Experimental method for treating fracture based on shock waves

Abstract

The invention relates to the field of fracture treatment analysis, and discloses an experimental method for treating fracture based on shock waves, which comprises the following steps: firstly, after giving a femoral fracture model to a mouse, percutaneously injecting hyaluronic acid hydrogel containing icariin, and carrying out shock wave treatment 7 days and 14 days after a fracture operation; the problems that in the prior art, the rehabilitation time of an existing fracture rehabilitation medicine for treating fracture is long, and the application of icariin and shock waves in fracture rehabilitation is not found yet are solved.

Description

Technical Field

[0001] This invention relates to the field of fracture treatment analysis, and more particularly to an experimental method for treating fractures based on shock waves. Background Technology

[0002] A fracture is a disruption of the integrity or continuity of bone. It is often caused by external forces such as falls, sprains, compression, weight-bearing, or overuse. Symptoms include fractures, comminuted bone fragments, overlapping fractures, bleeding, swelling, and severe pain at the fracture site.

[0003] Currently, when people suffer fractures due to external injuries, they generally undergo fracture treatment through reduction, fixation, functional exercises, and medication. Commonly used medications for fracture treatment include calcium supplements, vitamin D, nonsteroidal anti-inflammatory drugs (NSAIDs), and traditional Chinese medicine for promoting blood circulation and removing blood stasis. However, the rehabilitation time for fracture rehabilitation medications and exercises currently used is very long, and they cannot achieve very good rehabilitation results. Summary of the Invention

[0004] The present invention aims to provide an experimental method for treating fractures based on shock waves, in order to solve the problems that existing fracture rehabilitation drugs have long recovery times and that the application of icariin and shock waves in fracture rehabilitation has not yet been discovered.

[0005] To achieve the above objectives, the present invention provides the following method:

[0006] The present invention provides an experimental method for treating fractures based on shock waves:

[0007] S1: A femoral fracture model was created in mice, and fracture reduction surgery was performed on the mice. After the fracture reduction surgery, hyaluronic acid hydrogel was injected percutaneously into the mice.

[0008] S2: The femur of the mice that had been percutaneously injected with hyaluronic acid hydrogel was treated twice with shockwave therapy;

[0009] S3: After administering shockwave therapy to the femur of the mice twice, the recovery progress of the mice was monitored.

[0010] Preferably, the hyaluronic acid hydrogel contains icariin.

[0011] Preferably, the concentration of icariin is 0.05-0.06 mg / ml.

[0012] Preferably, the timing of the two shockwave treatments on the femur of the mice after percutaneous injection of hyaluronic acid hydrogel is 7 days and 14 days after the percutaneous injection of hyaluronic acid hydrogel.

[0013] Preferably, the shockwave frequency of the two shockwave treatments administered to the femur of the mice that have been percutaneously injected with hyaluronic acid hydrogel is 1 bar, 400 times.

[0014] The beneficial effects of this invention are reflected in the following aspects: The core advantage of this invention in selecting icariin to promote fracture healing lies in its unique advantage of synergistic effects across multiple targets and mechanisms. Compared with traditional drugs or single components, it is more differentiated in terms of healing efficiency, safety, and efficacy. Specifically, this can be described from the following three aspects:

[0015] (1) The mechanism of action is more comprehensive, directly targeting the core aspects of fracture healing.

[0016] Fracture healing involves four stages: inflammation resolution, cartilage formation, callus formation, and callus remodeling. Icariin can specifically regulate multiple stages, rather than simply promoting osteogenesis.

[0017] Anti-inflammatory and improved blood circulation: By inhibiting the release of inflammatory factors such as TNF-α and IL-6, it reduces local swelling in the early stage of fracture, while promoting the proliferation of vascular endothelial cells, accelerating microvascular reconstruction at the fracture site, and providing sufficient oxygen and nutrients for healing.

[0018] Promotes cartilage and callus formation: Increases osteoblast activity and number (Figure A, Figure B), prevents bone loss, and accelerates the transformation of cartilage into callus.

[0019] (2) The study results found that uCT X-ray data

[0020] Compared to traditional drugs, it has the advantages of both "high efficacy" and "safety".

[0021] Compared with Western medicine: Traditional Western medicines such as bone peptides and calcium supplements can only supplement nutrition or activate osteoblasts, and have a weak effect on inflammation regulation and blood circulation improvement; while icariin can shorten fracture healing time through multi-target synergy, and does not have the risk of hypercalcemia caused by calcium supplements or allergic reactions to bone peptide drugs.

[0022] Compared with traditional Chinese medicine: Traditional bone-setting Chinese medicines such as Jiegu Qili tablets are mostly compound preparations with complex ingredients and difficult to control the effective concentration precisely; icariin is a single monomeric component extracted from epimedium, with a clear target and controllable dosage, which is convenient for industrial production and stable control of clinical efficacy, while avoiding the possible metabolic burden on the liver and kidneys of compound Chinese medicines.

[0023] (3) It has broader clinical application potential and is suitable for the needs of special populations.

[0024] For the elderly / osteoporosis population: Icariin not only promotes fracture healing and increases bone density, but also treats fractures and prevents osteoporosis, solving the problem of slow healing in elderly patients due to insufficient bone mass after fracture.

[0025] For diabetic patients with fractures: Diabetic patients are prone to vascular lesions and osteoblast dysfunction due to the high sugar environment. Icariin can protect the vascular endothelium and alleviate the inhibition of fracture healing by high sugar, which is an advantage that traditional drugs rarely have.

[0026] In summary, the advantage of icariin is not simply its ability to promote healing, but rather its ability to address the pain points of traditional drugs in fracture healing, such as "single action, unstable efficacy, and poor compatibility with special populations," through multi-mechanism synergy, high safety, and broad compatibility. It provides a more efficient and precise new direction for fracture healing treatment, meeting the core requirements of patented technology for innovation and application value.

[0027] The choice of shockwave therapy is not simply a matter of adding to existing methods, but rather based on its core value of synergistically enhancing drug efficacy through its physical and biological effects, and overcoming the limitations of single-drug intervention. Its specific advantages and mechanisms of action can be elaborated below based on existing research findings:

[0028] (1) Improve the local microenvironment to pave the way for drug efficacy.

[0029] Shock waves can break down local microcirculatory barriers at fracture sites through cavitation (generating and rupturing microbubbles) and mechanical stress, promoting capillary regeneration and blood perfusion (studies show it can increase local blood flow by 30%-50%), while accelerating the clearance of inflammatory factors (such as IL-1β and TNF-α). This effect can create a "high blood supply, low inflammation" microenvironment for the targeted delivery of subsequent drugs (such as icariin), solving the problem of ineffective drug penetration in ischemic and highly inflammatory areas.

[0030] (2) Activate osteogenic-related signaling pathways and synergistically enhance osteogenic effects with drugs.

[0031] Shock waves can activate key osteogenic signaling pathways such as BMP / Smad and Wnt / β-catenin, enhancing osteoblast activity and proliferation; simultaneously, they inhibit osteoclast differentiation, reducing bone loss. This mechanism, combined with the osteogenic effects of drugs (such as icariin), forms a dual activation of "physical + chemical" action. Studies have shown that the combination of these two can increase callus area by 40%-60% and significantly shorten fracture healing time.

[0032] (3) Promotes callus remodeling and enhances bone biomechanical strength after healing.

[0033] In the later stages of fracture healing, shockwave therapy can promote the transformation of immature woven bone into mature lamellar bone by regulating the alignment of collagen fibers; it also increases the amount of calcium salt deposition in the callus (increasing bone mineral density), ultimately enhancing the fracture and compression resistance of the healing site. Animal experiments have shown that the maximum bone load value in the shockwave combined with drug therapy group was 25%-35% higher than that in the drug-only group, reducing the risk of poor fracture healing.

[0034] Clinical advantages of shockwave therapy: non-invasive, highly safe, widely applicable, overcoming the limitations of traditional treatments.

[0035] (1) Non-invasive procedure, reducing treatment-related risks

[0036] Compared with surgical interventions (such as open reduction and internal fixation), shockwave therapy does not require invasive procedures and can avoid complications such as surgical infection and loosening of internal fixation; moreover, the treatment process is not painful (only a slight local soreness), and patient compliance is significantly higher than that of invasive treatments.

[0037] (2) It has a wide range of applications, especially suitable for refractory fractures.

[0038] For special cases where single drug treatment is ineffective (such as delayed healing / nonunion fractures, osteoporotic fractures in the elderly, and fractures associated with diabetes), shockwave therapy offers even greater advantages.

[0039] Shockwave therapy can break the "repair stagnation" state of local tissues and reactivate the healing process for delayed-healing fractures, with a clinical efficacy rate of 70%-80%. Shockwave therapy can improve vascular endothelial function in a high-glucose environment, alleviate microcirculation disorders, and work synergistically with drugs to solve the core problem of "high-glucose inhibiting osteogenesis".

[0040] (3) It is easy to operate, cost-controllable, and convenient for clinical promotion.

[0041] Shockwave therapy equipment is of moderate size and can be performed in outpatient settings, with a single treatment time of only 15-20 minutes; it also requires no special postoperative care, and the treatment cost is lower than that of surgery or long-term intravenous medication, making it more in line with the needs of large-scale clinical application. Attached Figure Description

[0042] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0043] Figure 1 A schematic flowchart of an experimental method for treating fractures based on shock waves, provided in an embodiment of the present invention;

[0044] Figure 2 A comparative graph showing the changes in bone volume fraction (BV / TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), bone mineral density (BMD), and trabecular bone separation (Tb.Sp) values ​​for different shock wave energies and impact frequencies provided in this embodiment of the invention.

[0045] Figure 3 The following graphs are provided for embodiments of the present invention: A is a graph showing changes in osteocyte activity over 1-14 days; B is a graph showing changes in osteocyte number over 1-14 days; C is a graph showing changes in osteocyte activity during microvascular reconstruction at the fracture site; D is a graph showing changes in the number of osteocytes during microvascular reconstruction at the fracture site; E is a graph showing changes in the number of osteocytes inhibiting the release of the inflammatory factor TNF-α; and F is a graph showing changes in the number of osteocytes inhibiting the release of the inflammatory factor IL-6.

[0046] Figure 4 Provided for embodiments of the present invention: A is a schematic diagram comparing bone healing speed in elderly / osteoporosis populations; B is a schematic diagram comparing bone healing speed in diabetic patients with fractures;

[0047] Figure 5 This is a comparison chart of experimental results of using icariin and shockwave therapy provided in an embodiment of the present invention. Detailed Implementation

[0048] To enable those skilled in the art to better understand the present invention, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0049] The terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this invention are used to distinguish different objects, not to describe a specific order. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or end that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or ends.

[0050] In this document, the term "embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of the invention. The appearance of this phrase in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0051] Currently, when people suffer fractures due to external injuries, they generally undergo fracture treatment through reduction, fixation, functional exercises, and medication. Commonly used medications for fracture treatment include calcium supplements, vitamin D, nonsteroidal anti-inflammatory drugs (NSAIDs), and traditional Chinese medicine for promoting blood circulation and removing blood stasis. However, the rehabilitation time for fracture rehabilitation medications and exercises currently used is very long, and they cannot achieve very good rehabilitation results.

[0052] The present invention aims to provide an experimental method for treating fractures based on shock waves, in order to solve the problems that existing fracture rehabilitation drugs have long recovery times and that the application of icariin and shock waves in fracture rehabilitation has not yet been discovered.

[0053] like Figure 1 As shown in the figure, a specific embodiment of the present invention provides an experimental method for treating fractures based on shock waves, comprising the following steps:

[0054] S1: A femoral fracture model was established in mice, and fracture reduction surgery was performed on the mice. After the fracture reduction surgery, hyaluronic acid hydrogel was injected percutaneously into the mice.

[0055] In this embodiment of the invention, the hyaluronic acid hydrogel contains icariin; the concentration of icariin is 0.05-0.06 mg / ml.

[0056] S2: The femur of mice that had been percutaneously injected with hyaluronic acid hydrogel was treated twice with shockwave therapy.

[0057] In this embodiment of the invention, the femur of mice that have undergone percutaneous injection of hyaluronic acid hydrogel was treated with shockwave therapy twice at two times: 7 days and 14 days after the percutaneous injection of hyaluronic acid hydrogel; the shockwave frequency for the two shockwave therapy sessions on the femur of mice that have undergone percutaneous injection of hyaluronic acid hydrogel was 1 bar, 400 times.

[0058] S3: After two shockwave treatments of the femur in mice, the recovery progress of the mice was monitored.

[0059] Example:

[0060] like Figure 2As shown, we set up different groups: low energy group (L, 1 bar), medium energy group (M, 2 bar), and high energy group (H, 4 bar). The number of shock wave impacts were divided into 200, 400, and 800, forming a model group. The models were: low energy 200 impacts (L-200), low energy 400 impacts (L-400), low energy 800 impacts (L-800), medium energy 200 impacts (M-200), medium energy 400 impacts (M-400), medium energy 800 impacts (M-800), and high energy 200 impacts (H-200), high energy 400 impacts (H-400), and high energy 800 impacts (H-800). Experimental results showed that administering low energy (1 bar) for 400 impacts resulted in a bone volume fraction (BV) of 200 impacts. The values ​​of / TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and bone mineral density (BMD) were significantly increased, while trabecular bone separation (Tb.Sp) was significantly decreased. Therefore, the final shock wave frequency was 1 bar, 400 times.

[0061] like Figure 5 As shown in Tables 1 and 2, the dosage of icariin was calculated based on the body weight of humans and mice according to "Pharmacological Experimental Methodology". The drug was administered at a dose of 60 mg / kg postoperatively. The effects of icariin and shockwave therapy on recovery time were investigated.

[0062] Table 1. Recovery time corresponding to different dosages of icariin

[0063] Epimedium glycoside dosage 0mg / kg 15mg / kg 30mg / kg 60mg / kg 120mg / kg Recovery time 4 weeks 4 weeks 4 weeks 3 weeks 3 weeks

[0064] Table 2. Rehabilitation duration corresponding to different rehabilitation treatment methods

[0065] Grouping Model group icariin group Shockwave group Icariin + Shockwave Group Recovery time 4 weeks 3 weeks 3 weeks 2.5 weeks

[0066] The beneficial effects of this invention are reflected in the following aspects: The core advantage of this invention in selecting icariin to promote fracture healing lies in its unique advantage of synergistic effects across multiple targets and mechanisms. Compared with traditional drugs or single components, it is more differentiated in terms of healing efficiency, safety, and efficacy. Specifically, this can be described from the following three aspects:

[0067] (1) The mechanism of action is more comprehensive, directly targeting the core aspects of fracture healing.

[0068] Fracture healing involves four stages: inflammation resolution, cartilage formation, callus formation, and callus remodeling. Icariin can specifically regulate multiple stages, rather than simply promoting osteogenesis.

[0069] Anti-inflammatory and improved blood circulation: By inhibiting the release of inflammatory factors such as TNF-α and IL-6. Figure 3 As shown in E and F, it reduces local swelling in the early stages of fracture, while promoting vascular endothelial cell proliferation and accelerating microvascular remodeling at the fracture site, such as... Figure 3As shown in C and D, sufficient oxygen and nutrients are provided for healing.

[0070] Promotes cartilage and callus formation: Increases osteoblast activity and number, such as Figure 3 As shown in A and B, this helps prevent bone loss and accelerates the transformation of cartilage into callus.

[0071] (2) The study results found that uCT X-ray data

[0072] Compared to traditional drugs, it has the advantages of both "high efficacy" and "safety".

[0073] Compared with Western medicine: Traditional Western medicines such as bone peptides and calcium supplements can only supplement nutrition or activate osteoblasts, and have a weak effect on inflammation regulation and blood circulation improvement; while icariin can shorten fracture healing time through multi-target synergy, and does not have the risk of hypercalcemia caused by calcium supplements or allergic reactions to bone peptide drugs.

[0074] Compared with traditional Chinese medicine: Traditional bone-setting Chinese medicines such as Jiegu Qili tablets are mostly compound preparations with complex ingredients and difficult to control the effective concentration precisely; icariin is a single monomeric component extracted from epimedium, with a clear target and controllable dosage, which is convenient for industrial production and stable control of clinical efficacy, while avoiding the possible metabolic burden on the liver and kidneys of compound Chinese medicines.

[0075] (3) It has broader clinical application potential and is suitable for the needs of special populations.

[0076] For the elderly / osteoporosis-prone population: Icariin not only promotes fracture healing and increases bone density, but also treats fractures and prevents osteoporosis, addressing the problem of slow healing in elderly patients due to insufficient bone mass after fractures. Figure 4 As shown in Figure A.

[0077] For diabetic patients with fractures: Diabetic patients are prone to vascular complications and impaired osteoblast function due to the high-sugar environment. Icariin can protect the vascular endothelium and alleviate the inhibitory effect of high sugar on fracture healing, an advantage rarely found in traditional drugs. Figure 4 As shown in B.

[0078] In summary, the advantage of icariin is not simply its ability to promote healing, but rather its ability to address the pain points of traditional drugs in fracture healing, such as "single action, unstable efficacy, and poor compatibility with special populations," through multi-mechanism synergy, high safety, and broad compatibility. It provides a more efficient and precise new direction for fracture healing treatment, meeting the core requirements of patented technology for innovation and application value.

[0079] The choice of shockwave therapy is not simply a matter of adding to existing methods, but rather based on its core value of synergistically enhancing drug efficacy through its physical and biological effects, and overcoming the limitations of single-drug intervention. Its specific advantages and mechanisms of action can be elaborated below based on existing research findings:

[0080] (1) Improve the local microenvironment to pave the way for drug efficacy.

[0081] Shock waves can break down local microcirculatory barriers at fracture sites through cavitation (generating and rupturing microbubbles) and mechanical stress, promoting capillary regeneration and blood perfusion (studies show it can increase local blood flow by 30%-50%), while accelerating the clearance of inflammatory factors (such as IL-1β and TNF-α). This effect can create a "high blood supply, low inflammation" microenvironment for the targeted delivery of subsequent drugs (such as icariin), solving the problem of ineffective drug penetration in ischemic and highly inflammatory areas.

[0082] (2) Activate osteogenic-related signaling pathways and synergistically enhance osteogenic effects with drugs.

[0083] Shock waves can activate key osteogenic signaling pathways such as BMP / Smad and Wnt / β-catenin, enhancing osteoblast activity and proliferation; simultaneously, they inhibit osteoclast differentiation, reducing bone loss. This mechanism, combined with the osteogenic effects of drugs (such as icariin), forms a dual activation of "physical + chemical" action. Studies have shown that the combination of these two can increase callus area by 40%-60% and significantly shorten fracture healing time.

[0084] (3) Promotes callus remodeling and enhances bone biomechanical strength after healing.

[0085] In the later stages of fracture healing, shockwave therapy can promote the transformation of immature woven bone into mature lamellar bone by regulating the alignment of collagen fibers; it also increases the amount of calcium salt deposition in the callus (increasing bone mineral density), ultimately enhancing the fracture and compression resistance of the healing site. Animal experiments have shown that the maximum bone load value in the shockwave combined with drug therapy group was 25%-35% higher than that in the drug-only group, reducing the risk of poor fracture healing.

[0086] Clinical advantages of shockwave therapy: non-invasive, highly safe, widely applicable, overcoming the limitations of traditional treatments.

[0087] (1) Non-invasive procedure, reducing treatment-related risks

[0088] Compared with surgical interventions (such as open reduction and internal fixation), shockwave therapy does not require invasive procedures and can avoid complications such as surgical infection and loosening of internal fixation; moreover, the treatment process is not painful (only a slight local soreness), and patient compliance is significantly higher than that of invasive treatments.

[0089] (2) It has a wide range of applications, especially suitable for refractory fractures.

[0090] For special cases where single drug treatment is ineffective (such as delayed healing / nonunion fractures, osteoporotic fractures in the elderly, and fractures associated with diabetes), shockwave therapy offers even greater advantages.

[0091] Shockwave therapy can break the "repair stagnation" state of local tissues and reactivate the healing process for delayed-healing fractures, with a clinical efficacy rate of 70%-80%. Shockwave therapy can improve vascular endothelial function in a high-glucose environment, alleviate microcirculation disorders, and work synergistically with drugs to solve the core problem of "high-glucose inhibiting osteogenesis".

[0092] (3) It is easy to operate, cost-controllable, and convenient for clinical promotion.

[0093] Shockwave therapy equipment is of moderate size and can be performed in outpatient settings, with a single treatment time of only 15-20 minutes; it also requires no special postoperative care, and the treatment cost is lower than that of surgery or long-term intravenous medication, making it more in line with the needs of large-scale clinical application.

[0094] The above descriptions are merely embodiments of the present invention. Commonly known technical solutions or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. An experimental method for treating a bone fracture based on a shock wave, characterized by, The method comprises: S1: administering a femur fracture model to a mouse, performing a fracture reduction operation on the mouse, and performing percutaneous injection of hyaluronic acid hydrogel on the mouse after the fracture reduction operation; S2: administering shock wave treatment twice to the femur of the mouse that has been injected with the hyaluronic acid hydrogel; S3: monitoring the recovery progress of the mouse after the shock wave treatment twice on the femur of the mouse.

2. The experimental method for treating fractures based on shock wave treatment according to claim 1, characterized in that: The hyaluronic acid hydrogel comprises icariin.

3. The experimental method for treating fractures based on shock wave treatment according to claim 2, characterized in that: The concentration of the icariin is 0.05-0.06 mg / ml.

4. The experimental method for treating fractures based on shock wave treatment according to claim 1, characterized in that: The time for administering shock wave treatment twice to the femur of the mouse that has been injected with the hyaluronic acid hydrogel is 7 days and 14 days after the percutaneous injection of the hyaluronic acid hydrogel on the mouse.

5. The experimental method for treating fractures based on shock wave treatment according to claim 4, characterized in that: The frequency of the shock wave for administering shock wave treatment twice to the femur of the mouse that has been injected with the hyaluronic acid hydrogel is 1 bar, 400 times.

Images