Rapid control method for bleeding in surgical operation

Abstract

The invention discloses a rapid control method for bleeding in a surgical operation, belongs to the technical field of hemostasis in the surgical operation, and constructs a synergistic hemostasis system of physical blockage of a nano material, precise release of blood coagulation factors and activation of blood coagulation through bioelectrical stimulation. The method comprises the complete processes of preoperative sterile treatment, nano-composite hemostatic material preparation, intra-operative material adaptation application, bioelectrical stimulation cooperative operation, postoperative continuous monitoring and the like. The nano composite hemostatic material is composed of a nano cellulose derivative and nanoparticles loaded with blood coagulation factors, and the activity of the blood coagulation factors and the biocompatibility of the material are guaranteed through a mild preparation process; in the operation, the material is applied to a bleeding part in a powder, film or gel shape according to specific conditions such as the size of a bleeding point and the bleeding amount; meanwhile, a bioelectrical stimulation device is matched, initial parameters are set according to the physique and bleeding type of a patient, weak pulse current is applied through an electrode attached to healthy tissue, and the material is cooperated to play a role in stopping bleeding.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of surgical hemostasis, in particular to a surgical bleeding rapid control method. BACKGROUND

[0002] Bleeding control in surgery is a key link to ensure the safety of surgery and reduce postoperative complications. Existing hemostatic techniques are mainly divided into three categories: physical hemostasis (such as compression, ligation), chemical hemostasis (such as hemostatic materials) and biological stimulation hemostasis (such as electrical stimulation), but all have obvious limitations: Physical hemostasis relies on the experience of doctors, and for small blood vessel bleeding or large area wound bleeding, compression hemostasis is low in efficiency (hemostasis time is usually 5-10 minutes), and is easy to cause tissue damage; ligation hemostasis is only suitable for visible large blood vessels and cannot cover diffuse bleeding; Chemical hemostatic materials (such as gelatin sponge, nanocellulose material) mainly rely on physical water absorption to form a gel to block the bleeding point, or release a single coagulation factor to activate coagulation, but the release rate of coagulation factor is uncontrollable, and in the face of high pressure bleeding scenes such as arterial bleeding, the hemostasis time still needs 4-8 minutes, and when used alone, it is easy to be washed away by blood; Biological electrical stimulation hemostasis activates platelets through weak current, but existing technology does not combine hemostatic materials, and only relies on electrical stimulation to change the surface charge of platelets to activate the coagulation cascade reaction, which is low in efficiency, and the hemostasis time is as long as 6-12 minutes, and the electrical stimulation parameters lack individualized adjustment, which is easy to cause electrical damage to the surrounding normal tissues.

[0003] At present, there is no technology to combine the physical blocking-coagulation factor release function of nanometer hemostatic materials with the platelet activation function of biological electrical stimulation, which cannot realize the dual synergistic hemostasis of "physical barrier + biological activation", resulting in the risk of not timely hemostasis and excessive blood loss in complex surgical operations (such as liver resection, heart surgery).

[0004] Therefore, a rapid, efficient and safe synergistic hemostasis method in surgery is needed to solve the above problems. SUMMARY

[0005] In view of the low efficiency and limited application scene of existing surgical hemostasis technology, the present application provides a surgical bleeding rapid control method, which synchronously exerts force from two aspects of physical blocking and biological chemical coagulation through the synergistic effect of nanometer composite hemostatic material and biological electrical stimulation, shortens the hemostasis time, improves the hemostasis effect, and at the same time guarantees the biocompatibility and operation safety.

[0006] Technical Solution: To solve the above-mentioned technical problems, according to one aspect of the present invention, more specifically, a method for rapid control of surgical bleeding, a synergistic system of "physical obstruction by nanomaterials - precise release of coagulation factors - activation of coagulation by bioelectric stimulation" is constructed, comprising the following steps: S1. Preparation of nanocomposite hemostatic materials Nanoparticles loaded with coagulation factors: Prepared using biodegradable materials such as gelatin and chitosan as carriers via an emulsification-crosslinking method. Key control measures include solvent selection and low-temperature operation to protect the activity of coagulation factors. Solvent compatibility principle: Select mild and biocompatible solvents according to the characteristics of the carrier material, and avoid using strong acids and bases (pH range of 5.5-7.5) or high-concentration organic solvents (such as pure acetone and xylene) to prevent peptide bond breakage or spatial conformation changes of coagulation factors. Specific solvent selection: Deionized water (pH 6.0-7.0) is used for gelatin and sodium alginate; 1% low-concentration acetic acid solution (pH 5.5-6.0, to avoid denaturation of coagulation factors caused by high concentration of acetic acid) is used for chitosan; and a mixed solvent of anhydrous ethanol and water (volume ratio 1:4, to reduce damage to coagulation factors by organic solvents) is used for polylactic acid-glycolic acid copolymer. Active protection measures: The stirring and emulsification processes after adding coagulation factors are carried out at a low temperature of 4-8℃, and the cross-linking reaction temperature does not exceed 25℃. High temperature (>37℃) or vigorous stirring (>300rpm) should be avoided throughout the process to prevent loss of coagulation factor activity. Activity testing standards: After preparation, the prothrombin time method is used to ensure that the coagulation factor activity retention rate is ≥90%, and the coagulation factor released within 10 minutes in the in vitro release experiment still maintains ≥85% activity.

[0007] S2, Intraoperative application of nanocomposite hemostatic materials Choose the appropriate material type based on the specific condition of the bleeding site, ensuring full contact between the material and the bleeding site: Small bleeding points (area ≤1cm) 2 (Bleeding volume ≤ 0.2 mL / min): The nanocomposite hemostatic material is made into powder and applied at a rate of 0.1-0.2 g / cm³ using a sterile powder sprayer. 2 Spray the powder evenly onto the bleeding site. The powder quickly absorbs water and gels upon contact with blood, forming a tight blocking layer. Large wound area (area > 1cm) 2 For bleeding > 0.2 mL / min: The nanocomposite hemostatic material is made into a film (thickness 1-3 mm) or a gel (viscosity 500-1000 mPa・s). The film material is directly covered on the wound and gently pressed to fix it. The gel material is filled into the depressions of the wound with a syringe to ensure that there are no gaps or omissions.

[0008] S3, Coordination of Bioelectric Stimulation A customized bioelectric stimulation device is used to enhance the coagulation effect through weak pulsed current. The specific operation is as follows: Equipment parameter settings: Set initial parameters according to the patient's physical condition (such as weight and blood pressure) and bleeding type (venous bleeding / arterial bleeding): For venous bleeding, the current intensity is 10-30μA, the pulse frequency is 0.5-1Hz, and the duration is 5-10 minutes; for arterial bleeding, the current intensity is 30-50μA, the pulse frequency is 1-2Hz, and the duration is 10-15 minutes. Electrode placement: Use flexible electrodes with platinum alloy or polyimide base-gold coating (biocompatibility > 99%). Place the electrodes on healthy tissue 0.5-2cm around the bleeding site to avoid direct contact with the bleeding point, which could cause current dispersion. Control the contact pressure between the electrode and the tissue at 5-10kPa to prevent displacement or tissue damage. Dynamic control: During electrical stimulation, heart rate, systolic blood pressure and blood oxygen saturation are collected in real time by a vital signs monitor. If the bleeding volume does not drop to ≤0.5mL / min, the current intensity is increased by 5μA every 3 minutes (not exceeding the upper limit of 50μA). If the heart rate is >100 beats / min or the systolic blood pressure is <90mmHg, electrical stimulation is paused for 2 minutes and then the parameters are adjusted and continued.

[0009] Furthermore, the following steps are also included: S0. Preoperative aseptic treatment: The nanocomposite hemostatic material is sterilized by gamma irradiation (dose 25-30kGy) to ensure that the sterility level meets the requirements of surgical procedures; the electrodes are sterilized by plasma (time 5-10 minutes) to remove surface impurities and enhance biocompatibility. S4. Postoperative monitoring: After hemostasis is completed, observe the bleeding site every 8 hours for 24-72 hours after the operation and record whether there is rebleeding, local redness and swelling or exudation. If rebleeding occurs (bleeding volume > 0.1 mL / min), repeat steps S2-S3 and extend the duration of electrical stimulation by 3-5 minutes to ensure stable hemostasis.

[0010] The beneficial effects of the surgical bleeding rapid control method of the present invention are as follows: (1) This invention combines the physical blocking function of nanocomposite hemostatic materials with the coagulation activation effect of bioelectric stimulation. It not only blocks the bleeding channel by forming a physical barrier quickly through the material, but also activates the coagulation cascade reaction with the help of weak pulse current. It exerts force simultaneously from two core levels of physical and biochemical, achieving a hemostatic effect of "1+1>2", which effectively solves the problem of low hemostatic efficiency when the existing technology is used alone.

[0011] (2) This invention addresses different types of bleeding that may occur during surgery. The method can flexibly adapt various forms of hemostatic materials such as powder, film, and gel according to the area of ​​the bleeding point, the amount of bleeding, and the type of bleeding (venous / arterial bleeding). At the same time, the bioelectric stimulation parameters can be adjusted in a targeted manner. Whether it is a small bleeding point in a microvascular, diffuse bleeding in a large wound, or high-pressure arterial bleeding, it can achieve precise and effective hemostasis, greatly expanding the scope of application.

[0012] (3) The material preparation process in this invention adopts mild solvent and low temperature operation process to avoid destroying the activity of coagulation factors and the biocompatibility of materials. In addition, strict aseptic treatment is carried out before the operation to reduce the risk of infection. The bioelectric stimulation adopts electrode materials with excellent biocompatibility. By controlling the electrode placement position, contact pressure and current parameters, direct damage to the bleeding site and surrounding normal tissues is avoided. The patient's vital signs are monitored in real time throughout the process, and the operation plan is dynamically adjusted to effectively avoid adverse reactions caused by improper parameters, ensure the safety of patients during the operation, and reduce the occurrence of postoperative complications such as redness, swelling, exudation and rebleeding.

[0013] (4) This invention forms a complete standardized process from preoperative preparation, intraoperative operation to postoperative monitoring. Each step has clear operational logic and judgment criteria, avoiding the excessive reliance on doctors' operational experience in traditional hemostasis methods. Through individualized parameter setting and dynamic adjustment mechanism, the stability and consistency of hemostasis effect are ensured. Even in complex surgical procedures, blood loss can be effectively controlled, providing a stable guarantee for the smooth progress of the operation and further improving the overall safety and reliability of the surgery. Attached Figure Description

[0014] The present invention will now be described in further detail with reference to the accompanying drawings and specific implementation methods.

[0015] Figure 1 This is a process flow diagram of the present invention. Detailed Implementation

[0016] The present invention will be described in detail below with reference to the accompanying drawings and embodiments. It should be noted that, unless otherwise specified, the embodiments and features described in the present application can be combined with each other.

[0017] To make the technical solution of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0018] Example 1: Rapid control of small bleeding points (venous bleeding) S1, Preparation of Nanocomposite Hemostatic Materials Preparation of nano-carboxymethyl cellulose sodium (CMCNa): CMCNa (molecular weight 50000 Da) was dissolved in deionized water to prepare a 3wt% solution. The solution was ultrasonically treated for 30 minutes (power 300W), then dialyzed for 48 hours using a dialysis bag with a molecular weight cutoff of 10000 Da. The solution was then freeze-dried to obtain nano-CMCNa powder with a particle size of 30-50 nm. Preparation of thrombin-loaded gelatin nanoparticles: Gelatin (molecular weight 15000 Da) was dissolved in deionized water (pH 6.5, mild solvent to avoid denaturation of thrombin) at 50℃ to prepare a 5wt% solution. Thrombin solution (concentration 1 mg / mL) was added, with a mass ratio of gelatin to thrombin of 10:1. The mixture was stirred evenly at 6℃ to form the aqueous phase.

[0019] Liquid paraffin and Span-80 were mixed at a volume ratio of 10:1 to form the oil phase. The aqueous phase was added to the oil phase at a volume ratio of 1:5. The mixture was stirred at 3000 rpm for 30 minutes to form a W / O emulsion. 25 wt% glutaraldehyde solution (5% of the gelatin mass) was added and the mixture was stirred for another 2 hours to crosslink. The nanoparticles were collected by centrifugation at 8000 rpm for 15 minutes, washed three times with petroleum ether, and vacuum dried to obtain gelatin nanoparticles with a size of 80-120 nm and a thrombin loading of 8 wt%. Composite: Nano-CMCNa powder and gelatin nanoparticles are mixed at a mass ratio of 3:1 and ground evenly to obtain nano-composite hemostatic powder.

[0020] S2, Intraoperative Application and Bioelectric Stimulation Preoperative treatment: The nanocomposite hemostatic powder was sterilized by 25kGy γ-ray irradiation, and the platinum alloy electrode (0.5cm×1cm) of the bioelectric stimulation device was sterilized by plasma for 10 minutes; Materials used: A venous bleeding point (0.5 cm in area) was found in the forearm during surgery. 2 (Bleeding rate 0.15 mL / min) Wipe away surface blood with sterile gauze, then apply nano-composite hemostatic powder at a concentration of 0.1 g / cm³. 2 Apply the dosage (0.05g total) to the bleeding point; Electrical stimulation procedure: Set the parameters of the bioelectric stimulation device: current intensity 20μA, pulse frequency 1Hz, duration 8 minutes; place the electrodes on the skin tissue 0.8cm around the bleeding point, and start the device to apply the pulsed current; Monitoring and adjustment: Monitor heart rate (maintain 75-85 beats / min) and systolic blood pressure (maintain 110-120 mmHg) during the process. After 3 minutes of electrical stimulation, the bleeding volume drops to 0.05 mL / min. Maintain the parameters for 2 minutes and then stop electrical stimulation.

[0021] S3, Hemostatic effect Bleeding completely stopped after electrical stimulation was stopped. Observations at 24, 48, and 72 hours postoperatively showed no re-bleeding at the bleeding site, no redness or swelling of the local skin, and good tissue healing.

[0022] Example 2: Rapid control of large-area wounds (arterial bleeding) S1, Preparation of Nanocomposite Hemostatic Materials Preparation of nano-hydroxyethyl cellulose (HEC): HEC was dissolved in deionized water to prepare a 2wt% solution, which was ultrasonically treated for 40 minutes (power 400W) and dialyzed in a dialysis bag (molecular weight cutoff 15000Da) for 72 hours to obtain a nano-HEC solution with a particle size of 50-80nm. Preparation of chitosan nanoparticles loaded with coagulation factor XIII: Chitosan (90% degree of deacetylation) was dissolved in 1% acetic acid solution (pH 5.8, low concentration of acetic acid balances the solubility of chitosan and the activity of coagulation factor XIII) to prepare a 3wt% solution, and coagulation factor XIII solution (0.5 mg / mL) was added. The mass ratio of chitosan to coagulation factor XIII was 15:1. The mixed solution was added dropwise to a 0.1 wt% sodium tripolyphosphate solution (dropping rate 1 mL / min), and stirred at 2000 rpm for 30 minutes. The nanoparticles were collected by centrifugation at 10000 rpm for 20 minutes and washed twice with deionized water to obtain chitosan nanoparticles with a size of 120-180 nm and a loading of 12 wt%. Gel preparation: The nano HEC solution and chitosan nanoparticles were mixed at a volume ratio of 5:1, and 1 wt% glycerol (thickener) was added. The mixture was stirred until homogeneous to obtain a nanocomposite hemostatic gel with a viscosity of 800 mPa·s.

[0023] S2, Intraoperative Application and Bioelectric Stimulation Preoperative treatment: Hemostatic gel was sterilized by 30kGy γ-ray irradiation, and flexible conductive electrode (polyimide base + gold coating, size 2cm×4cm) was sterilized by plasma for 5 minutes. Material Application: During partial liver resection surgery, arterial bleeding occurred in the wound (3cm×5cm) (bleeding volume 0.3mL / min). After rinsing the wound with sterile saline, hemostatic gel was evenly applied to the wound to a thickness of 2mm. Electrical stimulation procedure: Set the electrical stimulation parameters: current intensity 40μA, pulse frequency 1.5Hz, duration 12 minutes; cover the gel surface with the flexible electrode, fix the edges with sterile tape, and keep the electrode 1cm away from the wound. Monitoring and adjustment: After 5 minutes of electrical stimulation, the patient's systolic blood pressure dropped to 88 mmHg. Electrical stimulation was paused for 2 minutes, and the current intensity was adjusted to 35 μA before continuing. After 8 minutes of electrical stimulation, the bleeding rate dropped to 0.4 mL / min. The parameters were maintained for 3 minutes before stopping.

[0024] S3, Hemostatic effect Bleeding completely stopped after electrical stimulation was stopped. There was no bleeding from the wound 72 hours after the operation. Pathological sections showed no necrosis in the local tissue, good regeneration of hepatocytes, and no obvious inflammatory reaction.

[0025] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for rapid control of surgical bleeding, characterized in that, Includes the following steps: S1: Prepare a nanocomposite hemostatic material, wherein the nanocomposite hemostatic material is composed of nanoscale cellulose derivatives and nanoparticles loaded with coagulation factors; S2: During the operation, the nanocomposite hemostatic material prepared in step S1 is applied to the bleeding site in an appropriate form according to the size of the bleeding point and the amount of bleeding. S3: Using a bioelectric stimulation device, apply a weak pulsed current near the bleeding site to achieve hemostasis in conjunction with the nanocomposite hemostatic material in step S2; S4: After hemostasis is completed, continuously observe the bleeding site for 24-72 hours after the operation to see if there is rebleeding, local redness or swelling or exudation. If rebleeding occurs, repeat steps S2-S3 and extend the duration of electrical stimulation by 3-5 minutes. In step S1, when preparing the nanocomposite hemostatic material, it is necessary to control the particle size of the nanocellulose derivative and the synthesis process of the nanoparticles loaded with coagulation factors, and to precisely control the size, shape and coagulation factor loading of the nanoparticles. In step S3, the current intensity, pulse frequency and duration parameters of the bioelectric stimulation device are adjustable. Initial parameters need to be set according to the patient's physical condition and bleeding type. During operation, the electrode is attached to the tissue near the bleeding site, and the patient's vital signs are monitored in real time and the electrical stimulation parameters are dynamically adjusted.

2. The method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S1, the nanoscale cellulose derivative is one or more of sodium carboxymethyl cellulose, hydroxyethyl cellulose, or hydroxypropyl methyl cellulose, and its particle size ranges from 20 to 100 nm.

3. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S1, the carrier of the nanoparticles loaded with coagulation factors is one or more of gelatin, chitosan, sodium alginate or polylactic acid-glycolic acid copolymer, the size range of the nanoparticles is 50-200 nm, and the loading amount of coagulation factors is 5-15 wt%.

4. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S1, the nanoparticles loaded with coagulation factors are prepared using an emulsification-crosslinking method or a solvent evaporation method. Specific steps include: The carrier material is dissolved in a mild biocompatible solvent, wherein gelatin and sodium alginate are suitable for deionized water, chitosan is suitable for a 1% acetic acid solution, and polylactic acid-glycolic acid copolymer is suitable for a mixed solvent of anhydrous ethanol and water at a volume ratio of 1:

4. The solvent must meet the requirements of pH range 5.5-7.5 and no organic solvent residue to avoid damaging the spatial structure of coagulation factors. Add coagulation factor solution and stir until homogeneous at a low temperature of 4-8℃. After emulsification to form an emulsion, add crosslinking agent to carry out crosslinking reaction. Finally, obtain nanoparticles loaded with coagulation factor by centrifugation, washing and purification. During the preparation process, the retention rate of coagulation factor activity must be controlled at ≥90%, and the prothrombin time method is used for detection.

5. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S2, the fitting shape is determined based on the bleeding situation: if the bleeding point area is ≤1cm 2 Furthermore, if the bleeding volume is ≤0.2 mL / min, the nanocomposite hemostatic material should be prepared into powder form and applied at a concentration of 0.1-0.2 g / cm³. 2 Apply the appropriate amount to the bleeding site; if the bleeding wound area is >1cm² 2 If the bleeding rate is >0.2 mL / min, the nanocomposite hemostatic material is made into a film with a thickness of 1-3 mm or a gel with a viscosity of 500-1000 mPa・s and applied to cover or fill the bleeding site.

6. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S3, the parameters of the weak pulse current are: current intensity 10-50μA, pulse frequency 0.5-2Hz, duration 5-15 minutes; the electrode is made of platinum alloy or biocompatible conductive material with polyimide substrate-gold coating, and the distance between the electrode and the bleeding site is 0.5-2cm.

7. A method for rapid control of surgical bleeding according to claim 1, characterized in that, It also includes step S0: preoperative sterilization of the nanocomposite hemostatic material by gamma irradiation and plasma sterilization of the electrodes of the bioelectric stimulation device (5-10 minutes).

8. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S3, the vital signs monitored in real time include heart rate, systolic blood pressure, and blood oxygen saturation; when the bleeding volume at the bleeding site drops to ≤0.5mL / min, the current electrical stimulation parameters are maintained for 2-3 minutes and then the electrical stimulation is stopped.

9. A method for rapid control of surgical bleeding according to claim 1, characterized in that, In step S1, the coagulation factor is one or more of thrombin, coagulation factor XIII or coagulation factor VII, and the encapsulation rate of the coagulation factor in the nanoparticles is ≥85%, and the amount released within 10 minutes in the in vitro release experiment accounts for 40-60% of the total load.

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