CN104740678B - Application of the giant salamander mucus in adhesive is prepared - Google Patents

Application of the giant salamander mucus in adhesive is prepared Download PDF

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Publication number
CN104740678B
CN104740678B CN201510155072.8A CN201510155072A CN104740678B CN 104740678 B CN104740678 B CN 104740678B CN 201510155072 A CN201510155072 A CN 201510155072A CN 104740678 B CN104740678 B CN 104740678B
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China
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adhesive
giant salamander
tissue
salamander mucus
prepared
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CN201510155072.8A
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Chinese (zh)
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CN104740678A (en
Inventor
商海涛
王莹
陈兵
苟强
魏泓
邢孟秋
周明辉
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Chongqing Changsheng Lake Fish Bio Polytron Technologies Inc
Wei Hong
Xing Mengqiu
Zhou Minghui
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CHONGQING KUIXU BIOLOGICAL SCIENCE & TECHNOLOGY Co Ltd
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Abstract

The invention discloses application of the giant salamander mucus in adhesive is prepared, using giant salamander mucus there is the characteristics of bond properties is strong after freeze-dried powder is made, and because the adhesive derives from giant salamander mucus, for natural component, security is good, and with preferable biocompatibility, it is degradable, tissue adhesive is can act as, is that medically surface of a wound bonding, tissue adhesion, organ bonding etc. provide new material.

Description

Application of the giant salamander mucus in adhesive is prepared
Technical field
The invention belongs to technical field of biological material, and in particular to a kind of application of giant salamander mucus in adhesive is prepared.
Background technology
Adhesive is the sticking material of tool, and the material of two kinds of separation can link together by its viscosity.According to original Material source can be divided into natural glue and artificial adhesive.Tissue adhesive is to refer to polymerize in vivo, thus triggers tissue Between or tissue with it is non-tissue (such as implant) between bonding, and with control bleed (hemostasis) and prevent gas and liquid flowing One class biomaterial of functions such as (sealings).Relative to clinical traditional fixation and suture material or apparatus (such as suture, rivet Deng), tissue adhesive have easy to use, wound it is small, using painful it is small, postoperative need not remove and operative scar is small etc. Advantage, and can also realize that the fixed point of medicine discharges as the carrier of hemostasis, antibacterial and anti-inflammation drugs, therefore clinically have There is wide application potential.
Clinically wide variety of tissue adhesive is mainly cyanoacrylate and fibrin at present, but due to Respective inherent defect can not turn into preferable tissue adhesive.Although the synthetic work Shang Kai of Novel cyano acrylate Exhibition, but its polymer film is frangible, may be shifted in active organization, and large area wound is dfficult to apply to, it is particularly it Unfavorable tissue reaction and cause the tumour of experimental animal to limit it further to apply.Fibrin adhesive curing is slow, machinery Intensity difference, and with the danger of virus infection, and can not be with body tissue covalent bond.
In addition, gelatin (GRF or GRFG), polyethylene glycol (PEG) hydrogel, polyurethane binder Etc. (polyurethanes) also there are certain application in other tissue adhesives.Gelatin (be derived from organism) for a class gelatin- The tissue adhesive that benzenediol-formalin or gelatin-glutaraldehyde are made, although it provides high adherence, formalin Or glutaraldehyde can carry out cross-linking reaction with the protein of target tissue, produce tissue toxicity.Polyethylene glycol (PEG) water-setting peptization it is swollen Rate is more than 400%, and its cohesive needs relatively dry surface.Make in polyurethane binder (polyurethanes) Material aromatic diisocyanate is poisonous to organism.
Therefore, be badly in need of providing a kind of natural biological sources and quantity it is sufficient, good biocompatibility, adhesive strength it is high, can Biodegradable tissue adhesive.
The content of the invention
In view of this, the application it is an object of the invention to provide giant salamander mucus in tissue adhesive is prepared, is developed The new application of giant salamander mucus, adhesive field is not there is provided new material.
For achieving the above object, the present invention provides following technical scheme:
1st, application of the giant salamander mucus in adhesive is prepared.
It is preferred that, described adhesive is tissue adhesive.
It is furthermore preferred that the tissue adhesive is used for the surface of a wound, tissue, organ, rubber, metal or paper bonding.
The beneficial effects of the present invention are:The invention discloses application of the giant salamander mucus in adhesive is prepared, the bonding Agent derives from giant salamander mucus, and composition is natural, and security is good, and bonding strength is high, can be used as tissue adhesive or other bondings Agent, for the bonding such as the surface of a wound, tissue, organ, rubber, metal or paper, with wound healing time faster, inflammatory reaction it is light, scar The advantages of trace is small, is with a wide range of applications.
Brief description of the drawings
In order that the purpose of the present invention, technical scheme and beneficial effect are clearer, the present invention provides drawings described below:
Fig. 1 is the bonding strength measurement result of different adhesives.
Fig. 2 is that adhesive bonds experiment and tradition suture comparing result (A in vitro:Adhesive bonds experiment in vitro;B:Tradition Suture result).
Fig. 3 is Post operation different time healing state (A:Adhesive bonds experimental result in vitro;B tradition sutures result).
Fig. 4 is vitro in organ's adhesion characteristic result (A of adhesive:Kidney adhesion results;B:Heart adhesion results).
Embodiment
Below in conjunction with accompanying drawing, the preferred embodiments of the present invention are described in detail.It is unreceipted specific in embodiment The experimental method of condition, generally according to normal condition or according to the condition proposed by manufacturer.
The collection of giant salamander mucus directly scrapes sassafras method using skin:Fresh and alive giant salamander is specially cleaned into body surface with clear water, removed The impurity such as cast off a skin, be subsequently placed in dry box, giant salamander body surface is scraped with flat, until giant salamander body surface secretes a large amount of milkys Mucus, scraping was collected in culture dish, made mucus thickness about 1cm in culture dish.The collection of giant salamander mucus can also use existing Electrostimulation or etherization method collection, specific method see Publication No. 104223121A and 104206502A China specially Profit.
Embodiment 1
The method that adhesive is prepared using giant salamander mucus, is comprised the following steps:The culture dish for collecting giant salamander mucus is put -80 DEG C overnight it is frozen into solid, then with vacuum freeze drier vacuum be 19pa, temperature be -50 DEG C at freezing vacuum Dry 48 hours;Smash lyophilized giant salamander mucus to pieces the rearmounted broken machine of temperature low-temperature submicron powder again and be crushed to 300 mesh, finally with 5 × 104Gy dosage 60Co gamma-rays radiation sterilizations, obtain tissue adhesive, aseptic packaging is standby.The temperature of wherein low-temperature grinding is less than 37 DEG C, add liquid nitrogen ultramicro grinding best results.
Embodiment 2
The method that adhesive is prepared using giant salamander mucus, is comprised the following steps:The culture dish for collecting giant salamander mucus is put -20 DEG C overnight it is frozen into solid, then with vacuum freeze drier vacuum be 10pa, temperature be -70 DEG C at freezing vacuum Dry 56 hours;Smash lyophilized giant salamander mucus to pieces rearmounted low-temperature submicron powder broken machine again and be crushed to 500 mesh, finally with 5 × 104Gy Dosage 60Co gamma-rays radiation sterilizations, obtain tissue adhesive, aseptic packaging is standby.Wherein the temperature of low-temperature grinding is less than 37 DEG C Can, add liquid nitrogen ultramicro grinding best results.
Embodiment 3
The method that adhesive is prepared using giant salamander mucus, is comprised the following steps:The culture dish for collecting giant salamander mucus is direct Put in vacuum drying chamber, 48h is dried under 37 DEG C of vacuum, then smash dry giant salamander mucus to pieces rearmounted low-temperature submicron powder broken machine powder 1000 mesh are broken to, finally with 2 × 104Gy dosage 60Co gamma-rays radiation sterilizations, obtain tissue adhesive, aseptic packaging is standby.Its The temperature of middle low-temperature grinding is less than 37 DEG C, adds liquid nitrogen ultramicro grinding best results.
Embodiment 4
The method that adhesive is prepared using giant salamander mucus, is comprised the following steps:The culture dish for collecting giant salamander mucus is direct Put in vacuum drying chamber, 48h is dried under 20 DEG C of vacuum, then smash dry giant salamander mucus to pieces rearmounted low-temperature submicron powder broken machine powder 800 mesh are broken to, finally with 2 × 104Gy dosage 60Co gamma-rays radiation sterilizations, obtain tissue adhesive, aseptic packaging is standby.Wherein The temperature of low-temperature grinding is less than 37 DEG C, adds liquid nitrogen ultramicro grinding best results.
Embodiment 5
Skin is carried out to adhesive made from above-described embodiment 1~4 and bonds experiment in vitro, it is specific as follows:Use hydraulic pressure ten thousand Energy testing machine (UTM) determines tissue adhesive to the cohesive of pigskin, comprises the following steps that:Pig skin of back is cleaned up, 2 pieces of 2cm × 10cm skins are taken, subcutaneous fat is removed, then implemented in 1 piece of skin medial surface one end 2cm × 2cm areas even spread Adhesive 100mg made from example 1~4, another piece of skin inner opposite end 2cm × 2cm area presses with finger bonding with the skin 30 seconds, bonding strength is then detected, while using Fibrin Glue and cyanoacrylate as control, as a result such as table 1 and Fig. 1 institutes Show.As a result show, the bonding strength average out to 0.5MPa of obtained adhesive, the bonding strength is viscous far above Fibrin Glue Intensity is closed, but less than cyanoacrylate.
Table 1, the bonding strength of different tissues adhesive are determined
Adhesive Composition Bonding strength (Mpa)
Giant salamander mucus adhesive Giant salamander mucus freeze-dried products 0.500±0.150
Fibrin Glue Fibrinogen 5wt% 0.025±0.003
Cyanoacrylate Cyanoacrylate 0.710±0.135
It can be seen from the results above that adhesive adhesive strength produced by the present invention is high, adhesive can act as.And by In ingredient origin in giant salamander, composition is pure natural, and security is good, degradable, therefore can be used as tissue adhesive.
Embodiment 6
Surface of a wound bonding experiment is carried out to adhesive made from above-described embodiment 1~4, is specially:Using Kunming (KM) mouse as Experimental animal, takes KM mouse 18,20 ± 4g of body weight.Mouse one day before surgery is anaesthetized, shaving, depilation, second day with small Mouse mass fraction is anaesthetized for 3% yellow Jackets, with Iodophor, the ethanol disinfection operative site that volume fraction is 70%, hand Art knife is experimental group doing skin incision 2cm, left side respectively by the left and right sides of boundary of back center backbone, and right side is control Group.Experimental group is bonded using adhesive made from embodiment 1~4 to wound, and lower embodiment 1~4 is spread in wound joint Obtained adhesive 5mg, is then gently drawn with tweezers in interface both sides, as a result as shown in A in Fig. 2.As a result show, it is viscous through adhesive The visible dermis surface of a wound has been bonded together after conjunction, and surface of a wound covering sterilizing petrolatum gauze, last outside elastoplast encloses chest and abdomen Portion's wrapping one is enclosed.Control group docks skin original position, and tradition 4 pins of suture are carried out with gutstring, and the surface of a wound covers sterilizing petrolatum gauze, Last outside elastoplast encloses thorax abdomen and wraps up a circle, as shown in B in Fig. 2.Then 6 mouse sights were taken respectively in postoperative 14 days Wound healing situation is examined, as a result as shown in Figure 3.
From the figure 3, it may be seen that in situ can be healed using the mouse and tradition suture mouse wound of invention adhesives, but tradition Suture mouse healing time slower, and inflammatory reaction is substantially, scar is obvious.
Embodiment 7
Organ is carried out to adhesive made from above-described embodiment 1~4 and bonds experiment in vitro, it is specific as follows:Use hydraulic pressure ten thousand Energy testing machine (UTM) determines cohesive of the tissue adhesive to pig organ otch, and specific method is as follows:Pig part kidney is taken respectively And heart, the transverse incision more than 1/2 section is made of scalpel, in adhesive made from tangent plane side even spread embodiment 1~4 200-500mg, finger pressing bonding in situ 30 seconds, then detects bonding strength (Fig. 4), while with Fibrin Glue and cyano group third Olefin(e) acid ester can good bond as control, as a result kidney cutting part.The bonding strength average out to 0.5MPa of obtained adhesive, The bonding strength is far above the bonding strength of Fibrin Glue, but less than cyanoacrylate.
Embodiment 8
Hydroxyapatite powder 5g or so is taken, adhesive 100-300mg made from above-described embodiment 1~4 is added, added double Water 200-800 μ L are steamed, are stirred, globulate is extruded, after natural drying, can bond as a globular solids.
Embodiment 9
2 pieces of coins are taken, respectively take one side to be bedewed with water, wherein made from one piece of coin side even spread embodiment 1~4 Then 2 pieces of coins are bedewed side overlapping about 1/2, finger pressing bonding in situ 30 seconds, then detection bonding by adhesive 100mg Intensity.As a result 19 ± 5Jm of overlapping shearing stress average out to of obtained adhesive is shown-2
Embodiment 10
2cm × 15cm filter paper bar 2 is made with ordinary filter paper, and 1 filter paper one end 2cm places are added dropwise 1 and dripped about 100 μ L, filter Paper is dripped, and water suction is got wet rapidly at place, diffusion area about 2cm × 2cm, in adhesive made from wet place's even spread embodiment 1~4 50mg, it is then that another 1 filter paper one end is overlapping with the wet place of the filter paper that drips (2cm × 2cm), after natural drying, detect bonding strength. As a result 23 ± 5Jm of overlapping shearing stress average out to of obtained adhesive is shown-2
Embodiment 11
2cm × 15cm latexes bar 2 is made with emgloves, and 1 filter paper one end 2cm places dropwise addition 1 is dripped about 100 μ L, Adhesive 50mg made from even spread embodiment 1~4 at water droplet, then by another 1 latex bar one end and adhesive coating Overlapping (2cm × 2cm), after natural drying, detects overlapping shearing stress (lap-shear), as a result shows the weight of obtained adhesive 25 ± 5Jm of folded shearing stress average out to-2
The above results, which are indicated, is had good bond properties by adhesive produced by the present invention, can be used as adhesive In the bonding of tissue, organ, metal, rubber, paper, powdered substance etc..And bond properties is good, and application prospect is extensive.
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although logical Cross above preferred embodiment the present invention is described in detail, it is to be understood by those skilled in the art that can be Various changes are made to it in form and in details, without departing from claims of the present invention limited range.

Claims (2)

1. application of the giant salamander mucus in tissue adhesive is prepared.
2. application according to claim 1, it is characterised in that:The tissue adhesive is used for the surface of a wound, tissue, organ, rubber Glue, metal or paper bonding.
CN201510155072.8A 2015-04-02 2015-04-02 Application of the giant salamander mucus in adhesive is prepared Expired - Fee Related CN104740678B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108066369A (en) * 2016-11-16 2018-05-25 太鲵生物科技(天津)有限公司 A kind of preparation method of giant salamander pituitary extract
CN106361776B (en) * 2016-11-16 2024-03-19 张家界金姑大鲵开发有限公司 Giant salamander mucus used for hemostasis
CN106581736B (en) * 2016-12-28 2020-04-21 安顺市四海农业科技开发有限公司 Medical adhesive taking giant salamander body surface mucus as raw material and preparation method thereof
CN106693039B (en) * 2017-01-24 2019-10-01 南开大学 A kind of preparation method of the medical aquogel with good biological adhesiveness
CN107412845B (en) * 2017-08-10 2020-09-11 魏泓 Giant salamander secretion biomembrane and preparation method and application thereof
CN107456599B (en) * 2017-08-10 2020-09-01 魏泓 Antibacterial giant salamander secretion biomembrane and preparation method and application thereof
CN107279508A (en) * 2017-08-15 2017-10-24 正安县正鲵养殖农民专业合作社 Chinese medicine fodder for cultivating giant salamander
US20220267655A1 (en) * 2019-02-26 2022-08-25 Stomatological Hospital Of Chongqing Medical University Medical adhesive and the preparation method and use thereof
CN110559469B (en) * 2019-02-26 2021-08-03 重庆医科大学附属口腔医院 Medical adhesive
CN112891380B (en) * 2021-01-13 2023-03-10 金华市鼎鑫大鲵驯养繁殖场 Extraction method of giant salamander mucus and grease and pharmaceutical product thereof
CN116077717B (en) * 2021-11-05 2024-01-30 重庆医科大学附属口腔医院 Bioburden system for wound healing and application thereof

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CN102335288A (en) * 2010-07-20 2012-02-01 陕西理工学院 Giant salamander skin mucus scalding ointment
CN103829235B (en) * 2014-01-11 2015-07-01 陕西理工学院 Preparation method of giant salamander skin mucus whole powder

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Address after: 405400 fourth floor, Kaizhou Avenue cinema, Hanfeng, Kaixian County, Chongqing

Patentee after: Chongqing Changsheng lake fish bio Polytron Technologies Inc.

Patentee after: Zhou Minghui

Patentee after: Wei Hong

Patentee after: Xing Mengqiu

Address before: 405400 fourth floor, Kaizhou Avenue cinema, Hanfeng, Kaixian County, Chongqing

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Address after: 405400 fourth floor, Kaizhou Avenue cinema, Hanfeng, Kaixian County, Kaizhou District, Chongqing

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Address before: 405400 fourth floor, Kaizhou Avenue cinema, Hanfeng, Kaixian County, Chongqing

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Inventor after: Shang Haitao

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Granted publication date: 20171024