Patent Application
20080032127
A; Chemical crosslinking
B: Pseudo-crosslinking
C: Non-crosslinking
In the following, the invention is explained in more detail by examples; however, it is not limited to these. Further, in the following, “part” means “part by weight”.
2-Ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 50 parts, N-vinyl-2-pyrrolidone 50 parts and ethyl acetate 300 parts were placed in a separable flask with a stirring apparatus and a reflux-cooling apparatus, and warmed to 75° C. under stirring and replacing with nitrogen. Benzoyl peroxide 2 parts was dissolved in ethyl acetate 20 parts; the solution was divided in 5 portions; one portion among these was added to the separable flask, and polymerization started. From 2 hours after the initiation of the reaction, the remaining 4 portions was added at every 1 hour interval, and the reaction was continued further for 2 hours. Further, after the initiation of the reaction, ethyl acetate was added 4 times at every 2 hours interval in every 50 parts to adjust a viscosity. After the reaction, the mixture was cooled, followed by addition of ethyl acetate to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight.
Except making the monomer composition in Example 1 butyl acrylate 300 parts, hydroxyethyl acrylate 60 parts and N-vinyl-2-pyrrolidone 40 parts, all was made in the same way to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight.
Except a change that the monomer composition in Example 1 became 2-ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 60 parts , N-vinyl-2-pyrrolidone 30 parts and ethyl acetate 50 parts, and the initiator was azobisisobutylnitrile in stead of benzoyl peroxide, all was made in the same way to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight.
Except that the monomer composition in Example 1 was 2-ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 5 parts and N-vinyl-2-pyrrolidone 80 parts, all was made in the same way to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight.
The pressure-sensitive adhesive agent's solution obtained in Examples 1, 2 or 3, or the comparative example 1 was added with a plasticizer and a pseudo-crosslinking compound, and the all the liquid was stirred homogeneously by a dissolver to obtain a mix liquid. The obtained mix liquid was coated on a PET film of thickness 35 μm, which is treated with silicon, so that the thickness of the pressure-sensitive adhesive agent after drying became 100 μm, and dried, and then, the above-described pressure-sensitive adhesive agent was laminated on the PET film of thickness 35 μm to obtain a pressure-sensitive adhesive sheet for the skin. Then, the prepared sheet was cut in width 1 cm as a tape form, and after it was adhered closely on a Bakelite board in the sticking area of 1 cm×1 cm by at 25° C. by shuttling a roller of load 500 g, the board was placed vertically to measure a shearing strain migration length (3 g, 2 min.) and a shearing strain migration length (8 g, 5 min.)
In Table 1 in the following, the compositions of the pressure-sensitive adhesive sheets for the skin and the measurement results of shearing strain migration length, which were prepared and measured above, are shown as the examples. In Table 2, as the comparative examples, the results prepared and measured according to the examples are shown. Further, as to the pseudo-crosslinking compounds, each of a reagent special grade was used.
In Table 3, the measurement values in the chemical crosslinking and the ionic crosslinking. As the chemical crosslinking agents, Coronate HL (manufactured by Nihon Polyurethane) and aluminum acetylacetonate (reagent special grade) were used.
Each sheet prepared as described above was cut in 20 cm2, and the weight of the pressure-sensitive adhesive layer (W1) was measured. Then, the sheet was immersed in ethyl acetate and let it stand for 3 days to extract a solvent soluble part. After that, the insoluble part was taken out, dried and followed by measurement of the weight of the pressure-sensitive adhesive layer (W2) to calculate a gel percentage by the below equation. The results are shown in Table 4.
(W2×100)/(W1×A/B)
A: (pressure-sensitive adhesive agent+crosslinking agent) weight, B: (pressure-sensitive adhesive agent+plasticizer+crosslinking agent) weight
As for the above-obtained test sheet, the following evaluation was carried out, and the results are shown in Table 5. Each test sheet (20 cm2) was stuck on upper arm parts of five adult males, and peeled off after 24 hours. A skin condition after 1 hour from peeling off was observed by visual inspection, and evaluated according to the below evaluation standard to make the mean value of the total sum of evaluation points of 5 persons the index number.
0: No rash, 1: Very slight rash in a barely detectable degree, 2: Apparent rash, 3: Rash in a medium degree, 4: Strong rash with a deep red color
Each transdermal absorption preparation was stuck on upper arm parts of five adult males, and peeled off after 24 hours. A sticking condition of the sheet on the skin just before peeling off was observed by visual inspection, and evaluated according to the below evaluation standard.
◯: Complete sticking for almost all members, Δ: Partial peeling off for 1-3 persons, ×: peeling off for 4-5 persons
Each transdermal absorption preparation was stuck on upper arm parts of five adult males, and peeled off after 24 hours. A sticking condition of the sheet on the skin just after peeling off was observed by visual inspection, and evaluated according to the below evaluation standard.
◯: No glue residue for almost all members, Δ: Partial glue residue for 1-3 persons, ×: Glue residue for 4-5 persons
Except blending the alkyl acrylate composition containing the Examples 4 or 5, or the comparative examples 4 or 5 as a constituent and the skin valuable as shown in Table 6, a medicinal patch or a cosmetic patch was prepared and evaluated in the same way described above. The results are shown in Table 6. In the table, H is indomethcin, K is ketoprofen, and E is vitamin E respectively.
A test piece (2.5×2.5 cm) of the tape preparation was stuck on a shaven back of a Japanese White rabbit and peeled off after 24 hours. A skin rash condition after 1 hour from peeling off was observed by visual inspection. Further, in the test, the formation of edema and incrustation was not detected. Each preparation was stuck to 4 rabbits in total. The degree of rash was evaluated according to the below evaluation standard by 5 steps of 0-4. ∘: no rash, 1: very slight rash in a barely detectable degree, 2: apparent rash, 3: rash in a medium degree, 4: strong rash with a deep red color. The mean value of the total sum of an evaluation point in each rabbit, which was divided by 4, was made a skin irritation index number of each tape preparation.
In the same operation as the above irritation property test, the tape preparation was stuck to a rabbit skin, and the presence or absence of the sticking property just before peeling off was observed by visual inspection. The evaluation standard is as follows.
0: No peeling off of preparation; 1: Partial peeling off is detected; 2: Apparent peeling off is detected
The mean value (a value in which the total sum of an evaluation point was divided by 4) was made a sticking property index number of each tape preparation.
2-Ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 50 parts, N-vinyl-2-pyrrolidone 30 parts and ethyl acetate 300 parts were placed in a separable flask with a stirring apparatus and a reflux-cooling apparatus, and warmed to 75° C. under stirring and replacing with nitrogen. Benzoyl peroxide 2 parts was dissolved in ethyl acetate 20 parts; the solution was divided in 5 portions; one portion among these was added to the separable flask, and polymerization started. From 2 hours after the initiation of the reaction, the remaining 4 portions was added at every 1 hour interval, and the reaction was continued further for 2 hours. Further, after the initiation of the reaction, ethyl acetate was added 4 times at every 2 hours interval in every 50 parts to adjust a viscosity. After the reaction, the mixture was cooled, followed by addition of ethyl acetate to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight and viscosity 1.2×104 cps.
Except making the monomer composition in Example 18 2-ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 50 parts, acrylic acid 20 parts and N-vinyl-2-pyrrolidone 80 parts, all was made in the same way to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight and viscosity 1.8×104 cps.
Except that the monomer composition in Example 18 was 2-ethylhexyl acrylate 300 parts, hydroxyethyl acrylate 10 parts, acrylic acid 3 parts and N-vinyl-2-pyrrolidone 80 parts, all was made in the same way to obtain a pressure-sensitive adhesive agent's solution of solid-part concentration 30% by weight and viscosity 1.5×104 cps.
The pressure-sensitive adhesive agent's solution obtained in Example 18 or 19, or the comparative example 15 was added with a plasticizer and a pseudo-crosslinking compound, and the all the liquid was stirred homogeneously by a dissolver to obtain a mix liquid. The obtained mix liquid was coated on a PET film of thickness 35 μm, which is treated with silicon, so that the thickness of the pressure-sensitive adhesive agent after drying became 100 μm, and dried, and then, the above-described pressure-sensitive adhesive agent was laminated on the PET film of thickness 35 μm to obtain a pressure-sensitive adhesive sheet for the skin (patch). Then, the prepared sheet was cut in width 1 cm as a tape form, and after it was adhered closely on a Bakelite board in the sticking area of 1 cm×1 cm by at 25° C. by shuttling a roller of load 500 g, the board was placed vertically to measure a shearing strain migration length (3 g, 2 min.) and a shearing strain migration length (8 g, 5 min.).
In Table 7 described below, the compositions and the measurement results of shearing strain migration length of the pressure-sensitive adhesive sheets for the skin (patches), which were prepared and measured above, are shown as the examples. In Table 8, as the comparative examples, the results prepared and measured according to the examples are shown. Further, as to the pseudo-crosslinking compounds, each of a reagent special grade was used. In practical blending, oxo acid was added in a designated amount as 5% aqueous solution. A case in which the shearing strain migration length is more than 2 mm was made ≧2. Other pseudo-crosslinking compounds were added in a designated amount as 5% tetrhydrofuran solution.
Since the composition and the patch (trasdermal absorption preparation, cosmetic sheet) using it is the constitution as described above, a favorable sticking property with well-balanced pressure-sensitive adhesiveness and cohesive force is shown; and therefore, when peeling off there is no glue residue, and a skin irritation due to a mechanical irritation and the like such as injury of a keratin layer of a skin surface and hair tearing can be reduced. Consequently, the invention greatly contributes to the development of patch production industries and the related industries.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2004-002491 | Jan 2004 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP05/00104 | 1/7/2005 | WO | 00 | 10/26/2006 |
