Pharmaceutical composition for treating fracture as well as preparation method and application of pharmaceutical composition

Abstract

The invention relates to a pharmaceutical composition for treating fracture and a preparation method and application thereof.The pharmaceutical composition is prepared from radix dipsaci, sticktight, herba cepbalanoplosis segeti, crab shells, maltose, distiller's yeast and sesame oil, and the preparation method comprises the steps that the crab shells are smashed into fine powder; cleaning the fresh medicinal materials of sticktight, teasel root and common cephalanoplos herb with clear water, grinding into medicinal slurry, adding crab shell powder, maltose and distiller's yeast, continuously grinding uniformly, fermenting for 3-5 days at the temperature of 30-35 DEG C, airing to form thick paste, adding sesame oil, and stirring until the paste is uniform. The pharmaceutical composition can achieve multi-dimensional synergistic interaction, and the fracture treatment effect is remarkably improved.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a pharmaceutical composition for treating fractures, a preparation method thereof and an application thereof. Background Art

[0002] Currently, a variety of traditional Chinese medicine ointments are used as adjunctive treatments for fractures in traditional Chinese medicine external treatments. Common formulations often incorporate herbs such as Drynaria fortunei, natural copper, and Eupolyphaga sinensis, which are known for promoting blood circulation, removing blood stasis, and strengthening bones and tendons. For example, patent number CN200810140828.1, entitled "A topical medication for treating fractures and traumatic injuries, comprising frankincense, myrrh, natural copper, earthworms, safflower, dragon's blood, Sichuan papaya, Drynaria fortunei, herba scutellariae, borneol, and musk"; and patent number CN201711044741.X, entitled "A topical ointment for fracture trauma and its preparation method, comprising natural copper, safflower, myrrh, dragon's bone, musk, dragon's blood, Panax notoginseng, frankincense, Drynaria fortunei, borneol, and sesame oil." Both ointments utilize Drynaria fortunei, frankincense, and myrrh as primary ingredients, supplemented with borneol to enhance transdermal penetration. Some prior art also mentions the use of calcined crab shells as a medicinal supplement for calcium supplementation, or the use of alcoholic beverages as adjuvants to enhance drug permeability. In terms of preparation methods, traditional plasters are mostly prepared by decoction, extraction, concentration and then mixing with a matrix, or directly grinding the raw herbs into powder.

[0003] The technical problems existing in the existing technology are as follows: (1) Limitations of formula compatibility: Traditional formulas tend to focus on warming and blood-activating drugs (such as frankincense and myrrh), which can easily cause local skin burning and allergies when used externally for a long time, and are not adaptable enough to the early stage of fracture blood stasis and heat syndrome. At the same time, the existing calcium source supplements mostly rely on calcined natural copper or oyster shells, which have low calcium release efficiency, and high-temperature calcination may destroy the active ingredients (such as chitin). (2) Imbalance between efficacy and safety: Most existing ointments lack a cold-heat balance design. A high proportion of warming and blood-activating drugs may aggravate local inflammatory reactions, while a single cold-cooling drug can easily cause blood stasis and affect callus formation. At the same time, although the existing transdermal penetration enhancers (such as borneol) can improve the absorption rate, they are highly irritating and not conducive to long-term application. (3) Defects in the preparation method: Traditional water decoction or direct grinding methods are difficult to fully release the active ingredients in fresh medicinal materials (such as flavonoids and organic acids in Bidens pilosa and Thistle), resulting in reduced bioavailability. In addition, the existing technologies mostly use vaseline or honey alone as the matrix, which has insufficient adhesion and sustained release effects, and is prone to cracking and falling off, affecting continuous drug delivery. (4) Single function: Existing technologies mostly focus on promoting blood circulation and removing blood stasis or simply supplementing calcium, and fail to simultaneously achieve the multi-dimensional synergistic effects of "removing blood stasis-supplementing calcium-promoting permeation-sustaining release", resulting in a prolonged fracture healing period. Summary of the Invention

[0004] To address these technical challenges, the inventive team devised a combination of "both cold and warm, dynamic and static" medicinal herbs (e.g., Dipsacus root with Bidens pilosa / Cycis serrata), which both inhibits inflammation and promotes bone regeneration. They also innovatively used uncalcined crab shells as a direct medicinal ingredient, preserving the natural structure of chitin and calcium carbonate and improving calcium utilization efficiency. They also introduced a fermentation process using koji to activate the enzymatic hydrolysis of fresh medicinal herbs and enhance the release of active ingredients. Meanwhile, fermentation products (such as organic acids) form a flexible, sustained-release matrix with maltose, extending the duration of drug action. These improvements systematically address existing issues such as unbalanced compatibility, high transdermal irritation, and low calcium source utilization, significantly enhancing the safety and efficacy of external fracture treatment.

[0005] The purpose of the present invention is to provide a pharmaceutical composition for treating bone fractures.

[0006] Another object of the present invention is to provide a method for preparing a pharmaceutical composition for treating fractures.

[0007] Another object of the present invention is to provide an application of a pharmaceutical composition in the preparation of a drug for treating fractures.

[0008] The pharmaceutical composition of the present invention comprises 10-20 parts of dipsaci, 10-20 parts of bidentata herb, 10-20 parts of thistle, 5-15 parts of crab shell, 5-10 parts of maltose, 3-6 parts of distiller's yeast and 5-10 parts of sesame oil.

[0009] Preferably, the pharmaceutical composition of the present invention is composed of 15 parts of Dipsacus asper, 15 parts of Bidens pilosa, 15 parts of Cirsium japonicum, 10 parts of crab shell, 8 parts of malt sugar, 5 parts of distiller's yeast, and 8 parts of sesame oil.

[0010] The preparation method of the pharmaceutical composition of the present invention comprises the following steps: (1) crushing crab shells; (2) preparing a medicinal slurry; (3) fermenting; (4) preparing a thick paste; and (5) forming.

[0011] Preferably, the crab shell crushing in step (1) of the present invention is: crushing the crab shell into fine powder exceeding 100 mesh.

[0012] Preferably, the preparation of the medicinal slurry in step (2) of the present invention is as follows: fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium japonicum are washed with clean water, combined, and ground into medicinal slurry with a homogenizer, and then crab shell powder, malt sugar and distiller's yeast are added and continued to be ground evenly.

[0013] Preferably, the fermentation in step (3) of the present invention is as follows: the uniformly ground medicinal slurry is fermented at a temperature of 30-35° C. for 3-5 days.

[0014] Further preferably, the fermentation in step (3) of the present invention is as follows: the uniformly ground medicinal slurry is fermented at a temperature of 32° C. for 4 days.

[0015] Preferably, the thick paste of step (4) of the present invention is prepared by placing the fermented medicinal pulp under the sun to dry, stirring it from time to time, and drying it until it becomes a thick paste.

[0016] Preferably, the forming in step (5) of the present invention is as follows: adding sesame oil to the thick paste and stirring until the paste is uniform.

[0017] The invention relates to the use of the pharmaceutical composition in preparing a medicine for treating fractures.

[0018] Beneficial effects of the present invention: 1. Solve the imbalance problem of traditional external fracture treatment drug compatibility: Through a Chinese medicine compatibility system that balances cold and heat (the warmth of Dipsacus asper and wine yeast harmonizes with the cold of Bidens pilosa and Thistle), and combines movement and stillness (synergistically tonifying the kidney and strengthening the body with promoting blood circulation and removing blood stasis), it can promote bone regeneration and metabolic balance while avoiding the side effects of local overheating or cold stagnation and blood stasis.

[0019] 2. Innovative "substance-function" synergistic mechanism for bone repair: A "calcium supplement-channel dredging" linkage design utilizes crab shells to provide a calcium foundation and koji to promote transdermal drug absorption. This is combined with fermentation technology to enhance drug efficacy and activity, breaking through the limitation of traditional topical drugs that only focus on a single healing pathway.

[0020] 3. Optimize the process of external treatment formulations of traditional Chinese medicine: By combining the homogenization and fermentation of fresh medicinal materials with the preparation of a maltose sustained-release matrix, the bioavailability of drug ingredients can be improved, the application time of the paste can be extended, and a new type of external application preparation for bone injuries with both soft adhesion and sustained drug release can be formed.

[0021] 4. Provide safe and effective treatment options for closed fractures: Guided by the TCM external treatment concept of "tonifying through clearing and promoting growth through elimination," develop topical compound prescriptions with the effects of promoting blood circulation, dispersing blood stasis, and repairing tendons and bones, avoiding the metabolic burden of oral medications on the liver and kidneys, and meeting the clinical needs of local treatment of closed fractures.

[0022] 5. Multi-dimensional synergistic enhancement significantly improves the treatment effect of fractures: (1) Dynamically balanced compatibility system: Through the cold-heat balance design of "Dipsacus asper (warming and strengthening the foundation) + Bidens pilosa / Cyprinus citrifolia (cold and blood-dissolving)", the local inflammatory response is inhibited while promoting osteoblast activity. Clinical efficacy observation shows that the total effective rate of the present invention group is 100%, and the total effective rate of the control group (Huoxue Jiegusan group) is 83.3%. Among them, the significant effective rate of the present invention group is 90.0%, and the significant effective rate of the control group is 66.7%. The present invention group is significantly better than the control group. (2) "Material-function" dual repair mechanism: Uncalcined crab shells retain the natural composite structure of chitin and calcium carbonate. After fermentation treatment, the calcium ion release efficiency is increased by 54.4%. Combined with the transdermal synergistic effect of wine yeast, the synergistic enhancement of calcium deposition and drug penetration is achieved.

[0023] 6. Breaking through the limitations of traditional processes and improving drug efficacy utilization: (1) "Enzymatic hydrolysis-fermentation" coupling technology: Fresh medicinal materials are homogenized and fermented with wine yeast (30-35℃ / 3-5 days) to activate the endogenous enzymes of the medicinal materials. Compared with the traditional water extraction process, the total flavonoid extraction rate in the formula increased by 72.3%, and the organic acid extraction rate increased by 84.7%. (2) Intelligent sustained-release matrix construction: Maltose and sesame oil form a temperature-responsive gel network that can slowly release drug ingredients under the influence of body temperature. In vitro transdermal experiments show that the effective ingredients last for 24 hours, and the release time is extended by 3 times compared with the plaster without sesame oil.

[0024] 7. Clinical safety is significantly improved: In the clinical efficacy observation test, the plaster of the present invention did not cause allergic reactions, while 2 cases of skin allergies were found in the control group, indicating that the clinical safety of the plaster of the present invention is significantly better than that of the control group.

[0025] The number of parts can be μg, mg, g, kg and other weight units known in the medical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Release curve of total flavonoids in receptor fluid DETAILED DESCRIPTION

[0027] The present invention is described in detail below with reference to specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. Those skilled in the art will be able to make several modifications and improvements without departing from the scope of the present invention, all of which fall within the scope of protection of the present invention.

[0028] Example 1 Recipe: 150g of Dipsacus asper, 150g of Bidens pilosa, 150g of Cirsium japonicum, 100g of crab shell, 80g of malt sugar, 50g of wine yeast, and 80g of sesame oil.

[0029] Example 2 Prescription: 100g of Dipsacus asper, 100g of Bidens pilosa, 100g of Thistle, 50g of crab shell, 50g of malt sugar, 30g of wine yeast, and 50g of sesame oil.

[0030] Example 3 Recipe: 200g of Dipsacus asper, 200g of Bidens pilosa, 200g of Thistle, 150g of crab shell, 100g of malt sugar, 60g of wine yeast, and 100g of sesame oil.

[0031] Example 4 Prescription: 120g of Dipsacus asper, 120g of Bidens pilosa, 120g of Cirsium japonicum, 60g of crab shell, 60g of malt sugar, 40g of wine yeast, and 60g of sesame oil.

[0032] Example 5 Recipe: 140g of Dipsacus asper, 140g of Bidens pilosa, 140g of Cirsium japonicum, 70g of crab shell, 70g of malt sugar, 50g of wine yeast, and 70g of sesame oil.

[0033] Example 6 Recipe: 160g of Dipsacus asper, 160g of Bidens pilosa, 160g of Cirsium japonicum, 80g of crab shell, 80g of malt sugar, 50g of wine yeast, and 80g of sesame oil.

[0034] Example 7 Recipe: 180g of Dipsacus asper, 180g of Bidens pilosa, 180g of Cirsium japonicum, 100g of crab shell, 80g of malt sugar, 50g of wine yeast, and 60g of sesame oil.

[0035] Example 8 Recipe: 190g of Dipsacus asper, 190g of Bidens pilosa, 190g of Cirsium japonicum, 130g of crab shell, 90g of malt sugar, 60g of wine yeast, and 90g of sesame oil.

[0036] The formulations of Examples 1-8 were prepared according to any one of the preparation methods of Examples 9-14.

[0037] Example 9 Preparation method 1 (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0038] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0039] (3) Fermentation: The evenly ground medicinal pulp is fermented at 32°C for 4 days.

[0040] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0041] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0042] Example 10 Preparation method 2 (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0043] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0044] (3) Fermentation: The evenly ground medicinal pulp is fermented at 30°C for 5 days.

[0045] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0046] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0047] Example 11 Preparation method three (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0048] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0049] (3) Fermentation: The evenly ground medicinal pulp is fermented at 35°C for 3 days.

[0050] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0051] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0052] Example 12 Preparation Method 4 (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0053] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0054] (3) Fermentation: The evenly ground medicinal pulp is fermented at 32°C for 5 days.

[0055] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0056] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0057] Example 13 Preparation Method 5 (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0058] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0059] (3) Fermentation: The evenly ground medicinal pulp is fermented at 33°C for 4 days.

[0060] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0061] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0062] Example 14 Preparation Method 6 (1) Crab shell crushing: crush the crab shell into fine powder exceeding 100 mesh.

[0063] (2) Preparation of medicinal slurry: Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema with clean water, combine them, grind them into medicinal slurry with a homogenizer, then add crab shell powder, malt sugar and wine yeast, and continue to grind them evenly.

[0064] (3) Fermentation: Ferment the evenly ground medicinal pulp at 34°C for 4 days.

[0065] (4) Preparation of thick paste: Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0066] (5) Molding: Add sesame oil to the thick paste and stir until the paste is uniform.

[0067] In order to further verify the effectiveness of the present invention, the inventors conducted a series of verification tests, as follows: 1. Formula composition and compatibility 1. Formula composition The pharmaceutical composition is composed of the following ingredients by weight: 10-20 parts of Dipsacus root, 10-20 parts of Bidens pilosa, 10-20 parts of Cirsium japonicum, 5-15 parts of crab shell, 5-10 parts of maltose, 3-6 parts of distiller's yeast, and 5-10 parts of sesame oil. The sources of the medicinal materials in the composition are as follows: Dipsacus asper Wall. ex Henry (Dipsacus asper) is a fresh root of the Dipsacus family. It nourishes the liver and kidneys, strengthens bones and tendons, and heals fractures. Its standard is included in the 2020 edition of the Chinese Pharmacopoeia.

[0068] Bidens pilosa L. is the fresh whole herb of Bidens pilosa L., a plant of the Asteraceae family. It has the effects of clearing heat and detoxifying, dispersing blood stasis and reducing swelling. Its standard is included in the "Quality Standards for Traditional Chinese and Ethnic Medicinal Materials of Guizhou Province" (2003 edition).

[0069] Cirsium setosum (Willd.) MB., a plant of the Asteraceae family, is the fresh whole herb. It has the effects of cooling blood, stopping bleeding, dispersing blood stasis, detoxifying, and eliminating carbuncles. Its standard is included in the Chinese Pharmacopoeia (2020 edition).

[0070] Crab shell is the carapace of the Chinese mitten crab, Eriocheir sinensis H. Milne-Edwards, a member of the family Scyphidae. It has the effects of dispersing blood stasis and eliminating stagnation. Its standard is included in the "Shandong Province Traditional Chinese Medicine Standard" (2012 edition).

[0071] Maltose is a food made from starchy grains such as sorghum, rice, barley, and corn through fermentation and saccharification. It has the effects of tonifying the middle qi, moistening the lungs, and promoting salivation. The standard is included in the "Anhui Province Traditional Chinese Medicine Preparation Specifications" (2019 edition).

[0072] Jiuqu (drinking yeast) is a fermented product made from barley, peas, and other ingredients. It has the effects of warming the stomach, promoting digestion, dispersing blood stasis, and relieving pain. The standard is included in the "Hubei Province Traditional Chinese Medicine Quality Standards" (2009 edition).

[0073] Sesame oil is a fatty oil extracted from the mature seeds of Sesamum indicum L., a plant of the Sesamaceae family. It has laxative effects, promoting blood circulation and removing blood stasis. Its standard is included in the Chinese Pharmacopoeia (2020 edition).

[0074] 2. Compatibility The bitter and warm Radix Dipsaci in the formula enters the liver and kidneys, nourishes the kidneys and strengthens bones, heals injuries and relieves pain, and is an important medicine in orthopedics. Its external application can directly stimulate the activity of local osteoblasts and promote callus formation, so it is the main medicine; the Herba Bidens pilosa cools blood and disperses blood stasis, reduces swelling and detoxifies, and assists the main medicine in relieving local hematoma, heat and pain caused by fractures; the Herba Cirsii fructus is sour and cold and enters the liver meridian, promoting blood circulation and dispersing blood stasis, clearing away heat and dampness, and together with the Herba Bidens pilosa achieves the effect of removing blood stasis and relieving pain. The two medicines are used together with cold and warm properties to restrain the warm and dry nature of Radix Dipsaci, balance local blood stasis and heat toxins, and are together the auxiliary medicines; the salty crab shell Cold enters the kidneys and is rich in calcium carbonate and chitin, providing a material basis for bone repair and enhancing local calcium deposition. Yeast extract, which is pungent and warm, dredges the meridians, activates blood circulation and promotes qi, promotes transdermal absorption of drugs, and also serves as an antiseptic and enhances efficacy. These two, one tonic (calcium) and one purifier (drug penetration), jointly assist the main and auxiliary drugs in exerting their efficacy, thus acting as an adjuvant. Finally, maltose is used as the adjuvant, utilizing its sweet, slow-acting, and adhesive properties as a matrix to harmonize the various drugs, prolong the application time of the plaster, alleviate irritation, keep the plaster soft and smooth, and promote the slow release of the drug ingredients. The overall compatibility characteristics of this prescription are as follows: Combination of movement and stillness: Dipsacus asper to nourish the kidney and strengthen the body (stillness) is combined with Bidens pilosa and Cirsium japonicum to promote blood circulation and remove blood stasis (movement), promoting bone regeneration and metabolic balance. Internal and external linkage: Crab shell calcium supplementation (material basis) and wine yeast penetration promotion (functional regulation) help the drug to take effect locally. Balance of cold and heat: The warm nature of Dipsacus asper and Jiuqu counterbalances the cold nature of Bidens pilosa and Cirsium japonicum to avoid local overheating or cold stagnation. This prescription embodies the traditional Chinese medicine external treatment idea of "using clearance as supplement and using elimination to promote growth" for bone injury treatment. It has the effects of promoting blood circulation, dispersing blood stasis, repairing tendons and bones, and is suitable for various closed fractures.

[0075] 2. Preparation process research and test The method of using the formula is to make it into a plaster and apply it to the affected area once a day. The preparation method of the plaster is as follows: Step 1 (Crab shell crushing): Crush the crab shell into fine powder exceeding 100 mesh.

[0076] Step 2 (cleaning fresh medicinal materials): Wash the fresh medicinal materials Bidens pilosa, Dipsacus asper and Thistle with clean water.

[0077] Step 3 (homogenization): Combine the fresh herbs of Bidens pilosa, Dipsacus asper and Cirsium cyrtonema, and grind them into medicinal slurry using a homogenizer.

[0078] Step 4 (Continue to Grind): Add crab shell powder, malt sugar and wine yeast to the medicinal paste and continue to grind evenly.

[0079] Step 5 (fermentation): Ferment the slurry at a temperature of 30-35°C for 3-5 days.

[0080] Step 6 (drying): Place the fermented medicinal paste in the sun to dry, stirring it from time to time, and dry it until it becomes a thick paste.

[0081] Step 7 (forming): Add sesame oil and stir until the paste is uniform.

[0082] 3. Formulation and preparation method verification test 1. Test on the extraction rate of organic acids and total flavonoids in the formula Modern research shows that the main ingredients of the formula, Dipsacus asper and Bidens pilosa, that exert anti-inflammatory and analgesic effects and promote bone cell growth are flavonoids, while the main ingredients of thistle that exert pharmacological effects in this formula are flavonoids and organic acids. The present invention compares the extraction rates of total flavonoids and organic acids in traditional water decoction processes and this process. The test method is as follows: According to the formula ratio, take 150g of Dipsacus root, 150g of Bidens pilosa, and 100g of Cirsium cyrtonema. Take two portions, add water to one portion and boil it twice, each time for 0.5 hours. Filter, concentrate the filtrate and dilute to 500ml. Grind the other portion into a medicinal slurry using a homogenizer. Add crab shell powder, malt sugar, and distiller's yeast in equal proportions to the medicinal slurry, continue grinding until uniform, and ferment the slurry at a temperature of 30-35°C for 5 days. Filter, collect the filtrate, wash the filter residue with an appropriate amount of water, collect the washing liquid, and combine it with the filtrate to dilute to 500ml. The total flavonoid content was determined by ultraviolet spectrophotometry, and the organic acid content was determined by acid-base titration. The results are shown in Table 1: ; The experimental results show that the total flavonoids and organic acid contents in the extract obtained by fermentation using this process are significantly higher than those in the traditional water decoction extraction process. The total flavonoids extraction rate is increased by 72.3% compared with the water decoction process, and the organic acid extraction rate is increased by 84.7%.

[0083] 2. Determination of calcium ion release efficiency in plasters In order to determine the release efficiency of calcium ions after fermentation treatment of the present invention, the present invention team carried out the following experiments: According to the formula's proportions, take 150g of Dipsacus root, 150g of Bidens pilosa, and 100g of Cirsium sibiricum. Take two portions. Grind one portion into a slurry using a homogenizer. Add crab shell powder, malt sugar, and distiller's yeast in equal proportions to the slurry. Continue grinding until uniform. Ferment the slurry at 30-35°C for 5 days. Air dry the fermented slurry in the sun, stirring occasionally until it becomes a thick paste. Add sesame oil and stir until the paste is homogenized. Grind the other portion into a slurry using a homogenizer. Add crab shell powder, malt sugar, and distiller's yeast in equal proportions to the slurry. Continue grinding until uniform. Air dry the slurry in the sun, stirring occasionally until it becomes a thick paste. Add sesame oil and stir until the paste is homogenized. Take 10g of each paste, place it into equal-sized gauze sheets, and soak them in equal volumes (500ml) of simulated body fluid (SBF) solution for 1 hour. The Ca⁺ concentration in the solutions is measured. The results are shown in Table 2. ; The test results show that the calcium ion release effect of the plaster obtained by the fermentation method is significantly higher than that of the unfermented plaster, with the release amount increased by 54.4%.

[0084] 3. Determination of the duration of total flavonoid release in plasters The maltose and sesame oil of the present invention can form a temperature-responsive gel network that can slowly release the drug ingredients under the influence of body temperature. To determine the duration of release of the active ingredients, the invention team conducted the following experiments: According to the formula ratio, take 150g of Dipsacus root, 150g of Bidens pilosa and 100g of Cirsium chinense, grind them into a paste with a homogenizer, add crab shell powder, malt sugar and wine yeast in equal proportions to the paste, continue to grind evenly, ferment the paste at a temperature of 30-35℃ for 5 days, dry the fermented paste in the sun, stir it from time to time, dry it until it becomes a thick paste, divide it into 2 parts, set one aside, add sesame oil to the other part, stir, and stir until the paste is uniform. Take 20g of each of the above two pastes, use the Franz diffusion cell method to carry out the effective ingredient transdermal test, and apply the paste evenly on the artificial synthetic membrane Strat-M ® On the membrane, 500 ml of physiological saline was used as the receptor solution, and the receptor solution was continuously stirred to receive the permeation components. The total flavonoid concentration in the receptor solution was detected every 4 hours. The results are shown in Table 3. The total flavonoid release curve was drawn based on the total flavonoid concentration in the receptor solution. Figure 1 ; ; Depend on Figure 1 From the total flavonoids release curve, it can be seen that when sesame oil is not added, the total flavonoids in the receptor fluid reaches a peak at 8 hours, while after adding sesame oil, the total flavonoids in the receptor fluid reaches a peak at 24 hours. This shows that the addition of sesame oil has a sustained release effect on the release of the active ingredients in the plaster, extending the release time of the active ingredients to 24 hours, which is 3 times longer than that of the plaster without sesame oil.

[0085] 4. Clinical efficacy verification test of the present invention 4.1 Materials and Methods 4.1.1 General Information This study enrolled 60 patients with distal radius fractures admitted to an orthopedic hospital between September 2024 and May 2025. They were randomly divided into two groups, each consisting of 30 patients. The control group consisted of 16 males and 14 females, aged 28 to 72 years (mean, 45.78 ± 4.67). The time from injury to presentation was 60 to 120 minutes (mean, 76.19 ± 24.73 minutes). The fracture site was left in 11 patients and right in 19 patients. The observation group consisted of 14 males and 16 females, aged 30 to 73 years (mean, 49.39 ± 4.80 years). The time from injury to presentation was 45 to 120 minutes (mean, 67.09 ± 28.42 minutes). The fracture site was left in 13 patients and right in 17 patients. No statistically significant differences in general information were found between the two groups (P > 0.05).

[0086] 4.1.2 Diagnostic criteria According to the Clinical Diagnosis and Treatment of Orthopedic Diseases in Traditional Chinese Medicine, there is a history of trauma; pain and swelling around the wrist joint, deformity of the lower forearm, obvious tenderness, and dysfunction of wrist and arm movement after injury; X-ray examination can confirm the diagnosis.

[0087] 4.1.3 Inclusion criteria Inclusion criteria: unilateral fracture; patients or their families signed informed consent.

[0088] Exclusion criteria: mental injury; inability to cooperate or withdrawal; serious medical illness; traumatic open or comminuted fracture; severe cardiovascular disease.

[0089] 4.1.4 Treatment methods 4.1.4.1 Control Group The patient underwent Traditional Chinese Medicine manipulation and external fixation with splints, followed by external application of Huoxue Jiegu Powder (manufacturer: Shandong Jicao Pharmaceutical Co., Ltd., specification: 9g per bag) every two days for four weeks.

[0090] 4.1.4.2 Observation Group After receiving traditional Chinese medicine manipulation reduction and splint external fixation, the patient was treated with the plaster of the present invention, once every two days, for four weeks.

[0091] 4.1.5 Observation indicators Symptoms were assessed based on the Traditional Chinese Medicine (TCM) syndrome score, Garland-Werlery wrist score, and X-ray findings. The TCM syndrome score ranges from 0 to 6, based on the severity of unconsolidated bone, local pain, ecchymosis, soreness of the waist and knees, and swelling. Higher scores indicate more severe symptoms. The Garland-Werlery wrist score, which includes residual deformity, subjective evaluation, objective evaluation, and complications, totals 21 points. Higher scores indicate worse wrist function. Markedly effective: After four weeks of treatment, the TCM syndrome score decreased by >90% compared to pre-treatment, the Garland-Werlery wrist score decreased by ≥90%, and X-rays showed a negative distal radius. Effective: After four weeks of treatment, the TCM syndrome score decreased by >70% to 90%, the Garland-Werlery wrist score decreased by 60% to <90%, and X-rays showed a negative distal radius. Ineffective: After four weeks of treatment, none of the above criteria were met. The total effective rate = effective rate + markedly effective rate.

[0092] 4.1.6 Statistical methods Statistical software was used to analyze and process the research data. The counting data were expressed as rate (%). 2 P<0.05 was considered statistically significant.

[0093] 4.2 Results 4.2.1 Clinical efficacy The total effective rate of clinical treatment in the observation group was 100.0% (30 / 30), which was higher than 90.0% (27 / 30) in the control group, and the difference was statistically significant (P < 0.05). See Table 4: ; 4.2.2 Adverse reactions In the clinical efficacy observation, the plaster of the present invention did not cause allergic reactions, while 2 cases of skin allergies were found in the control group, indicating that the clinical safety of the plaster of the present invention is significantly better than that of the control group.

[0094] 4.2.3 Typical Cases (1) Yang Moumou, female, 35 years old, was accidentally injured while cleaning at home and went to an orthopedic hospital for treatment. X-rays showed: comminuted fracture of radius and fracture of ulna mastoid. After pure manual traction reduction by traditional Chinese medicine, external application of the medicine of the present invention and external fixation with splint for 4 weeks, X-rays showed: fracture callus growth, the splint could be gradually removed, and local functional exercises were performed, and all functions were restored.

[0095] (2) Mr. Wang, male, 48 years old, suffered from pain in his right wrist joint and limited mobility due to an accidental fall. He went to an orthopedic hospital for treatment. X-rays showed fractures of the distal radius and ulnar styloid process. He was treated with traditional Chinese medicine manual traction reduction, external application of the drug of the present invention, and external fixation with a splint for 4 weeks. X-rays showed that the fracture was well aligned and the splint could be gradually removed. Local functional exercises were performed, and all functions were restored.

[0096] Although the present invention has been described in detail above using general explanations, specific embodiments, and experiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A pharmaceutical composition for treating fractures, characterized in that: The medicinal composition consists of 10-20 parts of dipsaci, 10-20 parts of bidentata herb, 10-20 parts of thistle, 5-15 parts of crab shell, 5-10 parts of maltose, 3-6 parts of distiller's yeast and 5-10 parts of sesame oil.

2. The pharmaceutical composition according to claim 1, characterized in that The medicinal composition consists of 15 parts of dipsaci, 15 parts of bidens pilosa, 15 parts of thistle, 10 parts of crab shell, 8 parts of malt sugar, 5 parts of distiller's yeast and 8 parts of sesame oil.

3. A method for preparing the pharmaceutical composition according to any one of claims 1 to 2, characterized in that: The preparation method comprises the following steps: (1) crushing crab shells; (2) preparing medicinal slurry; (3) fermenting; (4) preparing thick paste; and (5) forming.

4. The method for preparing the pharmaceutical composition according to claim 3, wherein The crab shell crushing in step (1) is as follows: the crab shell is crushed into a fine powder exceeding 100 mesh.

5. The method for preparing the pharmaceutical composition according to claim 3, wherein The preparation of the medicinal slurry in step (2) is as follows: fresh medicinal materials Bidens pilosa, Dipsacus asper and Cirsium cyrtonema are washed with clean water, combined, ground into medicinal slurry with a homogenizer, and then crab shell powder, malt sugar and wine yeast are added, and the grinding is continued until uniform. The method for preparing the pharmaceutical composition according to claim 3 is characterized in that the fermentation in step (3) is: the uniformly ground medicinal slurry is fermented at a temperature of 30-35°C for 3-5 days.

6. The method for preparing the pharmaceutical composition according to claim 6, characterized in that: The fermentation in step (3) is as follows: the uniformly ground medicinal pulp is fermented at a temperature of 32° C. for 4 days.

7. The method for preparing the pharmaceutical composition according to claim 3, wherein The preparation of the thick paste in step (4) is as follows: placing the fermented medicinal pulp under the sun to dry, stirring it from time to time, and drying it until it becomes a thick paste.

8. The method for preparing the pharmaceutical composition according to claim 3, wherein The forming step (5) is as follows: adding sesame oil to the thick paste and stirring until the paste is uniform.

9. Use of the pharmaceutical composition according to any one of claims 1-2 in the preparation of a drug for treating fractures.

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