JPH08104625A - Application agent - Google Patents

Abstract

PURPOSE: To obtain an application agent capable of efficiently releasing a medi cine contained therein and effectively absorbing the medicine through the skin or a mucous membrane into the body by arranging a water absorbing filler preimpregnated with polyhydric alcohols, the medicine and a tacky base in combination on a support. CONSTITUTION: This application agent is obtained by arranging a water absorbing filler preimpregnated with a polyhydric alcohol and its derivative, a medicine and a tacky base in combination on a support and used for percutaneous or transmucosal administration of the medicine. A cross-linked polyacrylate and a cross-linked polyvinylpyrrolidone are especially preferred as the water absorbing filler and ethylene glycol, polyethylene glycol, glycerol, etc., are cited as the polyhydric alcohol. The polyhydric alcohol is preferably used in an amount of 50-200 pts.wt. based on 100 pts.wt. water absorbing filter. Steroidal antiinflammatory agents, vasodilators, hypotensive agents, antitussive expectorants, antitumor agents, peptidic hormones, etc., are cited as the medicine. The medicine release effects can further be improved by adding a plasticizer to the tacky base of the tacky agent layer.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a patch for transdermal administration or transmucosal administration of a drug.

[0002]

2. Description of the Related Art Conventionally, oral administration of a drug has been generally performed. For example, when an oral administration of a drug is performed, the drug absorbed in the intestine is metabolized in the liver, so that a considerable amount of the drug is produced. However, there is a problem that the drug is decomposed before it exerts a medicinal effect on the affected area, and further, a large amount of the drug is absorbed in a short time, so that side effects are likely to occur.

On the other hand, transdermal administration in which a drug (physiologically active substance) is absorbed through the skin using a percutaneous absorption preparation is performed. Unlike the above oral administration, this transdermal administration has the following advantages. (1) Absorbed drug reaches the affected area without being decomposed by metabolism in the liver, (2) Gastrointestinal disorder like oral administration is unlikely to occur, (3) Adjusted drug release amount Then, side effects caused by large amount of drug being absorbed in a short time can be reduced. (4) If it is possible to maintain a constant drug release rate for a long time, reduce the number of drug administrations. You can

However, even if a drug is administered using a percutaneous absorption preparation, it is difficult for the drug to penetrate the skin, and it is often impossible to administer a sufficient amount of the drug. For example, the stratum corneum on the surface of the skin has a barrier function for preventing the invasion of foreign substances into the body, so that it is difficult to absorb a sufficient amount of the drug through the skin to exert its drug effect.

[0005] In general, attempts have been made to increase the transdermal absorbability of a drug by adding a percutaneous absorption enhancer having a function of weakening the barrier function of the stratum corneum to the preparation. However, in general, a transdermal absorption enhancer having a large absorption promoting effect is highly irritating to the skin or mucous membranes, and a patch using such a transdermal absorption enhancer has a problem that its use is limited. was there.

Various studies have been conducted in order to solve the above problems. For example, Japanese Patent Application Laid-Open No. 4-13617 discloses a patch containing a water-absorbing filler. Absorbency was not yet sufficient.

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned drawbacks, and an object thereof is to efficiently release the drug contained therein and effectively to the skin or mucous membranes. It is to provide a patch that can be absorbed into the body through

[0007]

[Means for Solving the Problems]

In the patch of the present invention, a pressure-sensitive adhesive layer composed of a water-absorbing filler, a drug and a pressure-sensitive adhesive base, which is preliminarily impregnated with a polyhydric alcohol (derivative), is formed on a support.

As the above-mentioned support, those generally used as a support for patches can be used, and examples thereof include cellulose acetate, ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, polyamide, Resin films such as ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyvinylidene chloride: aluminum sheets and the like,
These may be used as a single layer sheet or may be used as a laminate of two or more kinds. Further, other than the aluminum sheet, it may be used as a woven fabric or a non-woven fabric.

Examples of the above-mentioned pressure-sensitive adhesive base include acrylic pressure-sensitive adhesives, rubber-based pressure-sensitive adhesives, silicone-based pressure-sensitive adhesives, etc. In view of pressure-sensitive adhesive properties and cost, acrylic pressure-sensitive adhesives and rubber-based pressure-sensitive adhesives are preferable. .

Examples of the acrylic pressure-sensitive adhesive include
Mainly composed of (meth) acrylic acid alkyl ester (co)
A polymer is preferably used, but it may be a copolymer with a functional monomer, a polyfunctional monomer, a vinyl compound or the like, which is copolymerizable with the (meth) acrylic acid alkyl ester.

As the above-mentioned (meth) acrylic acid alkyl ester, when the carbon number of the alkyl group is reduced, the cohesive force is improved but the adhesive force is decreased, and when the carbon number of the alkyl group is increased, the adhesive force is improved but the cohesive force is decreased. Those obtained from (4) to 18 aliphatic alcohols and (meth) acrylic acid are preferable, and for example, methyl methacrylate, ethyl methacrylate, butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate,
Examples include isooctyl (meth) acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, dodecyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, etc. They may be used or two or more may be used in combination.

Examples of the functional monomer include a monomer having a hydroxyl group, a monomer having a carboxyl group, a monomer having an amide group, a monomer having an amino group, and the like.

As the monomer having a hydroxyl group, for example, 2-hydroxyethyl (meth) acrylate, hydroxyalkyl (meth) acrylate such as hydroxypropyl (meth) acrylate, and the like are preferably used.

Examples of the above-mentioned monomer having a carboxyl group include α, β such as (meth) acrylic acid.
-Unsaturated carboxylic acid; maleic acid monoalkyl ester such as butyl maleate; (anhydrous) maleic acid, fumaric acid, crotonic acid, etc. are preferably used.

Examples of the amide group-containing monomer include alkyl (meth) acrylamides such as acrylamide, dimethyl acrylamide and diethyl acrylamide; alkyl ether methylol (meth) acrylamides such as butoxymethyl acrylamide and ethoxymethyl acrylamide; and diacetone acrylamide. It is preferably used.

As the monomer having an amino group, for example, dimethylaminoethyl acrylate is preferably used.

Examples of the polyfunctional monomer include, for example,
1,6-hexane glycol dimethacrylate, tetraethylene glycol diacrylate, trimethylolpropane triacrylate, divinylbenzene, divinyltoluene, diallyl phthalate and the like can be mentioned.

Examples of the vinyl compound include vinyl acetate,
Examples thereof include styrene, α-methylstyrene, N-vinyl-2-pyrrolidone, vinyl chloride, acrylonitrile, ethylene, propylene and butadiene, which may be copolymerized.

The content of the (meth) acrylic acid alkyl ester in the constituents of all the copolymers is preferably 50% by weight or more.

The (co) polymer mainly composed of the (meth) acrylic acid alkyl ester is usually prepared by blending the above-mentioned monomers in the presence of a polymerization initiator and carrying out solution polymerization. When performing solution polymerization, ethyl acetate or other polymerization solvent is added to a predetermined amount of various monomers, in an reactor equipped with a stirrer and a cooling reflux device, azobis,
7 in a nitrogen atmosphere in the presence of a polymerization initiator such as a peroxide type.
The reaction may be performed at 0 to 90 ° C for 8 to 40 hours. Further, the monomer may be charged all at once or dividedly.

As the azobis type polymerization initiator, 2,
2-azobis-iso-butyronitrile, 1,1'-azobis (cyclohexane-1-carbonitrile), 2,2'-
Examples thereof include azobis (2,4-dimethylvalerinitrile), and examples of the peroxide-based polymerization initiator include lauroyl peroxide, benzoyl peroxide, di (tert-butyl) peroxide, and the like.

Examples of the rubber-based pressure-sensitive adhesive include natural rubber, synthetic isoprene rubber, polyisobutylene, polyisoprene, polybutadiene, styrene-butadiene copolymer,
Examples of the main component include a styrene-isoprene copolymer and a styrene-isoprene-styrene block copolymer.

Examples of the above silicone-based pressure-sensitive adhesives include those containing silicon gum such as polyorganosiloxane as a main component.

As the adhesive other than the above, a polyvinyl ether adhesive, a polyurethane adhesive or the like can be used.

If desired, tackifiers, softeners, plasticizers, fillers, antioxidants, etc. may be added to the above-mentioned pressure-sensitive adhesive base. As the tackifier, for example, rosin,
Rosin-based resins such as hydrogenated rosin, disproportionated rosin and rosin ester; terpene-based resins such as α-pinene and β-pinene;
Terpene phenol resin; Petroleum resin; Alkyl-phenol resin; Xylene resin; Coumaron resin; Coumaron-
Examples thereof include indene resin.

Examples of the softening agent include liquid polybutene, mineral oil, lanolin, liquid isobutylene, liquid polyacrylate and the like.

As the plasticizer, it is necessary to adjust the viscosity of the pressure-sensitive adhesive layer, promote the transdermal or transmucosal absorbability of the drug described below, and be safe for the human body. . Examples of such plasticizers include cetyl octanoate, hexyl laurate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, octyl palmitate, butyl stearate, octyl stearate, octyl hydroxystearate, isononane. Monohydric alcohol fatty acid esters such as isotridecyl acid, ethyl oleate, decyl oleate, mink oil fatty acid ester, myristyl lactate; dibasic acids such as diisopropyl adipate, dioctyl adipate, diethyl sebacate, dioctyl sebacate, dioctyl succinate, etc. Ester; Propylene glycol dicaprate, glyceryl trioctanoate, glyceryl tri (octanoic acid / decanoate), glyceryl tripalmitate, sorbitan oleate, Polyhydric alcohol fatty acid esters such as sexual fatty oils; olive oil, safflower oil,
Animal and vegetable oils such as coconut oil fatty acid triglyceride and cottonseed oil;
Hydrocarbons such as scrawan, α-olefin oligomer, liquid paraffin and wax; alcohols such as cetanol, behenyl alcohol, 2-hexyldecanol, 2-octyldecanol and oleyl alcohol; ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether Amide compounds such as oleic acid amide and lauric acid monoethanolamide; silicones such as dimethylpolysiloxane and methylphenylpolysiloxane.

Since the cohesive force of the pressure-sensitive adhesive decreases as the amount of the plasticizer compounded increases, it is preferably 300 parts by weight or less, more preferably 3 to 200 parts by weight, relative to 100 parts by weight of the pressure-sensitive adhesive base. Is.

The above-mentioned water-absorbent filler is a compound (usually a polymer) capable of absorbing water and swelling, and has a small affinity with the adhesive base and the drug described later, and is in the form of fine particles in the adhesive base. Can be dispersed with. Examples of such a water-absorbent filler include crosslinked polyacrylic acid salt, crosslinked polyvinylpyrrolidone, crosslinked crystalline cellulose, crosslinked carboxymethyl cellulose, crosslinked hydroxyalkyl cellulose (for example, crosslinked hydroxypropylcellulose), crosslinked polyvinyl alcohol and the like. In particular, crosslinked polyacrylate and crosslinked polyvinylpyrrolidone are preferable.

Examples of the above-mentioned cross-linked polyacrylic acid salt include cross-linked polyacrylic acid salt and cross-linked starch-acrylic acid salt graft copolymer.

The crosslinked polyvinylpyrrolidone is prepared by copolymerizing N-vinyl-2-pyrrolidone and a polyfunctional monomer. Examples of the polyfunctional monomer used for the copolymerization include di (meth) acrylates such as hexamethylene glycol di (meth) acrylate, ethylene glycol di (meth) acrylate, and triethylene glycol di (meth) acrylate; trimethylolpropane tri Tri (meth) acrylates such as acrylates;
Examples thereof include tetra (meth) acrylates such as pentaerythritol tetramethacrylate; polyallyl compounds such as diethylene glycol bisallyl carbonate, triallyl glycerin and triallyl cyanurate; and polymaleimide compounds such as ethylene bismaleimide.

Further, N, N'-divinylimidazolidone,
Cyclic acid amide compounds such as N, N′-divinylhexahydropyrimidone and N-vinyl-3-ethylidene-pyrrolidone; divinylbenzene; methylenebisacrylamide;
It is also possible to use ethylidene bisvinylpyrrolidone; divinyl ketone; butadiene; isoprene and the like.

When the amount of the polyfunctional monomer used in the above copolymerization is reduced, the resulting crosslinked polyvinylpyrrolidone is dissolved in the adhesive base or is extremely swollen to have its particle structure in the adhesive layer. It becomes difficult to maintain, and when the amount becomes large, the obtained crosslinked polyvinylpyrrolidone hardly swells to the adhesive base and the drug release property of the adhesive layer cannot be enhanced. It is preferably 20% by weight.

Commercially available products of cross-linked polyvinylpyrrolidone include "Kolidone CL" manufactured by BASF and "Polyplasdone XL" manufactured by GAF. As a method for producing cross-linked polyvinylpyrrolidone, US Pat.
No. 9880, No. 3933766 and No. 3689439
No.

The water absorbent filler is impregnated with a polyhydric alcohol (derivative). Examples of the polyhydric alcohol (derivative) include ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, glycerin and the like.

When the amount of the polyhydric alcohol (derivative) impregnated into the water-absorbing filler is small, a sufficient accelerating effect cannot be obtained, and when it is too large, the water-absorbing filler excessively swells to form a uniform pressure-sensitive adhesive layer. Since it is difficult to form, it is preferably 20 to 500 parts by weight, and more preferably 50 to 200 parts by weight, relative to 100 parts by weight of the water absorbent filler.

If the amount of the water-absorbent filler compounded is small, a sufficient drug releasing effect cannot be obtained, and if it is too large, the adhesiveness of the patch is lowered and good patchability cannot be obtained.
It is preferably 0.5 to 20% by weight in the adhesive base.

The above-mentioned drugs include the following. Indomethacin, salicylic acid, aspirin, acetaminophenone, diclofenac sodium, ibuprofen, sulindac, naproxen, ketoprofen, flufenamic acid, ibufenac, fenbufen, alclofenac, phenylbutazone, mefenamic acid, bendazac, piroxicam, flurbiprofen, pentazocine , Buprenorphine hydrochloride, butorphanol tartrate and other antipyretic and anti-inflammatory analgesics; hydrocortisone,
Prednisolone, fluocinolone acetonide, fludoxycortide, methylprednisolone, hydrocortisone acetate, triamcinolone acetonide, dexamethasone,
Steroidal anti-inflammatory agents such as hetamethasone acetate, diflucortron valerate, propionclohetazole, and fluocinonide.

Diltiazem, verapamil, pentaerythritol tetranitrate, dipyridamole, isosorbide dinitrate,
Vasodilators such as nifedipine and nitroglycerin; propranolol, atenolol, pindolol, quinidine sulfate, azimarin, alprenolol hydrochloride, metoprolol tartrate, nadolol, timolol maleate, disopyramide and other hypertensive / arrhythmic agents; clonidine hydrochloride, captoril, hydrochloric acid Antihypertensive agents such as prazosin, benbutolol sulfate, guanabenz acetate, guanfacine hydrochloride, punazosin hydrochloride, ellanapril maleate, arotinolol hydrochloride, and bunitrolol hydrochloride.

Procaterol hydrochloride, terbutaline sulfate,
Fenoterol hydrobromide, tulobuterol hydrochloride, ambroxol hydrochloride, purbuterol hydrochloride, mabuterol hydrochloride, clenbuterol hydrochloride, trimethoquinol hydrochloride,
Antitussive expectorants such as formoterol fumarate; antitumor agents such as 5-fluorouracil, 1- (2-tetrahydrofuryl) -5-fluorouracil and mitomycin C.

Benzocaine, procaine, lidocaine,
Local anesthetics such as tetracaine; steroid hormones such as estrogen, estradiol, testosterone, progesterone and prostaglandins; peptide hormones such as insulin.

Asthma / nasal allergy therapeutic agents such as ketotifen fumarate, azelastine hydrochloride, sodium cromoglycate; antihistamines such as cycloheptadine hydrochloride, diphenhydramine hydrochloride, fenbenzamine, metaxidine; anticoagulants such as heparin; scopolamine, clopolmine. Antispasmodic such as fluperol.

Cerebral circulatory metabolism-improving agents such as pinpocetine, flunarizine hydrochloride, nicardipine hydrochloride, brovincamin fumarate, dihydroergotoxin mesylate, ifenprodil tartrate, isoxuprine hydrochloride; maprotiline hydrochloride,
Antidepressant / Anxiolytic drugs such as etizolam, diazepam, bromazepam, amitriptyline hydrochloride, mianserin hydrochloride; α
-Vitamin D such as calcidol, ergocasiferol
Agents: oral hypoglycemic agents such as glibenclamide and gliclazide.

Anti-ulcer agents such as grepopride malate, famotidine, glycopyrronium bromide, etc .; hypnotics such as phenobarbital, amobarbital; tetracycline,
Antibiotics such as chloramphenicol.

The compounding amount of the above-mentioned drug varies depending on the kind of the drug and the purpose of use of the preparation, but if the amount is small, a high release property of the drug cannot be obtained, and if the amount is large, the cohesive force and the adhesive force of the pressure-sensitive adhesive layer decrease. Usually, 0.1 to 30% by weight in the pressure-sensitive adhesive layer is preferable.

The patch of the present invention is produced according to a usual method for producing an adhesive tape. For example, solvent coating method,
Conventionally known methods for producing an adhesive tape such as a hot melt coating method, an electron beam curing method and an emulsion coating method can be used, but a solvent coating method is particularly preferably used.

In the solvent coating method, the adhesive base is diluted with a suitable solvent, and the above-mentioned drug, crosslinked polyacrylic acid salt and, if necessary, other additives are added to obtain a solution. The adhesive solution is applied to the surface of the support and dried to remove the solvent, whereby a pressure-sensitive adhesive layer can be formed on the support to prepare a patch. Further, this solution may be coated on a release paper and dried, and then transferred to a support to form an adhesive layer. Further, this release paper may be stuck until the time of use for the purpose of protecting the pressure-sensitive adhesive layer.

The thickness of the above-mentioned pressure-sensitive adhesive layer varies depending on the purpose of use, but when it becomes thin, the amount of drug per unit area of the patch becomes insufficient, and when it becomes thick, the drug contained in the pressure-sensitive adhesive layer near the support diffuses. This makes it difficult to reach the skin surface, and the drug in the adhesive layer will not be effectively used.
30 to 2,000 μm is preferable.

[0050]

Next, embodiments of the present invention will be described. (Example 1) A copolymer obtained by copolymerizing 45 parts by weight of 2-ethylhexyl acrylate and 55 parts by weight of 2-ethylhexyl methacrylate was dissolved in ethyl acetate to give an adhesive having a solid content concentration of 34% by weight. A base solution was obtained. Further, while stirring 100 parts by weight of a starch / acrylate graft copolymer crosslinked product (“SAN FRESH” manufactured by Sanyo Kasei Co., Ltd.) with a dissolver, 100 parts by weight of concentrated glycerin (manufactured by NOF Corporation) was sprayed to prepare glycerin. An impregnated crosslinked polyacrylate was obtained.

To the above adhesive base solution, 10% by weight ethyl isosorbide dinitrate acetate solution, glycerin-impregnated crosslinked polyacrylate and isopropyl myristate were added so as to have the composition shown in Table 1, and uniformly mixed by a dissolver. Then, an ethyl acetate dispersion solution having a solid content concentration of 30% by weight was prepared. This solution was coated on polyethylene terephthalate release paper so that the thickness after drying would be 100 mμ, and 60
It dried at 30 degreeC for 30 minutes, and formed the adhesive layer. Next, this adhesive layer is coated with polyethylene terephthalate / ethylene.
Transfer and lamination were performed on the polyethylene terephthalate side of the vinyl acetate copolymer laminated film (support) to prepare a patch.

(Comparative Examples 1 and 2) Patches were prepared in the same manner as in Example 1 except that the components having the compositions shown in Table 1 were used.

Example 2 A copolymer obtained by copolymerizing 85 parts by weight of 2-ethylhexyl acrylate and 15 parts by weight of N-vinyl-2-pyrrolidone was dissolved in ethyl acetate to obtain a solid content concentration. A 33.2% by weight adhesive base solution was obtained. Further, polyethylene glycol 200 (manufactured by Tokyo Kasei) while stirring 100 parts by weight of crosslinked polyacrylate (“Sun Fresh” manufactured by Sanyo Kasei) with a dissolver.
Spray 200 parts by weight of polyethylene glycol 20
A 0 impregnated crosslinked polyacrylate was obtained.

Indomethacin, polyethylene glycol 200-impregnated crosslinked polyacrylate and isopropyl myristate were added to the above adhesive base solution so as to have the composition shown in Table 1, and uniformly mixed with a dissolver to obtain a solid content concentration of 30. A wt% ethyl acetate dispersion solution was prepared. This solution was applied onto polyethylene terephthalate release paper so that the thickness after drying would be 50 mμ, and dried at 60 ° C. for 30 minutes to form an adhesive layer. Next, this pressure-sensitive adhesive layer was transferred and laminated on the polyethylene terephthalate side of a laminated film of polyethylene terephthalate / ethylene / vinyl acetate copolymer to prepare a patch.

(Comparative Examples 3 and 4) Patches were prepared in the same manner as in Example 2 except that the components having the compositions shown in Table 1 were used.

Example 3 100 parts by weight of concentrated glycerin (manufactured by NOF Corporation) was sprayed while stirring 100 parts by weight of crosslinked polyvinylpyrrolidone (Kolidone CL) with a dissolver to obtain glycerin-impregnated crosslinked polyvinylpyrrolidone. In the same adhesive base solution as in Example 1, 10 wt% ethyl isosorbide nitrate acetate solution, glycerol impregnated crosslinked polyvinylpyrrolidone and isopropyl myristate were added,
The components were added so as to have the composition shown in Table 2 and uniformly mixed by a dissolver to prepare an ethyl acetate dispersion solution having a solid content concentration of 30% by weight. A patch was prepared in the same manner as in Example 1 using this solution.

Comparative Examples 5 and 6 Patches were prepared in the same manner as in Example 3 except that the components having the compositions shown in Table 2 were used.

(Example 4) 100 parts by weight of cross-linked polyvinylpyrrolidone (Kolidone CL) was sprayed with 200 parts by weight of polyethylene glycol 200 (manufactured by Tokyo Chemical Industry Co., Ltd.) while stirring with a dissolver to obtain cross-linked polyvinyl pyrrolidone impregnated with polyethylene glycol 200. Obtained. Example 2
Indomethacin, polyethylene glycol 200-impregnated crosslinked polyvinylpyrrolidone and isopropyl myristate were added to the same adhesive base solution as in the above so as to have the composition shown in Table 1, and uniformly mixed with a dissolver to obtain a solid content concentration of 30% by weight. An ethyl acetate dispersion solution was prepared. A patch was prepared in the same manner as in Example 1 using this solution.

Comparative Examples 7 and 8 Patches were prepared in the same manner as in Example 4 except that the components having the compositions shown in Table 2 were used.

A drug release test was conducted on the patches obtained in the above Examples and Comparative Examples, and the results are shown in Tables 1 and 2. Drug release test The drug release test was carried out in accordance with the nude mouse skin permeation test. Fran
Fix the skin of the back of the nude mouse on the diffusion cell of z,
A patch of 3.14 cm ² (circle having a diameter of 1 cm) was applied to the skin surface side. The amount of drug (mg / cm ² ) transferred to the receptor solution on the back surface of the skin after 24 hours was measured by high performance liquid chromatography (HPLC). The diffusion cell was kept at a constant temperature of 37 ° C, and the receptor liquid was 20% by weight.
A polyethylene glycol aqueous solution was used.

[0061]

[Table 1]

[0062]

[Table 2]

[0063]

The composition of the patch of the present invention is as described above, and various drugs such as isosorbide nitrate and indomethacin can be effectively percutaneously or transmucosally absorbed. Furthermore, the drug release effect can be further improved by adding a plasticizer having plasticization to the adhesive base to the adhesive layer of the patch of the present invention.

Claims (1)

[Claims] 1. A patch comprising a water-absorbent filler, which is pre-impregnated with a polyhydric alcohol (derivative) on a support, a drug and an adhesive base.