MXPA99003954A - Adhesives with low level of residual monomers and process for manufacturing same - Google Patents
Adhesives with low level of residual monomers and process for manufacturing sameInfo
- Publication number
- MXPA99003954A MXPA99003954A MXPA/A/1999/003954A MX9903954A MXPA99003954A MX PA99003954 A MXPA99003954 A MX PA99003954A MX 9903954 A MX9903954 A MX 9903954A MX PA99003954 A MXPA99003954 A MX PA99003954A
- Authority
- MX
- Mexico
- Prior art keywords
- catalyst
- adhesive according
- adhesive
- polymer
- hydrogenation
- Prior art date
Links
- 239000000853 adhesive Substances 0.000 title claims abstract description 41
- 230000001070 adhesive Effects 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims description 31
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 229920000642 polymer Polymers 0.000 claims abstract description 55
- 239000002537 cosmetic Substances 0.000 claims abstract description 5
- 235000013305 food Nutrition 0.000 claims abstract description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 56
- 239000003054 catalyst Substances 0.000 claims description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 45
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 35
- XTXRWKRVRITETP-UHFFFAOYSA-N vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 21
- 229920001577 copolymer Polymers 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 14
- UTODFRQBVUVYOB-UHFFFAOYSA-P Wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000002815 homogeneous catalyst Substances 0.000 claims description 9
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 claims description 8
- 229910052759 nickel Inorganic materials 0.000 claims description 8
- 238000006116 polymerization reaction Methods 0.000 claims description 8
- PNEYBMLMFCGWSK-UHFFFAOYSA-N AI2O3 Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 7
- 239000002638 heterogeneous catalyst Substances 0.000 claims description 7
- 230000001225 therapeutic Effects 0.000 claims description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- -1 alkyl methacrylates Chemical class 0.000 claims description 5
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 238000007334 copolymerization reaction Methods 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 125000005250 alkyl acrylate group Chemical group 0.000 claims 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 2
- 230000035945 sensitivity Effects 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 21
- 239000000178 monomer Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 9
- 238000011068 load Methods 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 5
- 229940048053 acrylate Drugs 0.000 description 5
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 4
- VOZRXNHHFUQHIL-UHFFFAOYSA-N Glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000003999 initiator Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 230000001809 detectable Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Incidol Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- 210000003491 Skin Anatomy 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
- 239000002390 adhesive tape Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000000737 periodic Effects 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 239000011995 wilkinson's catalyst Substances 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N Azobisisobutyronitrile Chemical compound N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- 241001417527 Pempheridae Species 0.000 description 1
- 229940047670 SODIUM ACRYLATE Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M Sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 206010041662 Splinter Diseases 0.000 description 1
- 229940100640 Transdermal System Drugs 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 239000004840 adhesive resin Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KAKZBPTYRLMSJV-UHFFFAOYSA-N butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atoms Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 230000003247 decreasing Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium(0) Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008079 hexane Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 230000000379 polymerizing Effects 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 239000002569 water oil cream Substances 0.000 description 1
Abstract
An adhesive, which contains olefinic polymers and less than 1%by weight of free monomers, is manufactured via catalytic hydrogenation. It is preferably used in the area of cosmetics, in the food sector, in medicinal plasters and transdermal systems.
Description
ADHESIVES WITH LOW LEVEL OF MONOMER RESIDUES AND PROCESSES TO MANUFACTURE THE SAME
DESCRIPTION OF THE INVENTION
This invention relates to adhesives containing polymers with a very low content of monomer residues, with a process for their manufacture and their application.
Typically speaking, adhesive tapes, gummed or sticky plasters and the like are manufactured by coating films or paper with solutions or suspensions of polymers. Subsequently, organic solvents or water are removed by drying. Polyacrylate solutions in organic solvents are especially suitable. These polyacrylate solutions are usually manufactured by polymerizing acrylic acid, its ester, and in some cases, vinyl acetate, while adding free radical initiators, for example azobisisobutyronitrile or others. After the polymerization or copolymerization is complete, organic solvents are added to dilute to a solids content of about 40%, after which the solution is ready for coating.
Recently it has been recognized that this process has a limitation, especially in the cases of copolymerization, which is that the less reactive monomer escapes polymerization. For this reason, to arrive at a defined polymer in a reproducible base, an excess of this less reactive monomer is used, for example, vinyl acetate. In principle vinyl acetate is slower to react than acrylates since the double bond it contains is not conjugated with a carbonyl group. The disadvantage of adding an excess of vinyl acetate is that the proportion of free vinyl acetate in the solution can reach the amount of 7 to 8% in relation to the solids content. Due to the aforementioned dilution, this residual monomer content can be reduced to approximately 3%.
In general, residual monomer contents of this order of magnitude are undesirable in adhesives, particularly for applications in the medical cosmetic fields as well as for packaging in the food industry. In addition, maximum concentrations of residual monomers are prescribed by law in many countries. Therefore, there has been a broad campaign in the industry to reduce the residual polymer content in polymer solutions for the medical and food sectors.
An attempted method is known as fractional distillation. In this, the solvents that originate from the synthesis of the polymers are almost completely removed. Since the physical properties of vinyl acetate and ethyl acetate (boiling point and vapor pressure) differ very little, it is necessary either to evaporate to dry or constantly add the distilled ethyl acetate. Evaporating until dry can lead to such a high temperature load that the polymer can change. Adding the ethyl acetate that has been distilled leads to high solvent consumption and large amounts of solvent waste, an extremely expensive process.
Another method for removing residual monomers is to react to the residual monomer that was not converted with extremely reactive radical initiators based on organic peroxides, which are known as scavengers or scavengers. The drawback of this process is that the residual monomers are not removed but react to form oligomers that remain in the polymer.
A desirable process, therefore, should have the following advantages:
it must produce a polymer with an extremely low proportion of unconverted monomers or oligomers; the thermal load during the polymerization or during the removal of the solvent must be minimized; you should use only small amounts of organic solvents; you must avoid the use of sweepers or scavengers; and it must be economical.
It has been discovered that polymeric adhesives having a very low content of residual monomers can be manufactured by catalytic hydrogenation and achieved the above mentioned advantages.
The resulting adhesives comprise polymers prepared from olefinic monomers and contain a very low residual monomer content. These adhesives are suitable for use in technical applications, for example in adhesive tapes as office materials, or for cosmetic or medicinal applications, for example for the manufacture of sticky, gummed-on gum for electrodes, or transdermal therapeutic systems.
Thus, this invention is an adhesive comprising one or more polymers prepared from olefinic monomers, where the content of free residual monomers is less than 1% by weight, preferably less than 0.3% by weight, more preferably lower than 0.02% by weight, and more preferably less than 0.01% by weight, but not less than 0.0001% by weight.
The polymers can be either a homopolymer or a mixture of different homopolymers; a copolymer or a mixture of different copolymers; a block polymer or a mixture of different block polymers; or they can be either a mixture of one or more homopolymers, copolymers, or block polymers. The adhesives according to the invention may contain other substances, such as adhesive resins, for example, hydrogenated colofonium; however, they may also consist entirely of such polymers.
The invention relates specifically to pressure sensitive adhesives, especially those containing one or more copolymers from monomers such as acrylic acid, methacrylic acid, and acrylate and methacrylate esters, in which the ester part may contain up to 8 carbon atoms (C? -C8 alkyl) or those containing copolymers of the aforementioned monomers and monomers such as vinyl acetate or ethylene. Suitable acrylate and methacrylate esters are the methyl, ethyl, branched or straight chain esters of propyl, butyl, pentyl, hexyl, heptyl, or octyl, for example the ethylhexyl ester, hydroxy esters, for example hydroxyethyl ester.
The invention relates especially to pressure sensitive adhesives containing a copolymer of 2-ethylhexyl acrylate and vinyl acetate.
In another embodiment, this invention is a process for the manufacture of an adhesive comprising one or more olefinic polymers, wherein the content of free monomers is less than 1% by weight, the process comprises, after completing the polymerization or copolymerization of the polymer , the hydrogenation of the adhesive in an organic solvent in the presence of a heterogeneous or homogeneous catalyst.
Any suitable catalyst such as platinum, palladium, and palladium on activated carbon can be used. Other suitable heterogeneous catalysts are palladium on activated carbon and nickel on silica / alumina. A suitable homogeneous catalyst is tris (triphenylphosphine) rhodium chloride (1).
The hydrogenation process will take place at temperatures of up to 150 ° C and at hydrogen pressures of up to 100 bars, preferably at temperatures of up to 100 ° C and at hydrogen pressures of up to 80 bars, more preferably at temperatures up to 100 ° C and at pressures of hydrogen up to 52 bars, and more preferably at ambient temperature and at atmospheric pressure.
The hydrogenation can be carried out in any suitable organic solvent, particularly in a less polar organic solvent than water. A preferable solvent is ethyl acetate.
These adhesives are useful whenever there is a need for materials with low content of residual monomers, such as, for example, transdermal therapeutic systems and bandages, including transdermal systems that may have cosmetic utility, and also adhesives for packaging of food products. These adhesives can also be used in medicated gums, which for the purposes of the present include veterinary medicated gumming.
Particularly, this invention relates to transdermal therapeutic systems containing an adhesive according to the invention, especially pressure sensitive adhesives, for example a copolymer of 2-ethylhexyl acrylate and vinyl acetate. Such transdermal therapeutic systems typically consist of a reservoir containing the active agent to be released, and an adjacent layer made of a pressure sensitive adhesive that contacts the skin.
In such a system, however, the pressure sensitive adhesive can furthermore form a multi-layer or multi-layer matrix which is contacted with the skin and in which the active agent is present in dispersed or dissolved form. If the matrix is multilayer or multilayer, the individual layers may consist of different adhesives according to the invention.
The catalytic hydrogenation of C = C double bonds in alkenes in the presence of platinum or palladium or palladium on carbon (Pd / C) or other metals of the eighth auxiliary group of the periodic system (eg nickel) as a catalyst at atmospheric pressure or Increased hydrogen pressure and at an ambient temperature or higher temperatures itself has long been known. However, it was not expected that the present problem could be solved by applying the well known hydrogenation process, since the process has to be conducted under the most unfavorable conditions.
Prior to hydrogenation, for example, the concentration of residual monomers is very low (< 3%). Furthermore, as will be known, hydrogenation with metal catalysts takes place more unfavorably as the solvent used is more non-polar. As the hydrogenation takes place after the polymerization, in the present case in which the organic solvents are essentially non-polar, for example in ethyl acetate, this implies an additional unfavorable reaction condition. However, through the use of the process according to the invention, the residual monomer content can be successfully reduced to below 0.3% and even as low as 0.01%.
The fact that this is not a risky conclusion is demonstrated by the patent of E. U. A. 4,375,529 (de Fong et al.). That patent describes a method for reducing the residual monomer content in a water-oil emulsion containing partially polymerized acrylamide and sodium acrylate. The degree of polymerization described in that patent reaches only 80%, which implies the residual monomer concentration reaches approximately 20%.
The subsequent hydrogenation took place in water, which is a highly polar solvent. At the same time it was possible to use very high pressures. However, the residual monomer concentrations that were achieved were about 1% at most and, for the reasons outlined above, they are unacceptably high, and could likewise be achieved by means of suitable polymerization techniques.
The process according to the invention is carried out through the hydrogenation of a solution of the adhesive in organic solvents in the presence of a metal catalyst at temperatures up to 150 ° C, preferably up to 100 ° C and in a range of pressure from 0.3 bar to 100 bars, preferably from 0.5 bar to 80 bars.
A particularly preferred process is hydrogenation in the presence of platinum, palladium or palladium on carbon at ambient temperatures and atmospheric hydrogen pressure. The process according to the inversion can be conducted in the presence of other metals of the eighth auxiliary group of the periodic system for example, using nickel as a catalyst, at higher temperatures and at higher hydrogen pressures.
Preferred solvents are those that are of lower polarity than water (for example, those whose dielectric constant is less than that of water). A particularly preferred solvent is ethyl acetate.
It will be recognized that any unreacted monomer or byproducts of polymerization initiators that are present in the adhesive and that are potentially capable of reacting with the drug to be delivered to the transdermal system are undesirable in transdermal therapeutic systems. Therefore, it is a distinct advantage to be able to reduce the level of residual monomers or other reactive components to as low a level as possible for adhesives that will be used in such therapeutic systems.
In addition, using a hydrogenation technique to reduce the level of vinyl acetate produces ethyl acetate as the product. Since ethyl acetate is often the selection solvent for the adhesive, no component is added to the adhesive matrix.
The following examples will serve to further describe the invention, but are not intended to be a limitation. The descriptions of the hydrogenation and detection methods used in the examples are described in the procedures section following the examples.
EXAMPLES
Example 1. Hydrogenation of a vinyl acetate formulation. A copolymer prepared from vinyl acetate, 2-hydroxyethyl acrylate (2-HEA), 2-ethylhexylacrylate (2-EHA), and glycidyl methacrylate (GMA) at 10% solids in ethyl acetate was formulated, was hydrogenated under disclosed in Table 1 using the catalyst at 10% by weight of the polymer solution, and then evaluated for the residual vinyl acetate monomer (VAM). The data show that the reduction of residual vinyl acetate occurs, even under mild conditions of ambient temperature and a hydrogen atmosphere, using a palladium catalyst on activated carbon. The data also shows that the nickel supported catalyst, although not effective under mild conditions, is effective under the most vigorous conditions of 80 ° C and 52 bars of hydrogen. The experiment that did not use hydrogen was done to show that this reduction actually takes place and it is not just the absorption of the vinyl acetate in the catalyst's carbon. Although ideal conditions, 10% polymer solids and 10% catalyst loading were used, these experiments show that the residual monomer level of vinyl acetate can be reduced by catalytic reduction using either a palladium or nickel based catalyst , where the conditions are optimal for each catalyst. The preferred catalyst is the palladium catalyst.
Table 1
Effect of hydrogenation in the VAM
Notes: a. palladium on activated carbon
b. nickel in silica
c. nickel in silica / alumina
d. Ambient temperature and 1 hydrogen atmosphere
and. based on 100% polymer solids
Example 2. Effect of hydrogenation using more polymer solids. The experiments in this example were conducted to determine if the reduction could be obtained in solid materials of more than 10%. The hydrogenation was carried out in the same copolymer used in Example 1 under hydrogenation conditions of 80 ° C and 52 bars of hydrogen pressure, using either a palladium catalyst on activated carbon at 5% or a nickel on silica catalyst / 65% alumina, with the catalyst loaded to 10% by weight of the polymer solution. The results are shown in Table 2a and indicate that the level of residual VAM can be reduced below the level of 1000 ppm when the reaction is performed at any concentration at least up to about 50% solids.
Table 2a
Variation of polymer solids
Notes: a. based on 100% polymer solids
This is important because the viscosity of the matrix is greatly increased with the percentage of solids in the formulation as shown in Table 2b. In this way, the data in Table 2a further illustrate that hydrogenation is effective in very viscous matrices Table 2b
Viscosity table
Example 3. Effect of hydrogenation on other residual monomers.
The same copolymer used in Example 1 was tested in the presence of other monomers other than vinyl acetate after hydrogenation. The only monomer present at a detectable level was 2-EHA; residues of 2-HEA and GMA could be present, but were below detectable limits. The results are in Table 3, and show that when the residual vinyl acetate is reduced using the hydrogenation conditions already discussed, there are also residual acrylates.
Table 3
Effect of hydrogenation on 2-HEA
Example 4. Hydrogenation of the completely acrylate formulation. A completely acrylate copolymer was prepared from 2-ethylhexyl acrylate (2-EHA), methyl acrylate, acrylic acid, and glycidyl methacrylate, and formulated at 37% solids of the polymer in a solvent mixture of 54% ethyl acetate, 34.6% isopropanol, and 11.4% hexane. The polymer solution was subjected to hydrogenation conditions of 80 ° C and 52 bars of hydrogen pressure using a 65% silica / alumina nickel catalyst. The results are reported in table 4 and show that using the hydrogenation conditions already discussed, the level of residual acrylate monomers can be effectively reduced.
Table 4
Example 5. Level of used catalyst and residual catalyst. It is advantageous to keep the level of the catalyst as low as possible for reasons of economy and to facilitate the removal of the catalyst.
(a) In this example, the hydrogenation was conducted using 5% Pd on activated carbon at a catalyst loading level below 0.05% and 0.1% by weight of the polymer solution. The composition of the copolymer was that used in Example 1 and the polymer solution had 50% solids content. The hydrogenation conditions and the residue levels of the vinyl acetate monomer before and after the hydrogenation are reported in table 5. The results indicate that the hydrogenation was effective even when the catalyst load has a level of 0.05%.
In order to test the Pd residue content, the reduced polymer solution was filtered to remove the catalyst, and the Pd residue level was determined by atomic absorption tests. The filtration was performed using Miliporo filter paper of 3.0 μm at 4 bars and 60 ° C. The four examples in Table 5 showed low levels of Pd (< 2 ppm). One of the examples was left for two weeks, and after that time the Pd content was filtered and analyzed. This example did not show significant increases in the Pd content with respect to the filtrates directly after the hydrogenation. All four examples exhibited the same color after hydrogenation as the color of the polymer before hydrogenation. The results are reported in table 5.
Table 5
Catalyst level of Pd / C at 5%
Additional filtrations were performed using Miliporo filter paper of 5.0 μm of 1.0 μm. The 5.0 μm paper was not effective in removing the catalyst, but covering the paper with a Celita pad improves filtration. The 1.0 μm paper did not allow to pass to the solution of the polymer or to the catalyst at 60 ° C and up to a nitrogen pressure of 8 bars. To test the effective filtration on an industrial scale, commercial filter paper was used at 60 ° C and 7 bars to conduct a filtration in the same sample and was found effective to remove the catalyst.
(b) Residual nickel catalyst. A 50% solids polymer sample was hydrogenated under 52 bars of hydrogen pressure and 80 ° C using a 65% silica / alumina nickel catalyst with a catalyst load of 10% by weight of the polymer solution. The VAM residue in this example was 55 ppm based on 50% solids, and the nickel content, based on 50% solids in ethyl acetate, was 5J ppm.
Example 6. Hydrogenation with large particle catalyst. In the previous examples, the catalyst was used in powder form, and although the reduction worked very well, the filtration of this powder from the polymer solution at the end of the hydrogenation adds an extra step to the process. To avoid the need to filter, catalysts with large particles in the hydrogenation reaction were used in this example. The pellet or chip-shaped catalysts were suspended in a mesh wire basket in the reactor and the reactor mixing blades positioned directly to direct the flow of the polymer solution through the basket. This use of the catalyst with large particles simulates the types of systems used, for example, in conventional fixed bed continuous hydrogenation apparatus.
Two different catalysts were used: one of 3.2 mm palladium spheres in 0.50% alumina, and another in the form of a splinter in mesh of 4 X 8 palladium in 1.0% carbon). All reactions were carried out at 48 bars of hydrogen pressure and at the temperatures and times reported in Table 6 in polymer solutions at 50% polymer solids. The same copolymer used in example 1 was used. It can be observed in these data, that the hydrogenation can be carried out using catalysts with large particles.
Table 6
* All monomer concentrations are at 10% solids in the solution. The concentration of monomers based on 100% solids would be greater by a factor of 10.
Example 7. Hydrogenation with homogeneous catalysts. When heterogeneous catalysts are used in the hydrogenation processes, as was done in the previous examples, the catalyst is generally removed by filtration once the hydrogenation is complete. When a homogeneous catalyst is used, the filtration step can be avoided since the catalyst can be left in the solution because it is used in smaller amounts. This makes the process more efficient. In this example a homogeneous catalyst was used to hydrogenate the polymer solution of Example 1, containing about 16,000 ppm of vinyl acetate residues. Several homogeneous catalysts are known and used in the art for hydrogenating, and can be used for the hydrogenation processes disclosed in this description.
The specific catalyst used in this example was the Wilkinson catalyst, tris (triphenylphosphine) rhodium chloride (1), and was used in an amount of 1 ppm (approximately OJ ppm of rhodium), based on the total weight of the sample. The hydrogenation was carried out at 60 ° C for 16 hours using 48 bars of hydrogen. At this level the residue of the vinyl acetate monomer remained the same. The hydrogenation was repeated using 10 ppm of the Wilkilson catalyst (approximately 1 ppm of rhodium) at 60 ° C and 16 hours using 48 bars of hydrogen. In this second experiment, VAM residues were decreased from 16200 ppm to 2900 ppm.
Example 8. Hydrogenation of residual initiators. In order to test the effectiveness of the hydrogenation on the residual polymer initiators that may be present in the polymer solution, a sample of pressure-sensitive polymer containing 250 ppm of residual benzoyl peroxide is subjected to the hydrogenation conditions with palladium on activated carbon at 5% with a load of 0.05% by weight of the catalyst per polymer solids, at 60 ° C and 48 bars of hydrogen pressure for 16 hours. Analysis of the sample after hydrogenation did not reveal detectable benzoyl peroxide.
PROCEDURES
Waste detection method.
Each formulation was tested both before and after hydrogenation with respect to the contents of residual monomers or their byproducts by direct gas injection chromatography with a Hewlett-Packard 5890 GC / FID using an external standard. The conditions of the chromatography for the tests were:
Columns GC: 30 m X 0.53 mm I.D. DB -624 (3 μm film) or its equivalent.
Oven: 45 ° C for 5 min .; 30 ° C / min up to 230 ° C.
Injector: 180 ° C. Detector: 275 ° C Conveyor gas: 8 ml / min. of Helio.
Hydrogenation using heterogeneous catalysts.
A sample of the copolymer of Example 1, 1000 g at 50% solids in ethyl acetate, was poured into the reactor at 2000 ml par pressure and 0.5 g of palladium on activated carbon (5% Pd) powder was added as a catalyst. The reactor was sealed, then it was purged twice with 14 bars of nitrogen gas, and twice with 35 bars of hydrogen gas. The reactor was pressurized with 48 bars of hydrogen gas and heated to 60 ° C, which increased the pressure to 52 bars. The reaction mixture was stirred at 1000 RPM for 1 hour at 60 ° C. After cooling, the pressure of the vessel was discharged, and the ethyl acetate was added to dilute the mixture from 10% to 15% solids. The catalyst was removed by filtration through a 45 μm syringe filter.Hydrogenation using homogeneous catalysts.
A sample of 200 g of a 25% solution of the copolymer of example 1 was poured into the reactor at 2000 ml par pressure, and 10 ml of a stock solution of Wilkinson's catalyst (0.20 mg / ml in ethyl acetate) was added. . The reactor was sealed, purged twice with 28 bars of nitrogen gas, and twice with 35 bars of hydrogen gas. The reaction was pressurized with 44 bars of hydrogen gas and heated to 60 ° C, thus increasing the pressure to 48 bars. The reaction mixture was stirred at 1000 RPM for 16 hours at 60 ° C. After cooling, the pressure of the vessel was released.
Filtration pressure
To filter the catalyst powders of the polymer solution on a large scale, a Miliporo pressure filtration apparatus (Miliporo Waste Filtration System # YT30142HW 142 mm) was used. Following a hydrogenation experiment, reactor n was completely ventilated, nor was the polymer solution allowed to cool. And hydrogen was depressurized below 7 bars, and the vessel was repressured to 21 bar with nitrogen gas; this process was repeated twice to replace the hydrogen gas with nitrogen gas. The reaction mixture was then vented by means of a straight conduct within the filtration apparatus using a pressure of between 7 and 8 bars and a temperature of 50 ° C to 60 ° C. A reading of the temperature taken from the polymer solution leaving the filtration apparatus was 40 ° C. The filtration apparatus was kept warm throughout the filtration process by the use of a heating tape that was wound around the unit.
Claims (26)
1. An adhesive comprising one or more olefinic polym in which the content of free monomis less than 1% by weight.
2. The adhesive according to claim 1, wherein the content of free monomis less than 0.3% by weight.
3. The adhesive according to claim 1, wherein the content of free monomis less than 0.02% by weight.
4. The adhesive according to claim 1, wherein the content of free monomis less than 0.01% by weight.
5. The adhesive according to claim 1, wherein the polymer is a homopoiimer or a mixture of different homopolym
6. The adhesive according to claim 1, wherein the polymer is a copolymer or a mixture of different copolym
7. The adhesive according to claim 1, wherein the polymer is a block polymer or a mixture of different block polym
8. The adhesive according to claim 1, wherein the polymer is selected from the group consisting of a homopolymer, a copolymer, a block polymer, and mixtures thereof.
9. The adhesive according to claim 1, characterized in that it has properties of sensitivity to pressure.
10. The adhesive according to claim 9, wherein one or more polymare prepared from monomselected from the group consisting of acrylic acid, methacrylic acid, C 8 alkyl acrylates, and C 1 -C 5 alkyl methacrylates. .
11. The adhesive according to claim 9, wherein one or more of the polymare prepared from monomselected from the group consisting of acrylic acid, methacrylic acid, C 1 Cs alkyl acrylates, C 1 -C 5 alkyl methacrylates. , vinyl acetate and styrene.
12. The adhesive according to claim 11, wherein the polymer is a copolymer of 2-ethylhexyl acrylate and vinyl acetate.
13. A process for the manufacture of an adhesive according to claim 1, comprising after completion of the polymerization or copolymerization of the polymer or polym the hydrogenation of the adhesive in an organic solvent in the presence of a heterogeneous or homogeneous catalyst.
14. The process according to claim 13, wherein the catalyst is a heterogeneous catalyst, palladium on activated carbon.
15. The process according to claim 13, wherein the catalyst is heterogeneous catalyst, nickel in silica / alumina.
16. The process according to claim 13, wherein the catalyst is the homogeneous catalyst, tris (triphenylphosphine) rhodium chloride (1).
17. The process according to claim 13, wherein the hydrogenation takes place at temperatures of up to 150 ° C and at hydrogen pressures of up to 100 bars.
18. The process according to claim 13, wherein the hydrogenation takes place at temperatures of up to 100 ° C and at hydrogen pressures of up to 80 bars.
19. The process according to claim 13, wherein the hydrogenation takes place at temperatures of up to 100 ° C and at hydrogen pressures of up to 52 bars.
20. The process according to claim 13, wherein the hydrogenation takes place at room temperature and at atmospheric pressure in the presence of a platinum, paiadium, or palladium on carbon catalyst (Pd / C).
21. The process according to claim 13, wherein the organic solvent is less polar than water.
22. The process according to claim 21, wherein the organic solvent is ethyl acetate.
23. A transdermal therapeutic system comprising an adhesive according to claim 1.
24. A medicinal or veterinary medicinal use adhesive comprising adhesive according to claim 1.
25. The application of an adhesive according to claim 1, in the area of cosmetics, in the food sector, or in medicinal gumming or use of veterinary medicine.
26. The application of an adhesive according to claim 1, in transdermal systems.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19643959.0 | 1996-10-31 | ||
US08928313 | 1997-09-12 |
Publications (1)
Publication Number | Publication Date |
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MXPA99003954A true MXPA99003954A (en) | 2000-05-01 |
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