A portable hemostatic powder that can quickly stop bleeding, its preparation method and application

Abstract

This invention belongs to the field of hemostatic wound dressing technology, specifically relating to a portable hemostatic powder that can quickly stop bleeding, its preparation method, and its application. The hemostatic powder is prepared by physically mixing carboxymethyl chitosan, hydroxypropyl methylcellulose, and tannic acid. The amino groups in carboxymethyl chitosan electrostatically attract blood cells, promoting blood cell aggregation and thus accelerating coagulation. Hydroxypropyl methylcellulose has excellent hygroscopic properties, providing the powder with rapid blood absorption. Tannic acid, through its catechol groups, captures free radicals, possesses anti-inflammatory effects, and exhibits excellent wet tissue adhesion, synergistically stopping bleeding with carboxymethyl chitosan. The prepared hemostatic powder has the advantages of low cost, convenient preparation, portability, and rapid hemostasis.

Description

Technical Field

[0001] This invention belongs to the field of hemostatic wound dressing technology, specifically relating to a portable hemostatic powder that can quickly stop bleeding, its preparation method, and its application. Background Technology

[0002] Blood is a vital component for maintaining human life, playing a central role in key physiological functions such as oxygen transport, osmotic pressure balance, and immune defense. When traumatic bleeding occurs, rapid blood loss, if not controlled promptly, can easily lead to life-threatening risks such as shock and organ failure. Therefore, developing efficient and rapid hemostasis techniques is a significant and urgent need in clinical treatment.

[0003] Traditional hemostatic materials, such as gauze, cotton pads, or hemostatic sponges, while inexpensive and readily available, often adhere tightly to newly formed granulation tissue or blood clots after absorbing blood. Forcibly removing these materials during dressing changes or wound cleaning can easily cause secondary damage to the wound, leading to recurrent bleeding and increased patient suffering. To overcome this adhesion problem, novel hemostatic dressings based on biopolymers such as gelatin and alginate have been developed. However, these advanced dressings require specific storage conditions (such as low temperature and moisture protection), making storage and transportation inconvenient; furthermore, their relatively high manufacturing cost limits their accessibility and temporary application in emergency situations, battlefield medical care, or resource-scarce scenarios. Summary of the Invention

[0004] The purpose of this invention is to provide a portable hemostatic powder that can quickly stop bleeding, as well as its preparation method and application, thereby overcoming the shortcomings of the prior art, achieving efficient hemostasis, being easy to use, and having controllable costs.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: On the one hand, the present invention provides a hemostatic powder composed of carboxymethyl chitosan, hydroxypropyl methylcellulose and tannic acid, wherein the mass ratio of carboxymethyl chitosan and hydroxypropyl methylcellulose is (1-10):(1-10), and the amount of tannic acid added is 0.5%-3.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

[0006] Secondly, the present invention provides a method for preparing the hemostatic powder, wherein carboxymethyl chitosan and hydroxypropyl methylcellulose are mixed by physical mixing, and then tannic acid is added and mixed evenly to obtain the powder.

[0007] Thirdly, the present invention provides the use of the hemostatic powder in the preparation of products for promoting wound hemostasis.

[0008] The beneficial effects of this invention are: (1) The hemostatic powder of the present invention is composed of carboxymethyl chitosan, hydroxypropyl methylcellulose and tannic acid. Carboxymethyl chitosan is obtained by modifying chitosan and has excellent water solubility, antibacterial properties and excellent biocompatibility. Its amino groups can attract negatively charged blood cells and platelets through electrostatic attraction, promote the aggregation of blood cells and platelets, and thus promote coagulation. In addition, the positively charged amino groups can also destroy the cell membrane of bacteria and play a bactericidal role. Hydroxypropyl methylcellulose contains abundant hydroxyl groups and has hygroscopic and moisturizing properties. Tannic acid, as a polyphenol compound, has catechol groups that can capture free radicals, have anti-inflammatory and antibacterial properties, and have excellent wet tissue adhesion.

[0009] (2) This invention uses a physical mixing method to prepare hemostatic powder by mixing carboxymethyl chitosan, hydroxypropyl methylcellulose, and tannic acid. This preparation method is extremely simple and efficient, without involving complex chemical reactions, harsh solvent treatments, or high temperature and high pressure conditions. It retains the inherent biological activity of each component to the maximum extent, avoids performance loss that may be caused by chemical modification or harsh processing, and ensures batch-to-batch quality stability. It is easy to scale up production and significantly reduces equipment investment and production costs. Attached Figure Description

[0010] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0011] Figure 1 The infrared spectrum of CHT powder in Example 1 of this invention; Figure 2 The bar chart shows the tensile adhesion force of Comparative Example 1, Examples 1-7, and Yunnan Baiyao (YNBY) of the present invention. Figure 3 This invention includes blank, comparative example 1, examples 1-7, and in vitro coagulation graphs of Yunnan Baiyao and BleedStop; Figure 4 The in vitro coagulation time graphs of blank, comparative example 1, examples 1-7, Yunnan Baiyao and BleedStop are shown. Figure 5 Enlarged images of in vitro coagulation times for blank, comparative example 1, examples 1-7, Yunnan Baiyao, and BleedStop in this invention; Figure 6 The blood coagulation index histograms for blank, comparative example 1, examples 1-7, Yunnan Baiyao, and BleedStop in this invention; Figure 7Enlarged bar charts of the blood coagulation index of blank, comparative example 1, examples 1-7, Yunnan Baiyao and BleedStop in this invention. Detailed Implementation

[0012] Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be construed as limiting the scope of the invention. Specific conditions not specified in the embodiments are performed under conventional conditions or conditions recommended by the manufacturer. Components used, unless otherwise specified, are commercially available conventional products. For example, the purity of carboxymethyl chitosan (CMCS) may be 99%; the viscosity of hydroxypropyl methylcellulose (HMPC) may be 200,000; and the purity of tannic acid (TA) may be 98%.

[0013] The present invention first provides a hemostatic powder composed of carboxymethyl chitosan, hydroxypropyl methylcellulose and tannic acid, wherein the mass ratio of carboxymethyl chitosan and hydroxypropyl methylcellulose is (1-10):(1-10), and the amount of tannic acid added is 0.5%-3.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

[0014] This hemostatic powder is suitable for rapid hemostasis of moist wounds. Carboxymethyl chitosan, with its positive charge, strongly adsorbs blood cells and platelets through electrostatic interactions, efficiently initiating coagulation and also possessing antibacterial properties. Hydroxypropyl methylcellulose rapidly absorbs exudate, forming a moist gel barrier that provides an ideal microenvironment for coagulation and temporarily seals the wound. Tannic acid, with its catechol groups, achieves strong adhesion to moist tissues, scavenges free radicals for anti-inflammation, and synergistically enhances antibacterial activity. Through the combination of these three components, rapid adhesion and fixation, a rapid coagulation environment, and antibacterial and anti-inflammatory functions are achieved.

[0015] In some other embodiments, carboxymethyl chitosan and hydroxypropyl methylcellulose are used in a mass ratio of (6-8):(2-4), and the amount of tannic acid added is 1%-3% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

[0016] The formulation of this raw material ensures that the hemostatic powder has both highly efficient coagulant activity and suitable swelling and moisturizing properties: a high proportion of carboxymethyl chitosan provides sufficient cationic coagulant centers, while a moderate proportion of hydroxypropyl methylcellulose can absorb liquid to form a gel without excessive swelling that would affect stability; at the same time, tannic acid ensures strong adhesion to moist tissue and exerts anti-inflammatory and antibacterial effects, while avoiding the potential cytotoxicity or excessive cross-linking that could affect the material's performance.

[0017] In some other embodiments, carboxymethyl chitosan and hydroxypropyl methylcellulose are used in a mass ratio of 7:3, and the amount of tannic acid added is 2.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

[0018] In some other embodiments, the purity of carboxymethyl chitosan is ≥99% and the degree of carboxyl substitution is ≥80%.

[0019] In some other embodiments, the viscosity of hydroxypropyl methylcellulose is 150,000-250,000, manufactured by Jinzhou Fuqiang Fine Chemical Co., Ltd.

[0020] In some other embodiments, the purity of tannic acid is ≥98%.

[0021] In some other embodiments, the in vitro clotting time of the hemostatic powder is 0.035-0.045 min, the blood coagulation index is 0.08%-0.15%, and the tensile adhesion is 105-140 kPa.

[0022] This hemostatic powder has excellent comprehensive hemostatic and adhesive properties. Its in vitro clotting time is extremely short, which can instantly activate the coagulation cascade reaction and achieve rapid hemostasis. The blood clot formed is dense and has strong contractility, resulting in very little bleeding. At the same time, the high tensile adhesion strength ensures that the material has strong anti-peeling ability on wet and dynamic tissue surfaces, and can firmly adhere to the wound under blood flushing, continuously exerting a hemostatic effect.

[0023] Then, the present invention provides a method for preparing hemostatic powder, the steps of which are as follows: carboxymethyl chitosan and hydroxypropyl methylcellulose are mixed by physical mixing, and then tannic acid is added and mixed evenly to obtain the powder.

[0024] This preparation method employs a stepwise mixing process. First, carboxymethyl chitosan and hydroxypropyl methylcellulose are dry-mixed to form a uniformly dispersed composite matrix. The positively charged carboxymethyl chitosan and the neutral, hydrophilic hydroxypropyl methylcellulose are physically interwoven, providing a stable structural basis and synergistic hygroscopic-coagulating functions for the material. Subsequently, tannic acid is added. Its molecule is rich in catechol and phenolic hydroxyl functional groups, which can undergo dense hydrogen bonding, ionic interactions, and potential Michael addition reactions with the active groups in the pre-mixed composite matrix (such as the amino / carboxyl groups of carboxymethyl chitosan and the hydroxyl groups of hydroxypropyl methylcellulose). This sequence ensures that tannic acid is uniformly and fully "anchored" throughout the composite network, thereby maximizing its wet tissue adhesion, free radical scavenging, and antibacterial synergistic functions. Simultaneously, it avoids the problems of localized component aggregation or uneven reaction that may occur with direct blending, ensuring the uniformity and stability of product performance.

[0025] In some other embodiments, the physical mixing is performed by stirring or ball milling. This preparation method is extremely simple and efficient, without involving complex chemical reactions, harsh solvent treatments, or high-temperature and high-pressure conditions. It maximizes the preservation of the inherent biological activity of each component, avoids performance losses that may be caused by chemical modification or drastic processing, ensures batch-to-batch quality stability, facilitates large-scale production, and significantly reduces equipment investment and production costs.

[0026] Finally, this invention provides the use of hemostatic powder in the preparation of products for promoting wound hemostasis. This product is particularly suitable for treating surgical wounds, traumatic bleeding, and difficult-to-heal moist wounds with tissue fluid exudation.

[0027] The solution and effects of the present invention will be further explained below with reference to specific embodiments and comparative examples: Example 1 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a 7:3 mass ratio, and then 0.5% tannic acid (by mass of the total carboxymethyl chitosan and hydroxypropyl methylcellulose powders) was added and mixed thoroughly to obtain hemostatic powder (abbreviated as CHT), labeled as CHT. 0.5 powder.

[0028] Example 2 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a mass ratio of 7:3. Then, tannic acid at 1% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose powders was added and mixed evenly to obtain hemostatic powder, which was labeled as CHT1 powder.

[0029] Example 3 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a 7:3 mass ratio, and then tannic acid was added at 1.5% of the total mass of the carboxymethyl chitosan and hydroxypropyl methylcellulose powders. The mixture was then thoroughly mixed to obtain the hemostatic powder, labeled CHT. 1.5 powder.

[0030] Example 4 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a mass ratio of 7:3. Then, tannic acid at 2% of the total mass of the carboxymethyl chitosan and hydroxypropyl methylcellulose powders was added and mixed evenly to obtain hemostatic powder, labeled as CHT2 powder.

[0031] Example 5 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a 7:3 mass ratio, and then 2.5% tannic acid (by mass of the total carboxymethyl chitosan and hydroxypropyl methylcellulose powders) was added and mixed thoroughly to obtain a hemostatic powder labeled CHT. 2.5 powder.

[0032] Example 6 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a mass ratio of 7:3. Then, 3% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose powders was added with tannic acid. The mixture was stirred until homogeneous to obtain hemostatic powder, which was labeled as CHT3 powder.

[0033] Example 7 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a 7:3 mass ratio, and then tannic acid was added at 3.5% of the total mass of the carboxymethyl chitosan and hydroxypropyl methylcellulose powders. The mixture was then thoroughly mixed to obtain the hemostatic powder, labeled CHT. 3.5 powder.

[0034] Example 8 Unlike Example 5, carboxymethyl chitosan and hydroxypropyl methylcellulose powder were mixed in a 1:1 mass ratio, and then tannic acid was added at 2.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose powder. After mixing evenly, hemostatic powder was obtained.

[0035] Example 9 Unlike Example 5, carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a mass ratio of 10:10, and then tannic acid was added at a total mass of 2.5% of the carboxymethyl chitosan and hydroxypropyl methylcellulose powders. The mixture was then thoroughly mixed to obtain the hemostatic powder.

[0036] Comparative Example 1 Carboxymethyl chitosan and hydroxypropyl methylcellulose powders were mixed in a mass ratio of 7:3 and then mixed evenly to obtain hemostatic powder, which was labeled as CH powder.

[0037] Comparative Example 2 Unlike Example 5, hydroxypropyl methylcellulose was replaced with an equal amount of carboxymethyl chitosan, and then 2.5% tannic acid was added by weight. After mixing evenly, hemostatic powder was obtained.

[0038] Comparative Example 3 Unlike Example 5, carboxymethyl chitosan was replaced with an equal amount of hydroxypropyl methylcellulose, and then 2.5% tannic acid was added by weight. After mixing evenly, hemostatic powder was obtained.

[0039] Comparative Example 4 Unlike Example 5, three powders containing only a single component were prepared: hydroxypropyl methylcellulose powder, carboxymethyl chitosan powder, and tannic acid powder.

[0040] Comparative Example 5 Unlike Example 5, carboxymethyl chitosan and hydroxypropyl methylcellulose powder were mixed in a mass ratio of 7:3, and then tannic acid at 5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose powder was added and mixed evenly to obtain hemostatic powder.

[0041] Comparative Example 6 Unlike Example 5, carboxymethyl chitosan, hydroxypropyl methylcellulose powder, and tannic acid were mixed in one step.

[0042] Comparative Example 7 Unlike Example 5, commercially available Yunnan Baiyao (manufacturer: Yunnan Baiyao Group Co., Ltd., product batch number: marked YNBY) and BleedStop (made in the United States) were used.

[0043] Performance Characterization (1) Infrared spectra of carboxymethyl chitosan (CMCs), hydroxypropyl methylcellulose (HMPC), tannic acid (TA) and hemostatic powder (HTC).

[0044] like Figure 1 As shown, 1710 cm -1 This is the stretching vibration peak of the ester carbonyl group in TA, at 1200 cm⁻¹. -1 1080 cm -1 and 1030 cm -1 The stretching vibration peaks of phenolic CO and aromatic ring skeletons in TA are characteristic fingerprint regions of TA; at 2900 cm⁻¹ -1 The peak at 1080 cm⁻¹ represents the asymmetric / symmetric stretching peaks of -CH₃ (methoxy) and -CH₂- (hydroxypropyl / backbone) in HMPC. -¹ and 1030 cm -¹ The peaks at this location represent the stretching vibrations of COC and C-OH in the CMCS sugar ring, and these peaks all appear on the infrared curve of CHT, proving that the CHT powder composite was successfully completed.

[0045] (2) Tissue adhesion performance test Cut the pigskin into 1 A 6 cm specimen was prepared by coating two pieces of pigskin with carboxymethyl chitosan, hydroxypropyl methylcellulose, and tannic acid solutions, respectively. The two pieces of pigskin coated with the materials were then glued together and left at room temperature for 12 hours. The specimens were then tested according to the standards (F2255-05 and F2258-05) published by the American Society for Testing and Materials (ASTM).

[0046] like Figure 2 As shown, the tensile adhesion force of the hemostatic powder prepared in Example 5 was 134 kPa, which is 3 times that of Yunnan Baiyao (YNBY) powder, indicating that Example 5 has excellent adhesion properties.

[0047] (3) In vitro hemostasis time test Hemostatic powder (10 mg, Comparative Example 1, Examples 1-7) was added to a 96-well plate containing 50 μL of working solution (anticoagulated whole blood: 0.1 M calcium chloride solution = 9:1). The plate was then gently washed with PBS at predetermined time intervals until no significant change in the clot was observed. The time recorded at this point was the clotting time. BleedStop (BS), a US-marketed product, and Yunnan Baiyao (YNBY), a domestically produced product, were selected as positive control groups.

[0048] like Figure 3-5 As shown, the in vitro coagulation times for Comparative Example 1, Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, and Example 7 were 1.55, 0.0410, 0.0405, 0.04, 0.0395, 0.0386, 0.0390, and 0.04 min, respectively. The in vitro coagulation times for the YNBY group and the BS group were 1.5 min and 0.166 min, respectively. Compared with the blank (6.233 min) and the positive control group, the CHT series powders all achieved rapid in vitro coagulation.

[0049] (4) Blood coagulation index Place the hemostatic material at the bottom of a centrifuge tube, add 500 μL of blood (containing 100 μL of 0.2 M CaCl2), and incubate in a 37°C water bath for 7 min. Remove and photograph the solution. Then, carefully add 3 mL of PBS to the centrifuge tube to prepare a mixed solution. Measure the absorbance at 540 nm using a UV-Vis spectrophotometer using 2 mL of the mixed solution. The centrifuge tubes containing only anticoagulated blood were designated as the blank group, those containing blood containing 0.2 M CaCl2 were designated as the control group, and those containing the hemostatic material were designated as the experimental group. Each experiment was repeated three times. Calculate the blood coagulation index (BCI) using the formula: ; Among them, A s Indicates the absorbance of the supernatant of each group of samples; A n This indicates the absorbance of the supernatant in the blank control group.

[0050] like Figure 6-7 As shown: The blood coagulation index of Examples 1-7 was significantly lower than that of the control group, and all of them could achieve rapid in vitro coagulation.

[0051] The performance test results of the hemostatic powder in the examples and comparative examples are shown in Table 1. The antibacterial performance was tested using the following method: Mix 0.05 g of powder with 10 mL of bacterial solution (1×10⁻⁵ g of powder). 9Co-cultured with PBS (CFU / mL) for 24 h. 100 μL of bacterial culture was spread on an agar plate and incubated at 37 ℃ and 60% humidity for 24 h. The growth of colonies was recorded by counting CFU and taking pictures. The PBS co-culture group was used as a blank control.

[0052] The stability test method is as follows: Place a certain amount of powder in different proportions at room temperature, weigh the powder daily for 30 days. Powders with a stability period of less than 20 days are considered relatively stable.

[0053] Table 1 Performance Test Results

[0054] As shown in Table 1, the superior performance of the hemostatic powder of this invention relies on the synergistic effect of the precise ratio of the three components—carboxymethyl chitosan, hydroxypropyl methylcellulose, and tannic acid—and the stepwise physical mixing process. Any missing component, imbalanced ratio, or improper process will disrupt the integrated functions of electrostatic coagulation, hygroscopic gelation, tissue adhesion, and antibacterial and anti-inflammatory properties, leading to a significant decrease in hemostatic effect, adhesion strength, and antibacterial performance.

[0055] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A hemostatic powder, characterized in that, It is composed of carboxymethyl chitosan, hydroxypropyl methylcellulose and tannic acid, wherein the mass ratio of carboxymethyl chitosan and hydroxypropyl methylcellulose is (1-10):(1-10), and the amount of tannic acid added is 0.5%-3.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

2. The hemostatic powder according to claim 1, characterized in that, The mass ratio of carboxymethyl chitosan to hydroxypropyl methylcellulose is (6-8):(2-4), and the amount of tannic acid added is 1%-3% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

3. The hemostatic powder according to claim 2, characterized in that, The mass ratio of carboxymethyl chitosan to hydroxypropyl methylcellulose is 7:3, and the amount of tannic acid added is 2.5% of the total mass of carboxymethyl chitosan and hydroxypropyl methylcellulose.

4. The hemostatic powder according to claim 1, characterized in that, The purity of carboxymethyl chitosan is ≥99%, and the degree of carboxyl substitution is ≥80%.

5. The hemostatic powder according to claim 1, characterized in that, The viscosity of hydroxypropyl methylcellulose is 150,000-250,000.

6. The hemostatic powder according to claim 1, characterized in that, The purity of tannic acid is ≥98%.

7. The hemostatic powder according to claim 1, characterized in that, The in vitro clotting time of the hemostatic powder is 0.035-0.045 min, and the tensile adhesion is 105-140 kPa.

8. A method for preparing the hemostatic powder according to any one of claims 1-7, characterized in that, Carboxymethyl chitosan and hydroxypropyl methylcellulose are mixed by physical mixing, and then tannic acid is added and mixed thoroughly to obtain the final product.

9. The method for preparing hemostatic powder according to claim 5, characterized in that, The physical mixing is either stirring or ball milling.

10. The use of the hemostatic powder according to any one of claims 1-7 in the preparation of a product for promoting wound hemostasis.

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