WO2015085937A1 - Adhesive and preparation method therefor - Google Patents

Abstract

The present invention relates to the field of medical materials. Particularly, the present invention relates to an adhesive of α-cyanoacrylate and a preparation method therefor. An adhesive with desired viscosity is obtained by radiation crosslinking of the above adhesive. The method of the invention has a simple process and a short production cycle. The α-cyanoacrylate adhesive according to the invention does contain a thickening agent, and has good product homogeneity, a higher safety and a long shelf-life.

Description

Adhesive and preparation method thereof Technical field

The invention relates to the field of medical materials. In particular, the present invention relates to an adhesive mainly composed of α-cyanoacrylate and a process for preparing the same.

Background technique

Since the first introduction of the world's first α-cyanoacrylate rapid adhesive (α-glue) for bonding skin and hemostasis in 1958, the adhesive based on α-cyanoacrylate has been obtained. Rapid development. It has the following advantages: (1) single component, no solvent, no curing agent; (2) physical properties compatible with natural tissues; (3) stable chemical properties, no degradation of harmful substances; (4) good Biocompatibility, ie mechanical compatibility and histocompatibility, low toxicity, no carcinogenicity, no teratogenicity, no mutation, no hemolysis, no pyrogen, low cytotoxicity, no sensitization, no irritation, no carcinogenesis, itself Sterility, the formation of antibacterial zones for eleven bacteria, etc., which has aroused great interest in the medical community and has been applied in clinical practice.

Because α-cyanoacrylate medical adhesive can strongly bind the body tissue, the bonding speed is fast, non-toxic, no triad (ie, mutagenic, carcinogenic, teratogenic), solidified under normal temperature and pressure for several seconds. At the same time, it can produce strong bonding strength with human tissue, has little reaction to tissue, does not cause thrombus, can be easily sterilized, is easy to use, and easy to store. It has been recognized by the World Health Organization and is now widely used. Surgery and hemostasis for closing wounds, skin grafts, luminal organ connections, and visceral injuries such as liver, kidney, and gastrointestinal. In clinical applications, many traditional medical problems have been solved from surgical operations such as ENT and dermatology to medical treatment, and it has become a new technology in modern medicine, which will have a profound impact on surgery.

The α-cyanoacrylate monomer has a very low viscosity of only about 2 cps, which is dispersed during bonding, and is not suitable for porous materials and filling adhesives with large gaps. The medical α-cyanoacrylate adhesive has great fluidity when used, and is particularly easy to penetrate into the eyes when used in sensitive parts such as the eyes. This poses a danger, which limits its medical application to a certain extent. Therefore, the preparation of a specific viscosity of α-cyanoacrylate adhesive has important practical significance.

In the prior art, the method for increasing the viscosity of the α-cyanoacrylate adhesive is mainly to add various polymers as a thickener, and the following two methods can be summarized according to the type of the thickener:

1. Add a second chemical as a thickener, the most widely used is polymethyl methacrylate (PMMA). The specific method is as follows: firstly, various α-cyanoacrylates are mixed and formulated into a solvent in a prescribed ratio; then, the solvent is mixed with the washed and dried medical polymethyl methacrylate (PMMA) in a ratio of 2:1. Placed in a soaking container, stored in a dark place, soaked and dissolved at room temperature; after about 6 months, the dissolved part forms a viscous dissolved substance in the upper layer; the viscous dissolved substance is taken from the soaking container Transfer to a preparation container, dilute with the above solvent, and perform viscosity detection during the dilution process until the viscosity of the solution reaches the desired range; finally, add the solvent equivalent to the volume of the viscous lysate to the infusion container, and continue to soak, Dissolve, continue to take the upper layer of viscous solute, add the solvent equivalent to the volume of the viscous lysate, continue to soak and dissolve until the polymethyl methacrylate (PMMA) is completely dissolved.

The technical disadvantages of the above methods are:

1 long process cycle: thickener polymethyl methacrylate (PMMA) monomer has a small molecular weight (relative molecular weight of 84), its polymer structure is relatively tight, the α-cyanoacrylate monomer molecules in the solvent enter the poly Methyl methacrylate (PMMA) is difficult inside. The dissolution process is very slow, and it takes about six months to obtain a viscous solute for the preparation and production of medical glue products, which is not conducive to the production schedule.

2 After the medical glue product is used at the wound, the polymerization degradation is slow and the flexibility is poor: polymethyl methacrylate (PMMA) is a non-degradable polymer, and the formed polymer has high hardness, and the product is soft and certain. Patients are poorly tolerated when using exercise tissue. Moreover, the degradation time is longer than that of the α-cyanoacrylate polymer, which has a certain influence on the recovery of the patient's use site.

3 There is a certain safety risk: the molecular weight of polymethyl methacrylate (PMMA) monomer is small, and α-cyanoacrylate monomer with equivalent molecular weight is required to dissolve well, and α-cyanoacrylate with small molecular weight is small. Due to the shorter side chains, the biosafety is lower than that of the large alpha-cyanoacrylate monomers. Further, the α-cyanoacrylate monomer having a small molecular weight releases more polymerization heat when it is polymerized at the site of use, and is highly irritating to the site of use. In vitro cytotoxicity experiments have shown that when the number of side chain alkyl carbon atoms is greater than 4, the biosafety and irritation of α-cyanoacrylate to the human body has dropped to an acceptable level.

In addition, the thickener polymethyl methacrylate (PMMA) needs to add a certain amount of catalyst to promote polymerization in the production process. Different manufacturers and different batches have different production processes, and its biosafety evaluation is a relatively time-consuming problem. The cost of testing is also relatively high, which has a great impact on the procurement and cost of raw materials for medical adhesives.

2. Using an α-cyanoacrylate bulk polymer as a thickener, such as poly-α-cyanoacrylate: placing the α-cyanoacrylate monomer in a closed container at 40-50 ° C , placed for 40-50 hours, to obtain a solid polymer, the polymer was taken out of the container, aged at 40-50 ° C for 10-15 hours to obtain a solid α-cyanoacrylate polymer, and then Soaked in a solvent consisting of 90-100% by weight of butyl α-cyanoacrylate monomer and 0-10% by weight of octyl α-cyanoacrylate. The amount of butyl α-cyanoacrylate polymer is 10-15% by weight of the butyl cyanoacrylate monomer; after 1 to 1.5 months, a viscous liquid is formed, and then the butyl cyanoacrylate monomer is added to the liquid to adjust to the desired viscosity. That is to get medical glue.

The defects of the above processes are mainly:

1 complicated process, long production cycle: although the process time compared with the addition of polymethyl methacrylate (PMMA) as a thickener is shortened, about one cycle requires 1-1.5 months, but it takes a long time to go Aging, dissolution, etc., since the α-cyanoacrylate monomer is very sensitive to the environment, when a trace amount of anion such as a trace amount of water in the air exists, it initiates polymerization, and the dissolution process is very slow, and repolymerization may be initiated during the dissolution process. The entire production process for the environment, equipment The requirements are very strict and it is difficult to control re-aggregation.

2 The medical glue first polymerizes the α-cyanoacrylate monomer to be aged and then dissolved, and a large amount of α-cyanoacrylate which has been aged and deactivated in the product will prolong the bonding time of the adhesive and greatly reduce the Bond strength.

For example, CN102504708A discloses an adhesive having a polymethyl methacrylate, a methacrylate copolymer, an acrylic rubber, a cellulose derivative, a polyvinyl acetate or the like as a thickener; the thickener disclosed in US Pat. No. 3,742,018 is a polyethylene. Methyl ether; the polymeric thickener disclosed in US Pat. No. 5,328,687 includes polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polycaprolactone, lactic acid-caprolactone copolymer, poly-3-hydroxybutyric acid, poly-origin Acid esters, polyalkyl acrylates, copolymers of alkyl acrylates and vinyl acetates, polyalkyl methacrylates, copolymers of alkyl esters methacrylates and butadienes, etc.; US 3,527, 841 discloses universal and a cyanoacrylate adhesive composition for surgery, comprising a polylactic acid viscosity thickener and an acidic compound such as sulfur dioxide, and a radical stabilizer such as hydroquinone; and the thickener disclosed in US Pat. No. 4,534,422 is a polymethyl methacrylate; The thickeners disclosed in CN102178978A are polycyanoacrylates; the thickeners disclosed in US Pat. No. 20,120,264,846 A1 are one or more block polymers, preferably an addition polymer of a single polypropylene glycol to ethylene oxide ( Polyether) is added to the cyanoacrylate for use as a polymer and thickener. The thickeners disclosed in U.S. Patent 4,837, 260 are polyvinyl acrylates and other thickeners as listed in U.S. Patent 6,183,593.

The addition of a thickener such a method tends to introduce the third component into the adhesive body, which inevitably has compatibility problems. The amount of addition is also directly related to the viscosity of the composition. If too much is added, the main component is reduced, affecting the polymerization time and even hard to cure, so the viscosity range adjusted by this method is limited. Moreover, the third component added after the curing has an adhesive effect may precipitate, and the influence on the human body and the environment remains to be studied.

Summary of the invention

In view of the above problems, the present invention provides a method for preparing a specific viscosity of an α-cyanoacrylate adhesive without adding other chemical thickeners, mainly by applying a radiation crosslinking method to make α- The double bond of the cyanoacrylate is crosslinked, and the viscosity of the α-cyanoacrylate adhesive is adjusted by controlling the crosslinking temperature, the irradiation intensity, the crosslinking time, and the like. Experiments have shown that the cross-linked α-cyanoacrylate adhesive did not lose the bonding activity, and did not change significantly at room temperature for one year.

In particular, the invention relates to an alpha-cyanoacrylate adhesive having a viscosity of from 2 to 180 cps, preferably from 25 to 80 cps.

According to the invention, the alpha-cyanoacrylate adhesive is free of thickeners.

The invention relates to a preparation method of an α-cyanoacrylate adhesive, wherein an α-cyanoacrylate monomer is prepared by a radiation crosslinking method to obtain an adhesive main body, and the adhesive main body and the polymerization inhibitor are mixed in proportion to form a desired Viscosity alpha-cyanoacrylate adhesive. The radiation cross-linked radiation source includes, but is not limited to, ultraviolet rays, electron beams, gamma rays, neutron beams, and particle beams.

According to the invention, the adhesive body is prepared by the following steps:

a. The α-cyanoacrylate monomer (for example, the gas chromatographic normalization method determines the purity is greater than 99.8%) is placed in a closed light-transmissive container;

b. providing a high-energy ray irradiation apparatus, and providing a heating stage in the irradiation area of the high-energy ray irradiation apparatus;

c. placing the container containing the α-cyanoacrylate monomer on the heating table, setting the temperature, and then irradiating under the action of the high-energy ray irradiation device, by adjusting the power of the irradiation device The distance, the irradiation time and/or the heating temperature are used to control the degree of crosslinking to form the adhesive body.

According to the present invention, the high-energy ray irradiation apparatus is not particularly limited, and only the energy supplied by the high-energy ray irradiation apparatus is required to open the carbon-carbon double bond in the α-cyanoacrylate monomer. Those skilled in the art can select a suitable device based on existing common sense. For example, the high energy ray irradiation device is an ultraviolet lamp, a gamma ray irradiation device, and a beta electron beam device. In some embodiments of the invention, the ultraviolet lamp is a high pressure mercury lamp; in some embodiments of the invention, the gamma ray irradiation device is a Co60 cobalt source irradiation device.

According to the present invention, the distance between the high energy ray irradiation device and the α-cyanoacrylate monomer can be Adjustment. Preferably, the distance between the high-energy ray irradiation device and the α-cyanoacrylate monomer is 10-70 cm; more preferably, the distance between the high-energy ray irradiation device and the α-cyanoacrylate monomer is 20 -50cm.

According to the invention, the heating temperature is from 20 to 100 ° C, preferably from 40 to 80 ° C.

According to the invention, the irradiation time is from 10 to 100 min, preferably from 10 to 60 min.

According to the invention, the irradiation power of the high energy ray irradiation apparatus is from 500 to 5000 W, preferably from 1000 to 2500 W.

According to the present invention, the structure of the α-cyanoacrylate monomer is as follows:

Wherein n = 2-10, preferably n = 4-8.

According to the invention, the adhesive body comprises at the same time one or more of said alpha-cyanoacrylate monomers.

According to the invention, the polymerization inhibitor is mixed with the adhesive body in a proportion of from 200 ppm to 2000 ppm, preferably from 500 ppm to 1000 ppm.

According to the invention, the adhesive body is also mixed with a plasticizer.

According to the present invention, the radiation crosslinking method is high energy ray irradiation including, but not limited to, ultraviolet rays, beta electron beams, and gamma rays.

The invention describes a method for preparing a specific viscosity α-cyanoacrylate adhesive by a radiation crosslinking method, and the structure of the α-cyanoacrylate monomer is as follows:

Due to the strong electron-withdrawing group attached to the carbon-carbon double bond, the electron cloud distribution on the π-bond is very uneven. In the case of providing external energy, the electron absorbs energy easily and transitions, causing the double bond to open. Polymerization, the degree of polymerization is related to the amount of external energy. Therefore, the present invention performs irradiation cross-linking by means of high-energy ray, such as an ultraviolet irradiation device, by controlling the amount of energy, The α-cyanoacrylate monomer is initially polymerized to form an adhesive of a specific viscosity.

The α-cyanoacrylate of the present invention includes methyl α-cyanoacrylate, ethyl α-cyanoacrylate, propyl α-cyanoacrylate, butyl α-cyanoacrylate, and amyl α-cyanoacrylate. Acryl α-cyanoacrylate, heptyl α-cyanoacrylate, and octyl α-cyanoacrylate may be used in any one, two or more kinds. The viscosity of the α-cyanoacrylate adhesive varies with the degree of crosslinking. The degree of crosslinking depends on the external energy, and the external energy and the power, distance, heating temperature and irradiation time of the high-energy ray irradiation equipment during irradiation. The parameters are closely related, and those skilled in the art can adjust these parameters arbitrarily according to the desired viscosity. For example, by selecting the distance of the UV lamp and the irradiation time, the irradiation intensity is controlled within an appropriate range to adjust the viscosity of the adhesive.

The polymerization inhibitors and plasticizers of the present invention are conventional and are not limited. For example, the polymerization inhibitor includes hydroquinone, 4-methoxyphenol, butylhydroxyanisole, hydroquinone, sulfur dioxide, boron trifluoride, hydrogen fluoride, etc.; plasticizers include aliphatic dibasic acid esters, benzene Formates (including phthalates, terephthalates), benzene polyesters, benzoates, polyol esters, chlorinated hydrocarbons, epoxies, citrates, Polyester and the like.

The invention has the following characteristics:

1. Simple process: only need to charge α-cyanoacrylate monomer into a closed and transparent container, by adjusting the irradiation power, distance, irradiation time, irradiation intensity and temperature of high energy ray irradiation equipment Factors control the viscosity of the product.

2. Short production cycle: the production cycle of the adhesive with polymethyl methacrylate (PMMA) as a thickener is about 6 months, and the production cycle of the adhesive of α-cyanoacrylate bulk polymer as a thickener is about 1 -1.5 months, the production cycle of the method provided by the present invention varies slightly depending on the viscosity, but does not exceed one hour.

3. Does not affect the bonding time and bonding strength: since the second substance is not added as a thickener, the product has good homogeneity and can maintain the activity, so it does not affect the polymerization time of the monomer itself, and is applied to the wound when used. Rapid polymerization in 2-6 seconds, and the strength and toughness are ideal.

4. The product has a single component and high safety: the present invention places high-purity α-cyanoacrylate monomer (for example, gas chromatographic normalization method to determine its purity greater than 99.8%) under high energy ray irradiation equipment. Irradiation thickening, no second substance or aging-deactivated poly-α-cyanoacrylate exists, so that the product can not only reduce the heat of polymerization when polymerized at the site of use, but also greatly reduce the irritation.

5. Long shelf life: The products treated by the above method have good stability and are stored at room temperature for 1 year without significant change.

detailed description

In order to further understand the present invention, the preferred embodiments of the present invention will be described below in conjunction with the embodiments. These descriptions are merely illustrative of the features and advantages of the adhesives of the present invention and methods of making the same, and are not intended to limit the scope of the invention.

Embodiment 1

1 mL of α-cyanoacrylate (10.9% purity by gas chromatography normalization method) was added to each of 10 2 mL vials, and the inside air was replaced with high-purity argon and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 60 ° C, adjust the height of the UV lamp shelf to a distance of 30 cm, and use a 1000 W UV lamp. Photo, time is 10min, 15min, 20min, 25min, 30min, 35min, 40min, 45min, 50min, and finally by the rotary viscometer (model is BROOKFIELD VISCOMETER, DV-II+Pro, the viscosity values in the following examples are used The instrument measures the viscosity. The viscosity test method was as follows: 0.5 mL of the sample was tested in a rotary viscometer under anhydrous and oxygen-free conditions. The viscosity values of the adhesive body are shown in Table 1 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.1	5.6	11.3	25.7	44.8	156.2	/	/	/	/

(The part where the viscosity value is not filled is that α-cyanoacrylate has completely polymerized into a solid, the same below)

Embodiment 2

1 mL of butyl α-cyanoacrylate was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the air inside was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 60 ° C, adjust the height of the UV lamp shelf to a distance of 30 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, and finally the viscosity was measured by a rotary viscometer. The viscosity values measured on the main body of the adhesive are shown in Table 2 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.3	4.2	10.6	23.5	38.6	112.6	152.3	/	/	/

Embodiment 3

1 mL of α-cyanoacrylate (yield 99.9% by gas chromatography normalization method) was added to each of 10 2 mL vials, and the inside air was replaced with high-purity argon and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 60 ° C, adjust the height of the UV lamp shelf to a distance of 30 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 3 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.2	3.9	8.9	22.9	33.5	67.8	111	136.7	/	/

Embodiment 4

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 60 ° C, adjust the height of the UV lamp shelf to a distance of 30 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 4 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	3.1	6.9	11.0	25.6	44.8	90.8	121.2	143.6	/

Embodiment 5

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 80 ° C, adjust the height of the UV lamp shelf to a distance of 30 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was tested by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 5 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	5.8	15.6	25.3	51.8	81	135.6	/	/	/

Embodiment 6

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 60 ° C, adjust the height of the UV lamp shelf to a distance of 50 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 6 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	3.1	6.7	15.6	29.8	40.3	78.5	102.4	152.3	/

Example 7

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 80 ° C, adjust the height of the UV lamp shelf to a distance of 50 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 7 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	3.8	8.5	19.2	33.7	51.6	92.5	151.6	/	/

Example eight

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Will be 2,3,4,5,6,7,8,9, The No. 10 bottle was placed in the heating table in turn, the set temperature was 60 ° C, the height of the UV lamp shelf was adjusted to be 20 cm, and irradiated with a 2000 W UV lamp for 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, respectively. 40 min, 45 min, 50 min, and finally the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 8 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	5.6	15.3	31.5	68.8	85.6	94.7	102.6	152.6	180.8

Example nine

1 mL of α-cyanoacrylate octyl ester was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization method), and the inside air was replaced with high-purity argon gas and sealed.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 80 ° C, adjust the height of the UV lamp shelf to a distance of 20 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 9 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	8.0	20.6	61.8	103.2	155.4	/	/	/	/

Example ten

A mixture of 0.5 mL of octyl α-cyanoacrylate and 0.5 mL of butyl α-cyanoacrylate was added to each of 10 2 mL vials (the purity was 99.9% by gas chromatography normalization), and the air inside was replaced. For high purity argon, seal.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 40 ° C, and adjust the height distance of the UV lamp shelf. The sample is 30cm, irradiated with 2000W UV lamp for 10min, 15min, 20min, 25min, 30min, 35min, 40min, 45min, 50min. Finally, the viscosity is tested by rotary viscometer. The viscosity value of the adhesive body is shown in the following table. 10:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	3.4	7.5	17.4	28.9	40.3	65.6	72.6	81	105.4

Embodiment 11

Add 0.5 mL of a mixture of octyl α-cyanoacrylate and 0.5 mL of hexyl α-cyanoacrylate in 10 2 mL vials (the purity is 99.9% by gas chromatography normalization), and replace the air inside. For high purity argon, seal.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and the No. 1 bottle was used as a blank comparison sample, and no UV crosslinking was performed. Place the 2, 3, 4, 5, 6, 7, 8, 9, and 10 bottles in the heating table in turn, set the temperature to 40 ° C, adjust the height of the UV lamp shelf to a distance of 50 cm, and use a 2000 W UV lamp. Photographs were taken at 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min. Finally, the viscosity was measured by a rotary viscometer. The viscosity values of the adhesive body are shown in Table 11 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	2.8	5.8	11.2	18.9	25.7	40.2	65.4	91	105.8

Example twelve

Add 0.5 mL of a mixture of octyl α-cyanoacrylate and 0.5 mL of hexyl α-cyanoacrylate in 10 2 mL vials (the purity is 99.9% by gas chromatography normalization), and replace the air inside. For high purity argon, seal.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, wherein the No. 1 bottle was used as a blank contrast sample and was not cross-linked by β-electron beam irradiation. Bottles 2, 3, 4, 5, 6, 7, 8, 9, and 10 were sequentially placed in a beta electron beam irradiation chamber, and the irradiation time was 5 sec. Irradiation intensity. Set to 0.5KGy, 1KGy, 2KGy, 5KGy, 10KGy, 15KGy, 18KGy, 20KGy, 25KGy, and finally test the viscosity by rotary viscometer. The viscosity value of the adhesive body is shown in Table 12 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	2.6	3.8	5.2	7.9	11.7	23.2	65.4	87	/

Example thirteen

Add 0.5 mL of a mixture of octyl α-cyanoacrylate and 0.5 mL of hexyl α-cyanoacrylate in 10 2 mL vials (the purity is 99.9% by gas chromatography normalization), and replace the air inside. For high purity argon, seal.

The above 10 ampoules were sequentially labeled as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, wherein the No. 1 bottle was used as a blank contrast sample and was not cross-linked by γ-ray irradiation. The bottles of 2, 3, 4, 5, 6, 7, 8, 9, and 10 were sequentially placed in the gamma ray irradiation box, the irradiation time was 5 sec, the irradiation intensity was not set, and the irradiation box distance was set separately. It is set to 50m, 10m, 8m, 2m, 1m, 50cm, 25cm, 10cm, 1cm. Finally, the viscosity is tested by a rotary viscometer. The viscosity value of the adhesive body is shown in Table 13 below:

Numbering	1	2	3	4	5	6	7	8	9	10
											Viscosity / cps	2.5	2.6	3.1	4.6	8.1	25.3	58.6	97.3	/	/

The above description of the embodiments is merely for helping to understand the core idea of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the adhesive of the present invention and the preparation method thereof without departing from the principles of the present invention, but such improvements and modifications also fall within the scope of the present invention. Request for protection within the scope of the request.

Claims (21)

1. A method for preparing an α-cyanoacrylate adhesive, characterized in that an α-cyanoacrylate monomer is prepared by a radiation crosslinking method to obtain an adhesive main body, and the adhesive main body and the polymerization inhibitor are mixed in proportion to form A-cyanoacrylate adhesive of the desired viscosity.
2. The preparation method according to claim 1, wherein the adhesive body is prepared by the following steps:

   a. placing the α-cyanoacrylate monomer in a closed, light-transmissive container;

   b. providing a high-energy ray irradiation apparatus, and providing a heating stage in the irradiation area of the high-energy ray irradiation apparatus;

   c. placing the container containing the α-cyanoacrylate monomer on the heating table, setting the heating temperature, and then irradiating under the action of the high-energy ray irradiation device, by adjusting the irradiation device Irradiation power, distance, irradiation time, and/or heating temperature of the heating station are used to control the degree of crosslinking of the α-cyanoacrylate to form the adhesive body.
3. The preparation method according to claim 2, wherein the high-energy ray irradiation device is an ultraviolet lamp, a gamma ray irradiation device, and a beta electron beam device.
4. The preparation method according to claim 2, wherein the distance between the high-energy ray irradiation device and the α-cyanoacrylate monomer is adjustable.
5. The production method according to claim 2 or 4, wherein the distance between the high-energy ray irradiation apparatus and the α-cyanoacrylate monomer is from 10 to 70 cm.
6. The production method according to claim 5, wherein the distance between the high-energy ray irradiation device and the α-cyanoacrylate monomer is 20 to 50 cm.
7. The process according to claim 2, wherein the heating temperature is from 20 to 100 °C.
8. The production method according to claim 7, wherein the heating temperature is 40 to 80 °C.
9. The preparation method according to claim 2, wherein the irradiation time is from 10 to 100 min.
10. The preparation method according to claim 9, wherein the irradiation time is from 10 to 60 min.
11. The preparation method according to claim 2, wherein the high energy ray irradiation apparatus has an irradiation power of 500 to 5000 W.
12. The preparation method according to claim 11, wherein the high-energy ray irradiation apparatus has an irradiation power of 1000-2500 W.
13. The method according to claim 1, wherein the structure of the α-cyanoacrylate monomer is as follows:

    

    Where n = 2-10.
14. The preparation method according to claim 13, wherein n = 4-8.
15. The method according to claim 1, wherein the adhesive body simultaneously comprises one or more of the α-cyanoacrylate monomers.
16. The preparation method according to claim 1, wherein the polymerization inhibitor is mixed with the binder main body in a ratio of from 200 ppm to 2000 ppm.
17. The production method according to claim 16, wherein the polymerization inhibitor is mixed with the binder main body in a ratio of 500 ppm to 1000 ppm.
18. The method according to claim 1, further comprising mixing the adhesive body with a plasticizer.
19. An α-cyanoacrylate adhesive produced by the production method according to any one of claims 1 to 18.
20. The α-cyanoacrylate adhesive according to claim 19, wherein the adhesive body has a viscosity of from 2 to 180 cps.
21. The α-cyanoacrylate adhesive according to claim 20, wherein the adhesive body has a viscosity of 25 to 80 cps.