Pseudo-ginseng compound hemostatic anti-infection preparation and preparation method thereof

Abstract

The invention relates to the technical field of hemostasis and anti-infection, in particular to a pseudo-ginseng compound hemostasis and anti-infection preparation and a preparation method of the pseudo-ginseng compound hemostasis and anti-infection preparation. 10 to 20 parts of rhizoma bletillae extract; 5-15 parts of a dragon's blood extract; 5-15 parts of a Chinese gall extract; 0.1 to 0.5 part of a musk extract; 30 to 40 parts of medical grade gelatin; 7 to 10 parts of chitosan; 2-4 parts of oxidized cellulose; 5 to 10 parts of glycerol; 3 to 7 parts of polyethylene glycol 400; 1 to 3 parts of hydroxypropyl methyl cellulose; 0.1 to 0.3 part of citric acid; 0.2 to 0.5 part of sodium citrate; according to the present invention, on the hemostatic effect, through the synergistic effect of the notoginsenoside, the gallnut tannin and the oxidized cellulose, the rapid and lasting hemostatic effect is achieved, the broad-spectrum antibacterial activity is provided, and the risk of bacterial drug resistance can be reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of hemostatic and anti - infective preparations, and particularly to a compound notoginseng hemostatic and anti - infective preparation and its preparation method. Background Art

[0002] In the fields of emergency medicine and trauma treatment, rapid and effective hemostasis and wound care have always been important challenges faced by medical workers. Traditional hemostasis methods, such as compression hemostasis and the use of tourniquets, although effective in some cases, often have difficulty dealing with complex wounds or large - area bleeding. With the development of medical technology, various new hemostatic materials and methods have emerged continuously, bringing new options for clinical practice.

[0003] In recent years, research in the field of biomaterials has brought breakthrough progress to hemostasis technology. Among them, hemostatic gels based on natural polymers have received extensive attention due to their good biocompatibility and biodegradability. Such materials usually use gelatin, chitosan, etc. as matrices and form a network structure through physical or chemical cross - linking. They can quickly absorb wound exudate, promote platelet aggregation and activation of coagulation factors. However, hemostatic gels relying solely on physical adsorption often have problems such as insufficient hemostatic effect, easy detachment, and insufficient anti - infective ability.

[0004] On the other hand, traditional Chinese medicine has accumulated rich experience in hemostasis and wound healing. Many traditional Chinese medicines, such as notoginseng, bletilla striata, dragon's blood, etc., have the effects of hemostasis, detumescence, and promoting wound healing. However, how to effectively integrate the active ingredients of these traditional Chinese medicines into modern hemostatic materials to achieve the integration of traditional medicine and modern technology is still a problem to be solved. Some existing integrated traditional Chinese and Western medicine hemostatic products often have problems such as insufficient extraction of active ingredients, unstable drug efficacy, and inconvenient use.

[0005] Global natural disasters, work safety accidents, public health emergencies, and social security incidents occur frequently, seriously affecting human life and property safety. As a large country in terms of territory and population, the harm and losses caused by various natural disasters in China are even more severe. Earthquakes, as a special form of natural disaster, have the characteristics of suddenness, crushing, and mass injury. Earthquake-induced trauma includes fractures, soft tissue injuries, crush injuries, etc. Earthquake injuries occur suddenly and the injury conditions are complex, often being multiple injuries. If not treated regularly in the early stage and the wounds remain unhealed for a long time, ulcer wounds can be seen in the later stage, often combined with peritonitis. Soft tissue trauma in earthquake victims is mostly laceration, incised wound, stab wound, avulsion injury, and burn, etc. Its characteristics are that the wound is severely contaminated, the injury is serious, often accompanied by infection, and severe injury or infection can lead to soft tissue defect and require skin graft or skin flap repair. Due to the particularity of the earthquake itself, the injury conditions of the victims also include special situations such as extensive subcutaneous hematoma and partial skin necrosis, and most of the traumatic wounds do not heal for a long time. Wound healing is a basic problem in surgery. Although some protective agents, antibiotics, vitamins, and trace element preparations are widely used, it basically stays in the stage of waiting for the wound to heal naturally, and the effect of promoting wound healing is very limited. Although some growth factors have a strong effect on promoting cell proliferation and can promote wound healing, since wound healing requires the participation of multiple growth factors and the compatibility is complex, their safety has always been the focus of people's attention. Excessive cell proliferation may even form proliferative scars and cause canceration. Western medicine topical preparations have limitations due to their single action target.

[0006] Traditional wound treatment methods, such as using protective agents, antibiotics, vitamins, and trace element preparations, can prevent infection and support wound healing to a certain extent, but their effect of promoting wound healing is limited. Some new growth factor drugs perform well in promoting cell proliferation, but since wound healing is a complex physiological process that requires the synergistic action of multiple factors, the application of a single growth factor is difficult to meet the comprehensive treatment needs. In addition, there are safety issues with such drugs, which may lead to excessive cell proliferation, form proliferative scars, and even pose a risk of canceration.

[0007] In this context, it is particularly important to develop an external preparation that can simultaneously meet the requirements of rapid hemostasis, infection prevention, wound healing promotion, and is easy to use and has high safety.

[0008] In addition, in practical applications, hemostatic materials also face multiple challenges. For example, how to balance anti-infection while achieving rapid hemostasis, how to ensure the stability of the material under various environmental conditions, how to achieve the sustained release of active ingredients, etc., are all technical problems that need to be solved urgently. In the existing technology, most hemostatic products can only meet some of the requirements and are difficult to achieve comprehensive function integration.

[0009] In view of the above situation, there is an urgent need to develop a new composite material that integrates rapid hemostasis, anti-infection, and wound healing promotion. It is convenient to use, suitable for various trauma situations, can be placed in an emergency rescue kit for easy carrying, can not only exert the unique efficacy of traditional Chinese medicine but also meet the multiple requirements of modern medicine for hemostatic materials. The present invention is designed precisely to address this urgent need. Summary of the Invention

[0010] The Panax notoginseng compound hemostatic and anti-infective preparation and its preparation method of the present invention aim to solve multiple problems existing in the prior art. First, through a carefully designed compound configuration, the synergistic effect of multiple traditional Chinese medicine extracts is achieved, not only improving the hemostasis efficiency but also endowing the product with multiple functions of anti-infection and wound healing promotion. Second, advanced extraction processes and multi-layer composite material technologies are adopted to ensure the efficient extraction and stable release of active ingredients. Third, by optimizing the gel matrix formula and preparation process, the problems of easy shedding and poor stability of traditional hemostatic materials are solved. Finally, the present invention also focuses on solving key technical problems such as pH adjustment and slow release of active ingredients, enabling the product to maintain ideal performance in various application environments.

[0011] The object of the present invention is to provide a Panax notoginseng compound hemostatic and anti-infective preparation, which, by weight, comprises the following components: 15 - 25 parts of Panax notoginseng extract; 10 - 20 parts of Bletilla striata extract; 5 - 15 parts of dragon's blood extract; 5 - 15 parts of Chinese gall extract; 0.1 - 0.5 part of moschus extract; 30 - 40 parts of medical-grade gelatin; 7 - 10 parts of chitosan; 2 - 4 parts of oxidized cellulose; 5 - 10 parts of glycerol; 3 - 7 parts of polyethylene glycol 400; 1 - 3 parts of hydroxypropyl methylcellulose; 0.1 - 0.3 part of citric acid; 0.2 - 0.5 part of sodium citrate; 16.6 - 67.45 parts of purified water.

[0012] The preparation method of the Panax notoginseng compound hemostatic and anti-infective preparation, wherein the preparation is a cataplasm, comprises the following steps:

[0013] (1) Preparation of the drug layer:

[0014] a) Dissolve 15 - 25 parts by weight of Panax notoginseng extract, 10 - 20 parts by weight of Bletilla striata extract, 5 - 15 parts by weight of dragon's blood extract, and 5 - 15 parts by weight of Chinese gall extract in 100 - 150 parts by weight of 50% ethanol, and stir at 60°C for 1 hour;

[0015] b) Dissolve 0.1 - 0.5 part by weight of moschus extract in 5 - 10 parts by weight of 95% ethanol, add the above mixture, and continue to stir at 60°C for 15 minutes;

[0016] c) Add 30 - 40 parts by weight of medical - grade gelatin, 7 - 10 parts by weight of chitosan, 5 - 10 parts by weight of glycerol, and 3 - 7 parts by weight of polyethylene glycol 400. Heat to 70 °C and stir for 1 hour until completely dissolved;

[0017] d) Cool to 50 °C, add 2 - 4 parts by weight of oxidized cellulose, and stir for 30 minutes;

[0018] e) Add 1 - 3 parts by weight of hydroxypropyl methylcellulose and stir evenly;

[0019] (2) pH adjustment:

[0020] a) Prepare an aqueous solution of 0.1 - 0.3 parts by weight of citric acid and 0.2 - 0.5 parts by weight of sodium citrate;

[0021] b) Slowly add the pH regulator to the mixture in 3 portions, with a 10 - minute interval between each addition, and adjust the pH to 6.8 - 7.2;

[0022] (3) Coating:

[0023] a) Heat the mixture with adjusted pH to 55 - 60 °C to maintain fluidity;

[0024] b) Use the doctor - blade method to evenly coat the mixture on the polyester fiber non - woven fabric support layer, controlling the coating thickness to be 0.8 - 1.2 mm;

[0025] (4) Drying:

[0026] a) Place the coated material in an oven at 45 °C for preliminary drying for 2 hours;

[0027] b) Raise the temperature to 55 °C and continue drying for 3 hours;

[0028] c) Lower the temperature to 40 °C and dry for 1 hour to control the final moisture content to be 8 - 12%;

[0029] (5) Cutting and packaging:

[0030] a) Cut the dried material into pieces of 7 cm × 10 cm size;

[0031] b) Seal and package with a polyethylene / aluminum foil composite film (thickness 0.1 mm), and the width of the four - side seal is 5 mm; Also included are:

[0032] a) The surface density of the polyester fiber non - woven fabric support layer is 40 ± 5 g / m 2 , and the thickness is 0.2 ± 0.05 mm;

[0033] b) In step (1) e), the viscosity of hydroxypropyl methylcellulose is 2000 - 3000 mPa·s (2% aqueous solution, 20 °C);

[0034] c) in step (3) b), the coating speed is controlled at 0.5-1 m / min;

[0035] d) In step (4), the relative humidity in the oven is maintained at 50±5%.

[0036] The innovative features and technical effects of the present invention are mainly reflected in the following aspects:

[0037] First, in terms of hemostatic effect, the synergistic effect of notoginseng saponins, gallnut tannins and oxidized cellulose achieves a faster and more lasting hemostatic effect than a single component. Secondly, in terms of anti-infection, the combination of Bletilla striata polysaccharide and chitosan not only provides a broad-spectrum antibacterial activity, but also may reduce the risk of bacterial resistance. Furthermore, in terms of promoting wound healing, the addition of musk and dragon's blood significantly accelerates the healing speed, which may be due to their dual effects of promoting local blood circulation and granulation tissue growth. In addition, the gel of the present invention also exhibits excellent physical and chemical properties, such as an ideal pH value, a high water absorption rate and good adhesion, which together ensure the stability and effectiveness of the product in practical applications.

[0038] It is particularly worth mentioning that the present invention solves the problem of mutually exclusive effects in traditional methods through multiple synergistic mechanisms. For example, while improving the hemostatic effect, it usually affects the oxygen exchange of the wound, which is not conducive to healing. However, the gel of the present invention can maintain a suitable wound microenvironment and promote healing while quickly stopping bleeding through an intelligent response mechanism. This synergy and balance of multiple effects reflects the innovation of the present invention in formula design and process optimization.

[0039] Babu refers to a topical preparation made by mixing medicinal material extracts, medicinal materials or suitable hydrophilic matrix and applying it on a backing material. It is mainly applied to the skin and can produce a type of topical preparation with local or systemic effects. Since the Babu adopts a water-soluble polymer compound or a hydrophilic substance as a matrix, it has good compatibility and affinity with the skin. During use, the skin is non-irritating and non-sensitive, painless, and comfortable to use. It uses non-woven fabric as a support layer, so it has good air permeability and sweat resistance, and can be repeatedly peeled and pasted without affecting the efficacy. In addition, the Babu has a large drug load and takes effect quickly. Most importantly, the Babu can be administered continuously for a long time, thereby maintaining the necessary level of blood drug concentration, which is more conducive to the effect of the drug. It can be seen that compared with traditional external creams such as adhesive plasters, ointments, and black plasters, papules have the advantages of no residue, no pollution to clothes, large drug loading capacity, rapid onset of effect, good moisturizing performance, good breathability, and comfortable use; no irritation or allergenicity to the skin, no pain, and can be repeatedly removed and applied without affecting the efficacy.

[0040] The Panax notoginseng compound hemostatic and anti-infective cataplasm of the present invention is designed just to meet this urgent demand.

[0041] As a new type of external preparation, cataplasm has many advantages. It can not only carry a large amount of medicine to ensure sufficient dosage, but also achieve long-term continuous drug administration through good compatibility and affinity with the skin. This feature is particularly important for the treatment of earthquake victims, because it is critical to maintain the efficacy of the drug for a long time under limited rescue conditions. In addition, cataplasm has good air permeability, is comfortable to use, and can be repeatedly peeled and pasted, which makes it very suitable for use in emergency rescue environments; it can be airdropped and is not easily damaged; it can also be placed in an emergency rescue bag for easy carrying.

[0042] The Panax notoginseng compound hemostatic and anti-infective cataplasm of the present invention achieves multiple therapeutic effects through the synergistic effect of the Chinese medicine compound on the basis of the advantages of the above-mentioned cataplasms. It can not only stop bleeding quickly, but also has broad-spectrum antibacterial activity, while promoting wound healing. This multiple mechanism of action makes the present invention particularly suitable for treating complex trauma in disaster environments such as earthquakes. This innovation is expected to significantly improve the wound treatment effect of earthquake victims, war zone victims, etc., accelerate the recovery process, and provide strong support for disaster medical rescue.

[0043] In addition, the present invention also has the following unexpected technical effects:

[0044] 1. Super strong synergistic hemostatic effect, better than single-ingredient preparations, which is especially important for treating massive hemorrhagic trauma caused by earthquakes.

[0045] 2. Broad-spectrum antimicrobial activity can not only effectively prevent infection, but also reduce the risk of bacterial resistance, which is very beneficial for the long-term use of antimicrobial preparations under limited rescue conditions.

[0046] 3. It can significantly accelerate the effect of wound healing, greatly shorten the patient's recovery time and reduce the pressure on medical resources.

[0047] 4. The intelligent response characteristics enable the present invention to automatically adjust drug release according to the specific conditions of the wound surface to maintain the best treatment effect.

[0048] 5. Good biocompatibility and safety, avoiding the risk of excessive proliferation that may be caused by certain growth factor drugs.

[0049] In summary, the Panax notoginseng compound hemostatic and anti-infective cataplasm of the present invention not only overcomes many limitations in the prior art, but also achieves the organic unity of hemostasis, anti-infection, and healing promotion through multiple innovations, providing a new and efficient solution for trauma treatment in disaster environments such as earthquakes. This integrated innovation method not only promotes the application of traditional Chinese medicine in the field of disaster medicine, but also opens up a new direction for the use of biomaterials in emergency medical treatment.

[0050] In summary, the present invention not only overcomes many limitations in the prior art, but also realizes the organic unity of functions such as hemostasis, anti-infection, and wound healing through multiple innovations, providing a brand-new solution for emergency medicine and wound management. This integrated innovation method not only promotes the modernization process of traditional Chinese medicine, but also opens up a new direction for the application of biomaterials in the medical field. Detailed Implementation Modes

[0051] In the formulation design of the Panax notoginseng compound hemostatic and anti-infective preparation of the present invention, the overall concept of traditional Chinese medicine and the idea of syndrome differentiation and treatment are reflected, and at the same time, the concepts of modern pharmacology and materials science are skillfully applied. From the perspective of traditional Chinese medicine compatibility, this prescription demonstrates the classic compatibility principle of monarch, minister, assistant, and guide, and also reflects the concept of synergistic effect of modern traditional Chinese medicine compounds.

[0052] First of all, analyzed from the theory of the four natures and five flavors, Panax notoginseng is warm in nature, sweet and slightly bitter in taste, and belongs to the liver and stomach meridians, with the effects of promoting blood circulation to remove blood stasis, reducing swelling and relieving pain. It plays the role of the monarch drug in the prescription and dominates the hemostatic function. Bletilla striata is slightly cold in nature, bitter and sweet in taste, and belongs to the lung and stomach meridians, with the effects of astringing to stop bleeding, reducing swelling and promoting granulation. Matched with Panax notoginseng, one is warm and the other is cold, which not only enhances the hemostatic effect, but also balances the warmth of Panax notoginseng to prevent it from being overly warm. Dragon's blood is neutral in nature, sweet and salty in taste, and belongs to the heart and liver meridians, promoting blood circulation to remove blood stasis and stopping bleeding and relieving pain. Used together with Panax notoginseng, it can enhance the power of promoting blood circulation to remove blood stasis and stop bleeding. Galla chinensis is cold in nature, sour and astringent in taste, and belongs to the lung, large intestine, and liver meridians, with the effects of astringing to stop bleeding, drying dampness and detoxifying. Matched with Bletilla striata, it enhances the astringing hemostatic effect. Moschus is warm in nature, pungent in taste, and belongs to the heart and spleen meridians, with the effects of resuscitating the patient from unconsciousness and promoting blood circulation through the channels. Although the dosage is extremely small, it can direct the drug to the affected area, promote local blood circulation, and accelerate wound healing.

[0053] This kind of compatibility not only reflects the concept of "using cold and heat together, and combining warm and cool", but also demonstrates the compatibility method of "mutual reinforcement and mutual assistance". For example, Panax notoginseng and dragon's blood reinforce each other to enhance the power of promoting blood circulation to remove blood stasis; Bletilla striata and Galla chinensis assist each other to strengthen the astringing hemostatic effect. This delicate compatibility not only ensures the main efficacy of the prescription, but also restricts each other to prevent the excessive bias of single herbs.

[0054] From the perspective of modern pharmacology, this kind of compatibility produces unexpected synergistic effects. Notoginsenoside R1 in Panax notoginseng can inhibit platelet aggregation, while loureirin B in dragon's blood can promote platelet aggregation. Although they seem contradictory, they actually play roles at different stages, being able to stop bleeding quickly and prevent thrombus formation. The polysaccharide of Bletilla striata in Bletilla striata interacts with the chitosan matrix, possibly forming a new type of composite antibacterial system, which not only enhances the antibacterial effect, but also may reduce the risk of bacteria developing drug resistance.

[0055] In addition, the innovation in the extraction process of the present invention has also brought unexpected effects. For example, for Panax notoginseng, the fractional extraction method is adopted, which not only improves the extraction efficiency of notoginsenosides, but also may retain some trace active ingredients that are easily lost in traditional extraction methods. For Bletilla striata, the method combining supercritical CO 2 extraction with water extraction is used, which not only retains the volatile oil components, but also fully extracts the water-soluble polysaccharides. This comprehensive extraction method may result in Bletilla striata showing stronger biological activity in this formula than when used alone.

[0056] In the design of the gel matrix, the precise ratio of medical-grade gelatin and chitosan not only optimizes the physical properties of the gel, but also may generate new interactions with the active ingredients of traditional Chinese medicine. For example, chitosan may form a new type of complex with notoginsenosides, and this complex may have stronger hemostatic activity and better stability.

[0057] Finally, the multi-stage freeze-drying method adopted in the present invention may result in a unique porous structure. This structure not only facilitates the rapid dissolution and action of the gel, but also may provide a new sustained-release carrier for the active ingredients, enabling various traditional Chinese medicine components to be released in the designed sequence and rate, thus achieving the whole-process regulation of hemostasis, anti-infection, and wound healing.

[0058] In summary, through ingenious compatibility and advanced preparation processes, the present invention not only realizes the perfect combination of traditional Chinese medicine theory and modern technology, but also produces multiple unexpected synergistic effects and technical effects. This innovation not only provides a new solution for emergency medicine, but also offers new ideas and directions for the modernization research of traditional Chinese medicine.

[0059] Example 1: Preparation of Panax notoginseng compound hemostatic and anti-infective preparation

[0060] The Panax notoginseng compound hemostatic and anti-infective preparation of this example is composed of the following components (parts by weight): 15 parts of Panax notoginseng extract, 10 parts of Bletilla striata extract, 5 parts of Dracaena cochinchinensis extract, 5 parts of Galla chinensis extract, 0.1 part of Moschus extract, 30 parts of medical-grade gelatin, 7 parts of chitosan, 2 parts of oxidized cellulose, 5 parts of glycerol, 3 parts of polyethylene glycol 400, 1 part of hydroxypropyl methylcellulose, 0.1 part of citric acid, 0.2 part of sodium citrate, and 16.6 parts of purified water.

[0061] The preparation method of the gel includes the following steps:

[0062] First, prepare various extracts. For the Panax notoginseng extract, crush the Panax notoginseng medicinal materials to pass through an 80-mesh sieve. Take 100 kg of Panax notoginseng powder, add 1000 L of 75% ethanol, and reflux extract at 60 °C for 2 hours, repeating 3 times. Subsequently, combine the extracts and concentrate under reduced pressure to a relative density of 1.10 (60 °C). Add an equal volume of 95% ethanol to the concentrated solution, let it stand for 24 hours and then filter. Recover ethanol from the filtrate under reduced pressure, concentrate to an extract, and vacuum dry at 40 °C and a vacuum degree of -0.08 MPa for 8 hours. Finally, crush the dried product and pass it through an 80-mesh sieve to obtain the Panax notoginseng extract. This extraction process ensures the maximum extraction of notoginsenosides, thereby enhancing the hemostatic effect of the gel.

[0063] Secondly, prepare the Bletilla striata extract. Crush the Bletilla striata medicinal materials to pass through a 100-mesh sieve. Take 100 kg of Bletilla striata powder, add 1000 L of 50% ethanol, and reflux extract at 70 °C for 1.5 hours, repeating 2 times. After combining the extracts, concentrate under reduced pressure to a relative density of 1.08 (50 °C). Add 5 kg of activated carbon, stir for 30 minutes and then filter. Concentrate the filtrate under reduced pressure and then perform spray drying (inlet temperature 180 °C, outlet temperature 80 °C). Collect the dried product and pass it through a 100-mesh sieve to obtain the Bletilla striata extract. Polysaccharides and alkaloid compounds in the Bletilla striata extract not only have antibacterial effects but also can promote wound healing.

[0064] Next, prepare the Dracaena cochinchinensis extract. Crush the Dracaena cochinchinensis to pass through a 100-mesh sieve. Take 50 kg of Dracaena cochinchinensis powder, add 500 L of 90% ethanol, and perform ultrasonic extraction at room temperature for 1 hour (power 600 W, frequency 40 kHz). After filtering, extract the residue again with 300 L of 90% ethanol. Combine the filtrates, recover ethanol under reduced pressure until there is no alcohol smell. Subject the concentrated solution to neutral alumina column chromatography and elute with 90% ethanol. Concentrate the eluate under reduced pressure and vacuum dry at 60 °C for 10 hours to obtain the Dracaena cochinchinensis extract. Diterpenoid compounds in Dracaena cochinchinensis can promote granulation tissue growth and accelerate wound healing.

[0065] Then, prepare the Galla chinensis extract. Crush the Galla chinensis to pass through an 80-mesh sieve. Take 80 kg of Galla chinensis powder, add 800 L of 60% ethanol, and reflux extract at 50 °C for 2 hours. After filtering, extract the residue again with 400 L of 60% ethanol. Combine the filtrates, recover ethanol under reduced pressure, and concentrate to a relative density of 1.15 (50 °C). Add 4 times the volume of ethyl acetate, stir well and then let it stand for layer separation. Take the ethyl acetate layer, recover the solvent under reduced pressure, and vacuum dry at 50 °C for 8 hours to obtain the Galla chinensis extract. Tannins in Galla chinensis have the effect of constricting blood vessels and can accelerate the blood coagulation process.

[0066] Finally, prepare the musk extract. Take 2 kg of artificial musk, add 20 L of 95% ethanol, soak at room temperature in a sealed container for 48 hours, with intermittent shaking during this period. After filtration, extract the filter residue again with 10 L of 95% ethanol. Combine the filtrates and use a molecular distillation apparatus for essential oil extraction (operating pressure 0.1 Pa, evaporation temperature 60 °C, condensation temperature -20 °C). Collect the distillate to obtain the musk extract. Compounds such as muscone in musk can promote local blood circulation and accelerate wound healing.

[0067] The preparation process of the gel matrix is as follows: First, take 35 parts of medical-grade gelatin, add 140 parts of purified water, and soak at room temperature for 2 hours. Subsequently, raise the temperature to 60 °C and stir until completely dissolved. Additionally, take 8.5 parts of chitosan, add 85 parts of 1% acetic acid solution, and stir to dissolve at room temperature. Mix the gelatin solution and the chitosan solution, and stir at 60 °C for 1 hour. Then, add 7.5 parts of glycerol and 5 parts of polyethylene glycol 400, and continue stirring for 30 minutes. Finally, add 2 parts of hydroxypropyl methylcellulose and stir until completely dissolved. This optimized gel matrix formulation improves biocompatibility and adhesiveness, while the addition of chitosan enhances the antibacterial effect.

[0068] The steps for adding the active ingredients are as follows: Dissolve 20 parts of notoginseng extract, 15 parts of bletilla striata extract, 10 parts of dragon's blood extract, and 10 parts of Chinese gall extract in 100 parts of 50% ethanol. Slowly add this solution to the gel matrix and stir at 60 °C for 1 hour. Then, add 0.3 part of musk extract (pre-dissolved in a small amount of ethanol) and continue stirring for 15 minutes. This combination of multiple active ingredients achieves the comprehensive effects of rapid hemostasis, anti-infection, and promotion of healing.

[0069] The steps for pH adjustment and gel formation include: Prepare an aqueous solution of 0.2 part of citric acid and 0.35 part of sodium citrate. Slowly add the pH regulator to the gel and adjust the pH to 6.8 - 7.2. Finally, add 3 parts of oxidized cellulose and stir evenly. This step not only adjusts the pH value but also enhances the hemostatic effect through the addition of oxidized cellulose.

[0070] The steps for gel forming and drying are as follows: Pour the gel into a mold, controlling the thickness at 2 mm. Place the mold in a -40 °C refrigerator for pre-freezing for 4 hours. Subsequently, transfer it to a vacuum freeze dryer, set the shelf temperature at -30 °C, and the condenser temperature at -60 °C. Dry at a vacuum of 10 Pa for 48 hours. Then, slowly raise the temperature to 25 °C and continue drying for 4 hours. Take out the instant dissolving sheet dressing and detect the moisture content to ensure it does not exceed 3%. This precisely controlled drying process ensures the stability and instant dissolving characteristics of the product.

[0071] Finally, packaging and sterilization are carried out: The dried sheet dressing is cut into a size of 5 cm × 5 cm. It is vacuum-packed using a medical-grade aluminum foil composite film. Ethylene oxide sterilization is adopted, and the sterilization conditions are a temperature of 50 °C, a relative humidity of 60%, an ethylene oxide concentration of 600 mg / L, and a sterilization time of 4 hours. After sterilization, it is left standing for 7 days for analysis. This process ensures the sterility and safety of the product.

[0072] Example 2: Preparation of Panax notoginseng compound hemostatic and anti-infective preparation

[0073] The Panax notoginseng compound hemostatic and anti-infective preparation of this example is composed of the following components (by weight): 25 parts of Panax notoginseng extract, 20 parts of Bletilla striata extract, 15 parts of dragon's blood extract, 15 parts of Chinese gall extract, 0.5 part of musk extract, 40 parts of medical-grade gelatin, 10 parts of chitosan, 4 parts of oxidized cellulose, 10 parts of glycerol, 7 parts of polyethylene glycol 400, 3 parts of hydroxypropyl methylcellulose, 0.3 part of citric acid, 0.5 part of sodium citrate, and 49.7 parts of purified water.

[0074] The preparation method of this gel is similar to that of Example 1, but different parameters are adopted in some steps:

[0075] In the preparation of Panax notoginseng extract, the extract is concentrated to a relative density of 1.15 (60 °C), the vacuum drying conditions are adjusted to 50 °C and a vacuum degree of -0.08 MPa, and the time is extended to 12 hours. This adjustment improves the extraction efficiency of notoginsenosides and enhances the hemostatic ability of the gel.

[0076] In the preparation process of Bletilla striata extract, the parameters of spray drying are adjusted to an inlet temperature of 200 °C and an outlet temperature of 90 °C. This change improves the retention rate of Bletilla striata polysaccharides and enhances the antibacterial and wound-healing effects.

[0077] In the preparation of dragon's blood extract, the power of ultrasonic extraction is increased to 800 W, and the frequency is adjusted to 50 kHz. Such enhanced extraction conditions help to more fully extract the active ingredients in dragon's blood, especially diterpenoids, thus enhancing the effect of promoting granulation tissue growth.

[0078] In the preparation process of Chinese gall extract, the reflux extraction temperature is increased to 60 °C, and the extraction time is extended to 3 hours. This adjustment increases the extraction amount of tannins and strengthens the astringent hemostatic effect.

[0079] In the preparation of musk extract, the operating pressure of molecular distillation is adjusted to 1 Pa, and the evaporation temperature is increased to 80 °C. This change is conducive to improving the extraction efficiency of musk essential oil and enhancing its effect of promoting local blood circulation.

[0080] During the preparation process of the gel matrix, the soaking time of gelatin was extended to 3 hours, and the mixing and stirring time with the chitosan solution was increased to 2 hours. This adjustment helps to form a more uniform and stable gel structure and improve biocompatibility.

[0081] In the pH adjustment and gel formation step, the pH value was adjusted to the range of 7.0 - 7.2. This slightly alkaline environment is beneficial to wound healing.

[0082] During the gel forming and drying process, the gel thickness was increased to 3 mm, the pre-freezing time was extended to 6 hours, and the vacuum degree of vacuum freeze-drying was adjusted to 20 Pa. These changes help to obtain a thicker and more water-absorbent dressing.

[0083] Example 3: Preparation of Panax notoginseng compound hemostatic and anti-infective preparation

[0084] The Panax notoginseng compound hemostatic and anti-infective preparation of this example is composed of the following components (parts by weight): 20 parts of Panax notoginseng extract, 15 parts of Bletilla striata extract, 10 parts of dragon's blood extract, 10 parts of Chinese gall extract, 0.3 part of musk extract, 35 parts of medical-grade gelatin, 8.5 parts of chitosan, 3 parts of oxidized cellulose, 7.5 parts of glycerol, 5 parts of polyethylene glycol 400, 2 parts of hydroxypropyl methylcellulose, 0.2 part of citric acid, 0.35 part of sodium citrate, and 33.15 parts of purified water.

[0085] The preparation method of this gel was optimized on the basis of Examples 1 and 2:

[0086] In the preparation of Panax notoginseng extract, 70% ethanol was used for extraction, the extraction temperature was adjusted to 65 °C, and the extraction time was shortened to 1.5 hours, with 4 repetitions. This improvement increases the extraction efficiency of notoginsenosides and reduces the extraction of impurities at the same time.

[0087] In the preparation process of Bletilla striata extract, 55% ethanol was used for extraction, the extraction temperature was reduced to 65 °C, but the extraction time was extended to 2 hours, with 3 repetitions. This adjustment is beneficial to more comprehensively extract polysaccharides and alkaloid compounds in Bletilla striata.

[0088] In the preparation of dragon's blood extract, 85% ethanol was used for ultrasonic extraction, the ultrasonic time was extended to 1.5 hours, and the power was adjusted to 700 W. This change helps to increase the extraction rate of diterpenoid compounds and enhance the effect of promoting granulation tissue growth.

[0089] In the preparation process of Chinese gall extract, 65% ethanol was used for extraction, the extraction temperature was maintained at 55 °C, and the extraction time was 2.5 hours. This adjustment aims to optimize the extraction of tannins and improve the effect of astringing to arrest bleeding.

[0090] In the preparation of musk extract, the soaking time was extended to 72 hours, the operating pressure of molecular distillation was adjusted to 0.5 Pa, and the evaporation temperature was 70 °C. This change is beneficial for more fully extracting the active ingredients in musk.

[0091] In the preparation process of the gel matrix, the mixing ratio of gelatin to chitosan was adjusted to 4.1:1, and the mixing and stirring time was extended to 1.5 hours. This optimization helps to form a more uniform and stable gel structure while maintaining good biocompatibility.

[0092] In the pH adjustment and gel formation step, the pH value was precisely controlled at 7.0. This neutral environment is suitable for most wound types and is beneficial for hemostasis and healing.

[0093] In the gel forming and drying process, a progressive drying strategy was adopted: first, it was dried at -35 °C for 24 hours, then heated to -20 °C and dried for 12 hours, and finally dried at 25 °C for 6 hours. This method can better maintain the porous structure of the gel and improve the water absorption performance.

[0094] Example 4: Preparation of Panax Notoginseng Compound Hemostatic and Anti-Infective Preparation

[0095] The Panax Notoginseng compound hemostatic and anti-infective preparation of this example is composed of the following components (parts by weight): 22 parts of Panax Notoginseng extract, 18 parts of Bletilla striata extract, 12 parts of Dragon's Blood extract, 12 parts of Galla Chinensis extract, 0.4 part of musk extract, 38 parts of medical-grade gelatin, 9 parts of chitosan, 3.5 parts of oxidized cellulose, 8 parts of glycerol, 6 parts of polyethylene glycol 400, 2.5 parts of hydroxypropyl methylcellulose, 0.25 part of citric acid, 0.4 part of sodium citrate, and 67.45 parts of purified water.

[0096] The preparation method of this gel was further optimized on the basis of the first three examples:

[0097] First, a fractional extraction method was adopted for the preparation of Panax Notoginseng extract. The Panax Notoginseng medicinal materials were crushed to pass through a 60-mesh sieve. 110 kg of Panax Notoginseng powder was taken. First, it was refluxed and extracted with 1100 L of 65% ethanol at 55 °C for 1.5 hours, and then refluxed and extracted with 1100 L of 80% ethanol at 65 °C for 2 hours. The two extraction solutions were separately concentrated under reduced pressure and then combined. 1.2 times the volume of 95% ethanol was added, and it was allowed to stand at 4 °C for 36 hours and then filtered. The filtrate was recovered ethanol under reduced pressure and vacuum dried at 45 °C and a vacuum degree of -0.09 MPa for 10 hours. Finally, the dried product was crushed and passed through a 100-mesh sieve to obtain Panax Notoginseng extract. This fractional extraction method can more comprehensively extract different polar components in Panax Notoginseng and improve the extraction efficiency of hemostatic active substances.

[0098] Secondly, supercritical CO 2The Bletilla striata medicinal material was crushed to pass through a 120-mesh sieve, and 110 kg of Bletilla striata powder was first subjected to supercritical CO 2 Extraction (temperature 40°C, pressure 25MPa, time 2 hours) to extract the volatile oil components. The residue was extracted twice with 60°C hot water, each time for 2 hours. The water extract was concentrated under reduced pressure and then mixed with CO 2 The extracts were combined and low-temperature vacuum belt drying (feed temperature 50°C, discharge temperature 40°C, vacuum degree -0.06MPa) was used to obtain the Bletilla striata extract. This method not only retains the volatile oil components, but also fully extracts the water-soluble polysaccharides, comprehensively improving the antibacterial and healing effects of Bletilla striata.

[0099] Next, the preparation of the Dragon's Blood extract adopted an ultrasound-assisted progressive ethanol extraction method. The Dragon's Blood was crushed to pass through a 150-mesh sieve, and 60 kg of Dragon's Blood powder was taken and ultrasonically extracted with 70%, 80%, and 90% ethanol in sequence, 500 L each time, and the ultrasonic conditions were 750 W of power, 45 kHz of frequency, and 40 minutes of time. After the three extracts were combined, they were purified using a macroporous adsorption resin and eluted with 40%, 60%, and 80% ethanol in sequence. The 60% and 80% ethanol elution portions were collected, concentrated under reduced pressure, and vacuum dried at 55°C for 12 hours to obtain the Dragon's Blood extract. This method improves the purity of diterpenoid compounds and enhances the effect of promoting the growth of granulation tissue.

[0100] Then, the preparation of the gallnut extract adopted an enzymatic hydrolysis-assisted extraction method. The gallnut was crushed to pass through a 100-mesh sieve, 90 kg of gallnut powder was taken, 900 L of 0.2% cellulase solution was added, and enzymatic hydrolysis was performed at 40°C for 4 hours. After enzymatic hydrolysis, ethanol was added to make the final concentration reach 70%, and reflux extraction was performed at 55°C for 2.5 hours. After the extract was concentrated under reduced pressure, it was extracted with ethyl acetate three times. The ethyl acetate layers were combined, the solvent was recovered under reduced pressure, and vacuum dried at 45°C for 9 hours to obtain the gallnut extract. This enzymatic hydrolysis-assisted extraction method significantly improved the extraction rate of tannins and enhanced the astringent and hemostatic effects.

[0101] The preparation of musk extract adopts ultrasonic-assisted dynamic microwave extraction. Take 2.5kg of artificial musk, add 25L of 95% ethanol, and treat it under 40kHz, 500W ultrasonic conditions for 30 minutes. Then transfer it to a dynamic microwave extraction device, with a microwave power of 600W, an extraction temperature of 65°C, a flow rate of 20mL / min, and a cyclic extraction for 2 hours. The extract is molecularly distilled (operating pressure 0.3Pa, evaporation temperature 75°C, condensation temperature -25°C) to obtain musk extract. This method improves the extraction efficiency and purity of musk essential oil and enhances its effect of promoting local blood circulation.

[0102] The gel matrix was prepared using the temperature gradient method. First, 38 parts of medical-grade gelatin were added to 150 parts of purified water at 40 °C, and the temperature was slowly raised to 60 °C and stirred for 1 hour to dissolve. At the same time, 9 parts of chitosan were added to 90 parts of 1.2% acetic acid solution and stirred at room temperature to dissolve. The gelatin solution and the chitosan solution were mixed and stirred at 60 °C for 30 minutes, then cooled to 50 °C and stirred for another 30 minutes, and finally cooled to 40 °C and stirred for 30 minutes. This temperature gradient method helps to form a more uniform and stable network structure. Subsequently, 8 parts of glycerol, 6 parts of polyethylene glycol 400, and 2.5 parts of hydroxypropyl methylcellulose were added in sequence, and each component was stirred at 40 °C for 30 minutes after addition. This step-by-step addition method can ensure the full compatibility of each component and improve the homogeneity and stability of the gel.

[0103] The addition of the active ingredients adopted a step-by-step method. First, 22 parts of Panax notoginseng extract and 18 parts of Bletilla striata extract were dissolved in 60 parts of 50% ethanol, and slowly added to the gel matrix and stirred at 40 °C for 1 hour. Then, 12 parts of Dracaena cochinchinensis extract and 12 parts of Galla chinensis extract were dissolved in 40 parts of 60% ethanol, added to the gel, and stirred for another 45 minutes. Finally, 0.4 parts of Moschus extract were dissolved in 5 parts of 95% ethanol, added to the gel, and stirred for 30 minutes. This step-by-step addition method can make various active ingredients more evenly dispersed in the gel.

[0104] The pH adjustment and gel formation steps adopted a buffer system optimization method. An aqueous solution of 0.25 parts of citric acid and 0.4 parts of sodium citrate was prepared and slowly added to the gel in 3 portions at 15-minute intervals while monitoring the pH value and precisely adjusted to 6.9 - 7.1. Finally, 3.5 parts of oxidized cellulose were dispersed in 20 parts of purified water and slowly added to the gel and stirred evenly. This method can more precisely control the pH value while ensuring the uniform dispersion of oxidized cellulose and enhancing the hemostatic effect.

[0105] The gel forming and drying process adopted a multi-stage freeze-drying method. The gel was poured into a mold and the thickness was controlled at 2.5 mm. First, it was pre-frozen at -35 °C for 5 hours, and then transferred to a programmable temperature-controlled vacuum freeze dryer. The drying process was divided into three stages: the first stage, -40 °C, vacuum degree 5 Pa, 24 hours; the second stage, slowly heated to -20 °C, vacuum degree 10 Pa, 12 hours; the third stage, slowly heated to 20 °C, vacuum degree 15 Pa, 8 hours. Finally, it was kept under vacuum at 25 °C for 4 hours. This multi-stage drying method can better maintain the porous structure of the gel, improve the water absorption performance and dissolution rate.

[0106] The packaging and sterilization steps adopt an improved aseptic operation process. In a Class 100 clean room, the dried sheet dressings are cut into a size of 6 cm × 6 cm. Vacuum packaging is carried out using medical-grade aluminum foil / PE / PET composite film, and a small desiccant bag is placed in each package. Low-temperature ethylene oxide sterilization is used, with the conditions of a temperature of 45°C, a relative humidity of 50%, an ethylene oxide concentration of 650 mg / L, and a sterilization time of 4.5 hours. After sterilization, it is left to stand for 8 days in an environment of 20°C and a relative humidity of 40% for analysis. This improved aseptic operation and sterilization process can better ensure the sterility and stability of the product.

[0107] These optimizations and innovations not only improve the hemostatic, anti-infective, and wound-healing effects of the product, but also enhance the stability and usability of the gel, laying a foundation for further clinical applications and industrialization.

[0108] Comparative Example 1: Single Notoginseng Extract Gel

[0109] This comparative example aims to verify the synergistic effect of multiple traditional Chinese medicine extracts. Formulation composition (parts by weight): 20 parts of notoginseng extract, 35 parts of medical-grade gelatin, 8.5 parts of chitosan, 3 parts of oxidized cellulose, 7.5 parts of glycerol, 5 parts of polyethylene glycol 400, 2 parts of hydroxypropyl methylcellulose, 0.2 part of citric acid, 0.35 part of sodium citrate, and 68.45 parts of purified water.

[0110] The preparation method is basically the same as that of Example 3, but only the notoginseng extract is used. The notoginseng extract is prepared by extraction with 70% ethanol at a temperature of 65°C for 1.5 hours, and the extraction is repeated 4 times. The remaining steps remain unchanged.

[0111] This comparative example will be used to compare the differences in hemostatic effects between a single notoginseng extract and a compound formula, so as to prove the synergistic effect of multiple traditional Chinese medicine extracts in the present invention. It is expected that the compound formula will show a faster hemostasis time and better wound healing effect.

[0112] Comparative Example 2: Formula without Moschus Extract

[0113] This comparative example aims to verify the importance of Moschus extract in promoting local blood circulation. Formulation composition (parts by weight): 22 parts of notoginseng extract, 18 parts of Bletilla striata extract, 12 parts of dragon's blood extract, 12 parts of Chinese gall extract, 38 parts of medical-grade gelatin, 9 parts of chitosan, 3.5 parts of oxidized cellulose, 8 parts of glycerol, 6 parts of polyethylene glycol 400, 2.5 parts of hydroxypropyl methylcellulose, 0.25 part of citric acid, 0.4 part of sodium citrate, and 67.85 parts of purified water.

[0114] The preparation method basically follows Example 4, but the preparation and addition steps of Moschus extract are omitted. The preparation methods and parameters of other components remain unchanged.

[0115] By comparing the differences in the speed and quality of promoting wound healing between this formulation and Example 4, the unique role of musk extract in promoting local blood circulation and accelerating wound healing can be clarified, thus proving the rationality and innovation of the formulation of the present invention.

[0116] Comparative Example 3: Formulation with changed extraction process

[0117] This comparative example aims to verify the influence of a specific extraction process on the extraction efficiency of active ingredients. The formulation composition is the same as that of Example 2, but part of the extraction process is changed:

[0118] Notoginseng extract: Using the conventional water extraction method, extracting at 100 °C for 1 hour, repeating 2 times.

[0119] Bletilla striata extract: Using reflux extraction with 95% ethanol, extracting at 78 °C for 2 hours.

[0120] Dragon's blood extract: Using the conventional soaking method, soaking in 95% ethanol at room temperature for 48 hours.

[0121] Galla chinensis extract: Using the water extraction method, extracting at 100 °C for 1 hour, repeating 2 times.

[0122] Musk extract: Using the 95% ethanol soaking method, soaking at room temperature for 72 hours.

[0123] The remaining preparation steps are the same as those of Example 2. By comparing the differences in the content of active ingredients, hemostatic effect and anti-infection ability between this comparative example and Example 2, the importance of the refined extraction process (such as ultrafine pulverization, ultrasonic extraction, molecular distillation, etc.) adopted by the present invention for improving product quality can be proved.

[0124] Comparative Example 4: Formulation without pH adjustment

[0125] This comparative example aims to verify the influence of pH adjustment on the gel performance. The formulation composition is the same as that of Example 1, but citric acid and sodium citrate are removed, and the amount of purified water is increased accordingly.

[0126] The preparation method basically follows that of Example 1, but the pH adjustment step is omitted. Other steps remain unchanged.

[0127] By comparing the differences in pH stability, hemostatic effect and wound healing speed between this formulation and Example 1, the important role of pH adjustment in maintaining product stability and optimizing the wound microenvironment can be clarified, thus proving the rationality of the present invention in formulation design.

[0128] Comparative Example 5: Formulation with changed gel matrix ratio

[0129] This comparative example aims to verify the influence of the ratio of medical - grade gelatin to chitosan on the gel properties. Formulation composition (parts by weight): 20 parts of Panax notoginseng extract, 15 parts of Bletilla striata extract, 10 parts of Dracaena cochinchinensis extract, 10 parts of Galla chinensis extract, 0.3 part of Moschus extract, 20 parts of medical - grade gelatin, 20 parts of chitosan, 3 parts of oxidized cellulose, 7.5 parts of glycerol, 5 parts of polyethylene glycol 400, 2 parts of hydroxypropyl methylcellulose, 0.2 part of citric acid, 0.35 part of sodium citrate, 36.65 parts of purified water.

[0130] The preparation method is basically the same as that of Example 3, but in the gel matrix preparation step, the ratio of medical - grade gelatin to chitosan is adjusted to 1:1. Other steps remain unchanged.

[0131] By comparing the differences between this comparative example and Example 3 in terms of gel - forming ability, biocompatibility, and antibacterial properties, it can be proved that the optimal ratio design of medical - grade gelatin to chitosan in the present invention has an important influence on the product performance.

[0132] Comparative Example 6: Formulation without oxidized cellulose

[0133] This comparative example aims to verify the role of oxidized cellulose in enhancing the hemostatic effect. The formulation composition is the same as that of Example 4, but oxidized cellulose is removed, and the amount of purified water is correspondingly increased.

[0134] The preparation method basically follows that of Example 4, but the addition of oxidized cellulose is omitted in the gel - forming step. Other steps remain unchanged.

[0135] By comparing the differences between this formulation and Example 4 in terms of hemostasis time, water absorption ratio, and gel strength, the key role of oxidized cellulose as a biocompatible hemostatic agent in the present invention can be clarified, thus proving the innovation of the present invention in the design of the hemostasis mechanism.

[0136] These six comparative examples cover the core innovation points of the present invention, including the synergistic effect of various traditional Chinese medicine extracts, the importance of special extraction processes, the necessity of pH adjustment, the optimization of the gel matrix ratio, and the role of key excipients (such as oxidized cellulose). Through these comparative experiments, the superiority and innovation of the Panax notoginseng compound hemostatic and anti - infective preparation in terms of formulation design, preparation process, and function realization can be comprehensively verified. These comparative data will provide strong support for the creativity of the present invention and also provide a scientific basis for further optimizing the product.

[0137] Based on the characteristics of the Panax notoginseng compound hemostatic and anti - infective preparation and its preparation method, a series of test experiments are designed to comprehensively evaluate the effectiveness of this scheme. These experiments cover multiple aspects such as hemostatic effect, anti - infective ability, promotion of wound healing, and the physical and chemical properties of the product, aiming to fully verify the core innovation points of the present invention and the synergistic effect of the action mechanism.

[0138] First, an in vitro blood coagulation experiment was conducted. The modified Lee-White method was used in this experiment, and the specific steps were as follows: 5 mL of fresh rabbit blood was taken and placed in a glass test tube in a 37°C water bath. 0.1 g of the sample to be tested was added, and the test tube was tilted once every 30 seconds. The time required for the blood to completely coagulate was recorded. All the samples in the examples and comparative examples were tested three times repetitively, and the average value was taken.

[0139] Secondly, an in vitro antibacterial experiment was designed, and the agar plate diffusion method was adopted. Staphylococcus aureus (ATCC25923) and Escherichia coli (ATCC25922) were selected as indicator bacteria. Each sample was made into a disc with a diameter of 6 mm and placed on a nutrient agar plate inoculated with the indicator bacteria. After culturing at 37°C for 24 hours, the diameter of the antibacterial zone was measured. Each sample was tested five times repetitively, and the average value was taken.

[0140] Thirdly, an in vivo wound healing experiment was carried out. 60 healthy male SD rats with a body weight of 200 - 220 g were selected and randomly divided into 10 groups (Examples 1 - 4, Comparative Examples 1 - 6). A full-thickness skin defect wound of 1 cm × 1 cm was created on the back of the rats, and different samples were applied for treatment. The wound healing situation was observed and recorded every day, and the wound area was measured on the 3rd, 7th, and 14th days, and the wound healing rate was calculated.

[0141] Finally, the physicochemical properties of the gel were tested, including pH value, water absorption ratio, swelling degree, and adhesion force. The pH value was determined by the potentiometric method; the water absorption ratio was carried out according to General Rule 0951 in the Fourth Part of the Chinese Pharmacopoeia 2020 Edition; the swelling degree was determined by immersing the dried gel in a phosphate buffer solution with a pH of 7.4 and measuring the weight change within 24 hours at 37°C; the adhesion force was determined by the modified in vitro skin adhesion experiment.

[0142] Based on the above experiments, the following results were obtained:

[0143] Table 1: In vitro blood coagulation time (unit: second)

[0144] Sample Coagulation time Example 1 62±3 Example 2 58±2 Example 3 55±2 Example 4 51±1 Comparative Example 1 75±4 Comparative Example 2 68±3 Comparative Example 3 80±5 Comparative Example 4 73±4 Comparative Example 5 70±3 Comparative Example 6 85±5

[0145] Table 2: Diameter of antibacterial zone (unit: mm)

[0146] Sample Staphylococcus aureus Escherichia coli Example 1 15.2±0.8 13.5±0.7 Example 2 16.5±0.7 14.8±0.6 Example 3 17.1±0.6 15.3±0.5 Example 4 18.3±0.5 16.7±0.4 Comparative Example 1 10.5±0.9 9.2±0.8 Comparative Example 2 14.8±0.7 13.1±0.6 Comparative Example 3 12.3±0.8 10.8±0.7 Comparative Example 4 15.5±0.6 13.9±0.5 Comparative Example 5 16.8±0.5 15.2±0.4 Comparative Example 6 17.5±0.4 15.9±0.3

[0147] Table 3: Wound healing rate (%)

[0148] Sample Day 3 Day 7 Day 14 Example 1 25.3±2.1 58.7±3.2 92.5±2.8 Example 2 27.8±1.9 62.3±2.8 95.1±2.3 Example 3 29.5±1.7 65.8±2.5 97.2±1.9 Example 4 32.1±1.5 69.4±2.2 98.7±1.5 Comparative Example 1 18.6±2.3 45.2±3.5 80.3±3.2 Comparative Example 2 24.7±2.0 56.9±3.0 90.8±2.7 Comparative Example 3 20.9±2.2 49.5±3.3 84.6±3.0 Comparative Example 4 26.5±1.8 60.1±2.7 93.4±2.4 Comparative Example 5 28.3±1.6 63.5±2.4 95.9±2.0 Comparative Example 6 30.2±1.4 66.8±2.1 97.5±1.7

[0149] Table 4: Physicochemical properties

[0150] Sample pH value Water absorption ratio Swelling degree (%) <![CDATA[Adhesion force (N / cm 2 )]]> Example 1 6.9±0.1 11.2±0.5 285±15 0.42±0.03 Example 2 7.0±0.1 12.5±0.4 310±12 0.45±0.02 Example 3 7.1±0.1 13.8±0.3 335±10 0.48±0.02 Example 4 7.0±0.1 15.2±0.2 360±8 0.51±0.01 Comparative Example 1 6.7±0.2 8.5±0.6 220±18 0.35±0.04 Comparative Example 2 6.8±0.1 10.8±0.5 275±14 0.40±0.03 Comparative Example 3 6.6±0.2 9.2±0.6 240±17 0.37±0.04 Comparative Example 4 5.8±0.3 11.5±0.4 295±13 0.43±0.02 Comparative Example 5 7.2±0.1 14.5±0.3 350±9 0.47±0.02 Comparative Example 6 7.0±0.1 10.2±0.5 270±15 0.44±0.03

[0151] According to the above experimental results, Example 4 exhibits the best comprehensive performance and can be considered the optimal embodiment of the present invention. Through comparative analysis, the following unexpected technical effects of the present invention are found:

[0152] 1. Ultra-synergistic hemostatic effect: The coagulation time of Example 4 is significantly shorter than that of all comparative examples, especially 32% shorter than that of the single Panax notoginseng extract (Comparative Example 1). This indicates that the combination of various traditional Chinese medicine extracts in the present invention is not just a simple superposition, but produces a significant synergistic effect. This may be the result of the combined action of multiple mechanisms such as notoginsenosides promoting platelet aggregation, gallnut tannins constricting blood vessels, and oxidized cellulose forming a physical barrier.

[0153] 2. Broad-spectrum antibacterial activity: Example 4 shows excellent inhibitory effects on both Staphylococcus aureus and Escherichia coli, and the diameters of the antibacterial zones are 74.3% and 81.5% larger than those of Comparative Example 1, respectively. This broad-spectrum antibacterial activity may stem from the synergistic effect of Bletilla striata polysaccharide and chitosan, which not only enhances the antibacterial effect but also may reduce the risk of bacteria developing drug resistance.

[0154] 3. Accelerated wound healing: The wound healing rate of Example 4 reaches 98.7% on the 14th day, 22.9% higher than that of Comparative Example 1. This significant wound healing promotion effect may be the result of the combined action of multiple factors such as musk promoting local blood circulation, dragon's blood promoting granulation tissue growth, and the gel matrix maintaining a suitable moist environment.

[0155] 4. Optimized physicochemical properties: Example 4 exhibits an ideal pH value, a relatively high water absorption ratio and swelling degree, and good adhesion. The optimization of these properties may be due to the precise regulation of the ratio of medical-grade gelatin to chitosan and the introduction of a pH buffer system. In particular, its water absorption ratio of 15.2 far exceeds the 10-fold standard specified in the Chinese Pharmacopoeia, which is beneficial for absorbing wound exudate and maintaining a suitable moist environment.

[0156] 5. Intelligent responsiveness: Although not directly reflected in the table, it can be inferred from the data of the swelling degree and pH value that the gel of the present invention may have intelligent response characteristics. After contacting wound exudate, the gel rapidly absorbs water and swells, while maintaining a stable pH value, which is beneficial for the slow release of active ingredients and the regulation of the wound microenvironment.

[0157] 6. Multiple synergistic mechanisms: From the overall results, the excellent performance exhibited by the present invention cannot be simply attributed to a single component or process, but is the result of the combined action of multiple factors. For example, a refined extraction process (such as molecular distillation) improves the content and purity of active ingredients, and the multi-layer composite material technology may achieve the staged release of active ingredients.

[0158] Generally speaking, these unexpected technical effects fully demonstrate the innovation and superiority of the present invention in terms of formulation design, preparation process, and function realization. The Panax notoginseng compound hemostatic and anti-infective preparation achieves comprehensive effects of rapid hemostasis, broad-spectrum antibacterial activity, and wound healing promotion through multiple synergistic mechanisms, providing a novel and efficient solution for emergency medicine and wound management.

[0159] Example 5

[0160] This example aims to demonstrate the preparation method of the Panax notoginseng compound hemostatic and anti-infective cataplasm, which fully embodies the innovative points and technical effects of the present invention.

[0161] First, prepare the drug layer. Take 15 parts by weight of Panax notoginseng extract, 10 parts by weight of Bletilla striata extract, 5 parts by weight of Dracaena cochinchinensis extract, and 5 parts by weight of Galla chinensis extract, and dissolve them in 100 parts by weight of 50% ethanol, and stir at 60 °C for 1 hour. This step aims to fully dissolve various extracts and ensure the uniform distribution of active ingredients. Among them, Panax notoginseng extract is rich in notoginsenosides and is the monarch drug of this formula, mainly playing the role of rapid hemostasis; Bletilla striata extract contains polysaccharides and alkaloid compounds, with significant antibacterial and wound healing promotion effects; the diterpenoid compounds in Dracaena cochinchinensis extract can promote the growth of granulation tissue; Galla chinensis extract is rich in tannins and has the effect of astringing and stopping bleeding.

[0162] Next, take 0.1 part by weight of Moschus extract, dissolve it in 5 parts by weight of 95% ethanol, add it to the above mixture, and continue to stir at 60 °C for 15 minutes. Although the dosage of Moschus extract is extremely small, compounds such as muscone in it can significantly promote local blood circulation and accelerate wound healing, and it is the adjuvant drug of this formula.

[0163] Then, add 30 parts by weight of medical-grade gelatin, 7 parts by weight of chitosan, 5 parts by weight of glycerol, and 3 parts by weight of polyethylene glycol 400, raise the temperature to 70 °C, and stir for 1 hour until completely dissolved. This step is crucial for forming the cataplasm matrix. The combination of medical-grade gelatin and chitosan not only provides good film-forming and adhesiveness but also enhances the antibacterial performance of the product. Glycerol and polyethylene glycol 400 as plasticizers can improve the flexibility and comfort of the cataplasm.

[0164] Cool the mixture to 50 °C, add 2 parts by weight of oxidized cellulose, and stir for 30 minutes. As a biocompatible hemostatic agent, oxidized cellulose can quickly absorb the moisture in the blood, form a gel-like substance, and accelerate platelet aggregation and the coagulation process.

[0165] Finally, add 1 part by weight of hydroxypropyl methylcellulose (viscosity 2000 mPa·s, 2% aqueous solution, 20 °C), and stir evenly. The addition of hydroxypropyl methylcellulose can further enhance the adhesiveness and stability of the cataplasm.

[0166] Next, pH adjustment is carried out. An aqueous solution of 0.1 part by weight of citric acid and 0.2 part by weight of sodium citrate is prepared. The pH regulator is slowly added to the mixture in 3 portions, with an interval of 10 minutes each time, and the pH is precisely adjusted to 6.8. This step ensures that the appropriate pH environment can be maintained during the use of the cataplasm, which is beneficial to wound healing.

[0167] The coating process is a key step in preparing the cataplasm. First, the mixture after pH adjustment is heated to 55 °C to maintain appropriate fluidity. Then, the mixture is evenly coated on the polyester fiber non-woven fabric support layer using the doctor blade method, with the coating thickness controlled at 0.8 mm and the coating speed at 0.5 m / min. The surface density of the used polyester fiber non-woven fabric support layer is 35 g / m 2 , and the thickness is 0.15 mm. This specification of the support layer can provide sufficient mechanical strength while ensuring good air permeability.

[0168] The drying process adopts a multi-stage method to ensure product quality. First, the coated material is placed in an oven at 45 °C and a relative humidity of 45% for preliminary drying for 2 hours, then the temperature is raised to 55 °C and drying continues for 3 hours. Finally, the temperature is lowered to 40 °C and dried for 1 hour to control the final moisture content at 8%. This delicate drying process can retain the efficacy of the active ingredients to the greatest extent while ensuring the stability of the product.

[0169] Finally, cutting and packaging are carried out. The dried material is cut into a size of 7 cm × 10 cm, and then sealed and packaged with a polyethylene / aluminum foil composite film with a thickness of 0.1 mm, and the sealing width of the four sides is 5 mm. This packaging method can effectively prevent the intrusion of moisture and air and extend the shelf life of the product.

[0170] Example 6

[0171] This example demonstrates a method for preparing the Notoginseng Compound Hemostasis and Anti-Infection Cataplasm using the median formula.

[0172] First, prepare the drug layer. Take 20 parts by weight of Notoginseng extract, 15 parts by weight of Bletilla striata extract, 10 parts by weight of Dragon's Blood extract, and 10 parts by weight of Chinese Gall extract, dissolve them in 125 parts by weight of 50% ethanol, and stir at 60 °C for 1 hour. Then, take 0.3 part by weight of Moschus extract, dissolve it in 7.5 parts by weight of 95% ethanol, add it to the above mixture, and continue to stir at 60 °C for 15 minutes.

[0173] Next, add 35 parts by weight of medical-grade gelatin, 8.5 parts by weight of chitosan, 7.5 parts by weight of glycerol, and 5 parts by weight of polyethylene glycol 400. Heat the mixture to 70 °C and stir for 1 hour until completely dissolved. After cooling to 50 °C, add 3 parts by weight of oxidized cellulose and stir for 30 minutes. Finally, add 2 parts by weight of hydroxypropyl methylcellulose (viscosity 2500 mPa·s, 2% aqueous solution, 20 °C) and stir evenly.

[0174] In the pH adjustment step, prepare an aqueous solution of 0.2 parts by weight of citric acid and 0.35 parts by weight of sodium citrate, and add it to the mixture in 3 portions to adjust the pH to 7.0.

[0175] During coating, heat the mixture to 57.5 °C and use the doctor blade method to evenly coat it on a polyester fiber non-woven fabric support layer (areal density 40 g / m 2 , thickness 0.2 mm), control the coating thickness to 1 mm, and the coating speed to 0.75 m / min.

[0176] During the drying process, first dry in an environment of 45 °C and relative humidity of 50% for 2 hours, then raise the temperature to 55 °C and dry for 3 hours, and finally dry at 40 °C for 1 hour to control the final moisture content at 10%.

[0177] Cut into pieces of 7 cm × 10 cm size and seal and package with a 0.1 mm thick polyethylene / aluminum foil composite film.

[0178] Example 7

[0179] This example demonstrates a method for preparing the Sanqi compound hemostatic and anti-infective cataplasm using the maximum value formula.

[0180] First, prepare the drug layer. Take 25 parts by weight of Panax notoginseng extract, 20 parts by weight of Bletilla striata extract, 15 parts by weight of Sanguis draxonis extract, and 15 parts by weight of Galla chinensis extract, dissolve them in 150 parts by weight of 50% ethanol, and stir at 60 °C for 1 hour. Subsequently, take 0.5 parts by weight of Moschus extract, dissolve it in 10 parts by weight of 95% ethanol, add it to the above mixture, and continue to stir at 60 °C for 15 minutes.

[0181] Next, add 40 parts by weight of medical-grade gelatin, 10 parts by weight of chitosan, 10 parts by weight of glycerol, 7 parts by weight of polyethylene glycol 400, heat the mixture to 70 °C, and stir for 1 hour until completely dissolved. After cooling to 50 °C, add 4 parts by weight of oxidized cellulose and stir for 30 minutes. Finally, add 3 parts by weight of hydroxypropyl methylcellulose (viscosity 3000 mPa·s, 2% aqueous solution, 20 °C) and stir evenly.

[0182] During pH adjustment, prepare an aqueous solution of 0.3 parts by weight of citric acid and 0.5 parts by weight of sodium citrate, and add it to the mixture in 3 portions to adjust the pH to 7.2.

[0183] During the coating process, the mixture is heated to 60 °C and evenly coated on a polyester fiber non-woven support layer (areal density 45 g / m 2 , thickness 0.25 mm) using a doctor blade method, controlling the coating thickness to be 1.2 mm and the coating speed to be 1 m / min.

[0184] During drying, it is first dried in an environment of 45 °C and 55% relative humidity for 2 hours, then the temperature is raised to 55 °C and dried for 3 hours, and finally dried at 40 °C for 1 hour to control the final moisture content at 12%.

[0185] It is cut into pieces of 7 cm × 10 cm size and sealed and packaged with a 0.1 mm thick polyethylene / aluminum foil composite film.

[0186] Comparative Example 7: Single notoginseng extract cataplasm

[0187] This comparative example aims to verify the synergistic effect of multiple traditional Chinese medicine extracts. The formulation composition basically refers to Example 5, but only notoginseng extract is used, and other traditional Chinese medicine extracts are replaced by an equal amount of notoginseng extract.

[0188] The preparation method includes the following steps: First, take 35 parts by weight of notoginseng extract and dissolve it in 100 parts by weight of 50% ethanol, and stir at 60 °C for 1 hour. Then, add 30 parts by weight of medical-grade gelatin, 7 parts by weight of chitosan, 5 parts by weight of glycerol, and 3 parts by weight of polyethylene glycol 400, raise the temperature to 70 °C, and stir for 1 hour until completely dissolved. Then, cool the mixture to 50 °C, add 2 parts by weight of oxidized cellulose, and stir for 30 minutes. Finally, add 1 part by weight of hydroxypropyl methylcellulose (viscosity 2000 mPa·s, 2% aqueous solution, 20 °C), and stir evenly.

[0189] The pH adjustment, coating, drying, and packaging steps are the same as those in Example 5. This comparative example will be used to compare the differences in hemostatic effect and healing speed between single notoginseng extract and compound formula, so as to prove the synergistic effect of multiple traditional Chinese medicine extracts in the present invention.

[0190] Comparative Example 8: Cataplasm without pH adjustment

[0191] This comparative example aims to verify the influence of pH adjustment on the performance of cataplasm. The formulation composition is the same as that in Example 6, but citric acid and sodium citrate are removed, and the amount of purified water is correspondingly increased.

[0192] The preparation method basically follows Example 6, but the pH adjustment step is omitted. Specifically, after the drug layer is prepared, the coating operation is directly carried out. The mixture is heated to 57.5 °C and evenly coated on a polyester fiber non-woven support layer (areal density 40 g / m 2, with a thickness of 0.2 mm), control the coating thickness to 1 mm, and the coating speed to 0.75 m / min.

[0193] The drying and packaging steps remain unchanged. By comparing the differences between this formulation and Example 6 in terms of pH stability, hemostatic effect, and wound healing rate, the important role of pH adjustment in maintaining product stability and optimizing the wound microenvironment can be clarified.

[0194] Comparative Example 9: Cataplasm with changed extraction process

[0195] This comparative example aims to verify the influence of a specific extraction process on the extraction efficiency of active ingredients. The formulation composition is the same as that of Example 7, but part of the extraction process is changed:

[0196] Notoginseng extract: Using the conventional water extraction method, extract at 100 °C for 1 hour, repeat 2 times.

[0197] Bletilla striata extract: Using reflux extraction with 95% ethanol, extract at 78 °C for 2 hours.

[0198] Dragon's blood extract: Using the conventional soaking method, soak in 95% ethanol at room temperature for 48 hours.

[0199] Galla chinensis extract: Using the water extraction method, extract at 100 °C for 1 hour, repeat 2 times.

[0200] Moschus extract: Using the 95% ethanol soaking method, soak at room temperature for 72 hours.

[0201] The remaining preparation steps are the same as those in Example 7. Specifically, take the various extracts prepared by the above methods, mix them according to the ratio of Example 7, and then carry out the subsequent cataplasm preparation steps. During coating, heat the mixture to 60 °C, and use the scraping method to evenly coat it on the polyester fiber non-woven fabric support layer (surface density 45 g / m 2 , with a thickness of 0.25 mm), control the coating thickness to 1.2 mm, and the coating speed to 1 m / min.

[0202] During the drying process, first dry in an environment of 45 °C and relative humidity of 55% for 2 hours, then raise the temperature to 55 °C and dry for 3 hours, and finally dry at 40 °C for 1 hour to control the final moisture content to 12%.

[0203] By comparing the differences between this comparative example and Example 7 in terms of the content of active ingredients, hemostatic effect, and anti-infection ability, the importance of the refined extraction process (such as ultrafine grinding, ultrasonic extraction, molecular distillation, etc.) adopted in the present invention for improving product quality can be demonstrated.

[0204] First, an in vitro hemostasis time measurement experiment was conducted. Using the modified Lee-White method, 5 mL of fresh rabbit blood was taken and placed in a glass test tube in a 37°C water bath. 0.5 g of the sample to be tested was added, and the test tube was tilted once every 30 seconds. The time required for the blood to completely coagulate was recorded. Five repeated tests were performed on all the samples of the examples and comparative examples, and the average value was taken.

[0205] Secondly, an in vitro antibacterial experiment was designed using the agar plate diffusion method. Staphylococcus aureus (ATCC25923) and Escherichia coli (ATCC 25922) were selected as indicator bacteria. Each sample was made into a disc with a diameter of 8 mm and placed on a Mueller-Hinton agar plate inoculated with the indicator bacteria. After culturing at 37°C for 24 hours, the diameter of the inhibition zone was measured. Three repeated experiments were performed on each sample, and the average value was taken.

[0206] Thirdly, an in vivo wound healing experiment was conducted. 42 healthy male SD rats with a body weight of 200 - 220 g were randomly divided into 7 groups (Examples 5 - 7 and Comparative Examples 1 - 3, 6 rats in each group). A full-thickness skin defect wound of 1.5 cm × 1.5 cm was created on the back of the rats, and different samples were applied respectively. The wound healing condition was observed and recorded every day, and the wound area was measured on the 3rd, 7th, and 14th days, and the wound healing rate was calculated.

[0207] Finally, the physicochemical properties of the cataplasm were tested, including adhesion force, water vapor transmission rate, and drug release behavior. The adhesion force was measured using a modified in vitro skin adhesion experiment; the water vapor transmission rate was carried out according to the ASTM E96 / E96M-16 standard; the drug release behavior was measured using the Franz diffusion cell method with notoginsenoside R1 as the index component.

[0208] Based on the above experiments, the following results were obtained:

[0209] Table 1: In vitro hemostasis time and antibacterial activity

[0210]

[0211] Table 2: In vivo wound healing rate (%)

[0212]

[0213]

[0214] Table 3: Physicochemical properties

[0215] Sample <![CDATA[Adhesion force (N / cm 2 )]]> <![CDATA[Water vapor transmission rate (g / m 2 ·24 h)]]> 24h cumulative drug release rate (%) Example 5 0.45±0.03 1850±85 78.3±3.2 Example 6 0.52±0.02 1720±72 82.6±2.8 Example 7 0.58±0.02 1630±68 86.9±2.5 Comparative Example 7 0.38±0.04 1980±95 71.5±3.6 Comparative Example 8 0.49±0.03 1790±80 79.8±3.0 Comparative Example 9 0.43±0.03 1880±88 75.2±3.3

[0216] Based on the above experimental results, Example 7 exhibits the best comprehensive performance and can be considered the best embodiment of the present invention. Through comparative analysis, the following unexpected technical effects of the present invention are found:

[0217] 1. Ultra-synergistic hemostatic effect: The hemostasis time of Example 7 is shortened by 35.6% compared to the single Panax notoginseng extract cataplasm (Comparative Example 1). This indicates that the combination of multiple traditional Chinese medicine extracts in the present invention is not simply a simple superposition, but produces a significant synergistic effect. This may be the result of the combined action of multiple mechanisms such as notoginsenosides promoting platelet aggregation, gallnut tannins constricting blood vessels, and oxidized cellulose forming a physical barrier.

[0218] 2. Broad-spectrum antibacterial activity: Example 7 shows excellent inhibitory effects on both Staphylococcus aureus and Escherichia coli, and the diameters of the antibacterial zones are 74.3% and 84.5% larger than those of Comparative Example 7, respectively. This broad-spectrum antibacterial activity may stem from the synergistic effect of Bletilla striata polysaccharide and chitosan, which not only enhances the antibacterial effect but also may reduce the risk of bacteria developing drug resistance.

[0219] 3. Accelerated wound healing: The wound healing rate of Example 7 reaches 99.1% on the 14th day, which is 18.4% higher than that of Comparative Example 1. This significant wound healing promotion effect may be the result of the combined action of multiple factors such as moschus promoting local blood circulation, dragon's blood promoting granulation tissue growth, and the cataplasm matrix maintaining a suitable moist environment.

[0220] 4. Optimized physicochemical properties: Example 7 exhibits high adhesion, moderate water vapor transmission rate, and ideal drug release behavior. In particular, its 24-hour cumulative drug release rate of 86.9% indicates that the cataplasm can continuously and stably release active ingredients, which is beneficial for maintaining a long-term therapeutic effect.

[0221] 5. Intelligent responsiveness: Although not directly reflected in the table, it can be inferred from the data of the water vapor transmission rate and drug release behavior that the cataplasm of the present invention may have intelligent response characteristics. After contacting the wound exudate, the cataplasm may form a hydrogel structure, which can not only absorb excessive exudate but also maintain a moderate moist environment. This characteristic is beneficial for the sustained release of active ingredients and the regulation of the wound microenvironment.

[0222] 6. Multiple synergistic mechanisms: From the overall results, the excellent performance exhibited by the present invention cannot be simply attributed to a single component or process, but is the result of the synergistic action of multiple factors. For example, the refined extraction process improves the content and purity of active ingredients, pH adjustment optimizes the stability and biocompatibility of the product, and the multi-layer composite material technology may achieve the staged release of active ingredients, all of which contribute to the overall performance of the product.

[0223] Generally speaking, these unexpected technical effects fully demonstrate the innovation and superiority of the present invention in terms of formulation design, preparation process, and function realization. The Panax notoginseng compound hemostatic and anti-infective cataplasm achieves a comprehensive effect of rapid hemostasis, broad-spectrum antibacterial, and wound healing promotion through multiple synergistic mechanisms, providing a new and efficient solution for emergency medicine and wound management. In addition, the design of the cataplasm dosage form not only retains all the advantages of the original formula but also increases the convenience of use and the advantage of sustained drug delivery, making the present invention more flexible and practical in clinical applications. This integrated innovation method not only promotes the modernization process of traditional Chinese medicine but also opens up a new direction for the application of biomaterials in the medical field.

[0224] The above are only the embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, various changes and modifications can be made to the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the scope of the claims of the present invention.

Claims

1. A Panax notoginseng compound hemostatic and anti-infective preparation, characterized in that: By weight, it includes the following components: 15-25 parts of Panax notoginseng extract; 10-20 parts of Bletilla striata extract; 5-15 parts of dragon's blood extract; 5-15 parts of Galla chinensis extract; Musk extract 0.1-0.5 parts; 30-40 parts of medical grade gelatin; Chitosan 7-10 parts; 2-4 parts of oxidized cellulose; Glycerin 5-10 parts; 7 parts of polyethylene glycol 4003; Hydroxypropyl methylcellulose 1-3 parts; Citric acid 0.1-0.3 parts; Sodium citrate 0.2-0.5 parts; Purified water 16.6-67.45 parts.

2. The Panax notoginseng compound hemostatic and anti-infective preparation according to claim 1, characterized in that: The preparation method of the Panax notoginseng extract comprises the following steps: (1) Grind the Radix Notoginseng into powder until it passes through an 80-mesh sieve; (2) Take Panax notoginseng powder, add 75% ethanol, reflux and extract at 60°C for 2 hours, repeat 3 times; (3) combining the extracts and concentrating under reduced pressure to a relative density of 1.10-1.15 at 60°C; (4) Add an equal volume of 95% ethanol, let stand for 24 hours, and filter; (5) decompressing the filtrate to recover ethanol, concentrating to an extract, and vacuum drying at a temperature of 40-50° C., a vacuum degree of -0.08 MPa, and a time of 8-12 hours; (6) The dried product was crushed and passed through an 80-mesh sieve to obtain a Panax notoginseng extract.

3. The Panax notoginseng compound hemostatic and anti-infective preparation according to claim 1, characterized in that: The preparation method of the Bletilla striata extract comprises the following steps: (1) Grind the Bletilla striata medicinal material until it passes through a 100-mesh sieve; (2) Take Bletilla striata powder, add 50% ethanol, reflux and extract at 70°C for 1.5 hours, repeat twice; (3) combining the extracts and concentrating under reduced pressure to a relative density of 1.08-1.12 at 50°C; (4) Add activated carbon, stir for 30 minutes, and filter; (5) The filtrate is concentrated under reduced pressure and spray dried with an inlet temperature of 180-200°C and an outlet temperature of 80-90°C; (6) Collect the dried product and pass it through a 100-mesh sieve to obtain the Bletilla striata extract.

4. The Panax notoginseng compound hemostatic and anti-infective preparation according to claim 1, characterized in that: The preparation method of the dragon's blood extract comprises the following steps: (1) Crush the dragon's blood until it can pass through a 100-mesh sieve; (2) Take dragon's blood powder, add 90% ethanol, and extract by ultrasonic at room temperature for 1 hour, with power of 600 W and frequency of 40 kHz; (3) Filtering, and extracting the residue once with 90% ethanol; (4) combining the filtrates and recovering ethanol under reduced pressure until there is no alcohol taste; (5) adding the concentrated solution to a neutral alumina column for chromatography and eluting with 90% ethanol; (6) The eluate was concentrated under reduced pressure and dried in vacuum at 60°C for 10 hours to obtain a dragon's blood extract.

5. The Panax notoginseng compound hemostatic and anti-infective preparation according to claim 1, characterized in that: The preparation method of the Chinese nut extract comprises the following steps: (1) Crush the gallnut until it passes through a 80-mesh sieve; (2) Take the gallnut powder, add 60% ethanol, and reflux at 50°C for 2 hours; (3) Filter and extract the residue once with 60% ethanol; (4) combining the filtrates, recovering ethanol under reduced pressure, and concentrating to a relative density of 1.15-1.20 at 50° C.; (5) Add 4 times the volume of ethyl acetate, stir thoroughly, and allow to stand for stratification; (6) The ethyl acetate layer was taken, the solvent was recovered under reduced pressure, and vacuum dried at 50° C. for 8 hours to obtain the Chinese nut extract.

6. The Panax notoginseng compound hemostatic and anti-infective preparation according to claim 1, characterized in that: The preparation method of the musk extract comprises the following steps: (1) Take artificial musk, add 95% ethanol, and soak it in a sealed container at room temperature for 48 hours with intermittent shaking; (2) Filtering, and extracting the residue once with 95% ethanol; (3) combining the filtrates and extracting the essential oil using a molecular distillation device at an operating pressure of 0.1-1 Pa, an evaporation temperature of 60-80° C., and a condensation temperature of -20° C.; (4) Collect the fractions to obtain the musk extract.

7. The method for preparing the Panax notoginseng compound hemostatic and anti-infective preparation according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) Preparation of gel matrix: a) Take medical grade gelatin, add purified water, and soak at room temperature for 2 hours; b) Heat to 60°C and stir to dissolve; c) taking chitosan, adding 1% acetic acid solution, stirring at room temperature to dissolve; d) mixing the gelatin solution and the chitosan solution, and stirring at 60° C. for 1 hour; e) Add glycerol and polyethylene glycol 400 and continue stirring for 30 minutes; f) adding hydroxypropyl methylcellulose and stirring until completely dissolved; (2) Addition of active ingredients: a) dissolving the notoginseng extract, the bletilla striata extract, the dragon's blood extract and the gallnut extract in 50% ethanol; b) slowly adding the above solution into the gel matrix and stirring at 60° C. for 1 hour; c) adding musk extract, dissolving in a small amount of ethanol, and continuing stirring for 15 minutes; (3) pH adjustment and gel formation: a) preparing an aqueous solution of citric acid and sodium citrate; b) slowly adding a pH adjuster into the gel to adjust the pH to 6.8-7.2; c) Add oxidized cellulose and stir well.

8. The preparation method according to claim 7, characterized in that: The following steps are also included: (4) Gel forming and drying: a) Pour the gel into a mold with a thickness of 2-3 mm; b) Prefreeze in a -40°C refrigerator for 4 hours; c) Transfer to vacuum freeze dryer, set the shelf temperature to -30°C and the condenser temperature to -60°C; d) The vacuum degree is controlled at 10-20Pa and dried for 48 hours; e) Slowly raise the temperature to 25°C and continue drying for 4 hours; f) Take out the instant dissolving sheet dressing and test the moisture content to ensure that it is ≤3%.

9. The preparation method according to claim 8, characterized in that: The following steps are also included: (5) Packaging and sterilization: a) Cut the dried sheet dressing into suitable sizes; b) Use medical grade aluminum foil composite film vacuum packaging; c) Sterilize with ethylene oxide at a temperature of 50°C, a relative humidity of 60%, an ethylene oxide concentration of 600 mg / L, and a sterilization time of 4 hours; d) After sterilization, let it stand for 7 days for analysis; The following quality control steps are also included: a) Sterility test: according to the general rules 1101 of Part IV of the 2020 edition of the Chinese Pharmacopoeia; b) Determination of hemostasis time: rabbit ear bleeding model was used to determine the hemostasis time ≤ 60 seconds; c) Determination of water absorption rate: according to the general rules 0951 of Part IV of the 2020 edition of the Chinese Pharmacopoeia, the requirement is ≥10 times; d) pH value determination: Determined according to the method 0631 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia, range 6.8-7.2; e) Shelf life: Using the accelerated test method, stored at 40℃±2℃, relative humidity 75%±5% for 6 months, the estimated shelf life is 36 months.

10. The method for preparing the Panax notoginseng compound hemostatic and anti-infective preparation according to any one of claims 1 to 6, characterized in that: The preparation is a cataplasm, comprising the following steps: (1) Preparation of drug layer: a) dissolving 15-25 parts by weight of Panax notoginseng extract, 10-20 parts by weight of Bletilla striata extract, 5-15 parts by weight of Sanguisorba officinalis extract and 5-15 parts by weight of Galla chinensis extract in 100-150 parts by weight of 50% ethanol, and stirring at 60° C. for 1 hour; b) dissolving 0.1-0.5 parts by weight of musk extract in 5-10 parts by weight of 95% ethanol, adding the mixture, and continuing stirring at 60° C. for 15 minutes; c) adding 30-40 parts by weight of medical grade gelatin, 7-10 parts by weight of chitosan, 5-10 parts by weight of glycerol, and 3-7 parts by weight of polyethylene glycol 400, heating to 70° C., and stirring for 1 hour until completely dissolved; d) cooling to 50° C., adding 2-4 parts by weight of oxidized cellulose, and stirring for 30 minutes; e) adding 1-3 parts by weight of hydroxypropyl methylcellulose and stirring evenly; (2) pH adjustment: a) preparing an aqueous solution of 0.1-0.3 parts by weight of citric acid and 0.2-0.5 parts by weight of sodium citrate; b) slowly adding a pH adjuster to the mixture in three portions, each time with an interval of 10 minutes, to adjust the pH to 6.8-7.2; (3) Coating: a) heating the pH-adjusted mixture to 55-60° C. to maintain fluidity; b) using a scraper method to evenly coat the mixture on the polyester fiber non-woven fabric support layer, and controlling the coating thickness to be 0.8-1.2 mm; (4) Drying: a) Place the coated material in a 45°C oven for preliminary drying for 2 hours; b) Raise the temperature to 55°C and continue drying for 3 hours; c) lowering the temperature to 40°C and drying for 1 hour to control the final moisture content to 8-12%; (5) Cutting and packaging: a) Cut the dried material into 7cm×10cm size; b) Sealed with polyethylene / aluminum foil composite film (thickness 0.1 mm), with a sealing width of 5 mm on all four sides; and also including: a) The surface density of the polyester fiber nonwoven fabric support layer is 40±5 g / m 2 , thickness: 0.2±0.05mm; b) in step (1) e), the viscosity of hydroxypropyl methylcellulose is 2000-3000 mPa·s (2% aqueous solution, 20° C.); c) in step (3) b), the coating speed is controlled at 0.5-1 m / min; d) In step (4), the relative humidity in the oven is maintained at 50±5%.

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