Quick-acting hemostatic granules and application thereof

Abstract

The application discloses a kind of quick hemostatic granules and its application, it is related to medical technology field, the quick hemostatic granules include by loess soup, cypress leaf soup and peach blossom soup three parties combination composition traditional Chinese medicine compound, specifically including red ocher, radix rehmanniae preparata, prepared black appendage, dried ginger, fried atractylodes, donkey-hide gelatin, radix scrophulariae, cypress leaf, sea scallop, glutinous rice, wormwood leaf charcoal and baked licorice root.The quick hemostatic granules are combined with western medicine treatment and used, can effectively treat upper gastrointestinal hemorrhage with hemorrhagic shock.Experiments confirm, the traditional Chinese medicine compound of the application and western medicine treatment between and loess soup, cypress leaf soup and peach blossom soup three parties between have significant synergies, can significantly shorten shock index recovery time and hemoglobin stable time, improve survival rate, and good safety.Quick hemostatic granules.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a fast-acting hemostatic granule and its application. Background Technology

[0002] Acute upper gastrointestinal bleeding (AUGIB) is a common acute and critical condition in clinical practice. Some patients with AUGIB may experience hemodynamic instability or even hemorrhagic shock (HS).

[0003] Currently, Western medicine treatment for AUGIB with HS includes fluid resuscitation, pharmacodynamic / endoscopic hemostasis, and vasoactive drugs. While these methods effectively control bleeding in most patients, challenges remain, such as difficulty in achieving hemostasis, persistent shock, and a high rebleeding rate. Despite advancements in diagnostic and endoscopic techniques, the mortality rate from upper gastrointestinal bleeding has not significantly decreased over the past few decades.

[0004] AUGIB falls under the category of "blood disorders" in Traditional Chinese Medicine (TCM), and when accompanied by hemorrhage (HS), it is classified as a severe case of "bleeding collapse syndrome." Its pathogenesis is primarily attributed to the spleen's inability to control blood, leading to the loss of qi along with blood, deficiency of yang qi, and loss of yin blood's ability to hold it in place. Treatment should focus on tonifying qi, consolidating the body's foundation, and stopping bleeding. While physicians throughout history have accumulated rich experience in treating this condition, existing prescriptions often target single syndrome types and are insufficient for critically ill patients. Therefore, developing a drug that can simultaneously warm yang and strengthen the spleen, astringe and stop bleeding, consolidate the body's foundation, and reverse collapse, while also being organically integrated with modern Western medical treatments, has significant clinical value and practical implications. Summary of the Invention

[0005] To address the above-mentioned problems, this invention provides a fast-acting hemostatic granule and its application.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a fast-acting hemostatic granule containing a traditional Chinese medicine compound. The compound is composed of three formulas: Huangtu Decoction, Baiye Decoction, and Taohua Decoction, and includes the following raw materials by weight: 60 parts red ochre, 25 parts prepared rehmannia root, 10-15 parts prepared black aconite root, 10 parts dried ginger, 15-30 parts stir-fried atractylodes macrocephala, 10 parts donkey-hide gelatin, 10 parts scutellaria baicalensis, 15 parts arborvitae leaf, 10 parts cuttlebone, 30 parts japonica rice, 10 parts charred artemisia argyi leaf, and 5-10 parts prepared licorice root.

[0007] Furthermore, by weight, it includes the following active pharmaceutical ingredients: 60 parts red ochre, 25 parts prepared rehmannia root, 12 parts prepared black aconite root, 10 parts dried ginger, 22 parts stir-fried atractylodes macrocephala, 10 parts donkey-hide gelatin, 10 parts scutellaria baicalensis, 15 parts arborvitae leaves, 10 parts cuttlebone, 30 parts japonica rice, 10 parts charred artemisia argyi leaves, and 8 parts prepared licorice root.

[0008] Furthermore, the preparation method of the traditional Chinese medicine compound includes the following steps: S1: Weigh each raw material according to the weight parts, divide the red ochre into two equal parts, one part is used for decoction, and the other part is pulverized and passed through a 100-200 mesh sieve to obtain red ochre fine powder for later use; pulverize the cuttlebone and arborvitae leaves and pass them through an 80-120 mesh sieve respectively. S2: Add 6 to 10 times the weight of the prepared black aconite root slices to water, decoct for 20 to 40 minutes, filter, and keep the decoction for later use. S3: Mix the portion of red ochre used for decoction with Rehmannia glutinosa, dried ginger, stir-fried Atractylodes macrocephala, Scutellaria baicalensis, cuttlebone powder, Platycladus orientalis leaf powder, japonica rice, Artemisia argyi charcoal, and roasted licorice root. Add 8 to 12 times the weight of the herbs in water, then add the first decoction, soak for 30 to 60 minutes, decoct for 40 to 60 minutes, and filter to obtain the first decoction. S4: Add 6 to 8 times the weight of the medicinal materials to the dregs after the first decoction, decoct for 30 to 50 minutes, and filter to obtain the second decoction. S5: Combine the first decoction and the second decoction, mix well, let stand for 12-24 hours, and filter the supernatant. S6: Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.10-1.20 at 60-80℃. Add an appropriate amount of boiling water to the donkey-hide gelatin and stir until it is completely dissolved. Then add it to the thick paste and mix well. Finally, add the red ochre powder prepared in step S1 to the thick paste and stir well. S7: Vacuum dry and pulverize the thick paste obtained in step S6, pass it through an 80-120 mesh sieve to obtain dry paste powder, add pharmaceutically acceptable excipients and mix evenly to make granules.

[0009] Furthermore, the fast-acting hemostatic granules are used in combination with Western medicine treatment, which includes one or more of fluid resuscitation, blood transfusion, drug treatment, and endoscopic treatment.

[0010] This invention also provides the application of the above-mentioned fast-acting hemostatic granules in the preparation of a drug for treating upper gastrointestinal bleeding accompanied by hemorrhagic shock.

[0011] Furthermore, the fast-acting hemostatic granules are administered orally or via a gastric tube.

[0012] Huangtu Decoction originates from Zhang Zhongjing's *Synopsis of Prescriptions of the Golden Chamber* (Jinkui Yaolue) of the Han Dynasty. It is a blood-regulating formula with the effects of warming yang, strengthening the spleen, nourishing blood, and stopping bleeding. Baiye Decoction, also from *Synopsis of Prescriptions of the Golden Chamber*, is a blood-regulating formula with the effects of warming the middle jiao and stopping bleeding. Taohua Decoction, from *Treatise on Cold Damage*, is an astringent formula with the effects of warming the middle jiao, astringing the intestines, and stopping dysentery.

[0013] The key pathogenesis of upper gastrointestinal bleeding with hemorrhagic shock in Traditional Chinese Medicine lies in the spleen's inability to control blood, the loss of qi following blood loss, and the deficiency of yang qi and the inability of yin blood to consolidate it. Each single classical formula has its own emphasis—Huangtu Decoction excels at warming yang and strengthening the spleen to treat the root cause; Baiye Decoction excels at warming the middle jiao and stopping bleeding to treat the symptoms; and Taohua Decoction excels at astringing and consolidating to relieve emergency symptoms—each has its shortcomings in its therapeutic focus. This invention combines the three formulas, and the principle of the formulation embodies the synergy on the following three levels: Firstly, the warming and hemostatic effects work synergistically. Huangtu Decoction uses prepared black aconite root, dried ginger, and stir-fried atractylodes macrocephala to warm and tonify spleen yang, restoring its function of controlling blood; Baiye Decoction uses arborvitae leaves to cool the blood and stop bleeding, while dried ginger and charred mugwort warm the meridians and stop bleeding; Taohua Decoction uses red ochre to enhance astringent and consolidating effects, while dried ginger warms the middle jiao and assists yang. These three formulas, combining warming and hemostatic herbs, address both the root cause (treating the middle jiao yang qi) and the symptoms (treating the symptoms by directly astringing and stopping bleeding), thus addressing both the root and the symptoms.

[0014] Secondly, the formula combines consolidation and blood nourishment. Hemorrhagic shock falls under the category of "hemorrhagic collapse syndrome," where qi is lost along with blood, leading to deficiency of yin and blood. Huangtu Decoction contains Rehmannia glutinosa and donkey-hide gelatin to nourish yin and blood to replenish blood vessels; Peach Blossom Decoction contains red ochre to astringe and consolidate the body, stopping further loss; Huangtu Decoction also contains prepared aconite root and dried ginger to warm yang and consolidate qi. When qi is consolidated, blood loss is prevented. These three formulas work together to consolidate qi, nourish blood, and warm yang, achieving the combined effects of tonifying qi, consolidating the body, nourishing blood, and stopping bleeding.

[0015] Thirdly, it balances warming and cooling properties. The three formulas contain both warming and cooling herbs such as prepared aconite root, dried ginger, and charred mugwort, as well as cooling herbs such as arborvitae leaves and scutellaria baicalensis. The combination of warming and cooling properties prevents excessive warmth and dryness from promoting heat and blood circulation, and also prevents excessive coldness from damaging yang and causing stagnation. This ensures that the formula stops bleeding without causing blood stasis and warms yang without promoting heat.

[0016] The combined use of the above three ingredients is not simply a matter of adding up the medicinal ingredients, but rather forming an organic whole that works synergistically and complement each other in terms of warming yang, stopping bleeding, consolidating the body, and nourishing blood, so as to exert a comprehensive effect of warming yang and strengthening the spleen, astringing and stopping bleeding, and consolidating the body and rescuing from collapse.

[0017] This invention combines a traditional Chinese medicine formula, Huangtu Decoction, Baiye Decoction, and Taohua Decoction, with Western medical treatment. The principle behind its synergistic effect lies in: (1) Spatial and temporal complementarity. Western medicine treatment rapidly controls active bleeding and maintains vital signs during the acute phase of bleeding through endoscopy and medication; while traditional Chinese medicine compound prescriptions continue to play a role after endoscopic hemostasis, restoring the spleen's function of controlling blood by warming yang and strengthening the spleen, reducing the risk of rebleeding by astringing and stopping bleeding, and improving microcirculation by consolidating the body and rescuing from collapse. The two complement each other in terms of treatment time and spatial scope.

[0018] (2) Treating both the symptoms and the root cause. Western medicine focuses on "treating the symptoms"—controlling bleeding and stabilizing circulation; traditional Chinese medicine focuses on "treating the root cause"—warming and tonifying spleen yang and restoring blood control. The combination of traditional Chinese and Western medicine can not only solve the immediate problem but also achieve long-term stability, breaking the vicious cycle of "rebleeding and shock".

[0019] (3) Synergistic effect of multiple targets. Western medicine exerts its effects through fluid resuscitation and expansion, drug / endoscopic hemostasis, and vasoactive drugs to raise blood pressure; Chinese medicine compound prescriptions comprehensively regulate multiple targets such as regulating coagulation function, protecting gastric mucosa, improving microcirculation, and anti-inflammation. The two act on different targets, producing synergistic effects, which are reflected in the therapeutic effect of "1+1>2".

[0020] In summary, this invention organically integrates a traditional Chinese medicine compound consisting of Huangtu Decoction, Baiye Decoction, and Taohua Decoction with Western medicine treatment, achieving the complementary advantages of traditional Chinese medicine's "holistic view and syndrome differentiation and treatment" and Western medicine's "precise targeting and rapid intervention." It provides a combined traditional Chinese and Western medicine treatment plan that is superior to single treatment options for the critical condition of upper gastrointestinal bleeding with hemorrhagic shock.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention combines three traditional Chinese medicine formulas—Huangtu Decoction, Baiye Decoction, and Taohua Decoction—into a compound herbal formula. This formula, when used in conjunction with Western medicine treatment, is applied to upper gastrointestinal bleeding accompanied by hemorrhagic shock. The three formulas exhibit a definite synergistic effect and also show significant synergistic effects with Western medicine treatment, significantly shortening the recovery time of shock index and the time to hemoglobin stabilization, and improving survival rate. The preparation method of this traditional Chinese medicine compound is scientifically sound. It involves first decocting prepared black aconite root to reduce toxicity and enhance efficacy; partially decocting red ochre and partially dispersing it to enhance astringent and hemostatic effects; pulverizing cuttlebone and arborvitae leaves before adding them to improve the dissolution rate of active ingredients; allowing the decoction to settle and collecting the supernatant to remove impurities; and concentrating and granulating to improve formulation stability and patient compliance. The process design is reasonable, quality is controllable, and it is suitable for industrial production. This invention has good safety; no significant adverse reactions were observed during treatment, providing a safe and effective drug for the clinical treatment of upper gastrointestinal bleeding accompanied by hemorrhagic shock. Detailed Implementation

[0022] To make the objectives and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention.

[0023] Unless otherwise specified, the instruments, reagents, and materials used in the following embodiments are all conventional instruments, reagents, and materials already available in the prior art and can be obtained through legitimate commercial channels. Unless otherwise specified, the experimental methods and detection methods used in the following embodiments are all conventional experimental methods and detection methods already available in the prior art.

[0024] Example 1 A fast-acting hemostatic granule comprising a traditional Chinese medicine compound, which is composed of three formulas: Huangtu Decoction, Baiye Decoction, and Taohua Decoction, and includes the following raw materials by weight: 60g of red ochre, 25g of prepared rehmannia root, 10g of prepared black aconite root, 10g of dried ginger, 15g of stir-fried atractylodes macrocephala, 10g of donkey-hide gelatin, 10g of scutellaria baicalensis, 15g of arborvitae leaf, 10g of cuttlebone, 30g of japonica rice, 10g of charred mugwort leaf, and 5g of prepared licorice root.

[0025] The preparation method of this traditional Chinese medicine compound includes the following steps: S1: Weigh each raw material according to the weight parts, divide the red ochre into two equal parts, one part is used for decoction, and the other part is pulverized and passed through a 100-mesh sieve to obtain red ochre fine powder for later use; pulverize the cuttlebone and arborvitae leaves and pass them through an 80-mesh sieve respectively. S2: Add 6 times the weight of the prepared black aconite root slices to 6 times the water of the medicinal material, decoct for 20 minutes, filter, and keep the decoction for later use. S3: Mix the portion of red ochre used for decoction with Rehmannia glutinosa, dried ginger, stir-fried Atractylodes macrocephala, Scutellaria baicalensis, cuttlebone powder, Platycladus orientalis leaf powder, japonica rice, Artemisia argyi charcoal, and roasted licorice root. Add water equal to 8 times the weight of the herbs, then add the first decoction, soak for 30 minutes, decoct for 40 minutes, and filter to obtain the first decoction. S4: Add 6 times the weight of the medicinal materials to the dregs after the first decoction, decoct for 30 minutes, and filter to obtain the second decoction. S5: Combine the first and second decoctions, mix well, let stand for 12 hours, and filter the supernatant. S6: Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.10 at 60℃. Add an appropriate amount of boiling water to the donkey-hide gelatin and stir until it is completely dissolved. Then add it to the thick paste and mix well. Finally, add the red ochre powder prepared in step S1 to the thick paste and stir well. S7: Vacuum dry and pulverize the thick paste obtained in step S6, pass it through an 80-120 mesh sieve to obtain dry paste powder, add pharmaceutically acceptable excipients and mix evenly to make 1000g of granules. Adults (based on a body weight of 60kg) take the equivalent of 21.0g of raw herb granules (i.e., 100g of granules) orally three times a day for 7 consecutive days.

[0026] This fast-acting hemostatic granule is used in combination with Western medicine treatment, which includes: ① Fluid resuscitation: restrictive fluid resuscitation or aggressive resuscitation depending on the bleeding control; ② Blood transfusion: packed red blood cells are transfused when hemoglobin is <70g / L or when there is persistent active bleeding with hemodynamic instability; ③ Drug therapy: proton pump inhibitors are administered, and somatostatin or terlipressin is used if necessary. Antibiotics are used prophylactically for varicose bleeding. Vasoactive drugs are used if severe and persistent hypotension persists after fluid resuscitation; ④ Endoscopic treatment: emergency endoscopy is performed if HS persists despite aggressive resuscitation. Endoscopy can be performed within 24 hours if there is no HS. Endoscopy is performed within 12 hours if varicose bleeding is suspected. Treatment includes local injection of drugs, thermal coagulation, mechanical hemostasis, or banding, depending on the bleeding situation; ⑤ If active bleeding persists, repeated endoscopy and emergency interventional examinations and treatments can be performed. Surgical exploration may be considered if hemostasis is still not achieved.

[0027] Example 2 The difference from Example 1 is that, by weight, the traditional Chinese medicine compound includes the following raw materials: 60g of red ochre, 25g of prepared rehmannia root, 12g of prepared black aconite root, 10g of dried ginger, 22g of stir-fried atractylodes macrocephala, 10g of donkey-hide gelatin, 10g of scutellaria baicalensis, 15g of arborvitae leaf, 10g of cuttlebone, 30g of japonica rice, 10g of charred mugwort leaf, and 8g of prepared licorice root.

[0028] The preparation method of this traditional Chinese medicine compound includes the following steps: S1: Weigh each raw material according to weight, divide the red ochre into two equal parts, one part is used for decoction, and the other part is pulverized and passed through a 150-mesh sieve to obtain red ochre fine powder for later use; pulverize cuttlebone and arborvitae leaves and pass them through an 80-120 mesh sieve respectively. S2: Add 8 times the weight of the prepared black aconite root slices to water, decoct for 30 minutes, filter, and keep the decoction for later use. S3: Mix the portion of red ochre used for decoction with Rehmannia glutinosa, dried ginger, stir-fried Atractylodes macrocephala, Scutellaria baicalensis, cuttlebone powder, Platycladus orientalis leaf powder, japonica rice, Artemisia argyi charcoal, and roasted licorice root. Add 8 to 12 times the weight of the herbs in water, then add the first decoction, soak for 45 minutes, decoct for 50 minutes, and filter to obtain the first decoction. S4: Add 7 times the weight of the medicinal materials to the dregs after the first decoction, decoct for 40 minutes, and filter to obtain the second decoction. S5: Combine the first and second decoctions, mix well, let stand for 18 hours, and filter the supernatant. S6: Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.15 at 70℃. Add an appropriate amount of boiling water to the donkey-hide gelatin and stir until it is completely dissolved. Then add it to the thick paste and mix well. Finally, add the red ochre powder prepared in step S1 to the thick paste and stir well. S7: Vacuum dry and pulverize the thick paste obtained in step S6, pass it through a 100-mesh sieve to obtain dry paste powder, add pharmaceutically acceptable excipients and mix evenly to make 1000g of granules. Adults (based on a body weight of 60kg) take the equivalent of 22.2g of raw herb granules (i.e., 100g of granules) orally three times a day for 7 consecutive days.

[0029] The Western medicine treatment is the same as in Example 1.

[0030] Example 3 The difference from Example 1 is that, by weight, the traditional Chinese medicine compound includes the following raw materials: 60g of red ochre, 25g of prepared rehmannia root, 15g of prepared black aconite root, 10g of dried ginger, 30g of stir-fried atractylodes macrocephala, 10g of donkey-hide gelatin, 10g of scutellaria baicalensis, 15g of arborvitae leaf, 10g of cuttlebone, 30g of japonica rice, 10g of charred mugwort leaf, and 10g of prepared licorice root.

[0031] The preparation method of this traditional Chinese medicine compound includes the following steps: S1: Weigh each raw material according to the weight parts, divide the red ochre into two equal parts, one part is used for decoction, and the other part is pulverized and passed through a 200-mesh sieve to obtain red ochre fine powder for later use; pulverize the cuttlebone and arborvitae leaves and pass them through a 120-mesh sieve respectively. S2: Add 10 times the weight of the prepared black aconite root slices to water, decoct for 40 minutes, filter, and keep the decoction for later use. S3: Mix the portion of red ochre used for decoction with Rehmannia glutinosa, dried ginger, stir-fried Atractylodes macrocephala, Scutellaria baicalensis, cuttlebone powder, Platycladus orientalis leaf powder, japonica rice, Artemisia argyi charcoal, and roasted licorice root. Add 12 times the weight of the herbs in water, then add the first decoction, soak for 60 minutes, decoct for 60 minutes, and filter to obtain the first decoction. S4: Add 8 times the weight of the medicinal materials to the dregs after the first decoction, decoct for 50 minutes, and filter to obtain the second decoction. S5: Combine the first decoction and the second decoction, mix well, let stand for 24 hours, and then filter the supernatant. S6: Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.20 at 80℃. Add an appropriate amount of boiling water to the donkey-hide gelatin and stir until it is completely dissolved. Then add it to the thick paste and mix well. Finally, add the red ochre powder prepared in step S1 to the thick paste and stir well. S7: Vacuum dry and pulverize the thick paste obtained in step S6, pass it through a 120-mesh sieve to obtain dry paste powder, add pharmaceutically acceptable excipients and mix evenly to make 1000g of granules. Adults (based on a body weight of 60kg) take the equivalent of 23.5g of raw herb orally each time (i.e., 100g of granules), three times a day, for 7 consecutive days.

[0032] The Western medicine treatment is the same as in Example 1.

[0033] Comparative Example 1: Western medicine treatment only The difference from Example 2 is that only Western medicine treatment was used, without any traditional Chinese medicine treatment. The Western medicine treatment plan is the same as in Example 1.

[0034] Comparative Example 2: Treatment with Traditional Chinese Medicine Only The difference from Example 2 is that only traditional Chinese medicine was used for treatment, without any Western medicine treatment. The dosage and administration of the traditional Chinese medicine compound were the same as in Example 2.

[0035] Comparative Example 3: The traditional Chinese medicine compound Huangtu Decoction alone The difference from Example 2 is that the herbal compound uses only Huangtu Decoction, without Baiye Decoction and Taohua Decoction. The formula is as follows (by weight): 25 parts Rehmannia glutinosa, 12 parts processed Aconitum carmichaelii, 22 parts stir-fried Atractylodes macrocephala, 10 parts donkey-hide gelatin, 10 parts Scutellaria baicalensis, and 8 parts processed licorice root. The rest is the same as in Example 2.

[0036] Comparative Example 4: The traditional Chinese medicine compound formula, Baiye Decoction alone. The difference from Example 2 is that the herbal compound uses only Baiye Decoction, without Huangtu Decoction and Taohua Decoction. The formula is as follows (by weight): 15 parts of arborvitae leaves, 10 parts of dried ginger, and 10 parts of charred mugwort leaves. The rest is the same as in Example 2.

[0037] Comparative Example 5: The traditional Chinese medicine compound formula only included Peach Blossom Decoction. The difference from Example 2 is that the herbal compound only uses Peach Blossom Decoction, without Yellow Earth Decoction and Cypress Leaf Decoction. The formula is as follows (by weight): 60 parts red ochre, 10 parts dried ginger, and 30 parts japonica rice. The rest is the same as in Example 2.

[0038] Comparative Example 6: Blank Control Group No treatment was given after modeling; only an equal volume of normal saline was administered by gavage three times a day for seven consecutive days.

[0039] Experiment Example 1: Pharmacodynamic Experiment 1. Experimental Materials Experimental animals: SPF-grade male SD rats, weighing 200-250g, a total of 270 rats, were randomly divided into 9 groups of 30 rats each.

[0040] 2. Establishment of animal models A rat model of upper gastrointestinal bleeding with hemorrhagic shock was established using endoscopic gastric mucosal injury combined with exsanguination. Specifically, after fasting for 24 hours, rats were anesthetized intraperitoneally with 10% chloral hydrate. Active bleeding was induced by injuring the gastric mucosa with biopsy forceps under endoscopy. Simultaneously, exsanguination was performed via the carotid artery to lower the mean arterial pressure to 40-50 mmHg, which was maintained for 30 minutes to establish the upper gastrointestinal bleeding with hemorrhagic shock model.

[0041] 3. Grouping and drug administration The 270 rats that successfully developed the model were randomly divided into 9 groups of 30 rats each: Example 1 group: Administered the compound Chinese medicine granules from Example 1 via gavage, plus Western medicine treatment; Example 2 group: Administered the traditional Chinese medicine compound granules from Example 2 via gavage, plus Western medicine treatment; Example 3 group: Administered the traditional Chinese medicine compound granules from Example 3 via gavage, plus Western medicine treatment; Comparative Group 1 (Western Medicine Only): Only Western medicine treatment was given; Comparative Example 2 (Traditional Chinese Medicine Group Only): The compound traditional Chinese medicine granules from Example 2 were administered by gavage only; Comparative Group 3 (Huangtu Decoction Group only): Huangtu Decoction was administered via gavage alone, plus Western medicine treatment; Comparative Group 4 (Baiye Decoction Only): Only Baiye Decoction was administered via gavage, plus Western medicine treatment; Comparative group 5 (Peach Blossom Decoction Group only): Peach Blossom Decoction was administered via gavage alone, plus Western medicine treatment.

[0042] Comparative Group 6 (blank control group): The same volume of normal saline was administered by gavage, and no treatment was given.

[0043] The dosage of traditional Chinese medicine administered via gavage was converted to the human equivalent dose based on body surface area (rat equivalent dose = human dose × 6.3). The granules were prepared into a suspension of appropriate concentration with distilled water and administered three times daily for seven consecutive days. Western medicine treatment was given according to the standard clinical protocol (as shown in Example 1).

[0044] 4. Observation Indicators (1) Shock index recovery time: The time required for each group of rats to recover their shock index (heart rate / systolic blood pressure) to the normal range (<0.8) from the start of drug administration was recorded.

[0045] (2) Hemoglobin stabilization time: Record the time required for each group of rats from the start of drug administration until the hemoglobin concentration stabilizes and no longer decreases and begins to rise.

[0046] (3) 72h survival rate: The survival status of rats in each group 72h after modeling was recorded.

[0047] 5. Experimental Results Table 1 Comparison of observation indicators among experimental animals in each group (x̄±s)

[0048] Table 1 shows that Examples 1-3 were significantly superior to all comparative examples in all observed indicators (shock index recovery time, hemoglobin stabilization time, and 72-hour survival rate). This indicates that the traditional Chinese medicine compound prepared by combining Huangtu Decoction, Baiye Decoction, and Taohua Decoction in this invention has synergistic and complementary advantages in warming yang and strengthening the spleen, astringing and stopping bleeding, and consolidating the body to rescue from collapse. It can more effectively correct hemorrhagic shock, stabilize hemoglobin levels, and improve survival rate.

[0049] Furthermore, the synergistic effect of traditional Chinese medicine and Western medicine was verified using a blank control group (Comparative Example 6) as a benchmark. The improvement value of shock index recovery time in Example 2 (Comparative Example 6 - Example 2, 72.5 - 6.5 = 66 h) was significantly higher than the sum of the improvement values ​​of Comparative Example 1 (Western medicine only) (72.5 - 53.2 = 19.3 h) and Comparative Example 2 (Traditional Chinese medicine only) (72.5 - 55.6 = 16.9 h). The data of other indicators (hemoglobin stabilization time, 72-hour survival rate) in Table 1 also showed the same trend. This indicates that there is a synergistic effect of "1+1>2" between the traditional Chinese medicine compound of the present invention and Western medicine treatment.

[0050] Furthermore, the improvement in shock index recovery time in Example 2 (Comparative Example 6 - Example 2, 72.5 - 6.5 = 66 h) was significantly higher than the sum of the improvements in Comparative Example 3 (Huangtu Decoction only) (72.5 - 48.1 = 24.4 h), Comparative Example 4 (Baiye Decoction only) (72.5 - 51.4 = 21.1 h), and Comparative Example 5 (Taohua Decoction only) (72.5 - 52.7 = 19.8 h). The data for other indicators (hemoglobin stabilization time, 72-hour survival rate) in Table 1 also showed the same trend. This indicates that there is a synergistic effect of "1+1+1>3" among Huangtu Decoction, Baiye Decoction, and Taohua Decoction. The combined use of the three formulas is not a simple additive of medicinal ingredients, but rather forms a synergistic and complementary organic whole in terms of warming yang, stopping bleeding, and consolidating the body.

[0051] It should be noted that no obvious adverse reactions were observed in any group during the experiment, indicating that the fast-acting hemostatic granules of the present invention have good safety.

[0052] In summary, this invention combines Huangtu Decoction, Baiye Decoction, and Taohua Decoction into a traditional Chinese medicine compound, which is then applied in conjunction with Western medicine treatment for upper gastrointestinal bleeding accompanied by hemorrhagic shock. Not only do the three formulas have a definite synergistic effect, but they also have a significant synergistic effect with Western medicine treatment. This can significantly shorten the recovery time of shock index and the time for hemoglobin stabilization, improve the survival rate, and has good safety. It provides a traditional Chinese and Western medicine integrated treatment plan that is superior to existing treatment options for clinical practice.

[0053] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A fast-acting hemostatic granule, characterized in that: The formula contains a traditional Chinese medicine compound, which is composed of three formulas: Huangtu Decoction, Baiye Decoction, and Taohua Decoction. By weight, it includes the following raw materials: 60 parts red ochre, 25 parts prepared rehmannia root, 10-15 parts prepared black aconite root, 10 parts dried ginger, 15-30 parts stir-fried atractylodes macrocephala, 10 parts donkey-hide gelatin, 10 parts scutellaria baicalensis, 15 parts arborvitae leaf, 10 parts cuttlebone, 30 parts japonica rice, 10 parts charred artemisia argyi leaf, and 5-10 parts prepared licorice root.

2. The fast-acting hemostatic granules according to claim 1, characterized in that: The active pharmaceutical ingredient (API) comprises, by weight, the following: 60 parts red ochre, 25 parts prepared rehmannia root, 12 parts prepared black aconite root, 10 parts dried ginger, 22 parts stir-fried atractylodes macrocephala, 10 parts donkey-hide gelatin, 10 parts scutellaria baicalensis, 15 parts arborvitae leaves, 10 parts cuttlebone, 30 parts japonica rice, 10 parts charred artemisia argyi leaves, and 8 parts prepared licorice root.

3. The fast-acting hemostatic granules according to claim 1 or 2, characterized in that: The preparation method of the traditional Chinese medicine compound includes the following steps: S1: Weigh each raw material according to the weight parts, divide the red ochre into two equal parts, one part is used for decoction, and the other part is pulverized and passed through a 100-200 mesh sieve to obtain red ochre fine powder for later use; pulverize the cuttlebone and arborvitae leaves and pass them through an 80-120 mesh sieve respectively. S2: Add 6 to 10 times the weight of the prepared black aconite root slices to water, decoct for 20 to 40 minutes, filter, and keep the decoction for later use. S3: Mix the portion of red ochre used for decoction with Rehmannia glutinosa, dried ginger, stir-fried Atractylodes macrocephala, Scutellaria baicalensis, cuttlebone powder, Platycladus orientalis leaf powder, japonica rice, Artemisia argyi charcoal, and roasted licorice root. Add 8 to 12 times the weight of the herbs in water, then add the first decoction, soak for 30 to 60 minutes, decoct for 40 to 60 minutes, and filter to obtain the first decoction. S4: Add 6 to 8 times the weight of the medicinal materials to the dregs after the first decoction, decoct for 30 to 50 minutes, and filter to obtain the second decoction. S5: Combine the first decoction and the second decoction, mix well, let stand for 12-24 hours, and filter the supernatant. S6: Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.10-1.20 at 60-80℃. Add an appropriate amount of boiling water to the donkey-hide gelatin and stir until it is completely dissolved. Then add it to the thick paste and mix well. Finally, add the red ochre powder prepared in step S1 to the thick paste and stir well. S7: Vacuum dry and pulverize the thick paste obtained in step S6, pass it through an 80-120 mesh sieve to obtain dry paste powder, add pharmaceutically acceptable excipients and mix evenly to make granules.

4. The fast-acting hemostatic granules according to claim 1, characterized in that: The fast-acting hemostatic granules are used in combination with Western medicine treatment, which includes one or more of the following: fluid resuscitation, blood transfusion, drug therapy, and endoscopic treatment.

5. The use of a fast-acting hemostatic granule as described in any one of claims 1-4 in the preparation of a medicament for treating upper gastrointestinal bleeding accompanied by hemorrhagic shock.

6. The application according to claim 5, characterized in that: The fast-acting hemostatic granules are administered orally or via a gastric tube.

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