JPS63141923A - Production of application agent - Google Patents

Abstract

PURPOSE:To obtain an application agent capable of blending a drug effect ingredient required for treatment without any limitation of blending, by applying a tacky adhesive in beltlike forms onto a support sheet and filling a different kind of tacky adhesive in gap parts between the plural formed layers of the beltlike tacky adhesive. CONSTITUTION:A sheet (S1) wound on a roll 5 is reversed from under a roll 2 and passed between rolls 1 and 2 and a tacky adhesive (A) is applied through slits of a slit sheet 4 to form beltlike tacky adhesive layers. A tacky adhesive (B) is then filled from a nozzle of a hot-melt coating applicator 10 in gap parts between the above-mentioned beltlike tacky adhesive layers and a release sheet (S2) drawn from a roll 8 is overlapped and laminated by rolls 6 and 7. The whole is simultaneously contact bonded to afford the aimed application agent having the beltlike tacky adhesive layers of different kinds alternately placed side by side.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a method for manufacturing a patch, and more particularly to a method for manufacturing a patch in which different strip-shaped adhesive layers are alternately connected.

(Prior art) Patches are known in which medicinal ingredient-containing layers, adhesive layers, water-retaining gel layers, etc. are applied alternately in spots or strips (JP-A-47-15685, JP-A-Sho 60-). No. 92/23, Utility Model Publication No. 58-4900), but the industrial method for producing it is not yet known.

(Problems to be Solved by the Invention) An object of the present invention is to provide an industrial manufacturing method capable of mass producing patches in which different types of band-shaped adhesive layers are alternately connected.

(Means for Solving the Problems) The present inventors have completed the present invention as a result of intensive research aimed at inventing a method for industrially manufacturing a patch in which different types of band-shaped adhesive layers are alternately connected. .

In the method of the present invention, a plurality of strip-shaped adhesive layers are formed by applying an adhesive on a support/table, and the adhesive is applied to a strip-shaped gap between the strip-shaped adhesive layers. This is a method for manufacturing a patch characterized by manufacturing a patch in which strip-shaped adhesive layers of different types are alternately connected by filling different types of adhesives.

In the present invention, the adhesive refers to a compound obtained by kneading a commonly used adhesion substance or hydrophilic adhesive substance with a medicinal component and/or other necessary ingredients.

Here, the medicinal ingredients are drugs that can be absorbed transdermally or are commonly used in patches, such as corticosteroids (eg, prednisolone, prednisolone acetate).

Hydrocortisone, Hydrocortisone Acetate, Hydrocortisone Butyrate Propionate, Betamethacin.

Petamethacin valerate, fluocinolone acetonide.

dexamethacin, etc.), anesthetics (e.g., pensicaine, lidocaine, ethyl aminobenzoate, etc.), antihistamines (e.g., diphenhydramine hydrochloride, incybenzyl hydrochloride, diphenylimidazole, etc.), antibacterial agents (e.g., benzalkonium chloride, nitrofurana,! '), antifungal agents (e.g., nystatin, undecylenic acid.

tolnaftate), analgesic anti-inflammatory agents (e.g., indomethacin, diclofenac sodium).

Flufenamic acid, sodium salicylate, Oubaku powder,
azulene, etc.), antibiotics (e.g., erythromycin, chloramphenicol, heptaphalexin, tetracycline, neomycin, penicillin, penicillin G sodium, etc.), patch medications (e.g., camphor,
Menthol, awafuji, purple root, 7 oils, thymol, acrinol.

(roto extract, chili pepper extract, etc.).

Other necessary ingredients include excipients (e.g. kaolin, bentonite, titanium oxide, zinc oxide.

calcium carbonate, magnesium aluminate metasilicate, etc.), tackifying ingredients (such as Logi/.

Modified rosin, hydrogenated rosin, petroleum resin, coumaron indene resin, polyterpene resin, polystyrene resin, hydroabiethyl alcohol, polybutene.

Liquid isoprene, etc.), antioxidants, fragrances, colorants, etc. can be used.

Examples of lipophilic adhesive substances include natural rubber.

Synthetic rubbers (in-prene rubber, styrene-isoprene-styrene co-M combination, styrene-butadiene-styrene copolymer, styrene-butadiene rubber, etc.), polyacrylic acid esters, and the like can be used.

Hydrophilic adhesive substances include polyvinyl alcohol, gelatin, polyacrylic acid, polyacrylic acid, polymethacrylic acid and its crosslinked gel, partially crosslinked liquid imprene rubber and emulsion of crosslinked product,
An emulsion of the synthetic rubber described above can be used.

Release sheet is polyethylene, polyvinyl chloride.

A synthetic resin film such as polyester, paper, aluminum foil, or a laminate sheet of these materials that has been treated with a release agent such as silicone is used.

The support sheet is made of fiber cloth such as non-woven fabric, cotton cloth, and Japanese paper.

Polyethylene, polyvinyl chloride, polynisrutile.

A synthetic resin film such as polypropylene, aluminum foil, or a laminate sheet thereof is used.

In the adhesive patch produced by the method of the present invention, adjacent strip-shaped adhesive layers are made of different adhesives.

Different adhesives include those with different medicinal ingredients, those with different adhesive substance systems such as hydrophilic and lipophilic, and those with the same medicinal ingredient and adhesive substance composition. There are various cases, such as different degrees of polymerization.

The lipophilic adhesive can be prepared, for example, by the following method.

The lipophilic adhesive substance is impregnated with liquid paraffin, etc., and tackifying ingredients, excipients, etc. are kneaded therein, and if necessary, a lipophilic medicinal ingredient is further kneaded to obtain a lipophilic adhesive.

Further, the hydrophilic adhesive can be prepared, for example, by the following method.

The hydrophilic adhesive substance (uncrosslinked if required to form a crosslinked gel) is mixed with alcohol, and excipients and the like are added thereto and kneaded.

Purified water is added to this, and if necessary to form a crosslinked gel, a crosslinking agent is also added and kneaded, and if necessary, a hydrophilic medicinal ingredient is further kneaded to obtain a hydrophilic adhesive.

A patch in which different types of band-shaped adhesive layers are alternately connected using the above-mentioned adhesive prepared in this way can be produced by the following method.

(1) Calendar Roll-Hot Melt Coating Method This method is carried out using a combination of a calender roll and a hot melt coating applicator.

FIG. 1 shows an example of the device.

In Fig. 1, a calender roll consisting of two vertical rolls 1 and 2 is attached to a frame 3, and a slit 4 is passed between the rolls 1 and 2, and both ends are attached to the frame 3. be.

Slit sheet 4 is made of stainless steel plate and Teflon.

It is made of cloth or board made of nylon, polyester, etc., and has many slits arranged at intervals. The width and spacing of the slits and grooves are determined according to the width and spacing of the band-shaped adhesive layer applied to the sheet s+ (supporting sheet).

The fc/hs+ wound around roll 5 is turned over from under roll 2 and passed between rolls 1 and 2, and then passed between the mating rolls consisting of two vertical rolls 6 and 7, and the nozzle pulled out from roll 8 ) While winding up on roll 9 together with S2 (release sheet), put adhesive A between rolls 1 and 2, and place roll 1 at the contact point with roll 2/-t S,
The adhesive A is applied onto the sheet SI by rotating it in the traveling direction of the sheet SI to form a plurality of strip-shaped adhesive A layers.

1 or 2 calender rolls combined vase roll 6.7 (7)
Place the hot melt coating applicator 10 at any position between the two, preferably as close as possible to the calendar coolant 1.2.

The applicator 10 is provided with a plurality of nozzles and adjusted so that each nozzle is located in each gap between the strip-shaped adhesive A layers on the sheet St.

A metering pump (not shown in the drawings) is connected to the applicator 10, and this metering pump is used to feed adhesive B, which is different from adhesive A, into the applicator 10 to advance the sheet S1./)Sr Adhesive B is poured out and filled into each of the above-mentioned voids.

This sheet SL was further advanced, passed between the rolls 6.7, and the sheet S2 was pasted onto the adhesive surface of 7-) Sl, and the whole was crimped, so that different types of strip-shaped adhesive layers A and B were alternately connected. It is wound up into a roll 9 as a patch.

If necessary, this patch is cut into a suitable size to produce a product.

(2) Hot-melt coating method This method is carried out using a plurality of hot-melt coating applicators.

FIG. 2 shows an example of the device.

In FIG. 2, a sheet SI (support sheet) wound around a roll 1 is reversed from below a roll 2, and then passed onto the roll 2 to advance.

A hot melt coating applicator 3 is installed at or near the position where the sheet) Sr is removed from the upper part of the support sheet reversing roll 2, and another hot melt coating applicator 4 is juxtaposed close thereto.

A metering pump (not shown in the drawings) is connected to the applicator 3, and the adhesive A is fed into the applicator 6 using this metering pump. Another metering pump (not shown in the drawings) is connected to the applicator 4, and the metering pump is used to feed adhesive B, which is different from adhesive A, into the applicator 4.

A plurality of nozzles are provided in the applicator 3 at appropriate intervals, and a plurality of band-shaped adhesive A layers are formed thereon while advancing St.

The applicator 4 is provided with a plurality of nozzles and adjusted so that each nozzle is located in each gap between the strip-shaped adhesive A layers on the sheet S1. Pour adhesive B into the gap above S while moving the piece S,
Fill.

This sea) Sr is further advanced and two vertical rolls 5
．． The sheet sz (no peeling)) &/-ts pulled out from the roll 7 by passing between the mating rolls consisting of 6,
The patch is pasted onto the V5 surface of the tape and pressed together, and wound up onto a roll 8 as a patch in which different types of band-shaped adhesive layers A and B are alternately connected.

If necessary, this patch is cut into a suitable size to produce a product.

In this method, the adhesive patch of the present invention can be similarly produced by forming an adhesive layer on a release sheet instead of forming an adhesive layer on a support sheet.

Figures 1 and 2 show cases in which there are two types of band-shaped adhesive layers, but in both methods, the spacing of the band slits, the number of hot melt coating applicators, the nozzle spacing, etc. are adjusted as appropriate. In particular, it is also possible to produce patches with three or more types of strip-shaped adhesive layers.

(Example) The present invention will be specifically described below with reference to Examples.

Example 1 (Calendar roll-hot melt coating method) (1) 30 parts of masticated natural rubber and 1 part of hydrogenated rosin
Add 0 parts and 27915 parts made of N and heat to 100-120°C.
Then, 20 parts of kaolin was added and kneaded. Next, the inside of the kneading tank was cooled to 40 to 70°C, and 1 part of methyl salicylate was added to d7! - Parts of camphor o, s + z - 2 parts of menthol and 3 parts of thymol α were mixed in advance to form a solution, which was added to this mixture and kneaded to obtain adhesive A.

(2) 4 parts gelatin, 1 part sodium polyacrylate, 2 parts carboxymethyl cellulose, 10 parts glycerin
After adding 10 parts of propylene glycol and 10 parts of propylene glycol and thoroughly kneading, 15 parts of kaolin was added and further thoroughly kneaded. Next, 1 part of tartaric acid and 0.1 part of aluminum silicate were added to 50 parts of purified water, and after kneading, 1 part of methyl salicylate and 0.1 part of dt-camphor were added to the mixture.
A solution prepared by mixing 5 parts of t-menthol and 1 part of t-menthol was further added to the mixture and kneaded to obtain adhesive B.

(3) According to the calender roll hot melt coating method described above, a Teflon plate having a number of 8 day wide slits at 811 III intervals was attached to the frame and combined with a calender roll consisting of two vertical rolls.

Put adhesive A between the calender rolls, and as the nonwoven fabric sheet progresses, apply 8 strip-shaped adhesive A layers with a width of 8 mm.
It was formed on a non-woven fabric sheet at intervals of 100 mm.

Place a hot melt coating applicator near the calender roll, align its nozzle with the gap between the strips of adhesive A layer on the nonwoven fabric sheet, and apply adhesive B fed with a metering pump into the gap. One side of the vinyl chloride sheet was poured and filled, and the vinyl chloride sheet was pressed and bonded together with a silicone-treated release sheet while being passed through a pair of rolls.

While this process continued, it was cut into a size of 16 (7) x 5.6 m to produce a patch in which adhesive strips A and B layers with a width of 8 m were arranged alternately without gaps.

This was made into a set of 6 sheets and sealed and packaged to produce a product.

Example 2 (Hot melt coating method) (1) After impregnating 10 parts of liquid paraffin into 10 parts of styrene-isoprene-styrene copolymer, the temperature was heated to about 100°C.
20 parts of hydrogenated rosin, 5 parts of zinc oxide and 1 part of citric acid were added and kneaded.

1 part of methyl salicylate and 1 part of dl-camphor in advance.

A solution obtained by mixing 0.5 part of t-menthol, 0.1 part of thymol and 0.5 part of peppermint oil was added to this mixture and kneaded at about 50°C to obtain adhesive A. .

(2) Add 10 parts of glycerin to 2.5 parts of sodium polyacrylate and 3 parts of methylcellulose, mix well, and mix 0.5 parts of tartaric acid and 0.1 part of aluminum oxide in purified water in advance. In addition, it was thoroughly kneaded.

Separately, 1 part of methyl salicylate, 0.5 part of t-meth/tol,
A solution containing 0.1 part of thymol, 1 part of dl-camphor, and 0.5 part of peppermint oil was prepared in advance, and this was added to the mixture and thoroughly kneaded to obtain adhesive B.

(3) According to the hot melt coating method,
Two hot melt coating applicators were juxtaposed near the support sheet inversion roll and each connected to a metering pump. Place the nozzle of the hot melt coating applicator closer to the support sheet reversal roll on the support sheet, and place a 10m wide adhesive layer on the support sheet.
Adjust the position of the nozzle of the other hot melt coating applicator to the gap between the strip-shaped adhesive layers formed on the support sheet.

Feed adhesive A into one hot-melt coating applicator with a metering pump, and feed adhesive B into the other hot-melt coating applicator with another metering pump, while advancing the flannel sheet.
Band-shaped adhesive A of m.

Layers B were formed alternately, and one side of the vinyl chloride sheet was pressed and bonded together with a silicone-treated release sheet while being passed between lamination rolls.

While the process was further progressing, it was cut into a size of 14 crn x 10 crn to produce a patch in which adhesive strips A and B layers of 10 widths were arranged alternately without gaps.

This was made into a set of 10 sheets and sealed and packaged to produce a product.

Example 3 (Calendar roll-hot melt coating method) (1) Styrene-inprene-styrene copolymer 1
0 parts and 10 parts of light liquid paraffin were mixed into 100 to 1
The mixture was uniformly dissolved at 20° C., and 60 parts of hydrogenated rosin, 3 parts of titanium oxide, and 20 parts of zinc oxide were added thereto and kneaded.

The temperature in this mixing tank was lowered to 40 to 70°C, and 10 parts of a co-melt solution containing t-menthol: salicylic acid glycol ester: methyl salicylate: dt-camphor in a ratio of 1:21:0.5 was added to sufficiently increase the temperature. Adhesive A was obtained by kneading.

(2) Add 710 parts of Kaori to 10 parts of glycerin to KDHU-
The mixture was uniformly dispersed using a type 2 kneader (trade name, manufactured by Fuji Denki Kogyo ■). 5 parts of sodium polyacrylate, 0.1 part of aluminum oxide, and 10 parts of propylene glycol were added to this and kneaded.

t-menthol: methyl salicylate: dt-camphor:
Peppermint oil: Niracol pBcs4 (product name).

A mixture of 1:2:α5:α5 manufactured by Nikko Chemicals Ltd.) was added to this mixture and thoroughly kneaded to obtain adhesive B.

(3) Using the adhesives A and B obtained in the previous section (1) and (2), a patch in which strip-shaped adhesive layers A and B with a width of 10 + II +++ are arranged alternately without gaps according to Example 1 (3). (161
Mx 5.6 cm) was manufactured.

This was made into a set of 6 sheets and sealed and packaged to produce a product.

Example 4 (Hot melt coating method 9) (1) After impregnating 15 parts of liquid paraffin into 20 parts of styrene-isoprene-styrene copolymer, the temperature was heated to about 100°C.
40 parts of Alcon P100 (trade name, Arayo Kagaku Kogyo Ichiri) and 2 parts of zinc oxide were added and kneaded. To this, 5 parts of methyl salicylate, 4 parts of t-menthol,
Adhesive A was obtained by adding 0.2 parts of thymol and 2 parts of purple root extract and thoroughly kneading the mixture.

(2) 40 parts of natural rubber and 20 parts of hydrogenated rosin at 80°C
2 parts of titanium oxide and 5 parts of heavy calcium carbonate were added and kneaded.

Add 1 part of methyl salicylate to this mixture at 40 to 50°C,
2 parts of di-camphor and 3 parts of di-menthol were added and thoroughly kneaded to obtain adhesive B.

(3) Using the adhesives A and B obtained in the previous section (1) and (2), paste strip-shaped adhesive layers A and E with a width of 6 ml+ arranged alternately without gaps according to Example 2 (3). agent (i 4mX
10crn) was produced.

This was made into a set of 10 sheets and sealed and packaged to produce a product.

(Effects of the Invention) By the method of the present invention, a patch in which a plurality of strip-shaped adhesive layers of different types containing medicinal ingredients and/or other necessary ingredients are lined up without gaps can be easily produced industrially using a simple device. It is possible to mass produce.

The patch manufactured by the method of the present invention can contain the medicinal ingredients necessary for treatment without being subject to formulation restrictions, and has good release properties of the medicinal ingredients, so it can significantly improve the therapeutic effect. can.

Furthermore, by coloring each adhesive, it is possible to obtain an adhesive with a beautiful adhesive layer surface.

[Brief explanation of the drawing]

FIG. 1 shows a calender roll included in the method of the present invention.
1 illustrates one embodiment of a hot melt coating method. FIG. 2 shows one embodiment of the hot melt coating method included in the method of the present invention. In Figure 1, A and B are different types of adhesives, SI
S2 is a support sheet, S2 is a release sheet, 1°2 is a calendar roll, 3 is a frame, 4 is a slit sheet, 5, 6. Otsu a9 represents a roll. In Figure 2, A and B are different types of adhesives, SI
is a support sheet, S2 is a release sheet, 1,2゜5,6
．． 7.8 represents the roll and 4 represents the hot melt coating applicator. Patent applicant: Taisho Pharmaceutical Co., Ltd., company/agent: Patent attorney Tomi Kitagawa

Claims (1)

[Claims] 1) Applying an adhesive in strips on a support sheet to form a plurality of strip-shaped adhesive layers, and filling the strip-shaped voids between the strip-shaped adhesive layers with an adhesive different from the above-mentioned adhesive. A method for producing a patch, which comprises producing a patch in which different types of band-shaped adhesive layers are alternately connected.