Traditional Chinese medicine composition for treating bone nonunion as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating bone nonunion and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 10 to 20 parts of herba epimedii, 18 to 25 parts of sambucus williamsii, 10 to 15 parts of radix echinopsis, 10 to 15 parts of rhizoma atractylodis, 10 to 20 parts of radix cyathulae, 10 to 20 parts of sedum aizoon, 10 to 15 parts of radix angelicae pubescentis, 10 to 15 parts of ligusticum wallichii, 10 to 20 parts of red ginseng, 10 to 15 parts of peach kernel and 5 to 10 parts of liquorice. According to the traditional Chinese medicine composition, all the raw material medicines and compatibility thereof are optimized, the effects of promoting blood circulation to remove blood stasis, relieving swelling and pain, tonifying the liver and kidney and promoting reunion of fractured bones are jointly achieved, the treatment characteristics of multi-component, multi-path and multi-target synergistic effects of traditional Chinese medicines are fully played, clinical healing of patients suffering from bone nonunion can be obviously improved, and the traditional Chinese medicine composition has good application and popularization value.

Description

Technical Field

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

[0002] Bone nonunion is one of the common complications after fracture surgery and is a problem that troubles many clinicians and patients. According to statistics, 5% to 10% of patients with fractures suffer from bone nonunion. There are various treatments for bone nonunion, including internal fixation, external fixation, bone and bone marrow transplantation, physical therapy, and biological therapy. More than 90% of bone nonunions can be treated with surgery, but it is expensive, traumatic, and there is still a 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 certain experience in treating bone nonunion. The Chinese medicine composition for treating bone nonunion provided by the prior art is composed of epimedium, cyathula, eucommia, angelica pubescens, ligusticum chuanxiong, peach kernel, licorice, etc., and is used for auxiliary treatment of patients with slow callus formation after fracture and bone nonunion by decocting with water. The composition mainly accelerates bone cell repair and callus formation through the pharmacological effects of promoting blood circulation and removing blood stasis, reducing swelling and relieving pain, and strengthening the kidney and bones. However, there are the following technical problems:

[0004] 1. Single ingredient: Although the existing composition has a certain effect of promoting blood circulation and removing blood stasis, the types and compatibility of medicinal materials are limited, and the synergistic effects of other medicinal materials that nourish the liver and kidneys and strengthen the tendons and bones, such as red ginseng and atractylodes, are not fully considered, which may lead to insufficient overall efficacy and prolonged treatment time.

[0005] 2. Insufficient dosage optimization: Existing technologies do not optimize the dosage ratio of medicinal materials according to the severity of the disease or physical constitution of different patients, and cannot achieve personalized medication.

[0006] 3. Lack of support for mechanism research: Existing technologies are mainly designed based on traditional Chinese medicine theories and lack specificity for the mechanism of nonunion formation. For example, in-depth research on the regulation of bone metabolism and bone cell activity may reduce the consistency of therapeutic efficacy.

[0007] Therefore, a Chinese medicine composition with more diverse ingredients, more reasonable dosage optimization and supported by modern pharmacological mechanisms is needed to improve the therapeutic effect. Summary of the invention

[0008] The object of the present invention is to provide a traditional Chinese medicine composition (elderberry prescription) for treating bone nonunion and a preparation method thereof, as well as the use of the traditional Chinese medicine composition or pharmaceutical preparation in preparing a drug for treating bone nonunion.

[0009] The inventors have discovered through research that a Chinese medicine composition consisting of Herba Epimedii, Herba Cibotii, Herba Yuzhouii, Herba Atractylodes, Herba Cynoglossi, Herba Sizhong, Herba Angelicae Pubescentis, Herba Ligustici Chuanxiong, Herba Glycyrrhizae, Herba Semen Persicae, and Radix Glycyrrhizae focuses on promoting blood circulation and removing blood stasis, relieving swelling and relieving pain, tonifying the liver and kidney, and strengthening tendons and bones, and has the effects of promoting blood circulation and removing blood stasis, relieving swelling and relieving pain, tonifying the liver and kidney, and strengthening tendons and bones, giving full play to the therapeutic characteristics of multi-component, multi-pathway, and multi-target synergistic effects of traditional Chinese medicine, and can significantly improve the clinical healing of patients with nonunion.

[0010] The first aspect of the present invention provides a traditional Chinese medicine composition for treating bone nonunion, wherein the traditional Chinese medicine composition is composed of the following raw materials in parts by weight:

[0011] 10-20 weight parts of Epimedium, 18-25 weight parts of Radix Angelicae Pubescentis, 10-15 weight parts of Rhizoma Chuanxiong, 10-20 weight parts of Rhizoma Cynomorii, 10-20 weight parts of Rhizoma Cynomorii, 10-20 weight parts of Rhizoma Cynomorii, 10-20 weight parts of Rhizoma Angelicae Pubescentis, 10-15 weight parts of Rhizoma Chuanxiong, 10-20 weight parts of Rhizoma Chinois, 10-15 weight parts of Rhizoma Pruni, and 5-10 weight parts of Radix Glycyrrhizae.

[0012] Further, the preferred traditional Chinese medicine composition of the present invention is composed of the following raw materials in parts by weight: 15 parts of epimedium, 20 parts of radix scutellariae, 15 parts of radix yuzhouni, 15 parts of atractylodes, 12 parts of cyathula capitata, 12 parts of radix scutellariae, 10 parts of angelica dahurica, 12 parts of rhizoma ligustici, 12 parts of rhizoma scutellariae, 10 parts of rhizoma pubescentis, 12 parts of rhizoma chuanxiong, 12 parts of rhizoma scutellariae, 10 parts of persica, and 9 parts of liquorice.

[0013] The Chinese medicine composition is formulated on the principle of promoting blood circulation and removing blood stasis, relieving swelling and relieving pain, nourishing the liver and kidney, and strengthening tendons and bones. The main drugs are epimedium and qianqianhuo, the assistant drugs are yuzhou loulu, atractylodes, chuanxiong, eucommia, the adjuvant drugs are angelica dahurica, chuanxiong, red ginseng, peach kernel, and liquorice is the guiding drug.

[0014] Epimedium in the prescription nourishes the liver and kidney, dispels wind and dampness, and promotes blood circulation and relieves pain, and promotes diuresis and unblocks the meridians, and is the main drug. The two drugs are used together to play the role of removing dampness and unblocking meridians to relieve pain, and nourishing the kidney to continue tendons and bones; the assistant drug Yuzhou Loulu unblocks tendons and relaxes the meridians, and Atractylodes removes dampness and removes numbness. The two drugs are used together to play the role of promoting blood circulation, removing blood stasis and relieving pain, and removing dampness and removing numbness, so as to strengthen the effect of continuing tendons, unblocking meridians and bones; the assistant drugs Achyranthes bidentata and Si Zhong play the role of promoting blood circulation, unblocking menstruation, nourishing the liver and kidney, and strengthening tendons and bones. It is assisted by Duhuo to dispel wind and dampness and relieve pain, Chuanxiong to promote qi and promote blood circulation and relieve pain, and Chishen to promote blood circulation and relieve blood stasis with peach kernel to relieve pain. The drugs are used together to play the role of promoting blood circulation and removing blood stasis, and strengthening tendons and bones. The assistant drug is liquorice to relieve urgency and relieve pain, and to harmonize the drugs. The present invention replenishes without stagnation, attacks without hurting the body, can relax tendons and unblock meridians, and can remove blood stasis and promote new blood. The combination of these medicines can promote blood circulation, remove blood stasis and relieve pain, nourish the liver and kidneys, strengthen tendons and bones. It can effectively relieve pain, inhibit the sympathetic nerves, excite the parasympathetic nerves to increase vasodilation, improve blood supply to the fracture end, promote callus formation at the fracture site, and accelerate the healing and recovery of the fracture end.

[0015] The second aspect of the present invention provides a pharmaceutical preparation having the above-mentioned Chinese medicine composition for treating bone nonunion as an active ingredient, wherein the pharmaceutical preparation is prepared by conventional preparation methods in the art into commonly used dosage forms in pharmacy, such as decoctions, granules, tablets, capsules, oral liquids, mixtures or syrups.

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

[0017] (A) weighing each medicinal material component, mixing, and soaking in boiling water for 8 hours, then boiling for 40 minutes, filtering, and obtaining a water extract of the Chinese medicine composition;

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

[0019] The third aspect of the present invention provides the use of the above-mentioned Chinese medicine composition and pharmaceutical preparation in the preparation of drugs for treating bone nonunion.

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

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

[0022] The types and mechanisms of the various drugs in the prescription of the present invention are as follows:

[0023] 1. Epimedium brevicornum is the dried aerial part of the Berberidaceae plant Epimedium brevicornum Maxim. It is pungent, sweet and warm in nature. It enters the liver and kidney meridians and has the effects of tonifying the kidney, strengthening yang and relieving pain, dispelling wind and dampness, and strengthening muscles and bones. It is often used to treat muscle and bone spasms, hemiplegia, and weakness of the waist and knees.

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

[0025] 2. The dried stems and branches of Sambucus racemosa L., a plant of the Caprifoliaceae family, are sweet, bitter, and neutral in nature. It enters the liver meridian. It has the effects of dispelling wind and unblocking meridians, promoting blood circulation and relieving pain, and promoting diuresis and reducing swelling. It is often used for rheumatic pain in the tendons and bones, swelling and pain from falls, fractures, and bleeding from trauma.

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

[0027] 3. Swisscentaury is the root of Uniflower Swisscentaury Root, a plant of the Asteraceae family. It is bitter in nature and cold in nature. It enters the stomach meridian, large intestine meridian, and liver meridian. It has the functions of clearing away heat and detoxifying, reducing swelling and draining pus, and unblocking tendons and veins. It is often used to treat dampness, tendon and vein stiffness, joint pain, scrofula and malignant sores.

[0028] The active ingredients of its decoction act on 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 increase with the increase of dosage. Through the analysis of related targets and pathways, it can promote fracture healing by regulating inflammatory factors, changing the signal transduction of tumor necrosis factor and chemokines.

[0029] 4. Atractylodes, a Chinese medicine name. It is the rhizome of Atractylodes atractylodes or Atractylodes rhizoma atractylodis of the Asteraceae family. It is pungent and bitter in nature and warm in nature. It enters the spleen meridian, stomach meridian, and liver meridian. It has the functions of strengthening the spleen, reducing swelling, and drying dampness. It is often used to treat edema, wind-cold dampness, foot paralysis, and dampness blocking the spleen.

[0030] Atractylodes contains vitamins related to calcium and phosphorus absorption, and its volatile oil has a stimulating effect on osteoblast and MG-63 cell proliferation and alkaline phosphatase activity, which promotes the proliferation of bone cells. Its active ingredient β-eucalyptol can also block the open and closed channels of N-choline receptors in the presynaptic and postsynaptic membranes of nerve endings, inhibit the release of neurotransmitters from the presynaptic membrane, accelerate the desensitization of N-choline receptors in the postsynaptic membrane, inhibit skeletal muscle contraction caused by nerve excitation, and has anti-rickets and anti-osteoporosis effects. In addition, atractylodes has anti-inflammatory and nerve nutrition effects, and has a certain effect on relieving pain at the fracture site.

[0031] 5. Sichuan Cyathula, a Chinese medicine name. It is the dried root of Achyranthes bidentata Blume. of the Amaranthaceae family. It is bitter, sour and flat in nature. It enters the liver and kidney meridians and has the effects of promoting blood circulation, tonifying the liver and kidneys, strengthening the tendons and bones, promoting diuresis and relieving stranguria, and guiding blood downward.

[0032] The cynanchum bidentata alcohol, total saponins and triterpenoid saponins contained in Sichuan cynanchum bidentata can increase serum osteocalcin (BGP), alkaline phosphatase (ALP) and blood calcium levels, and can effectively inhibit osteoclast formation, promote osteoblast proliferation and effectively increase bone mass, affecting the regulation of bone metabolism. In addition, the chemical components such as sterols and polysaccharides contained therein can inhibit the production of inflammatory factors, regulate chondrocyte metabolism, reduce ECM degradation, and resist oxidative stress, thereby affecting sugar metabolism and blood rheology, and resisting osteoporosis.

[0033] 6. Sizhong, a Chinese medicine name. It is the dried bark of Eucommia Bark, a plant of the Eucommia family. It is sweet, slightly spicy, and warm in nature. It enters the liver and kidney meridians and has the effects of nourishing the liver and kidneys, strengthening the tendons and bones, and improving back pain and weakness of the feet and knees.

[0034] 7. Ligusticum wallichii is the rhizome of the plant Ligusticum wallichii of the Umbelliferae family. It is pungent and warm in nature. It enters the liver meridian, gallbladder meridian, and pericardium meridian. It has the functions of promoting qi and blood circulation, relieving pain, dispelling wind and dampness, and relieving depression. It is often used to treat swelling and pain caused by falls, rheumatic pain, and stabbing pain in the chest and ribs.

[0035] 8. Red ginseng, a Chinese medicine name. It is the dried root and rhizome of Salviamiltiorrhiza Bge., a plant of the genus Salvia in the family Lamiaceae. It is bitter and slightly warm in nature. It enters the heart meridian and liver meridian. It has the effects of removing blood stasis and relieving pain, promoting blood circulation and regulating menstruation, cooling blood and eliminating carbuncle, and removing restlessness and calming the mind. It is used to treat joint pain, lumps, and accumulation.

[0036] 9. Peach kernel is the dried mature seed of Prunus persica (L.) Batsch, a plant of the Rosaceae family. It is bitter and sweet in nature and neutral in flavor. It enters the heart meridian, liver meridian, and large intestine meridian. It has the effects of promoting blood circulation and removing blood stasis, moistening dryness and lubricating the intestines. It is often used to treat traumatic injuries, blood stasis and swelling and pain, rheumatism, and constipation caused by blood dryness.

[0037] 10. Angelica pubescens Maxim.f.biserrata Shan et Yuan, a plant of the Umbelliferae family, is a dried root. It is bitter and pungent in nature and slightly moist. It enters the kidney and bladder meridians. It has the functions of dispelling wind, overcoming dampness and relieving pain. It is used to treat wind-cold-damp arthralgia, soreness of waist and knees, and cramps in hands and feet.

[0038] 11. Licorice is the root and rhizome of Glycyrrhiza uralensis Fisch. of the genus Licorice in the Leguminosae family. It is sweet and neutral in nature. It enters the spleen meridian, stomach meridian, and lung meridian. It has the effects of harmonizing the middle, relieving pain, detoxifying, and harmonizing various medicines.

[0039] Functions and Effects of the Invention

[0040] First, the present invention optimizes the raw materials and the compatibility between them, and works together to promote blood circulation and remove blood stasis, reduce swelling and relieve pain, nourish the liver and kidney, and repair tendons and bones, giving full play to the therapeutic characteristics of multi-component, multi-pathway, and multi-target synergistic effects of traditional Chinese medicine, which can significantly improve the clinical healing of patients with bone nonunion and has a good value for promotion and application.

[0041] The whole prescription of the present invention is formulated with the principles of promoting blood circulation and removing blood stasis, relieving swelling and relieving pain, nourishing the liver and kidney, and strengthening tendons and bones. The main drugs are Epimedium and Radix Piperis, the auxiliary drugs are Rhizoma Cynomorii, Rhizoma Atractylodis Macrocephalae, Rhizoma Cynoglossi, and Rhizoma Eucommiae, the adjuvant drugs are Radix Angelicae Pubescentis, Rhizoma Chuanxiong, Radix Glehniae, and Rhizoma Pruni, and Licorice is the guiding drug. The main drugs of the existing traditional Chinese medicine composition for treating bone nonunion do not include Epimedium and Radix Piperis, and the compatibility of Epimedium and Radix Piperis in the present application has certain creativity.

[0042] Second, as auxiliary evidence of the inventiveness of the claims of the present invention, it is also reflected in the following important aspects:

[0043] (1) The expected benefits and commercial value of the technical solution of the present invention after transformation are:

[0044] Through early animal experiments and clinical applications, the present invention has a significant promoting effect on fracture healing of patients with nonunion. After the technical solution of the present invention is converted, it can be applied to the clinic to the greatest extent, and can avoid reoperation of patients with nonunion, reduce the economic burden of patients with nonunion, and bring more economical and effective treatment plans for patients with nonunion. The Chinese medicine composition has the characteristics of promoting blood circulation and removing blood stasis, benefiting the kidney and continuing bones, rapidly promoting the growth of bone callus at the fracture end, and promoting fracture healing, greatly reducing the disability rate, and having good social and economic benefits. In addition, the dosage form of the preparation of the present invention is diverse, including decoction, granules, tablets, capsules, oral liquids, and mixtures. Diversified choices can be provided to clinicians and patients to meet the needs of treating nonunion to the greatest extent.

[0045] (2) The technical solution of the present invention fills the technical gap in the industry at home and abroad:

[0046] Through searching and reviewing the literature, it is found that the Chinese medicine composition currently used for treating bone nonunion after fracture surgery is rare and the pharmacology is unclear. The present invention provides a Chinese medicine composition for effectively treating bone nonunion and a preparation method thereof. The pharmacological mechanism of the relevant Chinese medicine is also explained, filling the gap in the Chinese medicine composition for bone nonunion after fracture surgery.

[0047] (3) The technical solution of the present invention solves the technical problems that people have been eager to solve but have never been able to solve successfully:

[0048] At present, more than 90% of bone 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 little trauma. In view of the above defects, the present invention provides a Chinese medicine composition for treating bone nonunion and a preparation method. From the perspective of clinical effect, the prescription of the present invention is significantly superior to other Chinese patent medicines such as: trauma bone setting tablets, bone pine treasure, etc. The key reason may be that the Chinese medicine prescription of the present invention has a major feature, the analgesic effect of elderberry: second only to morphine, equivalent to dimethylpyrrolidone (Pharmacopoeia can be checked), because the local pain after fracture is obvious, effective analgesia is needed to effectively promote the healing of fractures: the healing of fractures requires blood supply, and the healing of good blood supply is fast, and the healing of poor blood supply is slow. Then the quality of blood supply depends on the control of nerves to blood vessels. Before the fracture is healed, there are different degrees of pain in the local area. When the patient takes the prescription of the present invention, the pain is relieved, the parasympathetic nerves that control the limbs are excited, the sympathetic nerves are inhibited, the small blood vessels and microcirculation of the limbs are expanded, the blood supply of the fractured area becomes more, and the fracture slowly heals. At the same time, the combined medicines play a synergistic role: to promote blood circulation and remove blood stasis, reduce swelling and relieve pain, connect bones and tendons, and promote fracture healing in many aspects.

[0049] Therefore, the present invention can effectively improve fracture swelling and pain and promote fracture healing. In terms of social benefits, it can greatly reduce the economic burden of patients with nonunion and avoid reoperation injury, providing a better technical solution for the treatment of nonunion. At the same time, the present invention overcomes the technical bias in the field of nonunion treatment, adopts traditional Chinese medicine technical means that have been abandoned due to technical bias, and provides an effective and economical Chinese medicine composition, which has a significant effect on the treatment of nonunion. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 It is a flow chart of a method for preparing a Chinese medicine composition for treating bone nonunion provided by an embodiment of the present invention;

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

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

[0053] Figure 4 is a schematic diagram of callus volume provided by an embodiment of the present invention;

[0054] Figure 5 This is the first outpatient radiograph of Case 1 provided in the embodiment of the present invention;

[0055] Figure 6 The films of Case 1 taking Chinese medicine orally for 1, 2, 3, 4, and 5 months provided in an embodiment of the present invention;

[0056] Figure 7 This is the first outpatient radiograph of Case 2 provided in the embodiment of the present invention;

[0057] Figure 8 The radiographs of Case 2 taking Chinese medicine orally for 1, 2, 3, and 6 months provided in an embodiment of the present invention;

[0058] Fig. 9 The images are taken after and 6 months after the internal fixation in case 3 provided in the embodiment of the present invention;

[0059] Fig.10 The radiographs of Case 3 taking Chinese medicine orally for 1, 2, and 3 months provided in the embodiment of the present invention;

[0060] Fig.11 This is a postoperative radiograph of Case 4 provided in an embodiment of the present invention;

[0061] Fig.12 The film is taken for Case 4 taking Chinese medicine orally for 3, 4, 5 and 6 months provided by the embodiment of the present invention;

[0062] Fig.13 This is a radiograph taken 4 months after the internal fixation surgery in Case 5 provided in an embodiment of the present invention;

[0063] Fig.14 The radiographs of Case 4, provided in an embodiment of the present invention, taking Chinese medicine orally for 1, 2, and 5 months;

[0064] Fig.15 Ten months after surgery, the fracture line was clear, no callus grew, and the patient started taking traumatology bone-setting tablets;

[0065] Fig.16 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 1 month, and there was no obvious change in the X-ray film;

[0066] Fig.17 This is a 2-month X-ray of the bone setting piece for the Department of Traumatology provided in an embodiment of the present invention, showing no obvious changes;

[0067] Fig.18 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 3 months, and there was no obvious change in the X-ray film;

[0068] Fig.19 It is a 5-month X-ray of the bone setting piece of the Department of Orthopedics provided in the embodiment of the present invention, and there is no obvious change;

[0069] Fig. 20 Four months after surgery, the fracture line was clear, no obvious callus growth was observed, and the patient began to take the traumatology bone setting tablets;

[0070] Fig.21 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 1 month, and there was no obvious change in the X-ray film;

[0071] Fig. 22 The bone setting piece for the trauma department provided by the embodiment of the present invention was used for 2 months, and there was no obvious change in the X-ray film;

[0072] Fig.23 The trauma bone setting piece provided by the embodiment of the present invention was worn for 4 months, and there was no obvious change in the X-ray film. DETAILED DESCRIPTION

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

[0074] The experimental methods in the following examples that do not specify specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. The medicinal materials used in the examples of the present invention can be obtained from Chinese medicinal material sales companies unless otherwise specified. The medicinal materials obtained are Chinese medicinal material slices unless otherwise specified. The slices can be obtained from sales companies or processed after being obtained.

[0075] Example 1

[0076] A Chinese medicine composition for treating bone nonunion, the components and weight portions of which are: 15g of Epimedium, 15g of Cyathula officinalis, 15g of Sizhong, 10g of Yuzhou Lophatherum, 10g of Angelica dahurica, 20g of Radix Angelicae Pubescentis, 10g of Rhizoma Atractylodis Macrocephalae, 10g of Rhizoma Chuanxiong, 15g of Radix Glehniae, 10g of Semen Persicae, and 10g of Radix Glycyrrhizae. The above medicinal materials are decocted with water and taken twice, one dose per day, and the course of treatment is 30 days.

[0077] Example 2

[0078] The components and weight proportions of the Chinese medicine composition of this embodiment are: 20g of Epimedium, 20g of Cyathula, 10g of Sizhong, 10g of Yuzhou Lophatherum, 15g of Angelica dahurica, 25g of Radix Angelicae Pubescentis, 10g of Atractylodes, 15g of Ligusticum chuanxiong, 20g of Red Ginseng, 15g of Peach Kernel, and 5g of Licorice. The above medicinal materials are decocted to extract juice, which is taken in the morning and evening, one dose per day, and taken continuously for 40 days.

[0079] Example 3

[0080] The components and weight proportions of the Chinese medicine composition are: 10g of Epimedium, 10g of Cyathula officinalis, 20g of Sizhong, 15g of Yuzhou Lophatherum, 10g of Duhuo, 20g of Qianqianhuo, 15g of Atractylodes, 15g of Chuanxiong, 10g of Red Ginseng, 10g of Peach Kernel, and 10g of Licorice. After decocting twice, combine the decoction, take it in the morning, noon and evening, one dose per day, and the course of treatment is 20 days.

[0081] Example 4

[0082] The components and weight proportions of the Chinese medicine composition of this embodiment are: 15g of Epimedium, 15g of Cyathula officinalis, 15g of Sizhong, 15g of Yuzhou Lophatherum, 15g of Angelica dahurica, 20g of Radix Angelicae Pubescentis, 10g of Atractylodes, 15g of Rhizoma Chuanxiong, 15g of Radix Glehniae, 10g of Semen Persicae, and 10g of Licorice. Add appropriate amount of water to decoct the medicinal materials, take once in the morning and evening, one dose per day, and the course of treatment is 60 days.

[0083] Example 5

[0084] The Chinese medicine composition for treating bone nonunion has the following components and weight proportions: 12g of Epimedium, 15g of Cyathula officinalis, 12g of Sizhong, 15g of Yuzhou Lophatherum, 15g of Angelica dahurica, 18g of Pieris chinensis, 10g of Atractylodes macrocephala, 15g of Chuanxiong, 12g of Red Ginseng, 15g of Peach Kernel, and 8g of Licorice. One dose is decocted daily and taken twice, and the course of treatment is 45 days.

[0085] Example 6

[0086] The components and weight proportions of the Chinese medicine composition of this embodiment are: 20g of Epimedium, 18g of Cyathula, 15g of Sizhong, 15g of Yuzhou Lophatherum, 10g of Angelica dahurica, 25g of Herba Cibotii, 12g of Atractylodes, 10g of Ligusticum chuanxiong, 20g of Radix Glehniae, 10g of Semen Persicae, and 5g of Licorice. The above medicinal materials are decocted with water twice, the medicinal liquid is combined, and taken in the morning, noon and evening, one dose per day, and the course of treatment is 30 days.

[0087] The embodiment of the present invention provides a traditional Chinese medicine composition for treating bone nonunion, wherein the traditional Chinese medicine composition is prepared from the following raw materials: epimedium, qianqianhuo, yuzhou loulu, atractylodes, chuanxiong, sizhong, angelica dahurica, chuanxiong, red ginseng, peach kernel, and licorice.

[0088] Furthermore, the Chinese medicine composition is made of the following raw materials in parts by weight: 15g of Epimedium, 20g of Radix Piperis, 15g of Rhizoma Cibotii, 15g of Rhizoma Atractylodis Macrocephalae, 12g of Rhizoma Cynoglossi, 12g of Rhizoma Sieb., 10g of Rhizoma Angelicae Pubescentis, 12g of Rhizoma Chuanxiong, 12g of Rhizoma Ginseng, 10g of Rhizoma Prunellae, and 9g of Radix Glycyrrhizae.

[0089] like Figure 1 As shown, an embodiment of the present invention provides a method for preparing a traditional Chinese medicine composition for treating bone nonunion, comprising:

[0090] S101, weighing epimedium, cyathula, cyathula officinalis, yuzhou loquat, angelica dahurica, qianqianhuo, atractylodes, chuanxiong, red ginseng, peach kernel, and liquorice according to a certain ratio;

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

[0092] The present invention utilizes a Chinese medicine prescription to promote the healing of fractures. The specific mechanism is the pain-neurovascular axis theory, which causes severe pain after fracture, which can cause sympathetic nerve excitement and parasympathetic nerve inhibition, leading to the contraction of blood vessels in the limbs and insufficient blood supply. After applying the Chinese medicine composition of the present invention, pain is relieved, sympathetic nerves are inhibited, parasympathetic nerves are excited, and blood vessels around the fracture end are effectively expanded, blood supply around the fracture is improved, and fracture healing is promoted.

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

[0094] Figure 2 The gross morphological observation of fracture ends in different treatment groups (4 weeks after surgery) is shown:

[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, not completely connected, and had unclear boundaries with surrounding tissues.

[0096] Elderberry Kangfang low-dose group: Callus structure was visible at the fracture ends, and almost all of it was bone callus, which was tough to the touch and had a tendency to heal.

[0097] Elderberry Kangfang high-dose group: An enlarged fusiform callus structure was seen at the fracture ends, and all of it was bone callus, which was hard to the touch, and there was an obvious tendency for fracture healing.

[0098] Figure 3 The X-ray images of the three groups at day 0, week 2, and week 4 after surgery are shown:

[0099] Postoperative day 0: The fracture lines of the right femurs of the three groups of rats were obvious, the fracture ends were clear, the fracture alignment was good, and the fracture was fixed with Kirschner wires in a good position.

[0100] Second week after surgery: In the control group, the fracture line was obvious, a small amount of callus grew, and the density was not high; in the low- and high-dose bone setting formula groups, the fracture line was visible, the callus increased significantly, the periosteal reaction was obvious, and part of the callus grew into the fracture line.

[0101] At 4 weeks after surgery: the callus in the control group increased compared with before, and the fracture line was still visible; the callus in the low- and high-dose bone setting prescription groups expanded in a fusiform shape, and the density of the high-dose group was higher, and the fracture line disappeared.

[0102] The callus volume of the three groups of rats was measured at the second and fourth weeks after surgery. The Perkins callus volume measurement formula: 2πR1(R2-R1)L, (R1 = bone radius; R2 = callus radius; L = callus length) was used to calculate the callus volume. Figure 4 As shown:

[0103] Second week after surgery: The callus volumes in the low-dose and high-dose groups were greater than those in the control group, and there was a statistically significant difference between the low-dose group and the high-dose group.

[0104] At 4 weeks after surgery: The callus volumes of the low- and high-dose groups of the bone-setting formula were greater than those of the control group, and the high-dose group was greater than the low-dose group.

[0105] Examples of using the bone-setting and tendon-setting formula to promote postoperative bone nonunion and delayed fracture healing:

[0106] Case 1:

[0107] Male, 28 years old, underwent right femoral intramedullary nail fixation in another hospital on March 29, 2023, and nonunion occurred 1 year after surgery. In April 2024, he visited the outpatient clinic and started taking Chinese medicine regularly. Figure 5 As shown, PRP+artificial bone treatment was then performed, and the Chinese medicine of the embodiment of the present invention was taken orally for a long time after the operation. The radiographs of the patients taking the Chinese medicine for 1, 2, 3, 4, and 5 months were as follows: Figure 6 As shown, X-rays taken 5 months after taking Chinese medicine showed obvious formation of bone callus and trabeculae.

[0108] Case 2:

[0109] Male, 42 years old, underwent left tibial fracture plate internal fixation in the Sixth Hospital in August 2019, and the internal fixation was removed in 2022. In July 2023, he fell and fractured the left tibial shaft again. After 8 months of conservative treatment, the fracture healed poorly, so he was treated in the outpatient clinic in March 2024. The first outpatient radiograph was as follows Figure 7 As shown, PRP+artificial bone treatment was then performed, and the Chinese medicine of the embodiment of the present invention was taken orally for a long time after the operation. The radiographs of the patients taking the Chinese medicine for 1, 2, 3, and 6 months were as follows: Figure 8 shown.

[0110] Case 3:

[0111] Female, 45 years old, suffered multiple fractures of the lower left tibia and fibula due to trauma on January 5, 2024. She underwent open reduction and internal fixation of the left tibia and fibula on January 8. Fig. 9 As shown, 6 months after surgery, the fracture healing was poor, and he was admitted to the hospital for PRP + oral Chinese medicine treatment on July 10, 2024. After surgery, he took the Chinese medicine of the embodiment of the present invention for a long time. The radiographs taken after taking the Chinese medicine for 1, 2, and 3 months are as follows Fig.10 shown.

[0112] Case 4:

[0113] Male, 68 years old, suffered right femoral trochanteric and femoral shaft fractures due to a car accident on June 26, 2023, and underwent internal fixation treatment on June 28. He took Chinese medicine regularly after the operation, and the fracture healed well. Fig.11 As shown, the patients took the Chinese medicine of the embodiment of the present invention orally for a long time after surgery. The radiographs of the patients taking the Chinese medicine for 3, 4, 5, and 6 months were as follows: Fig.12 shown.

[0114] Case 5:

[0115] Female, 44 years old, suffered multiple fractures of the right tibia and fibula due to violent trauma on October 25, 2023. She underwent internal fixation treatment on October 30. The radiograph taken 6 months after internal fixation was as follows Fig.13 As shown, 4 months after surgery, the fracture healed poorly and PRP + oral Chinese medicine treatment was given. The radiographs taken after taking Chinese medicine for 1, 2, and 5 months were as follows: Fig.14 As shown, after taking Chinese medicine for 5 months after the operation, X-rays showed the formation of bone callus and trabeculae, and there were obvious signs of fracture healing compared with before.

[0116] From the clinical effect, the prescription of the present invention is obviously superior to other Chinese patent medicines such as: Shangke bone setting tablets, Gusongbao, etc. The key reason may be that the Chinese medicine prescription of the present invention has a major feature, the analgesic effect of elderberry: second only to morphine, equivalent to analgesic (Pharmacopoeia can be checked), because the local pain after fracture is obvious, effective pain relief is needed, and the healing of fracture can be effectively promoted: the healing of fracture requires blood supply, and the healing of good blood supply is fast, and the healing of poor blood supply is slow. Then the quality of blood supply depends on the control of blood vessels by nerves. Before the fracture is not healed, there are different degrees of pain in the local area. After the patient takes the prescription of the present invention, the pain is relieved, the parasympathetic nerves of the limbs are controlled to be excited, the sympathetic nerves are inhibited, the small blood vessels and microcirculation of the limbs are expanded, the blood supply of the fracture local area becomes more, and the fracture is slowly healed. At the same time, the prescription plays a synergistic role: to promote blood circulation and remove blood stasis, reduce swelling and relieve pain, connect bones and tendons, and promote the healing of fractures in many aspects.

[0117] In addition, the prescription of the present invention plays a synergistic role, can promote blood circulation and remove blood stasis, reduce swelling and relieve pain, and connect bones and tendons, thus promoting fracture healing from multiple aspects. Through this comprehensive conditioning, patients can not only relieve pain, but also accelerate the fracture healing process, achieving better therapeutic effects.

[0118] However, compared with similar Chinese patent medicines, such as traumatology bone setting tablets, the prescription of the present invention is significantly better than similar Chinese patent medicines, as shown in the following two cases:

[0119] For example, case 1: A 45-year-old woman had a right distal femoral fracture 10 months after surgery. The postoperative X-ray showed a clear fracture line, but no callus growth. One month after starting to take the traumatology bone setting tablets, there was no obvious change in the X-ray; after 2 months, there was no obvious change in the X-ray; after 3 months, there was still no change in the X-ray; after 5 months, there was still no change, and finally a second operation was performed.

[0120] Fig.15 Ten months after surgery, the fracture line was clear, no callus grew, and the patient started taking traumatology bone-setting tablets;

[0121] Fig.16 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 1 month, and there was no obvious change in the X-ray film;

[0122] Fig.17 This is a 2-month X-ray of the bone setting piece for the Department of Traumatology provided in an embodiment of the present invention, showing no obvious changes;

[0123] Fig.18 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 3 months, and there was no obvious change in the X-ray film;

[0124] Fig.19 It is a 5-month X-ray of the bone setting piece of the Department of Orthopedics provided in the embodiment of the present invention, and there is no obvious change;

[0125] For example, case 2: a 47-year-old male had a femoral shaft fracture 4 months after surgery. X-rays showed a clear fracture line and no obvious callus growth. After taking traumatology bone setting tablets for 1 month, there was no obvious change in the X-rays; after 2 months, there was still no obvious change in the X-rays; after 4 months, there was no significant change in the X-rays. Finally, 5 months later, the patient underwent a second operation.

[0126] Fig. 20 Four months after surgery, the fracture line was clear, no obvious callus growth was observed, and the patient began to take the traumatology bone setting tablets;

[0127] Fig.21 The bone setting piece for traumatology provided by the embodiment of the present invention was used for 1 month, and there was no obvious change in the X-ray film;

[0128] Fig. 22 The bone setting piece for the trauma department provided by the embodiment of the present invention was used for 2 months, and there was no obvious change in the X-ray film;

[0129] Fig.23 The trauma bone setting piece provided by the embodiment of the present invention was worn for 4 months, and there was no obvious change in the X-ray film.

[0130] These cases show that traumatology bone splints have limited effect in promoting fracture healing and fail to effectively accelerate the fracture healing process.

[0131] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A Chinese medicine composition for treating bone nonunion, characterized in that: The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 10-20 parts by weight of epimedium, 18-25 parts by weight of radix scutellariae, 10-15 parts by weight of rhizoma yuzhouii, 10-15 parts by weight of scutellariae atractylodes, 10-20 parts by weight of cyathulae chinensis, 10-20 parts by weight of rhizoma scutellariae, 10-20 parts by weight of rhizoma scutellariae, 10-15 parts by weight of radix angelicae pubescens, 10-15 parts by weight of rhizoma chuanxiong, 10-20 parts by weight of red ginseng, 10-15 parts by weight of semen persicae, and 5-10 parts by weight of liquorice.

2. The Chinese medicine composition for treating bone nonunion according to claim 1, characterized in that: The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 15 parts of epimedium, 20 parts of radix scutellariae, 15 parts of radix yuzhouensis, 15 parts of atractylodes, 12 parts of cyathulae, 12 parts of scutellariae, 10 parts of angelica dahurica, 12 parts of ligusticum wallichii, 12 parts of red ginseng, 10 parts of peach kernel and 9 parts of liquorice.

3. A method for preparing a Chinese medicine composition for treating bone nonunion according to any one of claims 1 to 2, characterized in that: The steps include: (1) Weigh out epimedium, radix scutellariae, rhizoma cyperi, rhizoma schizonepetae, rhizoma yuzhouensis, rhizoma pubescens, rhizoma pubescens, rhizoma atractylodis macrocephalae, rhizoma chuanxiong, rhizoma scutellariae ... (2) Soak in boiling water for 8 hours, then boil for 40 minutes and filter.

4. A pharmaceutical preparation containing the Chinese medicine composition as claimed in claim 1 or 2 as an active ingredient, characterized in that: The drug preparation is prepared into a common dosage form in pharmacy by a conventional preparation method in the art.

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

6. Use of the Chinese medicine composition according to claim 1 or 2 in preparing a drug for treating bone nonunion.

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