A traditional Chinese medicine composition for treating bone nonunion, a preparation method thereof and application thereof

Abstract

The present application relates to the field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating nonunion of bone and its preparation method and application. The traditional Chinese medicine composition is composed of the following raw medicinal materials: Herba Epimedii 10-20 parts by weight, Radix Angelicae Pubescentis 18-25 parts by weight, Radix Eupatorium Fortunei 10-15 parts by weight, Radix Atractylodis 10-15 parts by weight, Radix Cyathulae 10-20 parts by weight, Radix Angelicae Pubescentis 10-15 parts by weight, Radix Paeoniae Rubra 10-20 parts by weight, Semen Persicae 10-15 parts by weight, and Radix Glycyrrhizae 5-10 parts by weight. The present application optimizes the compatibility of each raw medicinal material and the compatibility between the raw medicinal materials, and has the effects of promoting blood circulation to remove blood stasis, reducing swelling and relieving pain, tonifying liver and kidney, and connecting bone and tendon, and fully plays the therapeutic characteristics of traditional Chinese medicine with multiple components, multiple pathways and multiple targets, and can obviously improve the clinical healing of patients with nonunion of bone, and has good popularization and application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for treating precancerous lesions of colorectal cancer and a pharmaceutical preparation thereof. BACKGROUND

[0002] Nonunion as one of the common complications after fracture surgery is a difficult problem that plagues many clinicians and patients. According to statistics, 5-10% of patients with fractures have nonunion. There are various treatment methods for nonunion, including internal fixation, external fixation, bone and bone marrow transplantation, physical therapy and biological therapy, etc. More than 90% of nonunion can be treated by surgery, but it is expensive, traumatic, and still has the possibility of nonunion. At present, there is a lack of a treatment method that is both economical and effective, and has less trauma.

[0003] Traditional Chinese medicine has also accumulated some experience in treating nonunion. The traditional Chinese medicine composition provided by the prior art is composed of Herba Epimedii, Radix Cyathulae, Eucommia ulmoides Oliv., Angelica sinensis, Radix Paeoniae Alba, Semen Persicae and Radix Glycyrrhizae, etc. It is used for the auxiliary treatment of patients with slow callus formation and nonunion after fracture by using the method of decocting with water. The composition mainly accelerates bone cell repair and callus formation through the pharmacological effects of promoting blood circulation to remove blood stasis, detumescence and analgesia, and tonifying kidney and strengthening bone. However, there are the following technical problems:

[0004] 1. Single composition: Although the existing composition has certain effects of promoting blood circulation to remove blood stasis, the types and compatibility of medicinal materials are limited, and the synergistic effect of other medicinal materials for tonifying liver and kidney and strengthening sinew and bone such as Radix et Rhizoma Ginseng and Rhizoma Atractylodis are not fully considered, which may lead to insufficient overall efficacy and prolonged treatment time.

[0005] 2. Insufficient dosage optimization: The prior art does not optimize the dosage proportion of medicinal materials according to the severity of the disease or the physical differences of different patients, and cannot achieve personalized medication.

[0006] 3. Lack of mechanism research support: The prior art is mainly designed based on traditional Chinese medicine theory, and lacks pertinence to the formation mechanism of nonunion, such as in-depth research on regulating bone metabolism and bone cell activity, which may reduce the consistency of efficacy.

[0007] Therefore, a traditional Chinese medicine composition with more diversified components, more reasonable dosage optimization and modern pharmacological mechanism support is needed to improve the treatment effect. SUMMARY

[0008] The purpose of the present application is to provide a traditional Chinese medicine composition for treating nonunion (Jieguxiang Decoction) and a preparation method thereof, and the application of the traditional Chinese medicine composition or the pharmaceutical preparation in preparing a drug for treating nonunion.

[0009] The inventor finds through research that the traditional Chinese medicine composition composed of Herba Epimedii, Radix Angelicae Pubescentis, Radix Eupatorium Fortunei, Radix Atractylodis, Radix Cyathulae, Radix Angelicae Pubescentis, Rhizoma Chuanxiong, Radix Paeoniae Alba, Semen Persicae, and Radix Glycyrrhizae has the effects of activating blood and resolving stasis, removing swelling and relieving pain, tonifying liver and kidney, and connecting sinews and strengthening bones, and fully plays the therapeutic characteristics of traditional Chinese medicine of multi-component, multi-pathway, and multi-target synergistic effect, and can obviously improve the clinical healing of patients with bone nonunion.

[0010] In a first aspect of the present application, a traditional Chinese medicine composition for treating bone nonunion is provided, which is composed of raw medicinal materials in the following proportions by weight:

[0011] Herba Epimedii 10-20 parts by weight, Radix Angelicae Pubescentis 18-25 parts by weight, Radix Eupatorium Fortunei 10-15 parts by weight, Radix Atractylodis 10-15 parts by weight, Radix Cyathulae 10-20 parts by weight, Radix Angelicae Pubescentis 10-15 parts by weight, Rhizoma Chuanxiong 10-15 parts by weight, Radix Paeoniae Alba 10-20 parts by weight, Semen Persicae 10-15 parts by weight, and Radix Glycyrrhizae 5-10 parts by weight.

[0012] Further, the preferred traditional Chinese medicine composition of the present application is composed of raw medicinal materials in the following proportions by weight: Herba Epimedii 15 parts, Radix Angelicae Pubescentis 20 parts, Radix Eupatorium Fortunei 15 parts, Radix Atractylodis 15 parts, Radix Cyathulae 12 parts, Radix Angelicae Pubescentis 10 parts, Rhizoma Chuanxiong 12 parts, Radix Paeoniae Alba 12 parts, Semen Persicae 10 parts, and Radix Glycyrrhizae 9 parts.

[0013] The traditional Chinese medicine composition has the principles of activating blood and resolving stasis, removing swelling and relieving pain, tonifying liver and kidney, and connecting sinews and strengthening bones. The monarch drug is Herba Epimedii and Radix Angelicae Pubescentis, the ministerial drug is Radix Eupatorium Fortunei, Radix Atractylodis, and Radix Cyathulae, the auxiliary drug is Radix Angelicae Pubescentis, Rhizoma Chuanxiong, Radix Paeoniae Alba, and Semen Persicae, and the ministerial drug is Radix Glycyrrhizae.

[0014] Herba Epimedii tonifies liver and kidney and expels wind and dampness, and Radix Angelicae Pubescentis activates blood and relieves pain, benefits water and dredges collaterals, and together they are the monarch drug. The two drugs together have the effects of expelling dampness, dredging collaterals, relieving pain, tonifying kidney, connecting sinews, and setting bones; the ministerial drug Radix Eupatorium Fortunei dredges collaterals and relaxes vessels, and Radix Atractylodis expels dampness and removes obstruction, and the two drugs together have the effects of activating blood and resolving stasis, expelling dampness and removing obstruction, to strengthen the effect of connecting sinews, dredging collaterals, and setting bones; the ministerial drug Radix Cyathulae and Radix Angelicae Pubescentis together have the effects of activating blood, dredging channels, tonifying liver and kidney, and strengthening sinews and bones; the auxiliary drug Radix Angelicae Pubescentis expels wind and dampness, Rhizoma Chuanxiong activates blood and relieves pain, Radix Paeoniae Alba and Semen Persicae activate blood and remove stasis, and the combination of the drugs together has the effects of activating blood and resolving stasis, and strengthening sinews and bones; the ministerial drug Radix Glycyrrhizae relieves pain and harmonizes the drugs. The present application tonifies without stasis and attacks without damaging normal function, and can both relax sinews and dredge collaterals, and remove stasis and generate new tissue. The combination of the drugs together has the effects of activating blood and resolving stasis, relieving pain, tonifying liver and kidney, connecting sinews, and strengthening bones, through effectively relieving pain, inhibiting sympathetic nerves, exciting parasympathetic nerves to increase the degree of vasodilation, improving blood supply at the fracture end, to promote the formation of callus at the fracture site, and accelerate the healing and recovery of the fracture end.

[0015] In a second aspect of the present application, there is provided a pharmaceutical preparation using the above-mentioned Chinese medicinal composition for treating bone nonunion as an active ingredient, which is prepared into a common dosage form in pharmacy, such as decoction, granule, tablet, capsule, oral liquid, mixture or syrup, etc. by using a conventional preparation method in the art.

[0016] Further, the pharmaceutical preparation of the present application can be prepared by the following method:

[0017] (A) The components of each medicinal material are weighed and mixed, then boiled with water for 8 hours, and boiled for 40 minutes, filtered to obtain the water extract of the Chinese medicinal composition;

[0018] (B) The water extract is added with a pharmaceutically acceptable carrier, and prepared by using a conventional preparation method in the art.

[0019] In a third aspect of the present application, there is provided the use of the above-mentioned Chinese medicinal composition and pharmaceutical preparation in the preparation of a medicament for treating bone nonunion.

[0020] The administration amount of the present application is a therapeutically effective amount, for example, about 2 g / kg body weight to about 5.5 g / kg body weight per day, and preferably about 3 g / kg body weight to about 4 g / kg body weight. The general administration time is 6-24 months, preferably 6-18 months, and more preferably 12-18 months. Of course, the administration time also needs to consider the administration route and the health status of the patient, which are within the skill of a skilled physician.

[0021] In addition, the Chinese medicinal composition of the present application can be used as the only active ingredient for treating bone nonunion, and can also be used together with other therapeutic agents.

[0022] The types and mechanisms of each drug in the composition of the present application are as follows:

[0023] 1. Epimedium, which is the dried aboveground part of Epimedium brevicornum Maxim. of the Berberidaceae family. It is pungent and sweet in nature, and warm in property. It is attributed to the liver meridian and kidney meridian, and has the effects of tonifying kidney and strengthening yang, relieving pain, dispelling wind and dampness, and strengthening sinews and bones. It is commonly used for treating sinew and bone spasm, hemiplegia, and weakness of waist and knees.

[0024] It plays a significant role in reducing blood calcium and increasing blood phosphorus by increasing the levels of serum BMP-7 and vascular endothelial growth factor (VEGF), and reducing the number of osteoclasts and the expression of IL-6, thereby promoting calcium and phosphorus deposition, significantly shortening the fracture healing time, and promoting fracture healing. In addition, VEGF promotes vascular endothelial generation and vascular endothelial proliferation by binding to vascular endothelial cell-specific receptors, improves local pain, inhibits sympathetic nerves to some extent, excites parasympathetic nerves, and provides a good blood supply environment for the fracture site, thereby promoting the repair of bone fracture damage.

[0025] 2. Qianqianhuo is the dried leafy stem branches of Sambucus racemosa L., a plant of the family Caprifoliaceae. It is sweet, bitter, and neutral in flavor, and belongs to the Liver Meridian. It has the effects of dispelling wind and dredging collaterals, promoting blood circulation to relieve pain, and promoting diuresis and detumescence. It is commonly used for rheumatic pain in the muscles and bones, traumatic swelling and pain, fractures, and traumatic bleeding.

[0026] On the one hand, it promotes the expression of type I collagen and the proliferation and differentiation of osteoblasts, can promote the activities of osteocalcin and alkaline phosphatase (ALP) of osteoblasts, and can also improve bone properties by inhibiting the bone resorption process and stimulating the bone formation process. On the other hand, it can reduce the levels of the main factors in the inflammatory pathway, such as IL-1β, IL-6, TNF-α, and COX-2, control the generation of nitric oxide in RAW264.7 cells caused by inflammatory stimulation, and has a significant effect on controlling local pain. In addition, it can also regulate the relationship between coagulation factors, platelets, and capillaries, inhibit the sympathetic nerve, and excite the parasympathetic nerve, so as to reduce the whole blood viscosity and erythrocyte sedimentation rate value, and achieve the effect of dilating blood vessels and improving the blood supply around the fracture site.

[0027] 3. Yuzhou loulu is the root of Rhaponticum uniflorum (L.) DC., a plant of the family Asteraceae. It is bitter in flavor and cold in nature, and belongs to the Stomach Meridian, Large Intestine Meridian, and Liver Meridian. It has the effects of clearing heat and detoxifying, reducing swelling and discharging pus, and dredging tendons and vessels. It is commonly used for treating damp arthralgia with tendon and vessel constriction, bone joint pain, scrofula, and malignant ulcers.

[0028] The active ingredients in its water decoction act on proteins such as inflammatory factors IL-6, IL-1β, TGF-β, chemokines CCL2, CXCL8, and MMP-9, and have anti-inflammatory, analgesic, and antibacterial effects. Its anti-inflammatory and analgesic effects do not strengthen with the increase of dosage. Through relevant target and pathway analysis, promoting fracture healing can be achieved by regulating inflammatory factors and changing the signal transduction of tumor necrosis factor and chemokines.

[0029] 4. Atractylodes lancea is a traditional Chinese medicine name. It is the rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz. of the family Asteraceae. It is pungent, bitter, and warm in flavor, and belongs to the Spleen Meridian, Stomach Meridian, and Liver Meridian. It has the effects of strengthening the spleen, reducing swelling, and drying dampness. It is commonly used for treating edema, wind-cold-damp arthralgia, foot flaccidity, and dampness stagnating the spleen.

[0030] Atractylodes lancea contains vitamins related to calcium and phosphorus absorption. Its volatile oil stimulates the proliferation of osteoblasts and MG-63 cells and the activity of alkaline phosphatase, playing a role in promoting the proliferation of bone cells. Its active ingredient, β-eudesmol, can also block two channels, the open type and the closed type, of N-cholinergic receptors on the presynaptic and postsynaptic membranes of nerve endings, inhibit the release of neurotransmitters from the presynaptic membrane, accelerate the desensitization of N-cholinergic receptors on the postsynaptic membrane, and inhibit the skeletal muscle contraction caused by nerve excitation, having anti-rickets and anti-osteoporosis effects. In addition, atractylon has anti-inflammatory and nerve-nourishing effects, which has a certain effect on relieving the pain at the fracture site.

[0031] 5. Cyathula officinalis, a traditional Chinese medicine name. It is the dried root of Achyranthes bidentata Blume., a plant of the genus Achyranthes in the family Amaranthaceae. It tastes bitter and sour, and is flat in nature. It belongs to the liver and kidney meridians, and has the effects of promoting blood circulation to dredge the meridians, tonifying the liver and kidney, strengthening the bones and muscles, promoting diuresis and removing dampness, and guiding blood downward.

[0032] The cyathinol, total saponins, and triterpenoid saponins contained in Cyathula officinalis can increase the levels of serum bone gla protein (BGP), alkaline phosphatase (ALP), and blood calcium content, and can effectively inhibit the formation of osteoclasts, promote the proliferation of osteoblasts, and effectively increase bone mass, affecting and regulating bone metabolism levels. In addition, the sterones, polysaccharides and other chemical components contained in it have the effects of inhibiting the production of inflammatory factors, regulating chondrocyte metabolism, reducing ECM degradation, and antioxidative stress, and then affect glucose metabolism blood rheology and anti-osteoporosis.

[0033] 6. Eucommia ulmoides, a traditional Chinese medicine name. It is the dried bark of Eucommia ulmoides, a plant of the Eucommiaceae family. It tastes sweet and slightly pungent, and is warm in nature. It belongs to the liver and kidney meridians, and has the effects of tonifying the liver and kidney, strengthening the bones and muscles, and improving soreness of the waist and spine and weakness of the feet and knees.

[0034] 7. Ligusticum chuanxiong is the rhizome of Ligusticum wallichii, a plant of the Umbelliferae family. It tastes pungent and is warm in nature. It belongs to the liver, gallbladder, and pericardium meridians. It has the effects of promoting qi circulation, activating blood circulation to relieve pain, dispelling wind and eliminating dampness, and relieving depression. It is commonly used to treat traumatic swelling and pain, rheumatic arthralgia, and stabbing pain in the chest and hypochondrium.

[0035] 8. Salvia miltiorrhiza, a traditional Chinese medicine name. It is the dried root and rhizome of Salvia miltiorrhiza Bge., a plant of the genus Salvia in the family Labiatae. It tastes bitter and is slightly warm in nature. It belongs to the heart and liver meridians. It has the effects of removing blood stasis and relieving pain, promoting blood circulation and regulating menstruation, cooling blood and dissipating carbuncles, and relieving restlessness and tranquility. It is used to treat bone joint pain, mass in the abdomen, and accumulation.

[0036] 9. Prunus persica, the dried ripe seed of Prunus persica (L.) Batsch, a plant of the Rosaceae family. It tastes bitter and sweet, and is flat in nature. It belongs to the heart, liver, and large intestine meridians. It has the effects of promoting blood circulation to remove blood stasis and moistening the intestines and relaxing bowel movements. It is commonly used to treat traumatic injuries, swelling and pain due to blood stasis, wind arthralgia, and constipation due to blood dryness.

[0037] 10. Duhuo, the dried root of Angelica pubescens Maxim. f. biserrata Shan et Yuan, Umbelliferae. Bitter; pungent; slightly wet. Belongs to kidney meridian and bladder meridian. It has the effects of expelling wind, overcoming dampness and relieving pain. It is used for treating wind-cold-damp arthralgia, soreness and pain of waist and knees, and pain of hands and feet.

[0038] 11. Gancao, the root and rhizome of Glycyrrhiza uralensis Fisch., Leguminosae. Sweet; flat. Belongs to spleen meridian, stomach meridian and lung meridian. It has the effects of harmonizing the middle, relieving acute and chronic pain, detoxifying and regulating various drugs.

[0039] Effects and advantages of the application

[0040] Firstly, the application preferably matches each raw drug and compatibility, and has the effects of activating blood and resolving stasis, removing swelling and relieving pain, tonifying liver and kidney, and connecting tendon and bone, fully plays the therapeutic characteristics of multi-component, multi-pathway and multi-target synergistic effect of traditional Chinese medicine, can obviously improve the clinical healing of patients with bone nonunion, and has good popularization and application value.

[0041] The whole prescription of the application is based on the principle of activating blood and resolving stasis, removing swelling and relieving pain, tonifying liver and kidney, and connecting tendon and bone. The monarch drug is Herba Epimedii and Radix Polygoni Multiflori, the ministerial drug is Radix Eupatorium, Rhizoma Atractylodis, Radix Cyathulae and Radix Eucommiae, the auxiliary drug is Radix Angelicae Pubescentis, Rhizoma Chuanxiong, Radix Panacis Quinquefolii and Semen Persicae, and Radix Glycyrrhizae is the ministerial drug. The monarch drug of the existing traditional Chinese medicine composition for treating bone nonunion does not contain Herba Epimedii and Radix Polygoni Multiflori, and the compatibility of Herba Epimedii and Radix Polygoni Multiflori in the application has certain creativity.

[0042] Secondly, the creativity of the claims of the application is also embodied in the following important aspects:

[0043] (1) The expected income and commercial value of the technical scheme of the application after transformation are:

[0044] Through the previous animal experiments and clinical application, the application has a significant promoting effect on the fracture healing of patients with bone nonunion. After the technical scheme of the application is transformed, it can be applied to the clinic to the greatest extent, can avoid reoperation of patients with bone nonunion, reduce the economic burden of patients with bone nonunion, and bring more economical and effective treatment schemes for patients with bone nonunion. The medicinal composition has the characteristics of activating blood and resolving stasis, tonifying kidney and connecting bone, rapidly promoting the growth of callus at the fracture end, and promoting fracture healing, greatly reducing the disability rate, and having good social and economic benefits. In addition, the preparation of the application has various dosage forms, including decoction, granules, tablets, capsules, oral liquid and mixture. It can provide diversified choices for clinicians and patients and meet the demand for treating bone nonunion to the greatest extent.

[0045] (2) The technical scheme of the application fills the technical gap in the industry at home and abroad:

[0046] Through searching and consulting literatures, at present, there are few Chinese medicine compositions for treating nonunion after bone fracture surgery and the pharmacology is not clear, the application provides a Chinese medicine composition for effectively treating nonunion and a preparation method thereof, and the pharmacological mechanism of related Chinese medicines is clarified, and the blank of the Chinese medicine composition for treating nonunion after bone fracture surgery is filled.

[0047] (3) The technical scheme of the application solves the technical problems that people have been eager to solve but have failed to solve successfully:

[0048] At present, more than 90% of nonunion can be treated by surgery, but the cost is high, the trauma is heavy, and there is still a possibility of nonunion, and at present, there is lack of a treatment method which is both economical and effective and has small trauma. The application provides a Chinese medicine composition for treating nonunion and a preparation method in view of the above defects. From the clinical effect, the composition is obviously better than other Chinese patent medicines such as Shangke Jiegu Tablet and Gusongbao. The key reason may be that the Chinese medicine composition of the application has a big feature, the analgesic effect of Jiegu: only next to morphine, equivalent to analgin (checkable in the pharmacopoeia), because the local pain after fracture is obvious, effective analgesia is needed to effectively promote the healing of fracture: the healing of fracture needs blood supply, and the blood supply is good, and the healing is fast, and the blood supply is poor, and the healing is slow. Then the good and bad of blood supply depends on the innervation of nerves to blood vessels, and before the nonunion of fracture, there is pain of different degrees in the local, and when the patient takes the composition of the application, the pain is relieved, the parasympathetic nerves of the limbs are excited, the sympathetic nerves are inhibited, the small blood vessels and microcirculation of the limbs are expanded, the local blood supply of the fracture is increased, and the fracture is slowly healed. At the same time, the composition plays a synergistic role: promoting blood circulation to remove blood stasis, relieving swelling and pain, setting bone and continuing tendon, and promoting the healing of fracture in many aspects.

[0049] Therefore, the application can effectively improve the swelling and pain of fracture and promote the healing of fracture in effect, can greatly reduce the economic burden of nonunion patients and avoid reoperation damage in social benefit, and provides a better technical scheme for the treatment of nonunion. At the same time, the application overcomes the technical prejudice in the treatment of nonunion, adopts the abandoned traditional Chinese medicine technical means due to technical prejudice, and provides an effective and economical Chinese medicine composition, which has a significant effect on the treatment of nonunion. BRIEF DESCRIPTION OF DRAWINGS

[0050] Figure 1 is a preparation method flow chart of the Chinese medicine composition for treating nonunion provided by the embodiment of the application;

[0051] Figure 2 is a schematic diagram of gross morphological observation of fracture ends provided by the embodiment of the application;

[0052] Figure 3 is an X-ray observation schematic diagram provided by the embodiment of the application;

[0053] Figure 4 is a bone callus volume diagram provided by the embodiment of the present application;

[0054] Figure 5 is a first clinic radiograph of case 1 provided by the embodiment of the present application;

[0055] Figure 6 is a radiograph of case 1 taking oral traditional Chinese medicine for 1, 2, 3, 4 and 5 months provided by the embodiment of the present application;

[0056] Figure 7 is a first clinic radiograph of case 2 provided by the embodiment of the present application;

[0057] Figure 8 is a radiograph of case 2 taking oral traditional Chinese medicine for 1, 2, 3 and 6 months provided by the embodiment of the present application;

[0058] Figure 9 is a radiograph of case 3 after internal fixation and 6 months after internal fixation provided by the embodiment of the present application;

[0059] Figure 10 is a radiograph of case 3 taking oral traditional Chinese medicine for 1, 2 and 3 months provided by the embodiment of the present application;

[0060] Figure 11 is a postoperative radiograph of case 4 provided by the embodiment of the present application;

[0061] Figure 12 is a radiograph of case 4 taking oral traditional Chinese medicine for 3, 4, 5 and 6 months provided by the embodiment of the present application;

[0062] Figure 13 is a radiograph of case 5 after internal fixation for 4 months provided by the embodiment of the present application;

[0063] Figure 14 is a radiograph of case 4 taking oral traditional Chinese medicine for 1, 2 and 5 months provided by the embodiment of the present application;

[0064] Figure 15 is a radiograph of case 5 after internal fixation for 4 months provided by the embodiment of the present application;

[0065] Figure 16 is a radiograph of case 5 after internal fixation for 4 months provided by the embodiment of the present application;

[0066] Figure 17 is a radiograph of case 5 after internal fixation for 4 months provided by the embodiment of the present application;

[0067] Figure 18 is a radiograph of case 5 after internal fixation for 4 months provided by the embodiment of the present application;

[0068] Figure 19 The X-ray film of the bone-setting film provided in this embodiment of the invention at 5 months showed no obvious changes;

[0069] Figure 20 Four months after the surgery, as provided in this embodiment of the invention, the fracture line was clear, there was no obvious callus growth, and the patient began taking traumatic bone-setting tablets.

[0070] Figure 21 The bone-setting tablets provided in this embodiment of the invention showed no significant changes on X-ray after one month of use;

[0071] Figure 22 The bone-setting tablets provided in this embodiment of the invention showed no significant changes on X-ray after 2 months of use;

[0072] Figure 23 The bone-setting tablets provided in this embodiment of the invention showed no significant changes on X-ray after 4 months of use. Detailed Implementation

[0073] The present invention will now be described in detail with reference to the embodiments, but the implementation of the present invention is not limited thereto.

[0074] Unless otherwise specified, experimental methods in the following examples are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise noted, the medicinal materials used in the embodiments of this invention can be obtained from Chinese medicinal herb sales companies. Unless otherwise noted, all obtained medicinal materials are processed Chinese medicinal herbs. These processed herbs can be obtained from sales companies or can be obtained through processing.

[0075] Example 1

[0076] A traditional Chinese medicine composition for treating nonunion of bones comprises the following components and their weight parts: Epimedium 15g, Achyranthes bidentata 15g, Codonopsis pilosula 15g, Echinops latifolius 10g, Angelica pubescens 10g, Cibotium barometz 20g, Atractylodes lancea 10g, Ligusticum chuanxiong 10g, Panax ginseng 15g, Prunus persica 10g, and Glycyrrhiza uralensis 10g. The above-mentioned herbs are decocted in water and taken in two divided doses, one dose per day, for a course of treatment of 30 days.

[0077] Example 2

[0078] The components and weight parts of the traditional Chinese medicine composition in this embodiment are as follows: Epimedium 20g, Achyranthes bidentata 20g, Codonopsis pilosula 10g, Echinops latifolius 10g, Angelica pubescens 15g, Cibotium barometz 25g, Atractylodes lancea 10g, Ligusticum chuanxiong 15g, Panax ginseng 20g, Prunus persica 15g, and Glycyrrhiza uralensis 5g. The above-mentioned medicinal materials are decocted to obtain the juice, which is taken in two divided doses, morning and evening, one dose per day, for 40 consecutive days.

[0079] Example 3

[0080] The components and weight parts of the traditional Chinese medicine composition are: Herba Epimedii 10g, Radix Cyathulae 10g, Radix Paeoniae Alba 20g, Radix Eupatorium 15g, Radix Angelicae Pubescentis 10g, Radix Angelicae Pubescentis 20g, Radix Atractylodis 15g, Rhizoma Chuanxiong 15g, Radix Panacis Majoris 10g, Radix Glycyrrhizae 10g. The decoction is prepared twice and combined, and taken in the morning, at noon and in the evening, one dose per day, and the treatment course is 20 days.

[0081] Example 4

[0082] The components and weight parts of the traditional Chinese medicine composition in the embodiment are: Herba Epimedii 15g, Radix Cyathulae 15g, Radix Paeoniae Alba 15g, Radix Eupatorium 15g, Radix Angelicae Pubescentis 15g, Radix Angelicae Pubescentis 20g, Radix Atractylodis 10g, Rhizoma Chuanxiong 15g, Radix Panacis Majoris 15g, Radix Glycyrrhizae 10g. The medicinal materials are added into water and decocted, and taken once in the morning and at night, one dose per day, and the treatment course is 60 days.

[0083] Example 5

[0084] The components and weight parts of the traditional Chinese medicine composition for treating bone nonunion are: Herba Epimedii 12g, Radix Cyathulae 15g, Radix Paeoniae Alba 12g, Radix Eupatorium 15g, Radix Angelicae Pubescentis 15g, Radix Angelicae Pubescentis 18g, Radix Atractylodis 10g, Rhizoma Chuanxiong 15g, Radix Panacis Majoris 12g, Radix Glycyrrhizae 8g. One dose is decocted per day, and taken twice, and the treatment course is 45 days.

[0085] Example 6

[0086] The components and weight parts of the traditional Chinese medicine composition in the embodiment are: Herba Epimedii 20g, Radix Cyathulae 18g, Radix Paeoniae Alba 15g, Radix Eupatorium 15g, Radix Angelicae Pubescentis 10g, Radix Angelicae Pubescentis 25g, Radix Atractylodis 12g, Rhizoma Chuanxiong 10g, Radix Panacis Majoris 20g, Radix Glycyrrhizae 5g. The above medicinal materials are decocted twice with water, the medicinal liquid is combined, and taken in the morning, at noon and in the evening, one dose per day, and the treatment course is 30 days.

[0087] The embodiment of the present application provides a traditional Chinese medicine composition for treating bone nonunion, which is made of the following raw materials: Herba Epimedii, Radix Angelicae Pubescentis, Radix Eupatorium, Radix Atractylodis, Radix Cyathulae, Radix Paeoniae Alba, Radix Angelicae Pubescentis, Radix Panacis Majoris, Radix Glycyrrhizae.

[0088] Further, the traditional Chinese medicine composition is made of the following raw medicinal materials with the following weight parts: Herba Epimedii 15g, Radix Angelicae Pubescentis 20g, Radix Eupatorium 15g, Radix Atractylodis 15g, Radix Cyathulae 12g, Radix Paeoniae Alba 12g, Radix Angelicae Pubescentis 10g, Rhizoma Chuanxiong 12g, Radix Panacis Majoris 12g, Radix Glycyrrhizae 9g.

[0089] As shown in the formula (I), the embodiment of the present application provides a preparation method of the traditional Chinese medicine composition for treating bone nonunion, which comprises the following steps: Figure 1

[0090] ​S101, weigh out the following ingredients in a certain proportion: Epimedium, Achyranthes bidentata, Smilax china, Leucas dahurica, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Panax ginseng, Prunus persica, and Glycyrrhiza uralensis.

[0091] S102, soak in boiling water for 8 hours, then boil for 40 minutes and filter.

[0092] This invention utilizes traditional Chinese medicine formulas to promote fracture healing. The specific mechanism is based on the pain-neurovascular axis theory: fractures cause severe pain, which excites the sympathetic nervous system and inhibits the parasympathetic nervous system, leading to vasoconstriction and insufficient blood supply to the limbs. After applying the traditional Chinese medicine composition of this invention, pain is relieved, the sympathetic nervous system is inhibited, and the parasympathetic nervous system is excited, effectively dilating blood vessels around the fracture site, improving blood supply to the fracture area, and promoting fracture healing.

[0093] A mouse model of bone nonunion was constructed and the mice were divided into a control group, a low-dose group of elderberry extract, and a high-dose group of elderberry extract.

[0094] Figure 2 Gross morphological observation of fracture ends in different treatment groups (4 weeks postoperatively):

[0095] Control group: The fracture ends were covered with fusiform callus structures, with more fibrous callus and a small amount of bony callus. The callus was soft, the connection was incomplete, and the boundary with the surrounding tissue was not clear.

[0096] Low-dose group of Elderberry Kangfang: Bone callus structure can be seen at the fracture ends, and almost all of them are bony callus. They are tough to the touch and show a tendency for fracture healing.

[0097] High-dose group of Elderberry Kangfang: Enlarged spindle-shaped callus structures can be seen at the fracture ends, and all of them are bony callus, which are hard to the touch, and the fracture healing trend is obvious.

[0098] Figure 3 The images shown are X-ray images from three groups taken on postoperative day 0, week 2, and week 4:

[0099] On postoperative day 0: The fracture line of the right femur of rats in all three groups was obvious, the edge of the fracture was clear, the fracture alignment was good, and it was fixed with Kirschner wires and in good position.

[0100] Week 2 post-surgery: In the control group, the fracture line was obvious, with a small amount of callus growth and low density; in the low- and high-dose bone-setting groups, the fracture line was visible, the callus increased significantly, the periosteal reaction was obvious, and some callus grew into the fracture line.

[0101] In the fourth week after surgery: the callus in the control group increased compared to before, but the fracture line was still visible; in the low- and high-dose groups of the bone-setting formula, the callus expanded in a spindle shape, and the high-dose group had a larger density, and the fracture line disappeared.

[0102] The callus volume of the rats in the three groups was measured at the 2nd week and the 4th week after the operation. The callus volume was calculated using the Perkins callus volume measurement formula: 2πR1(R2-R1)L, (R1 = bone radius; R2 = callus radius; L = callus length). The statistical results are shown in Table 1. Figure 4

[0103] At the 2nd week after the operation: the callus volume of the low-dose and high-dose groups of the Jiegushujin Fang was greater than that of the control group, and there was a statistical difference between the low-dose group and the high-dose group.

[0104] At the 4th week after the operation: the callus volume of the low-dose and high-dose groups of the Jiegushujin Fang was greater than that of the control group, and the high-dose group was greater than the low-dose group.

[0105] Jiegushujin Fang promotes the healing of postoperative bone nonunion and delayed fracture:

[0106] Case 1:

[0107] Male, 28 years old, underwent right femoral intramedullary nail internal fixation in an external hospital on March 29, 2023, and had bone nonunion 1 year after the operation. He was treated in the clinic in April 2024 and started to regularly take traditional Chinese medicine. The first clinic X-ray film is shown in FIG. 1, and then PRP + artificial bone treatment was performed. He took the traditional Chinese medicine of the present application for a long time after the operation. The X-ray films taken in the 1st, 2nd, 3rd, 4th, and 5th months of taking the traditional Chinese medicine are shown in FIGS. 2-6, respectively. After taking the traditional Chinese medicine for 5 months, the X-ray film showed obvious callus and trabecular bone formation. Figure 5 Figure 6

[0108] Case 2:

[0109] Male, 42 years old, underwent left tibial fracture plate internal fixation in a hospital in August 2019, and then the internal fixation was removed in 2022. He had left tibial fracture again due to falling injury in July 2023, and the fracture healed poorly after 8 months of conservative treatment. He was treated in the clinic in March 2024. The first clinic X-ray film is shown in FIG. 7, and then PRP + artificial bone treatment was performed. He took the traditional Chinese medicine of the present application for a long time after the operation. The X-ray films taken in the 1st, 2nd, 3rd, and 6th months of taking the traditional Chinese medicine are shown in FIGS. 8-11, respectively. Figure 7 Figure 8

[0110] Case 3:

[0111] Female, 45 years old, had left tibial and fibular fractures due to external injury on January 5, 2024, and underwent left tibial and fibular open reduction and internal fixation on January 8. The X-ray films taken after the internal fixation and 6 months after the internal fixation are shown in FIGS. 12 and 13, respectively. Six months after the operation, the fracture healed poorly, and he was hospitalized for PRP + oral traditional Chinese medicine treatment on July 10, 2024. He took the traditional Chinese medicine of the present application for a long time after the operation. The X-ray films taken in the 1st, 2nd, and 3rd months of taking the traditional Chinese medicine are shown in FIGS. 14-16, respectively. Figure 9 Figure 10

[0112] Case 4: ​​​​​​​

[0113] Male, 68 years old, 2023.06.26 due to traffic accident caused right trochanteric fracture, femoral shaft fracture, 06.28 internal fixation treatment. Regular postoperative use of traditional Chinese medicine, good fracture healing. Postoperative radiograph as shown, long-term postoperative oral administration of the traditional Chinese medicine of the embodiment of the present application, eating traditional Chinese medicine 3, 4, 5, 6 months of radiograph as shown. Figure 11 Figure 12

[0114] Case 5:

[0115] Female, 44 years old, 2023.10.25 due to violent trauma caused right tibial and fibular shaft fracture, 10.30 internal fixation treatment. 6 months after internal fixation, radiograph as shown, 4 months after operation, fracture healing is poor, PRP+oral administration of traditional Chinese medicine treatment, 1, 2, 5 months of radiograph as shown, 5 months after operation, radiograph shows callus and trabecular bone formation, obvious fracture healing signs compared with the previous. Figure 13 Figure 14

[0116] From the clinical effect, the composition of the present application is obviously better than other Chinese patent medicines such as: Shangke Jiegu tablets, Gushangbao, etc. The key reason may be that the traditional Chinese medicine composition of the present application has a big feature, the analgesic effect of Jiegu: only next to morphine, equivalent to Anpiron (checkable in pharmacopoeia), because the local pain after fracture is obvious, effective analgesia is needed to effectively promote the healing of fracture: fracture healing needs blood supply, good blood supply heals fast, poor blood supply heals slowly. Then the good and bad of blood supply depends on the innervation of nerves to blood vessels, before fracture healing, there is different degree of pain in the local, when the patient takes the composition of the present application, the pain is relieved, the parasympathetic nerves of extremities are excited, the sympathetic nerves are inhibited, the small blood vessels and microcirculation of extremities are expanded, the local blood supply of fracture is increased, and the fracture is slowly healed. At the same time, the composition of the present application plays a synergistic role: promoting blood circulation to remove blood stasis, relieving swelling and pain, setting bones and connecting tendons, and promoting fracture healing from multiple aspects.

[0117] In addition, the composition of the present application plays a synergistic role, can promote blood circulation to remove blood stasis, relieve swelling and pain, set bones and connect tendons, and promote fracture healing from multiple aspects. Through this comprehensive conditioning, the patient not only can relieve pain, but also can accelerate the fracture healing process, and achieve better treatment effect.

[0118] However, the composition of the present application is obviously better than the same Chinese patent medicine, such as: Shangke Jiegu tablets, etc., such as the following two cases:

[0119] ​​​​For example, Case 1: A 45-year-old female, 10 months after right distal femur fracture surgery, postoperative X-ray showed clear fracture line but no callus growth. After starting to take Shangke Gushu Pian for 1 month, X-ray showed no significant change; after 2 months, X-ray still showed no significant change; after 3 months, X-ray still showed no significant change; after 5 months, still no change, and finally a second surgery was performed.

[0120] Figure 15 is provided by the embodiments of the present application 10 months after surgery: clear fracture line, no callus growth, start taking Shangke Gushu Pian;

[0121] Figure 16 is provided by the embodiments of the present application taking Shangke Gushu Pian for 1 month, X-ray showed no significant change;

[0122] Figure 17 is provided by the embodiments of the present application taking Shangke Gushu Pian for 2 months, X-ray showed no significant change;

[0123] Figure 18 is provided by the embodiments of the present application taking Shangke Gushu Pian for 3 months, X-ray showed no significant change;

[0124] Figure 19 is provided by the embodiments of the present application taking Shangke Gushu Pian for 5 months, X-ray showed no significant change;

[0125] Again, Case 2: A 47-year-old male, 4 months after femoral shaft fracture surgery, X-ray showed clear fracture line and no obvious callus growth. After taking Shangke Gushu Pian for 1 month, X-ray showed no significant change; after 2 months, X-ray still showed no significant change; after 4 months, X-ray showed no significant change, and finally the patient underwent a second surgery after 5 months.

[0126] Figure 20 is provided by the embodiments of the present application 4 months after surgery: clear fracture line, no obvious callus growth, start taking Shangke Gushu Pian;

[0127] Figure 21 is provided by the embodiments of the present application taking Shangke Gushu Pian for 1 month, X-ray showed no significant change;

[0128] Figure 22 is provided by the embodiments of the present application taking Shangke Gushu Pian for 2 months, X-ray showed no significant change;

[0129] Figure 23 is provided by the embodiments of the present application taking Shangke Gushu Pian for 4 months, X-ray showed no significant change.

[0130] These cases show that Shangke Gushu Pian has limited effect in promoting fracture healing and fails to effectively accelerate the fracture healing process.

[0131] The above shows and describes the basic principles, main features and advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above-mentioned embodiments, and the above-mentioned embodiments and descriptions in the specification are only to illustrate the principles of the present application. Various changes and improvements can be made to the present application without departing from the spirit and scope of the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating bone nonunion, characterized in that, The traditional Chinese medicine composition is composed of raw medicinal materials in the following weight parts: Herba Epimedii 10-20 parts by weight, Radix Angelicae Pubescentis 18-25 parts by weight, Radix Eupatorium Fortunei 10-15 parts by weight, Radix Atractylodis 10-15 parts by weight, Radix Cyathulae 10-20 parts by weight, Radix Paeoniae Alba 10-20 parts by weight, Radix Angelicae Pubescentis 10-15 parts by weight, Rhizoma Chuanxiong 10-15 parts by weight, Radix et Rhizoma Ginseng 10-20 parts by weight, Semen Persicae 10-15 parts by weight, Radix Glycyrrhizae 5-10 parts by weight.

2. The traditional Chinese medicine composition for treating bone nonunion according to claim 1, characterized in that, The traditional Chinese medicine composition is composed of raw medicinal materials in the following weight parts: Herba Epimedii 15 parts, Radix Angelicae Pubescentis 20 parts, Radix Eupatorium Fortunei 15 parts, Radix Atractylodis 15 parts, Radix Cyathulae 12 parts, Radix Paeoniae Alba 12 parts, Radix Angelicae Pubescentis 10 parts, Rhizoma Chuanxiong 12 parts, Radix et Rhizoma Ginseng 12 parts, Semen Persicae 10 parts, Radix Glycyrrhizae 9 parts.

3. The preparation method of the traditional Chinese medicine composition for treating bone nonunion according to any one of claims 1-2, characterized in that, The method comprises the following steps: (1) Herba Epimedii, Radix Angelicae Pubescentis, Radix Cyathulae, Radix Paeoniae Alba, Radix Eupatorium Fortunei, Radix Angelicae Pubescentis, Radix Atractylodis, Rhizoma Chuanxiong, Radix et Rhizoma Ginseng, Semen Persicae and Radix Glycyrrhizae are weighed according to a certain ratio; (2) boiling water is used to soak for 8 hours, then boiled for 40 minutes, and filtered.

4. A pharmaceutical preparation of the traditional Chinese medicine composition according to claim 1 or 2 as an active ingredient, characterized in that, The pharmaceutical preparation is prepared into a common dosage form in pharmacy by using a conventional preparation method in the art.

5. The pharmaceutical preparation according to claim 4, characterized in that, The pharmaceutical preparation is a decoction, granules, tablets, capsules, oral liquid, mixture or syrup.

6. Use of the traditional Chinese medicine composition of claim 1 or 2 in the preparation of a drug for treating bone nonunion.

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