Use of guipi mixture in the preparation of a drug for treating osteomyelitis

Abstract

The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to the use of Guipi Mixture in the preparation of drugs for treating osteomyelitis. The Guipi Mixture of the present invention is prepared from the raw materials of Codonopsis pilosula, stir-fried Atractylodes macrocephala, roasted Astragalus membranaceus, roasted Glycyrrhiza uralensis, Poria cocos, processed Polygala tenuifolia, stir-fried Ziziphus jujuba var. spinosa, Arillus longan, Angelica sinensis, Aucklandia lappa, Fructus Jujubae, and Zingiber officinale. Animal pharmacodynamic experiments have confirmed that the Guipi Mixture of the present invention can significantly promote the closure of sinus tracts, improve anemia and promote osteogenesis, and improve the local bone infection microenvironment by regulating inflammatory factors, providing a new traditional Chinese medicine intervention path for the treatment of osteomyelitis, and having significant clinical significance and application value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the use of Guipi Heji in the preparation of drugs for treating osteomyelitis. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Osteomyelitis is an inflammatory or purulent disease of bone tissue caused by bacterial infection, often resulting from trauma, surgery, or spread from adjacent foci of infection. If acute treatment is incomplete, it can easily develop into chronic osteomyelitis, characterized by bone destruction, sequestrum formation, purulent discharge from sinuses, recurrent attacks, and a prolonged, difficult-to-cure course. Currently, Western medicine primarily employs lesion removal, antibiotic irrigation, and systemic anti-infective therapy, but this approach faces challenges such as bacterial resistance, high recurrence rates, and the need for multiple surgeries.

[0004] Traditional Chinese medicine has a long history and unique advantages in treating osteomyelitis, and there have been many related patent reports in recent years.

[0005] Chinese Patent Publication No. CN102552577A discloses a traditional Chinese medicine composition for treating bone tuberculosis and osteomyelitis, its preparation method, and its application. The composition contains 12 traditional Chinese medicines, including earthworm, astragalus, codonopsis, angelica, pangolin scales, white peony root, atractylodes macrocephala, saponins, licorice, rehmannia glutinosa, alisma plantago-aquatica, and poria cocos. It can be prepared as a powder or capsule and can be used in conjunction with external application strips or gauze strips such as red cinnabar and 91-dan.

[0006] Chinese patent CN105055596A discloses a formula for treating chronic osteomyelitis, namely, Heying Paidu Pill and its preparation method. The pill is made from 18 medicinal materials, including Salvia miltiorrhiza, Angelica sinensis, Astragalus membranaceus, Atractylodes macrocephala, Luffa cylindrica, Lonicera japonica, Codonopsis pilosula, Paeonia lactiflora, Poria cocos, Citrus reticulata peel, Aconitum carmichaelii, Aucklandia lappa, Glycyrrhiza uralensis, Ligusticum chuanxiong, Paeonia lactiflora, Morus alba twigs, Achyranthes bidentata, and Forsythia suspensa. Its formula primarily focuses on promoting blood circulation, removing blood stasis, harmonizing the body, and eliminating toxins, supplemented by methods to invigorate blood circulation, reduce swelling, regulate the liver and kidneys, and regulate qi and disperse stagnation. It is used to treat blood stasis and toxin accumulation in the middle and late stages of chronic osteomyelitis.

[0007] Chinese patent CN103877460A discloses a medicine for treating tuberculosis and osteomyelitis. This medicine is made by grinding 14 traditional Chinese medicinal herbs, including dried red-spined snake, dried centipede, astragalus, angelica, scutellaria, codonopsis, atractylodes, angelica dahurica, stemona, honeysuckle, rehmannia, licorice, achyranthes, and poria cocos, into powder and then refining them into pills with honey. The formula uses red-spined snake as the main ingredient, combined with centipede and honeysuckle to attack toxins and disperse nodules, and supplemented with astragalus and angelica to replenish qi and blood, for the treatment of bone and joint tuberculosis and osteomyelitis.

[0008] In the prior art, combination prescriptions such as clearing heat and detoxifying, promoting blood circulation to remove blood stasis, expelling pus by dredging toxins, and tonifying qi and blood are often used, and external medications or surgical debridement are often required. Guipi Mixture is derived from the classic famous prescription Guipi Decoction, which has traditionally been used to treat symptoms such as palpitations, insomnia, forgetfulness, poor appetite, metrorrhagia and metrostaxis caused by deficiency of both the heart and spleen and insufficiency of qi and blood. There have been no related reports on using Guipi Mixture to prepare drugs for treating osteomyelitis. Based on the theories of traditional Chinese medicine such as "bones rely on blood for nourishment", "the spleen governs muscles", "tonifying the earth to generate metal", and "when healthy qi exists inside the body, pathogens cannot invade", the present invention has for the first time discovered that by重用 Guipi Mixture to greatly tonify the qi and blood of the heart and spleen, sufficient healthy qi can be generated, toxins can be expelled outwards, necrotic tissues can be removed spontaneously, and new bones can grow spontaneously, thereby effectively treating chronic osteomyelitis, especially the syndrome with qi and blood deficiency and non-healing sinus tracts, which has significant clinical significance and application value. Summary of the Invention

[0009] The present invention provides a new use of Guipi Mixture in the preparation of drugs for treating osteomyelitis. The object of the present invention is achieved through the following technical solutions:

[0010] I. Technical Solution

[0011] The present invention provides the use of Guipi Mixture in the preparation of drugs for treating osteomyelitis.

[0012] The osteomyelitis is chronic osteomyelitis or acute osteomyelitis. Preferably, the osteomyelitis is chronic osteomyelitis of qi and blood deficiency type, or chronic osteomyelitis with at least one qi and blood deficiency syndrome such as non-healing sinus tract for a long time, thin and clear pus, sallow complexion, fatigue, palpitations, insomnia, and poor appetite.

[0013] The Guipi Mixture is made from the following raw materials in parts by weight: 68 parts of Codonopsis pilosula, 136 parts of stir-fried Atractylodes macrocephala, 68 parts of roasted Astragalus membranaceus, 34 parts of roasted Glycyrrhiza uralensis, 136 parts of Poria cocos, 136 parts of processed Polygala tenuifolia, 68 parts of stir-fried Ziziphus jujuba var. spinosa, 136 parts of Arillus longan, 136 parts of Angelica sinensis, 34 parts of Aucklandia lappa, 34 parts of Chinese date, and 17 parts of ginger.

[0014] The Guipi Mixture is an oral liquid preparation prepared by decocting the above raw materials with water, concentrating, and adding pharmaceutically acceptable excipients according to the conventional preparation method of traditional Chinese medicine mixtures.

[0015] Preferably, the preparation method of the Guipi Mixture is as follows: stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis are respectively distilled to extract volatile oils; the residue of Angelica sinensis is percolated with 50% ethanol as the solvent, the percolate is collected, and the ethanol is recovered; the residues of Atractylodes macrocephala and Aucklandia lappa and the other nine herbs such as Codonopsis pilosula are decocted with water three times, for 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time, the decoction liquids are combined, filtered, the filtrate is concentrated to an appropriate amount, combined with the above percolate, allowed to stand, filtered, the filtrate is concentrated to about 1000 ml, 3 g of sodium benzoate is added, cooled, the above volatile oils are added, and water is added to 1000 ml, and mixed evenly to obtain the product.

[0016] The Gui Pi He Ji can be used alone as the sole active ingredient, or it can be used in combination with one or more other drugs for treating osteomyelitis; the other drugs for treating osteomyelitis are selected from at least one of antibiotics, traditional Chinese medicines for clearing heat and detoxifying, traditional Chinese medicines for promoting blood circulation and removing blood stasis, and traditional Chinese medicines for promoting detoxification and draining pus.

[0017] The treatment of osteomyelitis includes one or more of the following: promoting sinus tract closure, reducing or eliminating purulent secretions, promoting the expulsion of dead bone, promoting new bone formation, and improving systemic symptoms of qi and blood deficiency.

[0018] The administration regimen of the Gui Pi He Ji is as follows: take it 3 times a day, each time in the form of 10-20ml of oral liquid preparation, for 4 weeks as one course of treatment, and take it for 2 to 6 consecutive courses of treatment.

[0019] II. Solution

[0020] The Gui Pi He Ji (Spleen-Nourishing Compound) of this invention is derived from the classic formula Gui Pi Tang (Spleen-Nourishing Decoction), but the dosage has been re-proportioned and the dosage form optimized based on the core pathogenesis of osteomyelitis: "prolonged illness severely damages Yin and Blood, leading to stagnation of the collaterals." The entire formula is meticulously formulated and clearly layered.

[0021] The principal herbs are Astragalus membranaceus (processed) and Angelica sinensis. Astragalus membranaceus is intended to "greatly replenish the Qi of the spleen and lungs." Qi can control blood, generate blood, and, more importantly, expel toxins—for chronic osteomyelitis, Astragalus membranaceus can invigorate the body's vital energy, lifting the damp toxins deeply embedded in the periosteum from the inside out, promoting wound healing. Angelica sinensis is the most abundant herb in the formula. A large dose of Angelica sinensis not only replenishes blood but also invigorates blood circulation, improving microcirculation around the bone ends and sinus tracts, and "harmonizes blood" to prevent stagnation. The combination of Astragalus membranaceus and Angelica sinensis is the essence of the Dang Gui Bu Xue Tang (Angelica Blood-Nourishing Decoction), but in this invention, the ratio of Astragalus membranaceus to Angelica sinensis is 1:2, emphasizing a strong replenishment of Yin and blood, as prolonged illness further damages Yin and depletes blood.

[0022] The assistant herbs are: stir-fried Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, and prepared licorice root. The primary function of these assistant herbs is to strengthen the spleen. The spleen is the foundation of acquired constitution and the source of qi and blood. Together, the principal and assistant herbs work synergistically: Astragalus membranaceus and Codonopsis pilosula replenish qi externally, while Atractylodes macrocephala and Poria cocos invigorate the spleen internally, ensuring a continuous flow of the essence of food and water into qi and blood, providing the material basis for "tissue regeneration and bone growth." Specifically, Atractylodes macrocephala and Poria cocos address the pathogenesis of "spleen deficiency and dampness retention" in chronic osteomyelitis—the clear, thin exudate is a manifestation of the spleen's inability to transform dampness. Poria cocos promotes diuresis without harming the body's vital energy, while Atractylodes macrocephala dries dampness and promotes tissue regeneration.

[0023] Adjuvant herbs: Longan pulp, stir-fried jujube seeds, and prepared polygala root. Patients with chronic osteomyelitis often suffer from long-term pain, leading to depletion of heart blood and restlessness, manifesting as insomnia, palpitations, and pale complexion. Polygala root is particularly crucial, not only calming the mind but also clearing phlegm, opening the orifices, and dissipating carbuncles and swellings, with special significance for the dissipation of deep bone abscesses. These three herbs assist the principal and assistant herbs, ensuring that the replenished blood returns to the heart. The heart governs blood vessels; sufficient heart qi ensures that blood can smoothly descend to the affected limb. Costus root, pungent, warm, and aromatic, can regulate qi, soothe the stomach, invigorate the spleen, and stimulate appetite, making the tonics less cloying and promoting qi circulation, thus aiding in the absorption of the tonics. It is a model of "active herbs" assisting "static herbs." Ginger and jujubes, used together, harmonize the ying and wei, guiding the medicinal qi to the surface of the muscles and limbs. For osteomyelitis in the extremities, it can help astragalus root expel toxins.

[0024] Guiding herb: Prepared licorice root. Licorice root not only tonifies the middle jiao (spleen and stomach), but also harmonizes the other herbs, alleviating the cloying richness of angelica and longan pulp, and moderating the warming dryness of astragalus and atractylodes, making the whole formula tonifying without being drastic, and stable and effective. Ginger and jujube also serve as guiding herbs here, directing the medicinal power from the spleen and stomach to the limbs.

[0025] Compared with the prior art, the technical advantages of the present invention are as follows:

[0026] 1. This is the first time that Gui Pi He Ji (a traditional Chinese medicine formula) has been used to prepare a drug for treating osteomyelitis, filling a technical gap in the field of orthopedic infectious diseases. It is especially suitable for chronic osteomyelitis of the Qi and Blood deficiency type and patients with symptoms of Qi and Blood deficiency such as unhealed sinus tracts and thin pus.

[0027] 2. This invention breaks with the traditional dosage conventions of Gui Pi Tang (Spleen-Nourishing Decoction), adjusting the ratio of Astragalus membranaceus to Angelica sinensis to 1:2, with a higher proportion of Angelica sinensis to strongly nourish Yin and blood, and promote blood circulation. Furthermore, it combines volatile oil extraction, ethanol percolation, and water decoction in the preparation process, improving the dissolution rate of the active ingredients. Pharmacodynamic verification shows that its core indicators, such as promoting sinus tract closure, improving anemia (Hb increased to 139.5 g / L), and promoting bone formation (OCN upregulation, CTX-I downregulation), are significantly superior to traditional Gui Pi Tang and the positive control drug.

[0028] 3. Comparative studies have confirmed that altering the proportion of the principal herb, reducing the dosage of spleen-strengthening herbs, replacing Polygala tenuifolia, or adding cold-natured herbs all significantly reduce the anti-inflammatory, antibacterial, sinus tract healing, and bone metabolism repair effects. This demonstrates that the complete formulation chain of this invention—"tonifying both Qi and blood—strengthening the spleen and removing dampness—nourishing the heart and calming the mind—guiding Qi"—is indispensable. In particular, the unique synergistic effect of Polygala tenuifolia in "resolving phlegm and dissipating nodules" and ginger and jujube in "guiding the medicine to the limbs" is non-obvious.

[0029] 4. Unlike existing technologies that rely solely on antibacterial or anti-toxic approaches, this invention employs a "strengthening the body's resistance and eliminating toxins" strategy to regulate inflammatory factors (reducing IL-6 and TNF-α and increasing IL-10). By addressing systemic blood and qi metabolism, it improves the local bone infection microenvironment, achieving a virtuous cycle of "strengthening the body's resistance, eliminating dampness and turbidity, expelling toxins, and promoting new bone growth." This provides a novel TCM intervention pathway for the treatment of chronic osteomyelitis. Detailed Implementation

[0030] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0031] Example 1: Gui Pi He Ji (Spleen-Nourishing Compound)

[0032] prescription: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 136g, processed Astragalus membranaceus 68g, processed Glycyrrhiza uralensis 34g, Poria cocos 136g, processed Polygala tenuifolia 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan pulp 136g, Angelica sinensis 136g, Aucklandia lappa 34g, jujube (pitted) 34g, fresh ginger 17g.

[0033] Preparation method:

[0034] The above twelve ingredients were used to extract volatile oils by distillation of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis. The residue of Angelica sinensis was percolated with 50% ethanol as a solvent, and the percolate was collected and the ethanol was recovered. The residues of Atractylodes macrocephala and Aucklandia lappa were decocted three times with water, the first time for 2 hours, the second time for 1.5 hours, and the third time for 1 hour. The decoctions were combined, filtered, and the filtrate was concentrated to an appropriate amount. It was then combined with the percolate, allowed to stand, filtered, and the filtrate was concentrated. 3g of sodium benzoate was added, cooled, and the above volatile oils were added. Water was added to 1000ml and mixed well to obtain the final product.

[0035] Comparative Example 1

[0036] formula: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 136g, processed Astragalus membranaceus 136g, processed Glycyrrhiza uralensis 34g, Poria cocos 136g, processed Polygala tenuifolia 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan aril 136g, Angelica sinensis 68g, Aucklandia lappa 34g, jujube 34g, fresh ginger 17g.

[0037] Preparation method:

[0038] The above twelve ingredients were used to extract volatile oils by distillation of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis. The Angelica sinensis residue was percolated with 50% ethanol as a solvent, and the percolate was collected and the ethanol was recovered. The residues of Atractylodes macrocephala and Aucklandia lappa were decocted three times with water along with the remaining nine ingredients (processed Astragalus membranaceus, processed Glycyrrhiza uralensis, Poria cocos, processed Polygala tenuifolia, stir-fried Ziziphus jujuba var. spinosa, longan pulp, jujube, and ginger). The decoctions were combined, filtered, and concentrated to an appropriate volume. The filtrate was combined with the percolate, allowed to stand, filtered, and concentrated. 3g of sodium benzoate was added, cooled, and the volatile oils were added. Water was added to 1000ml and mixed well to obtain the final product.

[0039] Comparative Example 2

[0040] formula: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 68g, processed Astragalus membranaceus 68g, processed Glycyrrhiza uralensis 34g, Poria cocos 68g, processed Polygala tenuifolia 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan pulp 136g, Angelica sinensis 136g, Aucklandia lappa 34g, jujube 34g, fresh ginger 17g.

[0041] Preparation method:

[0042] The preparation method of Tongyuan Guipi Compound is as follows: Stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis were separately distilled to extract volatile oils; the Angelica sinensis residue was percolated with 50% ethanol; the residues of Atractylodes macrocephala and Aucklandia lappa, along with the remaining Codonopsis pilosula, Astragalus membranaceus (processed), Glycyrrhiza uralensis (processed), Poria cocos, Polygala tenuifolia (processed), stir-fried Ziziphus jujuba var. spinosa, Longan aril, jujube, and ginger, were decocted three times with water (2 hours the first time, 1.5 hours the second time, and 1 hour the third time). The decoctions were combined, filtered, concentrated, combined with the percolate, allowed to stand, filtered, concentrated, 3g of sodium benzoate was added, cooled, the volatile oil was added, and water was added to 1000ml, then mixed well.

[0043] Comparative Example 3

[0044] formula: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 136g, roasted Astragalus membranaceus 68g, roasted Glycyrrhiza uralensis 34g, Poria cocos 136g, Albizia julibrissin bark 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan pulp 136g, Angelica sinensis 136g, Aucklandia lappa 34g, jujube 34g, fresh ginger 17g.

[0045] Preparation method:

[0046] The above twelve ingredients were used to extract volatile oils by distillation of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis. The residue of Angelica sinensis was percolated with 50% ethanol. The residues of Atractylodes macrocephala and Aucklandia lappa were decocted three times with water along with the remaining Codonopsis pilosula, Astragalus membranaceus (processed), Glycyrrhiza uralensis (processed), Poria cocos, Albizia julibrissin bark, stir-fried Ziziphus jujuba var. spinosa, Longan aril, jujube, and ginger (processed). The decoctions were combined, filtered, concentrated, and combined with the percolate. The mixture was allowed to stand, filtered, concentrated, and 3g of sodium benzoate was added. The mixture was cooled, the volatile oil was added, and water was added to 1000ml. The mixture was then mixed well.

[0047] Comparative Example 4

[0048] formula: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 136g, processed Astragalus membranaceus 68g, processed Glycyrrhiza uralensis 34g, Poria cocos 136g, processed Polygala tenuifolia 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan aril 136g, Angelica sinensis 136g, Aucklandia lappa 34g, jujube 34g, fresh ginger 17g, Lonicera japonica 68g, Forsythia suspensa 68g.

[0049] Preparation method:

[0050] The above fourteen ingredients were used to extract volatile oils by distillation of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis. The residue of Angelica sinensis was percolated with 50% ethanol. The residues of Atractylodes macrocephala and Aucklandia lappa were decocted three times with water along with the remaining Codonopsis pilosula, Astragalus membranaceus (processed), Glycyrrhiza uralensis (processed), Poria cocos, Polygala tenuifolia (processed), Ziziphus jujuba (stir-fried), Longan aril, Jujube, Zingiber officinale, Lonicera japonica, and Forsythia suspensa (processed), for the first time for 2 hours, for the second time for 1.5 hours, and for the third time for 1 hour. The decoctions were combined, filtered, concentrated, combined with the percolate, allowed to stand, filtered, concentrated, 3g of sodium benzoate was added, cooled, volatile oil was added, and water was added to 1000ml. The mixture was then stirred well.

[0051] Comparative Example 5

[0052] formula: Codonopsis pilosula 68g, stir-fried Atractylodes macrocephala 136g, processed Astragalus membranaceus 68g, processed Glycyrrhiza uralensis 34g, Poria cocos 136g, processed Polygala tenuifolia 136g, stir-fried Ziziphus jujuba var. spinosa 68g, longan aril 136g, Angelica sinensis 136g, Aucklandia lappa 34g.

[0053] Preparation method:

[0054] The above ten ingredients were used to extract volatile oils by distillation of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis. The residue of Angelica sinensis was percolated with 50% ethanol. The residues of Atractylodes macrocephala and Aucklandia lappa were decocted three times with water along with the remaining Codonopsis pilosula, Astragalus membranaceus (processed), Glycyrrhiza uralensis (processed), Poria cocos, Polygala tenuifolia (processed), Ziziphus jujuba (stir-fried), and Longan aril (processed). The decoctions were combined, filtered, concentrated, and combined with the percolate. The mixture was allowed to stand, filtered, concentrated, and 3g of sodium benzoate was added. The mixture was cooled, the volatile oil was added, and water was added to 1000ml. The mixture was then mixed well.

[0055] Comparative Example 6

[0056] Formula (based on 1000ml of mixture): Astragalus membranaceus 68g, Codonopsis pilosula 68g, Angelica sinensis 68g, Atractylodes macrocephala 68g, Poria cocos 68g, Paeonia lactiflora 68g, Rehmannia glutinosa 68g, Alisma plantago-aquatica 68g, Pheretima aspergillum 68g, Gleditsia sinensis 68g, Glycyrrhiza uralensis 34g, Tetrapanax papyriferus 10g.

[0057] Preparation method:

[0058] The above twelve ingredients are decocted three times with water: 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time. The decoctions are combined, filtered, and the filtrate is concentrated to about 1000ml. 3g of sodium benzoate is added and mixed well to obtain the final product.

[0059] Comparative Example 7

[0060] Formula (based on approximately 1000ml of the mixture): 18g of Atractylodes macrocephala, 18g of Poria cocos, 18g of Astragalus membranaceus, 18g of Longan pulp, 18g of Ziziphus jujuba var. spinosa, 15g of Salvia miltiorrhiza, 9g of Panax ginseng, 9g of Aucklandia lappa, 9g of Polygala tenuifolia, 3g of Angelica sinensis, 6g of Glycyrrhiza uralensis (processed), 3g of Scolopendra subspinipes, 5 slices of fresh ginger (about 5g), and 1 jujube (about 3g).

[0061] Preparation method:

[0062] For the above fourteen ingredients, grind the centipede into a fine powder and set aside. For the remaining ingredients—Atractylodes macrocephala, Poria cocos, Astragalus membranaceus, longan pulp, Ziziphus jujuba var. spinosa, Salvia miltiorrhiza, Panax ginseng, Aucklandia lappa, Polygala tenuifolia, Angelica sinensis, prepared licorice root, ginger, and jujube—add water and decoct three times: the first time for 2 hours, the second time for 1.5 hours, and the third time for 1 hour. Combine the decoctions, filter, concentrate the filtrate to an appropriate volume, add the centipede powder, mix well, and continue concentrating to approximately 1000 ml. Add 3g of sodium benzoate, mix well, and the product is ready.

[0063] Comparative Example 8

[0064] formula: Ginseng 1.25g, Costus root 1.25g, Atractylodes macrocephala 2.5g, Poria cocos 2.5g, Astragalus membranaceus 2.5g, Longan pulp 2.5g, Ziziphus jujuba seed 2.5g, Polygala tenuifolia 2.5g, Angelica sinensis 2.5g, Prepared licorice root 0.625g, five slices of ginger (about 5g), one jujube (about 3g).

[0065] Preparation method:

[0066] The above twelve ingredients are decocted twice with water. For the first decoction, add about 120ml of water, soak for 30 minutes, bring to a boil over high heat, then simmer over low heat for 40 minutes, and filter out the liquid. For the second decoction, add about 80ml of water, decoct for 30 minutes, and filter out the liquid. Combine the two decoctions, mix well, and concentrate to a volume of 28.5ml.

[0067] Pharmacodynamic experiment of Guipi Heji in the treatment of osteomyelitis

[0068] I. Model Establishment and Dosing Grouping Method

[0069] 1. Laboratory animals

[0070] SPF-grade male SD rats, weighing 200±20g. They were kept in a standard environment (temperature 22±2℃, humidity 50±10%, 12h light / 12h dark) with free access to water and food for one week to allow for acclimatization.

[0071] 2. Establishment of an osteomyelitis model

[0072] Anesthesia: Intraperitoneal injection of sodium pentobarbital (40 mg / kg).

[0073] Surgical procedure: The skin of the proximal medial aspect of the right tibia was prepared and disinfected. The skin and fascia were incised to expose the medial tibial bone surface. A bone hole (1 mm in diameter and approximately 3 mm deep) was drilled in the proximal metaphysis of the tibia using a miniature electric drill. Staphylococcus aureus suspension (ATCC29213, 1×10⁻⁶) was injected into the bone hole. 6 CFU / 0.1mL). The bone hole was sealed with bone wax, the wound was rinsed with physiological saline, and sutured layer by layer. Postoperative management: rats were housed individually and given intramuscular injections of penicillin (40,000 U / rat) for 3 consecutive days to prevent postoperative infection (without resistance to the model bacteria). Model validation: 7 days after surgery, 2 model rats (not included in the formal experiment) were randomly selected and sacrificed. Tibial bones were taken for bacterial culture and HE staining to confirm the successful establishment of the osteomyelitis model.

[0074] 3. Experimental grouping and drug dosage (13 groups in total, 10 rats in each group)

[0075] Blank control group: No model was established, and the same volume of physiological saline (2.7 mL / kg) was administered by gavage daily.

[0076] Model control group: After successful modeling, the model was administered an equal volume of physiological saline (2.7 mL / kg) by gavage daily.

[0077] Positive drug group: After successful modeling, clindamycin 75 mg / kg was administered by gavage daily.

[0078] Example 1 Low-dose group: After successful modeling, the patient was given Example 1 Guipi Heji by gavage daily, with a dosage of 2.7 mL / kg (equivalent to the human equivalent dose of 30 mL / 70 kg).

[0079] Example 1 High-dose group: After successful modeling, the patient was given Example 1 Guipi Heji by gavage daily, with a dosage of 5.4 mL / kg (equivalent to the human equivalent dose of 60 mL / 70 kg).

[0080] Comparative Example 1: After successful modeling, the traditional Chinese medicine composition of Comparative Example 1 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the effect of changing the ratio of the principal drug on the efficacy.

[0081] Comparative Example 2: After successful modeling, the traditional Chinese medicine composition of Comparative Example 2 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the effect of reducing the dosage of the spleen-tonifying medicine on the efficacy.

[0082] Comparative Example 3: After successful modeling, the Chinese herbal composition of Comparative Example 3 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the unique role of Polygala tenuifolia in the formula.

[0083] Comparative Example 4: After successful modeling, the traditional Chinese medicine composition of Comparative Example 4 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the effect of adding cold-natured herbs on the overall efficacy.

[0084] Comparative Example 5: After successful modeling, the Chinese herbal composition of Comparative Example 5 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the effects of ginger and jujube in regulating the body's vital energy and guiding the medicine to the limbs.

[0085] Comparative Example 6: After successful modeling, the traditional Chinese medicine composition of Comparative Example 6 was administered by gavage daily at a volume of 2.7 mL / kg to compare its efficacy with existing technologies.

[0086] Comparative Example 7: After successful modeling, the Chinese herbal composition of Comparative Example 7 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the efficacy of the combined approach of attacking toxins and clearing collaterals with tonifying.

[0087] Comparative Example 8: After successful modeling, the traditional Chinese medicine composition of Comparative Example 8 was administered by gavage daily at a volume of 2.7 mL / kg to evaluate the therapeutic effect of the classic Gui Pi Tang on osteomyelitis in rats.

[0088] 4. Administration method

[0089] Administration route: Gavage, once daily for 8 consecutive weeks (2 courses of treatment, 4 weeks each, with no interval).

[0090] Gavage time: 9:00-10:00 AM daily.

[0091] II. Observation Indicators and Detection Methods

[0092] 1. General condition and local manifestations

[0093] Overall condition: weight, mental state, activity, coat color, appetite, and stool characteristics.

[0094] Local manifestations: Degree of swelling in the affected limb. Whether a sinus tract has formed and the time of its closure. Characteristics of secretions (color, consistency / viscousness, amount, odor). Record the time for complete closure of the sinus tract (based on 3 consecutive days without exudation and with complete skin epithelial coverage).

[0095] 2. Microbiological testing (after euthanasia in week 8)

[0096] Under aseptic conditions, a tissue sample (approximately 0.5 g) was taken from the center of the lesion in the right tibia, homogenized, and cultured for bacteria (blood agar plate, 37°C for 24 h) to count the colonies (CFU / g tissue).

[0097] 3. Blood biochemistry and immune indicators (blood sample taken before sacrifice in week 8)

[0098] Complete blood count: WBC, RBC, HGB, and PLT are measured using a fully automated blood cell analyzer.

[0099] Inflammatory factors: Serum IL-6, TNF-α, and IL-10 levels were detected by ELISA.

[0100] Blood and Qi related indicators: serum iron (Fe), total iron-binding capacity (TIBC), hemoglobin (Hb), total protein (TP), and albumin (ALB).

[0101] 4. Bone metabolism biochemical indicators (week 8)

[0102] Serum alkaline phosphatase (ALP), osteocalcin (OCN), and type I collagen cross-linked C-terminal peptide (CTX-I).

[0103] III. Experimental Results and Analysis

[0104] 1. Core efficacy trial results

[0105] Table 1 General Conditions and Local Manifestations (Week 8)

[0106] Compared with the model group, p < 0.01.

[0107] The Gui Pi He Ji (a traditional Chinese medicine formula) of this invention demonstrates significant advantages in improving the overall condition and local lesion outcomes in osteomyelitis model animals, primarily reflected in its therapeutic logic of "tonifying the spleen and promoting tissue regeneration" and "externalizing toxin removal." In Example 1, both the high- and low-dose groups showed effects similar to clindamycin in promoting sinus tract closure, reducing limb swelling, and improving the characteristics of purulent discharge, with the high-dose group showing more stable performance. Comparative Example 1 showed significantly inferior local efficacy, indicating that simply enhancing qi tonification or adding cold-natured toxin-expelling drugs cannot effectively promote sinus tract healing; instead, it interferes with the "warming and lifting" effect, prolonging the course of the disease. Comparative Example 5 also showed inferior efficacy compared to Example 1, revealing that the role of ginger and jujube in harmonizing the qi and blood and guiding the medicine to the extremities is not dispensable but a crucial auxiliary factor in achieving "medicine reaching the affected area." Although Comparative Example 8 showed some effect, it was far inferior to the Gui Pi He Ji of this invention, which has undergone dosage reconfiguration and dosage form optimization. This proves that the dosage reconstruction of the classic formula in this invention is based on the precise intervention of the pathogenesis of osteomyelitis, which is "prolonged illness causing severe damage to Yin and Blood and stagnation of collaterals". This treatment approach has not been reported in the existing technology.

[0108] 2. Microbiology and Inflammatory Factors

[0109] Table 2. Bone tissue bacterial load and serum inflammatory factors (week 8)

[0110] Compared with the model group, p < 0.01.

[0111] From the perspective of anti-infection and inflammation regulation, the effect mode of the Gui Pi He Ji (Spleen-Nourishing Compound) of this invention is completely different from that of simple antibiotics or methods of attacking toxins and clearing collaterals, reflecting the profound scientific connotation of "strengthening the body's resistance to eliminate pathogens." Example 1 significantly reduced the count of viable bacteria in bone tissue, while downregulating pro-inflammatory factors IL-6 and TNF-α and upregulating anti-inflammatory factor IL-10. Its regulatory characteristics were not prominent in the positive control group, which mainly relied on direct bactericidal action and had limited upregulation of IL-10. Compared with Comparative Example 7, although the latter also reduced bacterial load, the increase in IL-10 level was insufficient, suggesting that it focused more on "attacking and dispersing" than "nourishing the body's resistance," making it difficult to sustainably improve the local immune microenvironment. In Comparative Example 4, the addition of cold-natured herbs resulted in a weaker improvement in inflammatory factors than in Example 1, indicating that excessive clearing and detoxification damaged spleen yang, which was detrimental to the body's resistance to pathogens. More importantly, changes in the proportion of the principal herb, the dosage of the spleen-strengthening herb, or the substitution of Polygala tenuifolia in proportions 1, 2, and 3 all resulted in a significant decrease in anti-inflammatory and antibacterial effects. This indicates that the multi-level combination of "tonifying both qi and blood, strengthening the spleen and removing dampness, nourishing the heart and calming the mind, and promoting qi circulation" in the formula of this invention has a synergistic effect. The absence of any one of these elements or any substitution will weaken the overall efficacy. This discovery exceeds the conventional understanding that Gui Pi Tang is only used for internal medicine deficiency syndromes.

[0112] 3. Qi and Blood Related Indicators

[0113] Table 3. Serum Nutrition and Hematopoietic Indicators (Week 8)

[0114] Compared with the model group, p < 0.01.

[0115] Regarding the improvement of systemic qi and blood deficiency secondary to osteomyelitis, the high-dose group in Example 1 of this invention showed good improvement in indicators such as hemoglobin, serum iron, total protein, and albumin. The hematopoietic support effect of Comparative Example 1 was significantly inferior to that of Example 1, confirming that for chronic osteomyelitis, a condition characterized by "prolonged illness depleting blood and damaging yin," emphasizing the use of Angelica sinensis is more important than simply strengthening Astragalus membranaceus to replenish qi, which contradicts the conventional thinking of "replenishing qi to generate blood." Comparative Example 2 resulted in lower protein synthesis indicators, indicating that strengthening the spleen and promoting digestion is the material basis for qi and blood generation; reducing the dosage weakens the source of transformation. Although Comparative Example 6 had some tonic effect, its overall effect was far lower than that of this invention, indicating that a combination of methods is not necessarily superior to a specific formula that focuses on the heart and spleen and directly replenishes qi and blood. Comparative Example 8 showed some improvement in anemia, but its ability to increase serum iron and albumin was insufficient, suggesting that this invention improved the dissolution of effective components through a compound preparation process; this dosage form improvement and dosage optimization resulted in combined benefits.

[0116] 4. Bone metabolism indicators

[0117] Table 4. Serum bone metabolism markers (week 8)

[0118] Compared with the model group, p < 0.01.

[0119] The restoration of bone remodeling balance is a fundamental marker of osteomyelitis healing. The advantage of this invention in this regard reveals the deep mechanism of "replenishing qi and blood to generate new bone," extending the traditional Chinese medicine concept of "the kidney governs bone" to the correlation axis of "spleen-qi and blood-bone metabolism." Example 1 effectively downregulates CTX-I, which reflects bone resorption, upregulates the bone formation marker OCN, and reduces ALP, which reflects bone injury repair stress, suggesting that it promotes the transition from "destructive bone remodeling" to "osteogenic repair." Comparative Example 3 is weaker than Example 1 in bone metabolism indicators, indicating that Polygala tenuifolia not only calms the mind and soothes the nerves, but its properties of "resolving phlegm, opening orifices, and dispersing carbuncles and swellings" make a unique contribution to the clearance of deep bone abscesses and the purification of the osteogenic microenvironment. This effect has long been overlooked in previous studies of Gui Pi Tang. Comparative Examples 6 and 7 failed to effectively increase OCN or decrease CTX-I, indicating that simple antibacterial or blood-activating and meridian-clearing methods are insufficient to initiate an efficient bone regeneration process. This invention provides sufficient nutritional matrix and regulatory signals for local bone formation by greatly nourishing the heart and spleen and strengthening the source of qi and blood production. This strategy of "solving local bone defects by starting with systemic metabolism" is unprecedented in existing osteomyelitis treatment patents. Furthermore, the difference in efficacy between different ratios further confirms that each herb and each pair of combinations in this formula serves the complete chain of "qi and blood replenishment - dampness and turbidity transformation - toxin elimination - new bone regeneration". Its comprehensive effect far exceeds the sum of individual herbs or simple combinations.

Claims

1. The use of Guipi Heji in the preparation of drugs for treating osteomyelitis.

2. Use according to claim 1, characterized in that, The osteomyelitis referred to is either chronic or acute osteomyelitis.

3. Use according to claim 1 or 2, characterized in that, The osteomyelitis mentioned is chronic osteomyelitis, or chronic osteomyelitis accompanied by at least one of the following symptoms of qi and blood deficiency: persistent sinus tract, thin and clear pus, sallow complexion, fatigue, palpitations, insomnia, and loss of appetite.

4. Use according to claim 1, characterized in that, The Gui Pi He Ji (a traditional Chinese medicine formula) is made from the following raw materials in parts by weight: Codonopsis pilosula 68 parts, stir-fried Atractylodes macrocephala 136 parts, processed Astragalus membranaceus 68 parts, processed Glycyrrhiza uralensis 34 parts, Poria cocos 136 parts, processed Polygala tenuifolia 136 parts, stir-fried Ziziphus jujuba var. spinosa 68 parts, longan pulp 136 parts, Angelica sinensis 136 parts, Aucklandia lappa 34 parts, jujube 34 parts, and fresh ginger 17 parts.

5. Use according to claim 4, characterized in that, The Gui Pi He Ji is an oral liquid preparation made by decocting and concentrating the above-mentioned raw materials with water and adding pharmaceutically acceptable excipients, in accordance with conventional Chinese medicine compound preparation methods.

6. Use according to claim 1, characterized in that, The Gui Pi He Ji is used alone as the sole active ingredient.

7. Use according to claim 1, characterized in that, The Gui Pi He Ji is used in combination with one or more other drugs for treating osteomyelitis; the other drugs for treating osteomyelitis are selected from at least one of antibiotics, traditional Chinese medicines for clearing heat and detoxifying, traditional Chinese medicines for promoting blood circulation and removing blood stasis, and traditional Chinese medicines for promoting detoxification and draining pus.

8. Use according to claim 1, characterized in that, The treatment of osteomyelitis includes one or more of the following: promoting sinus tract closure, reducing or eliminating purulent secretions, promoting the expulsion of dead bone, promoting new bone formation, and improving systemic symptoms of qi and blood deficiency.

9. Use according to claim 1, characterized in that, The preparation method of the Gui Pi He Ji is as follows: stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis are distilled to extract volatile oils; the Angelica sinensis residue is percolated with 50% ethanol as a solvent, the percolate is collected, and the ethanol is recovered; the residues of Atractylodes macrocephala and Aucklandia lappa are decocted with the remaining nine herbs, including Codonopsis pilosula, three times with water, the first time for 2 hours, the second time for 1.5 hours, and the third time for 1 hour, the decoctions are combined, filtered, the filtrate is concentrated to an appropriate amount, combined with the above percolate, allowed to stand, filtered, the filtrate is concentrated, 3g of sodium benzoate is added, cooled, the above volatile oil is added, water is added to 1000ml, and mixed well to obtain the product.

10. Use according to claim 1, characterized in that: The administration regimen of the Gui Pi He Ji is as follows: take it 3 times a day, each time in the form of 10-20ml of oral liquid preparation, for 4 weeks as one course of treatment, and take it for 2 to 6 consecutive courses of treatment.

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