Hemostatic wax and preparation method thereof

Abstract

The present invention proposes a hemostatic wax and a preparation method thereof, belonging to the technical field of hemostatic materials. The Chinese medicine extract is extracted with water from Panax notoginseng, Bletilla striata and Artemisia argyi, and added to the prepared hollow porous silica nanospheres, ferric chloride and ferrous chloride are added, ammonia water is added dropwise, and the mixture is stirred and precipitated to prepare magnetic drug-loaded nanospheres; the mixture is mixed with bone wax material and added to an aqueous solution containing sodium alginate, and a metal ion solution is added dropwise, solidified at room temperature, and filtered to prepare the hemostatic wax. The hemostatic wax prepared by the present invention is a hydrogel wax-like hemostatic material that can promote blood coagulation and has good plasticity and adhesion. It is used to control bleeding on bone wounds and can be completely degraded and absorbed within one month after use, thereby avoiding the risk of bone non-union and infection caused by foreign body occupation.

Description

Technical Field

[0001] The invention relates to the technical field of hemostatic materials, and in particular to a hemostatic wax and a preparation method thereof. Background Art

[0002] Bone wax, a commonly used hemostatic material, is widely used in orthopedic and neurosurgery procedures. It is suitable for hemostasis of various cancellous bone wounds, boasting excellent hemostatic effects and ease of use. However, fracture healing is a complex and continuous process. During the hematoma organization phase of a fracture, damage caused by the fracture leads to ruptured blood vessels, forming a hematoma around the fracture. The hematoma begins to coagulate into a blood clot containing reticulin within 24 hours. After 24 hours, organization and encapsulation begin, with fibrous tissue proliferation. After a highly complex fibrosis, a fibrous callus begins to form at the fracture end around 2 weeks later. During this period, the presence of foreign matter (including the fracture's own soft tissue or absorbable hemostatic materials) at the fracture surface can interfere with the organization of the hematoma, prolonging fracture healing and even leading to nonunion.

[0003] During spinal surgery, significant bleeding from the bone surface can significantly affect the surgical field of view and create significant inconvenience for the surgeon. Excessive blood loss can also impact the patient's recovery, necessitating prompt hemostasis. However, spinal surgeries such as scoliosis, cervical fusion, thoracic fusion, and lumbar fusion require bone fusion, otherwise, postoperative function can be significantly impacted, posing a safety hazard. While traditional bone wax offers excellent hemostatic properties, it is often not fully absorbed, leaving residue at the fracture site. This makes it unsuitable for hemostasis in spinal surgeries requiring spinal fusion.

[0004] Currently used bone wax is a mixture of 70% beeswax and 30% petrolatum. It has excellent softening properties, allowing it to be shaped after being rubbed soft by hand. It is non-toxic, but it is not degraded or absorbed by the body. However, since bone wax made from a mixture of beeswax and petrolatum cannot be absorbed by organisms, it remains in the body as a foreign body, increasing the probability of infection. Furthermore, due to the small molecular gaps, bone tissue cannot pass through the bone wax, which can hinder bone growth and lead to prolonged wound healing after surgery, necessitating postoperative debridement. This not only prolongs treatment time but also increases patient suffering. Summary of the Invention

[0005] The purpose of the present invention is to propose a hemostatic wax and a preparation method thereof. The hemostatic wax is a hydrogel wax-like hemostatic material that can promote blood coagulation, has good plasticity and adhesion, and is used to control bleeding from bone wounds. After use, it can be completely degraded and absorbed within one month, avoiding the risk of bone non-union and infection caused by foreign body occupation.

[0006] The technical solution of the present invention is achieved as follows:

[0007] The invention provides a preparation method of hemostatic wax. The method comprises the following steps: extracting Panax notoginseng, Bletilla striata and Artemisia argyi with water to obtain a traditional Chinese medicine extract, adding the extract to the prepared hollow porous silica nanospheres, adding ferric chloride and ferrous chloride, dripping ammonia water, stirring and sedimentation to obtain magnetic drug-loaded nanospheres; mixing the extract with a bone wax material, adding the extract to an aqueous solution containing sodium alginate, dripping a metal ion solution, solidifying at room temperature, filtering and obtaining the hemostatic wax.

[0008] As a further improvement of the present invention, the following steps are included:

[0009] S1. Preparation of Chinese herbal extracts: Panax notoginseng, Bletilla striata, and Artemisia argyi were dried and crushed to obtain Chinese herbal powder, extracted 2-3 times by boiling with water, filtered, and the filtrates were combined, concentrated and dried to obtain a Chinese herbal extract;

[0010] S2. Preparation of hollow porous silica nanospheres: Dissolve tetraethyl orthosilicate in ethyl acetate, add to an aqueous solution containing a surfactant and a porogen, emulsify, adjust the pH to alkaline, stir the reaction, centrifuge, wash, and dry to produce hollow porous silica nanospheres;

[0011] S3. Preparation of magnetic drug-loaded nanospheres: The herbal extract obtained in step S1 was dissolved in water, the hollow porous silica nanospheres obtained in step S2 were added, ferric chloride and ferrous chloride were added, ammonia was added dropwise, stirred and deposited, and heated to evaporate to obtain magnetic drug-loaded nanospheres;

[0012] S4. Preparation of bone wax material: Poloxamer and ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain bone wax material;

[0013] S5. Preparation of hemostatic wax: dissolve sodium alginate in water, add the magnetic drug-loaded nanospheres obtained in step S3 and the bone wax material obtained in step S4, stir and mix evenly, add dropwise the metal salt solution, solidify at room temperature, filter, and obtain hemostatic wax.

[0014] As a further improvement of the present invention, the mass ratio of Panax notoginseng, Bletilla striata and Artemisia argyi in step S1 is 5-7:2-3:1-2, the solid-liquid ratio of the Chinese medicine powder and water is 1:5-10 g / mL, and the boiling extraction time is 2-3 h.

[0015] As a further improvement of the present invention, the mass ratio of the ethyl orthosilicate, the surfactant and the porogen in step S2 is 15-20:1-2:0.5-1, the porogen is selected from at least one of hexadecyltrimethylammonium bromide, hexadecylbenzyldimethylammonium chloride, octadecyltrimethylammonium bromide and tetradecyltrimethylammonium chloride, and the adjusted pH value is 9-10.

[0016] As a further improvement of the present invention, the molar ratio of ferric chloride to ferrous chloride in step S3 is 1:1, the mass ratio of the traditional Chinese medicine extract, the hollow porous silica nanospheres, ferric chloride, and ammonia water is 5-10:12-17:2-4:2-3, and the concentration of the ammonia water is 15-20wt%.

[0017] As a further improvement of the present invention, the mass ratio of the poloxamer to the ethylene oxide propylene oxide random copolymer in step S4 is 3-7:3-7.

[0018] As a further improvement of the present invention, the poloxamer comprises poloxamer 188 and poloxamer 407 in a mass ratio of 5-10:3-5.

[0019] As a further improvement of the present invention, the mass ratio of sodium alginate, magnetic drug-loaded nanospheres, bone wax material and metal salt in step S5 is 15-20:5-7:4-5:1-2, the metal salt is selected from at least one of calcium chloride, aluminum chloride, ferric chloride, magnesium chloride and ferrous chloride, and the room temperature curing time is 20-30 min.

[0020] As a further improvement of the present invention, the present invention specifically comprises the following steps:

[0021] S1. Preparation of Chinese herbal extract: 5-7 parts by weight of Panax notoginseng, 2-3 parts by weight of Bletilla striata, 1-2 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2-3h, repeated 2-3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1: 5-10g / mL, filtered, the filtrate was combined, concentrated and dried to obtain a Chinese herbal extract;

[0022] S2. Preparation of hollow porous silica nanospheres: 15-20 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and 100 parts by weight of an aqueous solution containing 1-2 parts by weight of a surfactant and 0.5-1 parts by weight of a porogen was added. The mixture was emulsified at 12000-15000 r / min for 15-20 min, the pH value was adjusted to 9-10, and the reaction was stirred for 5-7 h, centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0023] S3. Preparation of magnetic drug-loaded nanospheres: 5-10 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 12-17 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 2-4 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride and ferrous chloride being 1:1, 2-3 parts by weight of 15-20wt% ammonia solution was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0024] S4 bone wax material preparation: 3-7 parts by weight of poloxamer and 3-7 parts by weight of ethylene oxide propylene oxide random copolymer was heated and dissolved to obtain a bone wax material;

[0025] The poloxamer comprises poloxamer 188 and poloxamer 407 in a mass ratio of 5-10:3-5;

[0026] S5. Preparation of hemostatic wax: 15-20 parts by weight of sodium alginate is dissolved in 100 parts by weight of water, 5-7 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 and 4-5 parts by weight of the bone wax material obtained in step S4 are added, the mixture is stirred and mixed evenly, 10 parts by weight of a solution containing 1-2 parts by weight of a metal salt is added dropwise, and the mixture is cured at room temperature for 20-30 minutes and filtered to obtain the hemostatic wax.

[0027] The present invention further protects a hemostatic wax prepared by the above preparation method.

[0028] The present invention has the following beneficial effects: The hemostatic Chinese medicine of the present invention comprises Panax notoginseng, Bletilla striata and Artemisia argyi. Panax notoginseng is suitable for bleeding syndrome caused by internal blood stasis and blood not circulating through the menstrual period. Symptoms include repeated bleeding, dark purple blood with blood clots, and can also be used for symptoms such as traumatic injury, stasis amenorrhea, and abdominal pain; Bletilla striata is suitable for bleeding syndrome caused by internal blood stasis and blood not circulating through the menstrual period. Symptoms include repeated bleeding, dark purple blood with blood clots, and can also be used for symptoms such as traumatic injury, stasis amenorrhea, and abdominal pain. Artemisia argyi is suitable for bleeding syndrome caused by deficiency-cold. Symptoms include prolonged bleeding, dark purple blood, and thin blood.

[0029] Poloxamer 188 is a nonionic surfactant that, when used in combination with phospholipids, forms a stable emulsion film, enhancing the stability of the interphase of drug delivery systems such as emulsions and lipid nanoparticles. As a surfactant, it can increase the surface solubility of various drugs, such as o-hydroxybenzoic acid (salicylic acid, the main active ingredient in aspirin and various analgesics), diazepam, and indomethacin, by forming micelles. The solubility of o-hydroxybenzoic acid in F68 increases with increasing surfactant concentration. Poloxamer 188 also has good compatibility with the skin and can effectively promote the absorption of topical medications by increasing skin permeability. Poloxamer 407, like poloxamer 188, belongs to the same family of polyoxyethylene / polyoxypropylene copolymers and therefore shares many similarities in physical and chemical properties. The resulting bone wax material exhibits excellent plasticity and adhesion, making it useful for controlling bleeding from bone wounds.

[0030] A mixture of nano-silica and magnetic ferroferric oxide can promote blood coagulation. By combining the magnetic properties of ferroferric oxide with the coagulation activity of thrombin, and through the action of an external magnetic field, the magnetic hemostatic nanoparticles are directly introduced into the body's circulatory system and then positioned in the bleeding area to achieve precise and rapid hemostasis.

[0031] The hemostatic wax prepared by the present invention is a hydrogel wax-like hemostatic material that can promote blood coagulation and has good plasticity and adhesion. It is used to control bleeding on bone wounds and can be completely degraded and absorbed within one month after use, avoiding the risk of bone non-union and infection caused by foreign body occupation. DETAILED DESCRIPTION

[0032] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0033] Example 1

[0034] This embodiment provides a hemostatic wax, and the preparation method specifically includes the following steps:

[0035] S1. Preparation of Chinese herbal extract: 5 parts by weight of Panax notoginseng, 2 parts by weight of Bletilla striata, and 1 part by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2h, repeated 2 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:5g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0036] S2. Preparation of hollow porous silica nanospheres: 15 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1 part by weight of sodium dodecylbenzenesulfonate and 0.5 parts by weight of hexadecyltrimethylammonium chloride. The mixture was emulsified at 12,000 r / min for 15 min, the pH value was adjusted to 9, and the reaction was stirred for 5 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0037] S3. Preparation of magnetic drug-loaded nanospheres: 5 parts by weight of the Chinese herbal extract obtained in step S1 was dissolved in water, 12 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 2 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride to ferrous chloride was 1:1, 2 parts by weight of 15wt% ammonia solution were added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0038] S4. Preparation of bone wax material: 3 parts by weight of poloxamer and 7 parts by weight of ethylene oxide propylene oxide random copolymer was heated and dissolved to obtain a bone wax material;

[0039] The poloxamer comprises poloxamer 188 and poloxamer 407 in a mass ratio of 5:3;

[0040] S5. Preparation of hemostatic wax: 15 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 5 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 and 4 parts by weight of the bone wax material obtained in step S4 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1 part by weight of calcium chloride was added dropwise, cured at room temperature for 20 minutes, filtered, and the hemostatic wax was obtained.

[0041] Example 2

[0042] This embodiment provides a hemostatic wax, and the preparation method specifically includes the following steps:

[0043] S1. Preparation of Chinese herbal extract: 7 parts by weight of Panax notoginseng, 3 parts by weight of Bletilla striata, and 2 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 3 h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:10 g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0044] S2. Preparation of hollow porous silica nanospheres: 20 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 2 parts by weight of sodium dodecylbenzenesulfonate and 1 part by weight of tetradecyltrimethylammonium chloride. The mixture was emulsified at 15,000 r / min for 20 min, the pH value was adjusted to 10, and the reaction was stirred for 7 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0045] S3. Preparation of magnetic drug-loaded nanospheres: 10 parts by weight of the Chinese herbal extract obtained in step S1 was dissolved in water, 17 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 4 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride to ferrous chloride was 1:1, 3 parts by weight of 20wt% ammonia solution was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0046] S4. Preparation of bone wax material: 7 parts by weight of poloxamer and 3 parts by weight of ethylene oxide propylene oxide random copolymer was heated and dissolved to obtain a bone wax material;

[0047] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 10:5;

[0048] S5. Preparation of hemostatic wax: 20 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 7 parts by weight of magnetic drug-loaded nanospheres obtained in step S3 and 5 parts by weight of bone wax material obtained in step S4 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 2 parts by weight of ferric chloride was added dropwise, cured at room temperature for 30 minutes, filtered, and the hemostatic wax was obtained.

[0049] Example 3

[0050] This embodiment provides a hemostatic wax, and the preparation method specifically includes the following steps:

[0051] S1. Preparation of Chinese herbal extract: 6 parts by weight of Panax notoginseng, 2.5 parts by weight of Bletilla striata, and 1.5 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2.5h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:7g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0052] S2. Preparation of hollow porous silica nanospheres: 17 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1.5 parts by weight of sodium dodecylbenzenesulfonate and 0.7 parts by weight of hexadecylbenzyldimethylammonium chloride. The mixture was emulsified at 13500 r / min for 17 min, the pH value was adjusted to 9.5, and the reaction was stirred for 6 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0053] S3. Preparation of magnetic drug-loaded nanospheres: 7 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 15 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 3 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride to ferrous chloride was 1:1, 2.5 parts by weight of 17wt% ammonia was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0054] S4. Preparation of bone wax material: 5 parts by weight of poloxamer and 5 parts by weight of ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain a bone wax material;

[0055] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 7:4;

[0056] S5. Preparation of hemostatic wax: 17 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 6 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 and 4.5 parts by weight of the bone wax material obtained in step S4 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1.5 parts by weight of magnesium chloride was added dropwise, cured at room temperature for 25 minutes, filtered, and the hemostatic wax was obtained.

[0057] Comparative Example 1

[0058] Compared with embodiment 3, the difference is that step S1 is not performed.

[0059] The specific steps include:

[0060] S1. Preparation of hollow porous silica nanospheres: 17 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1.5 parts by weight of sodium dodecylbenzenesulfonate and 0.7 parts by weight of hexadecylbenzyldimethylammonium chloride. The mixture was emulsified at 13500 r / min for 17 min, the pH value was adjusted to 9.5, and the reaction was stirred for 6 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0061] S2. Preparation of magnetic nanospheres: 22 parts by weight of the hollow porous silica nanospheres prepared in step S2 were added 3 parts by weight of ferric chloride and ferrous chloride, the molar ratio of ferric chloride and ferrous chloride being 1:1, 2.5 parts by weight of 17wt% ammonia solution was added dropwise, stirred and deposited, and heated to dryness to obtain magnetic nanospheres;

[0062] S3. Preparation of bone wax material: 5 parts by weight of poloxamer and 5 parts by weight of ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain a bone wax material;

[0063] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 7:4;

[0064] S4. Preparation of hemostatic wax: 17 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 6 parts by weight of magnetic nanospheres obtained in step S2 and 4.5 parts by weight of bone wax material obtained in step S3 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1.5 parts by weight of magnesium chloride was added dropwise, cured at room temperature for 25 minutes, filtered, and the hemostatic wax was obtained.

[0065] Comparative Example 2

[0066] Compared with embodiment 3, the difference is that step S2 is not performed.

[0067] The specific steps include:

[0068] S1. Preparation of Chinese herbal extract: 6 parts by weight of Panax notoginseng, 2.5 parts by weight of Bletilla striata, and 1.5 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2.5h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:7g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0069] S2. Preparation of magnetic drug-loaded nanospheres: 7 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 18 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride and ferrous chloride being 1:1, 10 parts by weight of 17wt% ammonia was added dropwise, stirred and deposited, and heated to dryness to obtain magnetic drug-loaded nanospheres;

[0070] S3. Preparation of bone wax material: 5 parts by weight of poloxamer and 5 parts by weight of ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain a bone wax material;

[0071] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 7:4;

[0072] S4. Preparation of hemostatic wax: 17 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 6 parts by weight of the magnetic drug-loaded nanospheres obtained in step S2 and 4.5 parts by weight of the bone wax material obtained in step S3 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1.5 parts by weight of magnesium chloride was added dropwise, cured at room temperature for 25 minutes, filtered, and the hemostatic wax was obtained.

[0073] Comparative Example 3

[0074] Compared with Example 3, the difference is that ferric chloride and ferrous chloride are not added in step S3.

[0075] The specific steps include:

[0076] S1. Preparation of Chinese herbal extract: 6 parts by weight of Panax notoginseng, 2.5 parts by weight of Bletilla striata, and 1.5 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2.5h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:7g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0077] S2. Preparation of hollow porous silica nanospheres: 17 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1.5 parts by weight of sodium dodecylbenzenesulfonate and 0.7 parts by weight of hexadecylbenzyldimethylammonium chloride. The mixture was emulsified at 13500 r / min for 17 min, the pH value was adjusted to 9.5, and the reaction was stirred for 6 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0078] S3 Preparation of drug-loaded nanospheres: 7 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 15 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, stirred and deposited, heated and evaporated to obtain drug-loaded nanospheres;

[0079] S4. Preparation of bone wax material: 5 parts by weight of poloxamer and 5 parts by weight of ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain a bone wax material;

[0080] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 7:4;

[0081] S5. Preparation of hemostatic wax: 17 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 6 parts by weight of drug-loaded nanospheres obtained in step S3 and 4.5 parts by weight of bone wax material obtained in step S4 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1.5 parts by weight of magnesium chloride was added dropwise, cured at room temperature for 25 minutes, filtered, and the hemostatic wax was obtained.

[0082] Comparative Example 4

[0083] Compared with embodiment 3, the difference is that step S4 is not performed.

[0084] The specific steps include:

[0085] S1. Preparation of Chinese herbal extract: 6 parts by weight of Panax notoginseng, 2.5 parts by weight of Bletilla striata, and 1.5 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2.5h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:7g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0086] S2. Preparation of hollow porous silica nanospheres: 17 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1.5 parts by weight of sodium dodecylbenzenesulfonate and 0.7 parts by weight of hexadecylbenzyldimethylammonium chloride. The mixture was emulsified at 13500 r / min for 17 min, the pH value was adjusted to 9.5, and the reaction was stirred for 6 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0087] S3. Preparation of magnetic drug-loaded nanospheres: 7 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 15 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 3 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride to ferrous chloride was 1:1, 2.5 parts by weight of 17wt% ammonia was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0088] S4. Preparation of hemostatic wax: 17 parts by weight of sodium alginate was dissolved in 100 parts by weight of water, 10.5 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 were added, stirred and mixed evenly, 10 parts by weight of a solution containing 1.5 parts by weight of magnesium chloride was added dropwise, cured at room temperature for 25 minutes, filtered, and the hemostatic wax was obtained.

[0089] Comparative Example 5

[0090] Compared with Example 3, the difference is that sodium alginate is not added in step S5.

[0091] The specific steps include:

[0092] S1. Preparation of Chinese herbal extract: 6 parts by weight of Panax notoginseng, 2.5 parts by weight of Bletilla striata, and 1.5 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2.5h, repeated 3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1:7g / mL, filtered, and the filtrate was combined and concentrated to obtain a Chinese herbal extract;

[0093] S2. Preparation of hollow porous silica nanospheres: 17 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and then added to 100 parts by weight of an aqueous solution containing 1.5 parts by weight of sodium dodecylbenzenesulfonate and 0.7 parts by weight of hexadecylbenzyldimethylammonium chloride. The mixture was emulsified at 13500 r / min for 17 min, the pH value was adjusted to 9.5, and the reaction was stirred for 6 h. The mixture was centrifuged, washed, and dried to obtain hollow porous silica nanospheres.

[0094] S3. Preparation of magnetic drug-loaded nanospheres: 7 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 15 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 3 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride to ferrous chloride was 1:1, 2.5 parts by weight of 17wt% ammonia was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres;

[0095] S4. Preparation of bone wax material: 5 parts by weight of poloxamer and 5 parts by weight of ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain a bone wax material;

[0096] The poloxamer comprises poloxamer 188 and poloxamer 407, with a mass ratio of 7:4;

[0097] S5. Preparation of hemostatic wax: 6 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 and 4.5 parts by weight of the bone wax material obtained in step S4 were stirred and mixed to obtain hemostatic wax.

[0098] Test Example 1

[0099] The hemostatic waxes prepared in Examples 1-3 of the present invention and Comparative Examples 1-5 were subjected to performance tests.

[0100] 1. Volume Swelling Rate: Using the liquid displacement method, soak the hemostatic bone wax material in a graduated cylinder and read the liquid level rise. The volume swelling rate is calculated as the percentage of the difference between the saturated volume V1 and the initial volume V0 as a percentage of the initial volume V0.

[0101] 2. Mass Swelling Rate: Using the weighing method, completely soak the hemostatic bone wax material, remove it, remove any excess unabsorbed water, and weigh it. The mass swelling rate is calculated as the percentage of the difference between the mass after saturated swelling, M1, and the initial mass, M0, as a percentage of the initial mass, M0.

[0102] The results are shown in Table 1.

[0103] Table 1

[0104] Group Volume swelling rate (%) Mass swelling rate (%) Example 1 755 2200 Example 2 759 2350 Example 3 762 2370 Comparative Example 1 747 2120 Comparative Example 2 690 1890 Comparative Example 3 620 1810 Comparative Example 4 735 2100 Comparative Example 5 220 550

[0105] It can be seen from the above table that the hemostatic waxes prepared in Examples 1-3 of the present invention have relatively high volume swelling rates and mass swelling rates.

[0106] Test Example 2

[0107] 80 healthy 12-month-old adult ordinary-grade small-tailed Han sheep were selected and divided into 10 groups, with 8 sheep in each group. The experimental sheep were divided into Example 1-3 and Comparative Example 1-5 groups, a control group, and a blank group. The experimental sheep were all subjected to median sternotomy to create a bone surface injury model. After the experimental sheep were anesthetized to satisfaction, a longitudinal incision was made on the sternum, and the sternum was split open with an oscillating saw to expose the cross-section of the sternum to see active bleeding. After using gauze to initially treat the bleeding, hemostatic wax and reference substance bone wax prepared in Example 1-3 or Comparative Example 1-5, which had been pre-kneaded to a plastic state, were used to pack two sections of the damaged sternum model in the experimental group and the control group, respectively, for hemostasis. The remaining two sections were pressed with gauze for hemostasis and hemostatic materials were used for the blank group. The hemostatic effect of each group of wounds was observed and recorded 3 minutes after the packing was completed. After observing that the experimental sheep had no abnormalities, the incisions were closed layer by layer. After waking up from anesthesia, they were placed in a breeding room for breeding.

[0108] The 3-minute hemostasis rate was observed. The rates of significant, effective, and ineffective hemostasis were calculated based on the intraoperative hemostatic effect. Hemostasis was categorized into three levels: ① Significant (complete cessation of wound bleeding, significant hemostasis, and strong adhesion without shedding); ② Effective (basic cessation of wound bleeding with minimal oozing around the wound, and relatively strong adhesion without shedding); and ③ Ineffective (significant oozing of wound blood, poor hemostasis, and loose adhesion with shedding).

[0109] The results are shown in Table 2.

[0110] Table 2

[0111] Group significant efficient invalid Efficiency (%) Blank group 0 0 8 0 control group 4 3 1 87.5 Example 1 8 0 0 100 Example 2 8 0 0 100 Example 3 8 0 0 100 Comparative Example 1 6 1 1 87.5 Comparative Example 2 6 2 0 100 Comparative Example 3 5 3 0 100 Comparative Example 4 3 3 2 75 Comparative Example 5 3 4 1 87.5

[0112] As can be seen from the above table, the hemostatic waxes prepared in Examples 1-3 of the present invention have a 100% effective hemostatic effect.

[0113] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing hemostatic wax, characterized in that: The Chinese medicine extracts are extracted with water from Panax notoginseng, Bletilla striata and Artemisia argyi, and the extracts are added to the prepared hollow porous silica nanospheres. Ferric chloride and ferrous chloride are added, and ammonia water is added dropwise. The extracts are stirred and precipitated to prepare magnetic drug-loaded nanospheres. The extracts are mixed with bone wax material and added to an aqueous solution containing sodium alginate. A metal ion solution is added dropwise, solidified at room temperature, and filtered to prepare hemostatic wax. The bone wax material is obtained by heating and dissolving a random copolymer of poloxamer and ethylene oxide and propylene oxide.

2. The preparation method according to claim 1, characterized in that The following steps are involved: S1. Preparation of Chinese herbal extracts: Panax notoginseng, Bletilla striata, and Artemisia argyi were dried and crushed to obtain Chinese herbal powder, extracted 2-3 times by boiling with water, filtered, and the filtrates were combined, concentrated and dried to obtain a Chinese herbal extract; S2. Preparation of hollow porous silica nanospheres: Dissolve tetraethyl orthosilicate in ethyl acetate, add to an aqueous solution containing a surfactant and a porogen, emulsify, adjust the pH to alkaline, stir the reaction, centrifuge, wash, and dry to produce hollow porous silica nanospheres; S3. Preparation of magnetic drug-loaded nanospheres: The herbal extract obtained in step S1 was dissolved in water, the hollow porous silica nanospheres obtained in step S2 were added, ferric chloride and ferrous chloride were added, ammonia was added dropwise, stirred and deposited, and heated to evaporate to obtain magnetic drug-loaded nanospheres; S4. Preparation of bone wax material: Poloxamer and ethylene oxide propylene oxide random copolymer were heated and dissolved to obtain bone wax material; S5. Preparation of hemostatic wax: dissolve sodium alginate in water, add the magnetic drug-loaded nanospheres obtained in step S3 and the bone wax material obtained in step S4, stir and mix evenly, add dropwise the metal salt solution, solidify at room temperature, filter, and obtain hemostatic wax.

3. The preparation method according to claim 2, characterized in that In step S1, the mass ratio of Panax notoginseng, Bletilla striata, and Artemisia argyi is 5-7:2-3:1-2, the solid-liquid ratio of the Chinese medicine powder and water is 1:5-10 g / mL, and the boiling extraction time is 2-3 hours.

4. The preparation method according to claim 2, characterized in that In step S2, the mass ratio of the ethyl orthosilicate, the surfactant, and the porogen is 15-20:1-2:0.5-1, the porogen is selected from at least one of hexadecyltrimethylammonium bromide, hexadecylbenzyldimethylammonium chloride, octadecyltrimethylammonium bromide, and tetradecyltrimethylammonium chloride, and the adjusted pH value is 9-10.

5. The preparation method according to claim 2, characterized in that In step S3, the molar ratio of ferric chloride to ferrous chloride is 1:1, the mass ratio of the traditional Chinese medicine extract, the hollow porous silica nanospheres, ferric chloride, and ammonia water is 5-10:12-17:2-4:2-3, and the concentration of the ammonia water is 15-20wt%.

6. The preparation method according to claim 2, characterized in that The mass ratio of the poloxamer to the ethylene oxide propylene oxide random copolymer in step S4 is 3-7:3-7.

7. The preparation method according to claim 6, characterized in that The poloxamer includes poloxamer 188 and poloxamer 407, with a mass ratio of 5-10:3-5.

8. The preparation method according to claim 2, characterized in that In step S5, the mass ratio of sodium alginate, magnetic drug-loaded nanospheres, bone wax material and metal salt is 15-20:5-7:4-5:1-2, the metal salt is selected from at least one of calcium chloride, aluminum chloride, ferric chloride and ferrous chloride, and the room temperature curing time is 20-30 minutes.

9. The preparation method according to claim 2, characterized in that The specific steps include: S1. Preparation of Chinese herbal extract: 5-7 parts by weight of Panax notoginseng, 2-3 parts by weight of Bletilla striata, 1-2 parts by weight of Artemisia argyi were dried and crushed to obtain Chinese herbal powder, and extracted by boiling with water for 2-3h, repeated 2-3 times, the solid-liquid ratio of the Chinese herbal powder and water was 1: 5-10g / mL, filtered, the filtrate was combined, concentrated and dried to obtain a Chinese herbal extract; S2. Preparation of hollow porous silica nanospheres: 15-20 parts by weight of tetraethyl orthosilicate was dissolved in 50 parts by weight of ethyl acetate, and 100 parts by weight of an aqueous solution containing 1-2 parts by weight of a surfactant and 0.5-1 parts by weight of a porogen was added. The mixture was emulsified at 12000-15000 r / min for 15-20 min, the pH value was adjusted to 9-10, and the reaction was stirred for 5-7 h, centrifuged, washed, and dried to obtain hollow porous silica nanospheres. S3. Preparation of magnetic drug-loaded nanospheres: 5-10 parts by weight of the herbal extract obtained in step S1 was dissolved in water, 12-17 parts by weight of the hollow porous silica nanospheres obtained in step S2 were added, 2-4 parts by weight of ferric chloride and ferrous chloride were added, the molar ratio of ferric chloride and ferrous chloride being 1:1, 2-3 parts by weight of 15-20wt% ammonia solution was added dropwise, stirred and deposited, heated and evaporated to obtain magnetic drug-loaded nanospheres; S4 bone wax material preparation: 3-7 parts by weight of poloxamer and 3-7 parts by weight of ethylene oxide propylene oxide random copolymer was heated and dissolved to obtain a bone wax material; The poloxamer comprises poloxamer 188 and poloxamer 407 in a mass ratio of 5-10:3-5; S5. Preparation of hemostatic wax: 15-20 parts by weight of sodium alginate is dissolved in 100 parts by weight of water, 5-7 parts by weight of the magnetic drug-loaded nanospheres obtained in step S3 and 4-5 parts by weight of the bone wax material obtained in step S4 are added, the mixture is stirred and mixed evenly, 10 parts by weight of a solution containing 1-2 parts by weight of a metal salt is added dropwise, and the mixture is cured at room temperature for 20-30 minutes and filtered to obtain the hemostatic wax.

10. A hemostatic wax prepared by the preparation method according to any one of claims 1 to 9.