and purple-backed amaranth. Reflux extract twice with ethanol-water solution, each reflux extraction time being 1-2 hours. Combine the filtrates, concentrate, vacuum dry, and pulverize to obtain the pre-extract. S2. Add the pre-extract, gelatin, collagen, trehalose, chitosan, and emulsifier to the acetic acid solution, homogenize for 1-3 min, lower to -20 to -40℃, keep warm for 10-30 min, raise to 40-50℃, keep warm for 5-10 min, lower again to -50 to -60℃, keep warm for 10-20 min, raise to room temperature, add dropwise to calcium chloride solution, let stand for 1-2 h, filter, and freeze dry.

6. The method for preparing the traditional Chinese medicine compound preparation that combines anti-infection and bone repair according to claim 5, characterized in that, In S1, the mass fraction of the ethanol aqueous solution is 50-70%.

7. The method for preparing the traditional Chinese medicine compound preparation that combines anti-infection and bone repair according to claim 5, characterized in that, In S1, during the reflux extraction process, the material-to-liquid ratio is 1:5-8.

8. The method for preparing the traditional Chinese medicine compound preparation that combines anti-infection and bone repair according to claim 5, characterized in that, In S2, the mass fraction of the acetic acid solution is 1-2%.

9. The method for preparing the traditional Chinese medicine compound preparation that combines anti-infection and bone repair according to claim 5, characterized in that, In S2, the homogenization rate is 5000-10000 r / min.

10. The use of the traditional Chinese medicine compound preparation that combines anti-infection and bone repair as described in any one of claims 1-4 in the preparation of a drug for treating osteomyelitis.

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