A biomimetic medical tissue adhesive and a preparation method thereof

Abstract

The application relates to the technical field of medical materials, and particularly discloses a kind of bionic medical tissue adhesive and a preparation method thereof.A kind of bionic medical tissue adhesive is made of raw materials containing the following weight parts: alpha-cyano octyl acrylate 30-35 parts;degradable polymer material 20-30 parts;gelatin 1-5 parts;polyethylene glycol 2-5 parts;sterile water 20-30 parts;sodium alginate 2-4 parts;antibacterial agent 8-10 parts;stabilizing protective agent 1-3 parts;mussel extract 1-3 parts;slug extract 1-3 parts;its preparation method is: polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stabilizing protective agent, mussel extract and slug extract are mixed, and stirred uniformly;then alpha-cyano octyl acrylate, degradable polymer material and gelatin are added, heated to 40-60 DEG C and stirred for 20-40 min, and the bionic medical tissue adhesive can be obtained.The bionic medical tissue adhesive of the application can better handle the skin tissue changes occurring in the proliferation period, so that the prominence of the scar formed in the later period is smaller, the whole is relatively flat and smooth, and thus the scar is greatly improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical materials, more particularly, it relates to a kind of bionic medical tissue adhesive and preparation method thereof. BACKGROUND

[0002] Medical gel is a kind of semi-solid substance usually transparent and viscous, commonly used in medical field finish paint, it not only can form protective barrier, thereby promoting the healing of wound, reducing bacterial infection and water loss, but also can use its own containing anesthetic, anti-inflammatory ingredients, etc., relieve pain and discomfort caused by trauma or inflammation.

[0003] In the process of wound repair, if the skin tissue is seriously damaged due to deep wound, scar is likely to occur after repair. In the process of scar formation, it is usually divided into four stages: one, hemostasis period, after skin damage, the first on the scene is the blood coagulation system, which can make the wound stop bleeding quickly in a short time; two, inflammation period, when the blood coagulation system completes the task, the immune system will start to eliminate dead cells and bacteria, and the wound may appear red, swollen and painful; three, proliferation period, mainly including epithelial formation and fibroplasia, epithelial cells are responsible for growing from the edge of the wound to the center, and mature to form complete skin, while fibroblasts are responsible for gathering in large quantities at the wound site to produce new collagen fibers to fill the damaged area; four, maturation period, at this time, the epidermis and dermis have been completely healed, and finally leave scars.

[0004] However, the existing medical gel tends to focus on the hemostasis period and the inflammation period in the application process, so it cannot well handle the changes of skin tissue in the proliferation period, resulting in prominent scar in the later period and uneven height. Therefore, there is an urgent need to propose a solution to solve the above technical problems. SUMMARY

[0005] In order to make the medical gel better handle the changes of skin tissue in the proliferation period in the process of wound repair, and improve the scar formed in the later period, the present application provides a kind of bionic medical tissue adhesive and preparation method thereof.

[0006] In the first aspect, the present application provides a kind of bionic medical tissue adhesive, which adopts the following technical scheme:

[0007] A kind of bionic medical tissue adhesive is made of raw materials containing the following weight parts:

[0008] Alpha-cyanoacrylic acid octyl ester 30-35 parts;

[0009] 20-30 parts of degradable polymer material;

[0010] 1-5 parts of gelatin;

[0011] 2-5 parts of polyethylene glycol;

[0012] Sterile water 20-30 parts;

[0013] Sodium alginate 2-4 parts;

[0014] Antibacterial agent 8-10 parts;

[0015] Stable protective agent 1-3 parts;

[0016] Mussel extract 1-3 parts;

[0017] Slug extract 1-3 parts;

[0018] The mussel extract is obtained by the following method:

[0019] After the mussel is shelled and treated, water is added and crushed, and then it is incubated at 75-85℃ for 20-24h. After cooling to room temperature, it is extracted with a mixed solvent of n-hexane, ethyl acetate and n-butanol. The obtained extract is dried to obtain the mussel extract;

[0020] The slug extract is obtained by the following method:

[0021] After the slug is vacuum freeze-dried, water is added and stirred in a water bath, and then an ethanol solution with a concentration of 60%-70% is added. After stirring, solid-liquid separation is performed. The obtained separation liquid is ultrafiltered, concentrated and dried to obtain the slug extract.

[0022] By adopting the above technical solution, the octyl alpha-cyanoacrylate, the degradable polymer material and the gelatin constitute the main matrix material of the biomimetic medical tissue adhesive, which can play excellent adhesion performance and make other component raw materials fully play a role in the mixed matrix. The mussel extract contains various active substances, which can not only be closely combined with the damaged skin tissue, but also stimulate and regulate the skin tissue changes occurring in the proliferation period to ensure the uniformity of the growing skin tissue; the slug extract can deeply and closely act on the deep skin tissue of the wound through three actions of electrostatic attraction, atomic covalent bond and physical structure mutual penetration, and regulate the changes of the new skin tissue in the proliferation period in the form of energy dissipation to achieve scar improvement; and the degradable polymer material, the mussel extract and the slug extract are used in combination, which can play an excellent synergistic effect, and through the penetration and degradation of the degradable polymer material, more space will be gradually reserved for the new skin tissue of the wound as the proliferation period is continuously extended. Through the cooperation and regulation of the mussel extract and the slug extract, the skin tissue changes occurring in the proliferation period can be better handled, so that the scar formed in the later stage is less prominent and more smooth and flat, and thus the scar is greatly improved, and the biomimetic medical tissue adhesive plays a more prominent application effect.

[0023] Preferably, the weight ratio of the degradable polymer material, mussel extract and slug extract is 18:1:1.

[0024] By adopting the above technical solution, the degradable polymer material, mussel extract and slug extract in the above ratio play a more excellent effect on each other in promoting wound repair, and have a more outstanding improvement effect on scar formation.

[0025] Preferably, in the extraction of the mussel extract, the weight mixing ratio of n-hexane, ethyl acetate and n-butanol is 1:0.7:3.

[0026] By adopting the above technical solution, the n-hexane, ethyl acetate and n-butanol in the above weight mixing ratio are used to extract the mussel, and the active substances in the obtained mussel extract are more abundant and have a higher content, such as polysaccharides, polyphenols, proteins, etc. Therefore, the mussel extract plays a more outstanding effect in application, and has a more excellent and stable regulating effect on the new skin tissue at the wound site in cooperation with the slug extract. Finally, the biomimetic medical tissue adhesive has a more excellent improvement effect on the later-formed scar.

[0027] Preferably, the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester, and the weight ratio of the biodegradable waterborne polyurethane and the degradable natural polyester is 1:(2.6-3.4).

[0028] By adopting the above technical solution, the biodegradable waterborne polyurethane and the degradable natural polyester are used to form the degradable polymer material in a specific weight range ratio. Not only can the biodegradable waterborne polyurethane and the degradable natural polyester form a stable mixed matrix with α-cyanoacrylic acid octyl ester and gelatin, so that the raw materials can be fully mixed and play an excellent and stable role, but also can form a two-stage gradient degradation mechanism in the proliferation period, reserve more space for the new skin tissue at the wound site, and release the mussel extract and the slug extract in stages. The adjustment ability to the skin tissue changes occurring in the proliferation period is stronger, and thus the improvement effect of the biomimetic medical tissue adhesive on the later-formed scar is more excellent.

[0029] Preferably, the weight ratio of the biodegradable waterborne polyurethane and the degradable natural polyester is 1:3.

[0030] By adopting the above technical solution, the biodegradable waterborne polyurethane and the degradable natural polyester in the above ratio play a more excellent effect in application, and the obtained biomimetic medical tissue adhesive has better quality.

[0031] Preferably, the components of the biomimetic medical tissue adhesive also add 0.8-1.6 parts by weight of a tissue conditioner, which is composed of plant extracts and hyaluronic acid modified carbon nanotube / chitosan composite material in a weight ratio of (1.4-1.8):1, and the hyaluronic acid modified carbon nanotube / chitosan composite material is obtained by the following method:

[0032] Take the carbon nanotube raw material, after acidification treatment, add it to the mixed solution of acetic acid and polyethylene glycol, ultrasonic dispersion, then add chitosan raw material and hyaluronic acid raw material, continue ultrasonic treatment at 30-40℃ for 15-20min, after high-speed shearing and vacuum drying, hyaluronic acid modified carbon nanotube / chitosan composite material can be obtained.

[0033] By adopting the above technical scheme, the hyaluronic acid modified carbon nanotube / chitosan composite material can quickly and uniformly conduct the mussel extract and slug extract into the wound, so that the biomimetic medical tissue adhesive can play a more excellent scar improvement effect. Among them, the carbon nanotube acts as a conduit and transmits the skin tissue bioelectricity at the wound, bringing a balance effect; chitosan can assist the uniform dispersion of carbon nanotube and integrate into each component raw material; hyaluronic acid can precisely match the wound with the guidance of carbon nanotube; at the same time, the plant extract is combined with the hyaluronic acid modified carbon nanotube / chitosan composite material, in the process, the plant extract not only plays its own stabilizing effect, but also combines with the hyaluronic acid molecule to be more compatible with the newly generated skin tissue at the wound, so that the application of the tissue conditioner can greatly improve the effect of the biomimetic medical tissue adhesive in improving the scar.

[0034] Preferably, the plant extract is one or a combination of several of the following: Dendrobium candidum extract, onion extract, and Gynura extract.

[0035] By adopting the above technical scheme, the above types of plant extracts can interact with hyaluronic acid molecules and play an excellent stabilizing effect, and the combination effect with the hyaluronic acid modified carbon nanotube / chitosan composite material is good, and the quality of the obtained biomimetic medical tissue adhesive is also high.

[0036] Preferably, the antibacterial agent is nano-zirconium phosphate silver.

[0037] By adopting the above technical scheme, nano-zirconium phosphate silver can release silver ions for a long time, play a broad-spectrum sterilization, strong antibacterial and repair and healing effect, so that the overall quality of the biomimetic medical tissue adhesive is more excellent when applied.

[0038] Preferably, the stabilizing protective agent is one or a combination of several of the following: carbomer, betadex, and polysorbate 80.

[0039] By adopting the technical scheme, the stable protective agent of the kind can be uniformly dispersed among other component raw materials and play a stable protection role, so that the biomimetic medical tissue adhesive is less affected by external environment changes and can play an excellent stable effect in promoting wound repair.

[0040] In a second aspect, the application provides a preparation method of a biomimetic medical tissue adhesive, which adopts the following technical scheme:

[0041] A preparation method of a biomimetic medical tissue adhesive, comprising the following steps:

[0042] (1) Preparing raw materials including alpha-cyanoacrylic acid octyl ester, degradable polymer material, gelatin, polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stable protective agent, mussel extract and slug extract according to a proportion;

[0043] (2) Mixing the polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stable protective agent, mussel extract and slug extract in step (1) and stirring uniformly; then adding the alpha-cyanoacrylic acid octyl ester, degradable polymer material and gelatin, and stirring at 40-60°C for 20-40 min to obtain the biomimetic medical tissue adhesive.

[0044] By adopting the technical scheme, the preparation method is simple in operation, suitable for large-scale industrial production, and the component raw materials are mixed by stirring twice, so that the degradable polymer material, mussel extract and slug extract can fully cooperate and stably play a role. Therefore, the overall applicability of the biomimetic medical tissue adhesive is excellent.

[0045] In summary, the application has the following beneficial effects:

[0046] 1. The degradable polymer material, mussel extract and slug extract are used in combination, which can deeply and closely act on the skin tissue deep in the wound, and play an excellent regulating role on the new skin tissue of the wound, so that the prominence of the scar formed in the later stage is smaller and the overall surface is smoother, thereby the biomimetic medical tissue adhesive has an outstanding scar improvement effect;

[0047] 2. The biodegradable waterborne polyurethane and the degradable natural polyester are combined to form the degradable polymer material, which can form a two-stage gradient degradation mechanism in the proliferation stage of wound repair, and cooperate with the mussel extract and slug extract for graded release, thereby the regulating ability of the skin tissue change at the wound is stronger, and the improvement effect of the biomimetic medical tissue adhesive on the scar formed in the later stage is more excellent;

[0048] 3. The addition of a tissue conditioner composed of plant extracts and hyaluronic acid modified carbon nanotube / chitosan composite material can quickly, accurately and affinitively act on the newly generated skin tissue at the wound site, uniformly deliver the mussel extract and snail extract, and regulate the bioelectric balance, so that the proliferation process is more uniform and stable, thereby greatly improving the scar improvement effect of the biomimetic medical tissue adhesive. DETAILED DESCRIPTION

[0049] The application will be further described in detail below in combination with examples.

[0050] The raw materials used in the preparation examples and examples of the present application are commercially available, except for special instructions:

[0051] The biodegradable waterborne polyurethane was obtained by self-preparation, and the preparation, characterization and performance regulation of the biobased degradable waterborne polyurethane were specifically referred to “Biobased degradable waterborne polyurethane preparation, characterization and performance regulation, Li Ting, et al.”. The polylactic acid-based waterborne polyurethane (PLA-WPU) and the polycaprolactone-based waterborne polyurethane (PCL-WPU) were prepared by internal emulsification method, and then the PCL-WPU and the PLA-WPU were physically blended to prepare the biobased degradable waterborne polyurethane (PLA-WPU-PCLX);

[0052] The degradable natural polyester was polycaprolactone with the product number HXKJ2023 purchased from Wuhan Huaxiang Kejia Biological Technology Co., Ltd.;

[0053] The Dendrobium candidum extract, onion extract and Centella asiatica extract were purchased from Lanzhou Waterless Biological Technology Co., Ltd.;

[0054] The nano zirconium phosphate silver was purchased from Wuhan Huaxiang Kejia Biological Technology Co., Ltd., with a specification of 200 mesh;

[0055] The mussels were purchased from Su Sen Haicheng City Seafood Wholesale Department in Beihai City;

[0056] The snails were purchased from Bozhou Qihongtang Pharmaceutical Co., Ltd.;

[0057] The carbon nanotubes were multi-walled carbon nanotubes with the product number CNT103 purchased from Zhongke Jin Yan (Beijing) Technology Co., Ltd.;

[0058] The chitosan was purchased from Shandong Fuxi Biological Technology Co., Ltd.;

[0059] The hyaluronic acid was purchased from Xi'an Qianuo Biological Technology Co., Ltd., with a specification of 800,000 medium molecular weight;

[0060] The polyethylene glycol was purchased from Shanxi Jinyang Pharmaceutical Auxiliary Material Co., Ltd., with a specification of polyethylene glycol 1500.

[0061] Preparation example of raw materials and / or intermediates

[0062] Preparation example 1

[0063] A mussel extract is obtained by the following method:

[0064] After the shell of the mussel is removed, the same weight of water is added and crushed, and then incubated at 80°C for 22h. After cooling to room temperature, 3 times the weight of a mixed solvent composed of n-hexane, ethyl acetate and n-butanol in a weight mixing ratio of 1:0.7:3 is used for extraction, 500W ultrasonic extraction is performed for 20min, the extraction temperature is 40°C, and the obtained extraction liquid is dried to obtain the mussel extract.

[0065] Preparation Example 2

[0066] A mussel extract is obtained by the following method:

[0067] After the shell of the mussel is removed, the same weight of water is added and crushed, and then incubated at 75°C for 24h. After cooling to room temperature, 3 times the weight of a mixed solvent composed of n-hexane, ethyl acetate and n-butanol in a weight mixing ratio of 1:0.7:3 is used for extraction, 500W ultrasonic extraction is performed for 20min, the extraction temperature is 40°C, and the obtained extraction liquid is dried to obtain the mussel extract.

[0068] Preparation Example 3

[0069] A mussel extract is obtained by the following method:

[0070] After the shell of the mussel is removed, the same weight of water is added and crushed, and then incubated at 85°C for 20h. After cooling to room temperature, 3 times the weight of a mixed solvent composed of n-hexane, ethyl acetate and n-butanol in a weight mixing ratio of 1:0.7:3 is used for extraction, 500W ultrasonic extraction is performed for 20min, the extraction temperature is 40°C, and the obtained extraction liquid is dried to obtain the mussel extract.

[0071] Preparation Example 4

[0072] A mussel extract is obtained by the following method, which is different from Preparation Example 1 in that the mixed solvent is composed of n-hexane, ethyl acetate and n-butanol in a weight mixing ratio of 1:1:5.

[0073] Preparation Example 5

[0074] A mussel extract is obtained by the following method, which is different from Preparation Example 1 in that the mixed solvent is composed of n-hexane, ethyl acetate and n-butanol in a weight mixing ratio of 1:0.5:2.

[0075] Preparation Example 6

[0076] A slug extract is obtained by the following method:

[0077] The snail is vacuum freeze-dried, and then equal mass of water is added for water bath stirring at 65℃ and at a stirring speed of 300r / min. Then 5 times mass of an ethanol solution with a concentration of 65% is added. After stirring for 20 min, solid-liquid separation is performed by standing. The separated liquid is subjected to ultrafiltration, and then concentrated and dried to obtain the snail extract.

[0078] Preparation Example 7

[0079] A snail extract is obtained by the following method:

[0080] The snail is vacuum freeze-dried, and then equal mass of water is added for water bath stirring at 65℃ and at a stirring speed of 300r / min. Then 5 times mass of an ethanol solution with a concentration of 60% is added. After stirring for 20 min, solid-liquid separation is performed by standing. The separated liquid is subjected to ultrafiltration, and then concentrated and dried to obtain the snail extract.

[0081] Preparation Example 8

[0082] A snail extract is obtained by the following method:

[0083] The snail is vacuum freeze-dried, and then equal mass of water is added for water bath stirring at 65℃ and at a stirring speed of 300r / min. Then 5 times mass of an ethanol solution with a concentration of 70% is added. After stirring for 20 min, solid-liquid separation is performed by standing. The separated liquid is subjected to ultrafiltration, and then concentrated and dried to obtain the snail extract.

[0084] Preparation Example 9

[0085] A hyaluronic acid modified carbon nanotube / chitosan composite material is obtained by the following method:

[0086] The carbon nanotube raw material is immersed in a 68% nitric acid solution, heated in a water bath to 70℃ and kept for 1.5h to complete the acidification treatment. Then the material is added to a mixed solution of 5 times mass of acetic acid solution and polyethylene glycol. After ultrasonic dispersion for 10 min at 500W, the chitosan raw material and the hyaluronic acid raw material are added. The mixture is continuously ultrasonically treated for 17.5 min at 35℃. After high-speed shearing and vacuum drying, the hyaluronic acid modified carbon nanotube / chitosan composite material is obtained.

[0087] Note: In the above extraction, the concentration of the acetic acid solution is 40%, the molecular weight of the polyethylene glycol is 2000, and the acetic acid solution and the polyethylene glycol are mixed to obtain a mixed solution with a weight ratio of 1:1. The weight ratio of the carbon nanotube raw material, the chitosan raw material and the hyaluronic acid raw material is 1:0.3:0.5.

[0088] Preparation Example 10

[0089] A hyaluronic acid modified carbon nanotube / chitosan composite material is obtained by the following method, which is different from that of Preparation Example 9.

[0090] Take carbon nanotube raw materials, immersed in 68% nitric acid water bath heating to 70℃ and keep 1.5h after acidification treatment, added to 5 times weight of acetic acid solution and polyethylene glycol mixed solution, 500W ultrasonic dispersion 10min after adding chitosan raw materials and hyaluronic acid raw materials, 40℃ continue ultrasonic treatment 15min, high speed shearing, vacuum drying, can obtain hyaluronic acid modified carbon nanotube / chitosan composite material.

[0091] Preparation Example 11

[0092] A kind of hyaluronic acid modified carbon nanotube / chitosan composite material, different from preparation example 9, is prepared by the following method:

[0093] Take carbon nanotube raw materials, immersed in 68% nitric acid water bath heating to 70℃ and keep 1.5h after acidification treatment, added to 5 times weight of acetic acid solution and polyethylene glycol mixed solution, 500W ultrasonic dispersion 10min after adding chitosan raw materials and hyaluronic acid raw materials, 30℃ continue ultrasonic treatment 20min, high speed shearing, vacuum drying, can obtain hyaluronic acid modified carbon nanotube / chitosan composite material.

[0094] Preparation Example 12

[0095] A kind of carbon nanotube / chitosan composite material, different from preparation example 9, is prepared without using hyaluronic acid raw materials.

[0096] Example

[0097] Example 1

[0098] A kind of biomimetic medical tissue adhesive, and its corresponding weight is shown in Table 1, and is prepared by the following steps:

[0099] (1) Prepare raw materials containing α-cyano acrylate, degradable polymer, gelatin, polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stabilizing protective agent, mussel extract and slug extract according to the ratio;

[0100] (2) Mix polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stabilizing protective agent, mussel extract and slug extract in step (1), stir at 300r / min for 20min, then add α-cyano acrylate, degradable polymer and gelatin, heat to 40-60℃ and stir for 20-40min, to obtain biomimetic medical tissue adhesive.

[0101] Note: In the above step (2), the embodiment is heated to 65°C and stirred for 30 min; the mussel extract is obtained from Preparation Example 1; the slug extract is obtained from Preparation Example 6; the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester at a weight ratio of 1:3; the antibacterial agent is nano-zirconium phosphate loaded with silver; and the stabilizing protective agent is carbomer.

[0102] Example 2-3

[0103] A biomimetic medical tissue adhesive differs from Example 1 in that the raw materials of each component and their corresponding weights are shown in Table 1.

[0104] Table 1 Raw materials of each component and their weight fractions (kg / portion) in Examples 1-3

[0105] Component Example 1 Example 2 Example 3 Octyl α-cyanoacrylate 32.5 30 35 Degradable high molecular material 25 20 30 Gelatin 3 1 5 Polyethylene glycol 3.5 2 5 Sterile water 25 20 30 Sodium alginate 3 2 4 Antibacterial agent 9 8 10 Stabilizing protective agent 2 1 3 Mussel extract 2 1 3 Snail extract 2 1 3

[0106] Example 4

[0107] A biomimetic medical tissue adhesive differs from Example 1 in that the mussel extract is obtained from Preparation Example 2.

[0108] Example 5

[0109] A biomimetic medical tissue adhesive differs from Example 1 in that the mussel extract is obtained from Preparation Example 3.

[0110] Example 6

[0111] A biomimetic medical tissue adhesive differs from Example 1 in that the mussel extract is obtained from Preparation Example 4.

[0112] Example 7

[0113] A biomimetic medical tissue adhesive differs from Example 1 in that the mussel extract is obtained from Preparation Example 5.

[0114] Example 8

[0115] A biomimetic medical tissue adhesive differs from Example 1 in that the slug extract is obtained from Preparation Example 7.

[0116] Example 9

[0117] A biomimetic medical tissue adhesive differs from Example 1 in that the slug extract is obtained from Preparation Example 8.

[0118] Example 10

[0119] A biomimetic medical tissue adhesive differs from Example 1 in that the stabilizing protective agent is a composition of betacyclodextrin and polysorbate 80 at a weight ratio of 1:1.

[0120] Example 11

[0121] A biomimetic medical tissue adhesive differs from Example 1 in that the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester in a weight ratio of 1:2.6.

[0122] Example 12

[0123] A biomimetic medical tissue adhesive differs from Example 1 in that the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester in a weight ratio of 1:3.4.

[0124] Example 13

[0125] A biomimetic medical tissue adhesive differs from Example 1 in that the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester in a weight ratio of 1:2.5.

[0126] Example 14

[0127] A biomimetic medical tissue adhesive differs from Example 1 in that the degradable polymer material is composed of biodegradable waterborne polyurethane and degradable natural polyester in a weight ratio of 1:3.5.

[0128] Example 15

[0129] A biomimetic medical tissue adhesive differs from Example 1 in that the component raw material does not contain biodegradable waterborne polyurethane.

[0130] Example 16

[0131] A biomimetic medical tissue adhesive differs from Example 1 in that the component raw material does not contain degradable natural polyester.

[0132] Example 17

[0133] A biomimetic medical tissue adhesive differs from Example 1 in that a tissue regulator is further added to the components, and the weight of the tissue regulator is 1.2 parts; the tissue regulator is composed of plant extract and hyaluronic acid modified carbon nanotube / chitosan composite material in a weight ratio of 1.6:1; the plant extract is dendrobium officinale extract, and the hyaluronic acid modified carbon nanotube / chitosan composite material is obtained in Preparation Example 9; and in the preparation of the biomimetic medical tissue adhesive, the tissue regulator is used together with α-cyanoctyl acrylate, degradable polymer material and gelatin.

[0134] Example 18

[0135] A biomimetic medical tissue adhesive, which is different from Example 17 in that the hyaluronic acid-modified carbon nanotube / chitosan composite material is obtained in Preparation Example 10.

[0136] Example 19

[0137] A biomimetic medical tissue adhesive, which is different from Example 17 in that the hyaluronic acid-modified carbon nanotube / chitosan composite material is obtained in Preparation Example 11.

[0138] Example 20

[0139] A biomimetic medical tissue adhesive, which is different from Example 17 in that the hyaluronic acid-modified carbon nanotube / chitosan composite material is replaced with the carbon nanotube / chitosan composite material obtained in Preparation Example 12.

[0140] Example 21

[0141] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is added in a weight amount of 0.8 parts.

[0142] Example 22

[0143] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is added in a weight amount of 1.6 parts.

[0144] Example 23

[0145] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is composed of a plant extract and a hyaluronic acid-modified carbon nanotube / chitosan composite material in a weight ratio of 1.4:1.

[0146] Example 24

[0147] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is composed of a plant extract and a hyaluronic acid-modified carbon nanotube / chitosan composite material in a weight ratio of 1.8:1.

[0148] Example 25

[0149] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is composed of a plant extract and a hyaluronic acid-modified carbon nanotube / chitosan composite material in a weight ratio of 1.3:1.

[0150] Example 26

[0151] A biomimetic medical tissue adhesive, which is different from Example 17 in that the tissue conditioner is composed of a plant extract and a hyaluronic acid-modified carbon nanotube / chitosan composite material in a weight ratio of 1.9:1.

[0152] Example 27

[0153] A biomimetic medical tissue adhesive differs from Example 17 in that the component raw material does not contain a plant extract.

[0154] Example 28

[0155] A biomimetic medical tissue adhesive differs from Example 17 in that the component raw material does not contain a hyaluronic acid modified carbon nanotube / chitosan composite material.

[0156] Example 29

[0157] A biomimetic medical tissue adhesive differs from Example 17 in that the plant extract is a Centella asiatica extract.

[0158] Example 30

[0159] A biomimetic medical tissue adhesive differs from Example 1 in that the total amount of the degradable polymer material, mussel extract and slug extract remains unchanged, and the weight ratio of the three is 18:1:1.

[0160] Comparative Example

[0161] Comparative Example 1

[0162] A biomimetic medical tissue adhesive differs from Example 1 in that the degradable polymer material is replaced with an equal mass of octyl alpha-cyanoacrylate and gelatin in the corresponding weight ratio.

[0163] The degradable polymer material, mussel extract and slug extract are used in combination, and in the process of promoting wound repair, they can deeply and closely act on the skin tissue deep in the wound, and exert excellent regulation on the newly formed skin tissue of the wound, so that the prominence of the scar formed in the later stage is smaller, and the overall is smoother, thereby the biomimetic medical tissue adhesive has an outstanding scar improvement effect.

[0164] Comparative Example 2

[0165] A biomimetic medical tissue adhesive differs from Example 1 in that the mussel extract is replaced with an equal mass of sterile water.

[0166] Comparative Example 3

[0167] A biomimetic medical tissue adhesive differs from Example 1 in that the slug extract is replaced with an equal mass of sterile water.

[0168] Comparative Example 4

[0169] A biomimetic medical tissue adhesive, which is different from Example 1 in that the degradable polymer material is replaced by α-cyanoacrylic acid octyl ester and gelatin in a corresponding weight ratio, and the mussel extract is replaced by sterile water.

[0170] Comparative Example 5

[0171] A biomimetic medical tissue adhesive, which is different from Example 1 in that the degradable polymer material is replaced by α-cyanoacrylic acid octyl ester and gelatin in a corresponding weight ratio, and the slug extract is replaced by sterile water.

[0172] Comparative Example 6

[0173] A biomimetic medical tissue adhesive, which is different from Example 1 in that the mussel extract is replaced by sterile water, and the slug extract is replaced by sterile water.

[0174] Comparative Example 7

[0175] A biomimetic medical tissue adhesive, which is different from Example 1 in that the degradable polymer material is replaced by α-cyanoacrylic acid octyl ester and gelatin in a corresponding weight ratio, the mussel extract is replaced by sterile water, and the slug extract is replaced by sterile water.

[0176] Performance test Test samples: The biomimetic medical tissue adhesives obtained in Examples 1-30 are used as test samples 1-30, and the biomimetic medical tissue adhesives obtained in Comparative Examples 1-7 are used as control samples 1-7.

[0177] Test method: 185 male New Zealand rabbits, each weighing 2-3 kg, were randomly divided into 37 groups, with 5 rabbits in each group. Each rabbit was prepared according to the standard model of clinical animal experiment burn to cause 30% TBSA superficial II degree burn. The 37 groups of rabbits were coated with test samples 1-30 and control samples 1-7 on the burn site, with a coating thickness of 0.1 mm. The coating was performed once every 6 hours until the burn site healed and stable scars were formed. The scars on each group of rabbits were scored, and the average value of the comprehensive score was recorded in Table 2. The scoring criteria are as follows.

[0178]

[0179] Table 2 Test results of test samples 1-30 and control samples 1-7

[0180]

[0181]

[0182] It can be seen from the combination of Examples 1-3 and Comparative Examples 1-7 and Table 2 that the use of the combination of the degradable polymer material, mussel extract and slug extract can make the biomimetic medical tissue adhesive have excellent improvement effect on the scar, and in the process of wound healing, it can play an excellent regulating role on the newly generated skin tissue, so that the scar is not prominent, and the high-low difference is small, and the overall roughness is light. When any one or two of the degradable polymer material, mussel extract and slug extract are used, the improvement effect on the scar is improved compared with the case where none of the three raw materials is used, but the improvement effect is limited, and is far inferior to the excellent scar improvement effect brought by the combination of the three raw materials. In combination with Example 30 and Table 2, it can be seen that when the weight ratio of the degradable polymer material, mussel extract and slug extract is 18:1:1, the effect brought by the combination of the three raw materials is relatively excellent.

[0183] In combination with Examples 1, 4-5 and Examples 6-7 and Table 2, it can be seen that in the extraction of mussel extract, when the weight mixing ratio of n-hexane, ethyl acetate and n-butanol is 1:0.7:3, the mussel extract obtained in the application has excellent scar improvement effect of the biomimetic medical tissue adhesive, and it is speculated that the active substance contained therein is relatively rich and has a high content, and the regulating effect on the newly generated skin tissue at the wound site is relatively excellent and stable.

[0184] In combination with Examples 1 and Examples 11-12 and Table 2, it can be seen that when the biodegradable waterborne polyurethane and the degradable natural polyester are used to form the degradable polymer material at a weight ratio of 1:(2.6-3.4), the biomimetic medical tissue adhesive applied to the wound repair can ensure that the scar formed in the later stage is not prominent, and the high-low difference is small, and the overall roughness is light. In combination with Examples 13-14 and Table 2, it can be seen that when the mixing ratio of the biodegradable waterborne polyurethane and the degradable natural polyester exceeds the above range, the improvement effect on the scar will be significantly deteriorated. In combination with Examples 15-16 and Table 2, it can be seen that when any one of the biodegradable waterborne polyurethane and the degradable natural polyester is used alone as the degradable polymer material, the scar will be relatively prominent and rough, so it can be seen that the combination of the two can bring more excellent effect, and the improvement effect on the scar formed in the later stage is more excellent.

[0185] It can be seen from the combination of Embodiment 1 and Embodiments 17-19 and Table 2 that the addition of the tissue regulator consisting of the plant extract and the carbon nanotube / chitosan composite modified by hyaluronic acid in a weight ratio of (1.4-1.8):1 can play an excellent role in the healing process of the wound surface, and greatly improve the scar formed in the later stage; in combination with Embodiment 20 and Table 2, it can be seen that the carbon nanotube / chitosan composite lacking hyaluronic acid can also bring about the improvement effect of the scar, but the effect is weak, and the uniformity and directivity of the effect on the wound surface are poor due to the lack of the precise positioning of hyaluronic acid; in combination with Embodiments 21-24 and Embodiments 25-28 and Table 2, it can be seen that when any one of the plant extract and the carbon nanotube / chitosan composite modified by hyaluronic acid is used alone or the ratio of the two raw materials exceeds the above range, the scar improvement effect is not ideal, and thus it can be seen that only when the plant extract and the carbon nanotube / chitosan composite modified by hyaluronic acid are used in a specific weight ratio, a more outstanding application effect can be brought about, and the scar improvement effect of the biomimetic medical tissue adhesive is greatly improved.

[0186] The specific embodiments are merely an explanation of the present application, and are not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the present specification, and the modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A biomimetic medical tissue adhesive, characterized by, It is made from raw materials containing the following weight parts: Octyl alpha-cyanoacrylate 30-35 parts; Degradable polymer material 20-30 parts; Gelatin 1-5 parts; Polyethylene glycol 2-5 parts; Sterile water 20-30 parts; Sodium alginate 2-4 parts; Antibacterial agent 8-10 parts; Stabilizing and protecting agent 1-3 parts; Mussel extract 1-3 parts; Slug extract 1-3 parts; The mussel extract is obtained by the following method: After the shell of the mussel is removed, it is crushed with water and incubated at 75-85°C for 20-24 hours. After cooling to room temperature, it is extracted with a mixed solvent of n-hexane, ethyl acetate and n-butanol. The obtained extract is dried to obtain the mussel extract; The slug extract is obtained by the following method: After vacuum freeze-drying of the slug, water is added and stirred in a water bath. Then, an ethanol solution with a concentration of 60%-70% is added. After stirring, the mixture is separated into solid and liquid. The separated liquid is ultrafiltrated, concentrated and dried to obtain the slug extract; The degradable polymer material is composed of biodegradable aqueous polyurethane and degradable natural polyester, and the weight ratio of biodegradable aqueous polyurethane to degradable natural polyester is 1:(2.6-3.4). The stabilizing and protecting agent is one or a combination of carbomer, betadex and polysorbate 80.

2. The biomimetic medical tissue adhesive according to claim 1, characterized in that: The weight ratio of the degradable polymer material, mussel extract and slug extract is 18:1:

1.

3. The biomimetic medical tissue adhesive according to claim 1, wherein: In the extraction of the mussel extract, the weight mixing ratio of n-hexane, ethyl acetate and n-butanol is 1:0.7:

3.

4. The biomimetic medical tissue adhesive of claim 1, wherein: The weight ratio of biodegradable aqueous polyurethane to degradable natural polyester is 1:

3.

5. The biomimetic medical tissue adhesive of claim 1, wherein: The biomimetic medical tissue adhesive further contains 0.8-1.6 parts of a tissue conditioning agent, which is composed of plant extract and hyaluronic acid modified carbon nanotube / chitosan composite material at a weight ratio of (1.4-1.8):

1. The hyaluronic acid modified carbon nanotube / chitosan composite material is obtained by the following method: The carbon nanotube raw material is acidified, added to a mixed solution of acetic acid and polyethylene glycol, ultrasonically dispersed, and then added with chitosan raw material and hyaluronic acid raw material. The mixture is continuously ultrasonically treated at 30-40°C for 15-20 min, and then high-speed sheared and vacuum dried to obtain the hyaluronic acid modified carbon nanotube / chitosan composite material.

6. The biomimetic medical tissue adhesive according to claim 5, characterized in that: The plant extract is one or a combination of Dendrobium officinale extract, onion extract and Gynura extract.

7. The biomimetic medical tissue adhesive according to claim 1, wherein: The antibacterial agent is nano zirconium phosphate silver.

8. The method for preparing the biomimetic medical tissue adhesive according to claim 1, characterized in that: The steps include: (1) Prepare raw materials containing octyl alpha-cyanoacrylate, degradable polymer material, gelatin, polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stabilizing and protecting agent, mussel extract and slug extract according to the proportion; (2) Mix polyethylene glycol, sterile water, sodium alginate, antibacterial agent, stabilizing and protecting agent, mussel extract and slug extract in step (1) and stir until uniform. Then add octyl alpha-cyanoacrylate, degradable polymer material and gelatin, and stir at 60-70°C for 20-40 min to obtain the biomimetic medical tissue adhesive.

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