Cyanoacrylate adhesive composition and method for making the same

Abstract

The present invention provides a method for making an adhesive composition. An adhesive substrate comprising at least a first cyanoacrylate monomer is provided and then mixed with a thickening agent containing polycyanoacrylate prepared by polymerization of a second cyanoacrylate monomer initiated with an aqueous solution of ammonium hydroxide or alcohol. In light of low boiling point of ammonium hydroxide and alcohol, they can be easily removed by heating at low temperature. As such, conventional premature polymerization of adhesive substrate owing to addition of a thickening agent containing residual accelerators can be overall improved.

Claims

1. A method of making an adhesive composition, comprising the steps of: (a) providing an adhesive substrate, the adhesive substrate comprising at least a first cyanoacrylate monomer; (b) providing a thickening agent, the thickening agent comprising at least a polycyanoacrylate, wherein the polycyanoacrylate is prepared by a method comprising the steps of: providing a second cyanoacrylate monomer; adding an aqueous solution of ammonium hydroxide or alcohol into the second cyanoacrylate monomer to initiate polymerization and forming a polymer of the second cyanoacrylate monomer; and heating and drying the polymer of the second cyanoacrylate monomer at 30 C.100 C. to remove the ammonium hydroxide or the alcohol; and (c) mixing the thickening agent with the adhesive substrate.

2. The method according to claim 1, wherein the first cyanoacrylate monomer or the second cyanoacrylate monomer is selected from the group consisting of alkyl 2-cyanoacrylate, cycloalkyl-2-cyanoacrylate, fluoroalkyl-2-cyanoacrylate, fluorocycloalkyl-2-cyanoacrylate, alkoxyalkyl-2-cyanoacrylate, alkoxycycloalkyl-2-cyanoacrylate, fluoroalkoxyalkyl-2-cyanoacrylate, and mixtures of two or more thereof.

3. The method according to claim 2, wherein the first cyanoacrylate monomer or the second cyanoacrylate monomer is selected from the group consisting of methyl 2-cyanoacrylate, ethyl 2-cyanoacrylate, n-propyl 2-cyanoacrylate, iso-propyl 2-cyanoacrylate, n-butyl 2-cyanoacrylate, iso-butyl 2-cyanoacrylate, hexyl 2-cyanoacrylate, n-octyl 2-cyanoacrylate, 2-octyl 2-cyanoacrylate, 2-methoxyethyl 2-cyanoacrylate, 2-ethoxyethyl 2-cyanoacrylate, 2-propoxyethyl 2-cyanoacrylate, and mixtures of two or more thereof.

4. The method according to claim 1, wherein step (c) further comprises adding at least a plasticizer and then mixing.

5. The method according to claim 4, wherein the plasticizer is selected from the group consisting of citric esters, glycerol esters, sebacic esters, fatty acid esters, cellulose esters, polyethylene glycol ethers, and mixtures of two or more thereof.

6. The method according to claim 5, wherein the plasticizer is tributyl 2-acetylcitrate.

7. The method according to claim 4, wherein step (c) further comprises adding a colorant, a free radical stabilizer or an anionic stabilizer and then mixing.

8. The method according to claim 1, wherein the thickening agent is about 0.5-25% by weight based on the total weight of the adhesive composition.

9. The method according to claim 8, wherein the thickening agent is about 1-10% by weight based on the total weight of the adhesive composition.

10. The method according to claim 9, wherein the thickening agent is about 1-5% by weight based on the total weight of the adhesive composition.

11. The method according to claim 1, wherein the aqueous solution of ammonium hydroxide is about 0.001-1% by weight.

12. The method according to claim 11, wherein the weight ratio of ammonium hydroxide to the second cyanoacrylate monomer is about 1:10000 to about 1:100.

13. The method according to claim 12, wherein the weight ratio of ammonium hydroxide to the second cyanoacrylate monomer is about 1:10000 to about 1:500.

14. The method according to claim 1, wherein the aqueous solution of alcohol is selected from the group consisting of methanol, ethanol, n-propanol, n-butanol, and mixtures thereof.

15. The method according to claim 14, wherein the aqueous solution of alcohol is about 0.1-1.5% by weight.

16. The method according to claim 15, wherein the aqueous solution of alcohol is the aqueous solution of ethanol.

17. The method according to claim 16, wherein the weight ratio of the alcohol to the second cyanoacrylate monomer is about 1:5000 to about 1:100.

18. The method according to claim 17, wherein the weight ratio of the alcohol to the second cyanoacrylate monomer is about 1:5000 to about 1:200.

19. The method according to claim 1, further comprising a step (d) of sterilizing the mixture of the thickening agent and the adhesive substrate.

20. An adhesive composition made by the method of claim 1.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

(1) The following description and examples illustrate a preferred embodiment of the present invention in detail. Those of skill in the art will recognize that there are numerous variations and modifications of this invention encompassed by its scope. Accordingly, the description of a preferred embodiment should not be deemed to limit the scope of the present invention.

(2) For preparing the adhesive composition of the present invention, a thickening agent, i.e. the polymer of the second cyanoacrylate monomer, should be made first. And then the thickening agent, in an amount depending on the demand, is added into the adhesive substrate containing the first cyanoacrylate monomer. After mixing, the resulting adhesive composition with the desired viscosity can be achieved.

(3) The first cyanoacrylate monomer or the second cyanoacrylate monomer may be selected from the group consisting of alkyl 2-cyanoacrylate, cycloalkyl-2-cyanoacrylate, fluoroalkyl- 2-cyanoacrylate, fluorocycloalkyl-2-cyanoacrylate, alkoxyalkyl-2-cyanoacrylate, alkoxycycloalkyl-2-cyanoacrylate, fluoroalkoxyalkyl-2-cyanoacrylate, and mixtures of two or more thereof. In order to obtain the optimum compatibility, e.g., dissolving the polymer of the second cyanoacrylate monomer well in the first cyanoacrylate monomer, the first cyanoacrylate monomer and the second cyanoacrylate monomer are prefer to, but not limited to, the same monomer.

(4) Further, the thickening agent (i.e. the polymer of the second cyanoacrylate monomer) may be poly alkyl 2-cyanoacrylates, poly cycloalkyl-2-cyanoacrylates, poly fluoroalkyl-2-cyanoacrylates, poly fluorocycloalkyl-2-cyanoacrylates, poly alkoxyalkyl-2-cyanoacrylates, poly alkoxycycloalkyl-2-cyanoacrylates, or poly fluoroalkoxyalkyl-2-cyanoacrylates. The preferred weight average molecular weight of the polymers is from about 5,000 to about 4,000,000; more preferably from about 5,000 to about 1,000,000.

(5) For the preparation of the thickening agent, an accelerator/initiator with a low boiling point, e.g., ammonium hydroxide, alcohol, but not limited to, can be added to start the polymerization. Utilizing the property of their relatively low boiling points, ammonium hydroxide or alcohol can evaporate or be easily removed in the following heating procedures. The alcohol can be selected from the group consisting of methanol, ethanol, n-propanol, butanol, and mixtures thereof. The alcohol having a lower boiling point such as methanol, ethanol, n-propanol or mixtures thereof is preferred.

(6) The amount of thickening agent (polycyanoacrylate) intended to be added to the adhesive substrate (cyanoacrylate monomers) is dependent upon the molecular weight of the polymers and the desired viscosity for the adhesive composition. The thickening agent typically may be about 0.5-25% by weight based on the total weight of the adhesive composition, preferably about 1-10% by weight, more preferably about 1-5% by weight.

(7) In addition, a plasticizer can also be added to the mixture of the first cyanoacrylate monomer and the thickening agent for desired viscosity and elasticity. The plasticizer may be selected from, but not limited to, the group consisting of citric esters, glycerol esters, sebacic esters, fatty acid esters, cellulose esters, polyethylene glycol ethers and mixtures of two or more thereof. Preferably, the plasticizer can be selected for example from the group consisting of glycerol triacetate, glycerol tripropionate, glycerol tributyrate, tricaproin, trivalerin, tricaprin, tributyl 2-acetylcitrate, isobutyl myristate, ethyl myristate, ethyl stearate, methyl sebacate, ethyl sebacate, ethylcellulose, polyethylene glycol diethers, and mixtures thereof. Tributyl 2-acetylcitrate is particularly more preferred.

EXAMPLE 1

(8) Preparation of Thickening Agent A

(9) For the preparation of the accelerator, 1800 ml of deionized water was first placed in a 2000 ml beaker, and then 0.7 g (0.04% by weight) of NH.sub.4OH (Showa Chemical Co., Lot. number 111024) was added with a pipette and mixed by stirring for about 5 minutes. Then the second cyanoacrylate monomer, 32 ml of n-butyl cyanoacrylate monomer (nBCA, Chemence Co.), was added into the NH.sub.4OH solution drop by drop and mixed by continuous stirring for about 0.5 hour.

(10) The resulting nBCA polymer, namely Thickening Agent A, was decanted and dried in the vacuum oven at 65 C. for 8 hours. The molecular weight of nBCA polymer was measured with a gel permeation chromatography (GPC). Consequently, the molecular weight of nBCA polymer, i.e. Thickening Agent A, is 57,300.

EXAMPLE 2

(11) Preparation of Adhesive A

(12) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent A prepared as described in Example 1 was then added slowly into the flask. Then they were mixed at 100 C. for 60 minutes to form Adhesive A. The viscosity of the Adhesive A was measured with a capillary viscometer. The viscosity of the Adhesive A is 43 cP at 20 C.

EXAMPLE 3

(13) Preparation of Adhesive B

(14) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent A prepared as described in Example 1 was then added slowly into the flask. 15 g of tributyl 2-acetylcitrate (ATBC, SAFC, Lot number MKBG8107V) was also added slowly subsequently, and then all were mixed at 100 C. for 60 minutes to form Adhesive B. The viscosity of the Adhesive B was measured with a capillary viscometer. The viscosity of the Adhesive B is 39 cP at 20 C.

EXAMPLE 4

(15) Preparation of Thickening Agent B

(16) For the preparation of the accelerator, 1800 ml of deionized water was first placed in a 2000 ml beaker, and then 1 g (0.06% by weight) of NH.sub.4OH (Showa Chemical Co., Lot. number 111024) was added with a pipette and mixed by stirring for about 5 minutes. Afterwards the second cyanoacrylate monomer, 32 ml of n-butyl cyanoacrylate monomer (nBCA, Chemence Co.), was added into the NH.sub.4OH solution drop by drop and mixed by continuous stirring for about 0.5 hour.

(17) The resulting nBCA polymer, namely Thickening Agent B, was decanted and dried in the vacuum oven at 65 C. for 8 hours. The molecular weight of nBCA polymer was measured with a gel permeation chromatography (GPC). Consequently, the molecular weight of nBCA polymer, i.e. Thickening Agent B is 41,200.

EXAMPLE 5

(18) Preparation of Adhesive C

(19) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent B prepared as described in Example 4 was then added slowly into the flask. After this, they were mixed at 100 C. for 60 minutes to form Adhesive C. The viscosity of the Adhesive C was measured with a capillary viscometer. The viscosity of the Adhesive C is 31 cP at 20 C.

EXAMPLE 6

(20) Preparation of Adhesive D

(21) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent B prepared as described in Example 4 was then added slowly into the flask. 15 g of tributyl 2-acetylcitrate was also added slowly subsequently, and then all were mixed at 100 C. for 60 minutes to form Adhesive D. The viscosity of the Adhesive D was measured with a capillary viscometer. The viscosity of the Adhesive D is 48 cP at 20 C.

EXAMPLE 7

(22) Accelerated Aging Test to Check the Stability of Adhesive B

(23) 0.8 ml of Adhesive B sample was placed in each aluminum tube and sealed. A total of 300 Adhesive B samples were prepared for the execution of the testing. Those Adhesive B samples were randomly separated into 5 groups (Group 1-5) consisting of 60 samples/each. Those samples were aged in an Environmental Chamber at 60 C. to simulate various aging time at 20 C. The results are shown in Table 1.

(24) TABLE-US-00001 TABLE 1 Group 1 2 3 4 5 Accelerated Aging 0 6 12 18 24 Equivalence (month) Absolute Viscosity 39 42 48 52 55 (cP) Wound Closure 9.2 8.7 8.7 8.3 8.1 Strength (N)

EXAMPLE 8

(25) Wound Closure Strength Test of Adhesive B

(26) After aging test (Example 7), the samples were tested for their wound closure strength according to ASTM F2458 wound closure strength test. In this test, a thin layer of adhesive sample was applied on a piece of porcine skin specimen with a cut in the middle to simulate wound. Then, the force to pull the wound apart was measured.

(27) Sufficient Adhesive B was first applied uniformly on a 2.5 cm1.0 cm area adjacent to the cut to bond 2 pieces of porcine skins together. 10 sets of specimens were prepared. They were then placed in a sealed plastic bag and conditioned in 301 C. for 1 hr15 min. Once the adhesive was cured, the specimens were allowed to cool to room temperature and were clamped between the upper and lower jaws of a universal test machine. The specimens were tested at a crosshead speed of 250 mm/min until failure. Both failure mode and peak load were recorded. The results of the wound closure strength test are shown in Table 1.

(28) As seen from Table 1, the viscosity of Adhesive B increased as time goes by, but the wound closure strength thereof reduced slightly and possesses 8.1N after 24 months' aging. Thus, the adhesive provided by the present invention can prevent cyanoacrylate monomer from premature polymerization and has a desirable viscosity for convenient application. In addition, it also maintains appropriate wound closure strength for a long period of time.

EXAMPLE 9

(29) Preparation of Thickening Agent C

(30) For preparation of the accelerator, 1800 ml of deionized water was first placed in a 2000 ml beaker, and then 5 g (0.3% by weight) ethanol (Echo Chemical Co.) was added and mixed by stifling for about 5 minutes. Afterwards the second cyanoacrylate monomer, 32 ml of n-butyl cyanoacrylate monomer (nBCA, Chemence Co.), was added into the ethanol solution drop by drop and mixed by continuous stirring for about 0.5 hour.

(31) The resulting nBCA polymer, namely Thickening Agent C, was decanted and dried in the vacuum oven at 65 C. for 8 hours. The molecular weight of nBCA polymer was measured with a gel permeation chromatography (GPC). Consequently, the molecular weight of nBCA polymer, i.e. Thickening Agent C, is 64,300.

EXAMPLE 10

(32) Preparation of Adhesive E

(33) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent C prepared in Example 9 was then added slowly into the flask. After this, they were mixed at 100 C. for 60 minutes to form Adhesive E. The viscosity of the Adhesive E was measured with a capillary viscometer. The viscosity of the Adhesive E is 47 cP at 20 C.

EXAMPLE 11

(34) Preparation of Adhesive F

(35) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent C prepared in Example 9 was then added slowly into the flask. 15 g of tributyl 2-acetylcitrate (ATBC, SAFC, Lot number MKBG8107V) was also added slowly subsequently. Then they were mixed at 100 C. for 60 minutes to form Adhesive F. The viscosity of the Adhesive F was measured with a capillary viscometer. The viscosity of the Adhesive F is 43 cP at 20 C.

EXAMPLE 12

(36) Preparation of Thickening Agent D

(37) For preparation of the accelerator, 1800 ml of deionized water was first placed in a 2000 ml beaker, and then 1.8 g (0.1% by weight) sodium bicarbonate (Sigma-Aldrich Co.) was added with a pipette and mixed by stirring for about 3 minutes. Afterwards the second cyanoacrylate monomer, 32 ml of n-butyl cyanoacrylate monomer (nBCA, Chemence Co.), was added into the sodium bicarbonate solution drop by drop and mixed by continuous stirring for about 0.5 hour.

(38) The resulting nBCA polymer was decanted and rinsed several times with deionized water and then decanted again. The bicarbonate therein was neutralized with 0.1N HCl and then nBCA polymer was rinsed again with deionized water. The resulting product was dried in the vacuum oven at 65 C. for 8 hours to form Thickening Agent D. The molecular weight of the Thickening Agent D is 43,100.

EXAMPLE 13

(39) Preparation of Adhesive G

(40) The first cyanoacrylate monomer, 285 g of 2-octyl cyanoacrylate monomer (2-OCA, the viscosity thereof is 6 cP at 20 C.), was poured into a 1 liter round bottom flask on a heater/mixer and stirred at 200 rpm. 15 g of Thickening Agent D prepared in Example 12 was then added slowly into the flask. 15 g of tributyl 2-acetylcitrate (ATBC, SAFC, Lot number MKBG8107V) was also added slowly subsequently; and then all were mixed at 100 C. for 60 minutes to form Adhesive G. The viscosity of the Adhesive G was measured with a capillary viscometer. The viscosity of the Adhesive G is 31 cP at 20 C.

EXAMPLE 14

(41) Accelerated Aging Test to Check the Stability of Adhesive G

(42) 0.8 ml of Adhesive G sample was placed in each aluminum tube and sealed. A total of 300 Adhesive G samples were prepared for the execution of the test. The Adhesive G samples were randomly separated into 5 groups (Group 6-10) consisting of 60 each. They were accelerately aged in an Environmental Chamber at 60 C. to simulate various aging time at 20 C. The results are shown in Table 2.

(43) TABLE-US-00002 TABLE 2 Group 6 7 8 9 10 Accelerated Aging 0 6 12 18 24 Equivalence (month) Absolute Viscosity 35 48 68 80 150 (cP) Wound Closure 9.6 8.9 7.5 6.1 4.2 Strength (N)

EXAMPLE 15

(44) Wound Closure Strength Test of Adhesive G

(45) After aging test (Example 14), the samples were tested for their wound closure strength according to ASTM F2458 wound closure strength test as described in Example 8.

(46) Sufficient Adhesive G was first applied uniformly on a 2.5 cm1.0 cm area adjacent to the cut to bond 2 pieces of porcine skins together. 10 sets of specimens were prepared. They were then placed in a sealed plastic bag and conditioned in 301 C. for 1 hr15 min. Once the adhesive was cured, the specimens were allowed to cool to room temperature and were clamped between the upper and lower jaws of a universal test machine. The specimens were tested at a crosshead speed of 250 mm/min until failure. Both failure mode and peak load were recorded. The results of the wound closure strength test are shown in Table 2.

(47) Referring to the results shown in Tables 1 and 2, the wound closure strength of Adhesive G has been reduced to 7.5N after 12 months' aging, and 4.2N after 24 months' aging. The adhesive thickened by polycyanoacrylate, which was prepared by conventional accelerators exhibits premature polymerization in a cyanoacrylate monomer adhesive due to its residual accelerators. Owing to this premature polymerization of adhesive substrate, either the wound bonding strength is reduced or the shelf life is shortened. However, with the thickening agent prepared by the ammonium hydroxide or alcohol provided by the present invention, the premature polymerization can be reduced and the adhesive having excellent properties can be used for various medical applications.