JPH04273818A - Percutaneous administration preparation - Google Patents
Percutaneous administration preparationInfo
- Publication number
- JPH04273818A JPH04273818A JP11964491A JP11964491A JPH04273818A JP H04273818 A JPH04273818 A JP H04273818A JP 11964491 A JP11964491 A JP 11964491A JP 11964491 A JP11964491 A JP 11964491A JP H04273818 A JPH04273818 A JP H04273818A
- Authority
- JP
- Japan
- Prior art keywords
- transdermal
- terodiline
- active ingredient
- mixture
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 229960005383 terodiline Drugs 0.000 claims abstract description 24
- UISARWKNNNHPGI-UHFFFAOYSA-N terodiline Chemical compound C=1C=CC=CC=1C(CC(C)NC(C)(C)C)C1=CC=CC=C1 UISARWKNNNHPGI-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960005434 oxybutynin Drugs 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 238000010521 absorption reaction Methods 0.000 claims description 15
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 5
- 230000001070 adhesive effect Effects 0.000 claims description 5
- 239000003623 enhancer Substances 0.000 claims description 5
- 229920002379 silicone rubber Polymers 0.000 claims description 5
- 239000004945 silicone rubber Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 2
- 244000043261 Hevea brasiliensis Species 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 239000003349 gelling agent Substances 0.000 claims description 2
- 229920003052 natural elastomer Polymers 0.000 claims description 2
- 229920001194 natural rubber Polymers 0.000 claims description 2
- 229920001289 polyvinyl ether Polymers 0.000 claims description 2
- MMOXZBCLCQITDF-UHFFFAOYSA-N N,N-diethyl-m-toluamide Chemical class CCN(CC)C(=O)C1=CC=CC(C)=C1 MMOXZBCLCQITDF-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 claims 1
- 229920003051 synthetic elastomer Polymers 0.000 claims 1
- 239000005061 synthetic rubber Substances 0.000 claims 1
- 239000002674 ointment Substances 0.000 abstract description 12
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 239000006071 cream Substances 0.000 abstract description 4
- 239000000243 solution Substances 0.000 abstract description 4
- 239000000725 suspension Substances 0.000 abstract description 3
- 239000000839 emulsion Substances 0.000 abstract description 2
- 239000003906 humectant Substances 0.000 abstract description 2
- 239000003381 stabilizer Substances 0.000 abstract description 2
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 239000011505 plaster Substances 0.000 abstract 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 239000003814 drug Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 238000012360 testing method Methods 0.000 description 6
- -1 Polypropylene Polymers 0.000 description 5
- 206010046543 Urinary incontinence Diseases 0.000 description 5
- 210000001015 abdomen Anatomy 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 206010069632 Bladder dysfunction Diseases 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- RNGHAJVBYQPLAZ-UHFFFAOYSA-N Terodiline hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)NC(C)(C)C)C1=CC=CC=C1 RNGHAJVBYQPLAZ-UHFFFAOYSA-N 0.000 description 4
- 239000011888 foil Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000012982 microporous membrane Substances 0.000 description 4
- 230000027939 micturition Effects 0.000 description 4
- 229960003959 terodiline hydrochloride Drugs 0.000 description 4
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229960003639 laurocapram Drugs 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920000098 polyolefin Polymers 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 2
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 2
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- CGVLVOOFCGWBCS-RGDJUOJXSA-N n-octyl β-d-thioglucopyranoside Chemical compound CCCCCCCCS[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O CGVLVOOFCGWBCS-RGDJUOJXSA-N 0.000 description 2
- 239000000123 paper Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 2
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- AWQFNUMHFNEWGS-UHFFFAOYSA-N 2-methylprop-1-ene;styrene Chemical group CC(C)=C.C=CC1=CC=CC=C1 AWQFNUMHFNEWGS-UHFFFAOYSA-N 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 206010027566 Micturition urgency Diseases 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229920003049 isoprene rubber Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000005011 phenolic resin Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 150000003097 polyterpenes Chemical class 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は尿失禁、尿意切迫感、頻
尿などの膀胱機能障害の治療薬に適用される経皮投与製
剤に関するものである。さらに詳しく述べると、テロジ
リン、オキシプチニンおよびそれらの塩のいずれかまた
はそれらの混合物を活性成分として含有することを特徴
とする経皮投与製剤に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a transdermal preparation suitable for treating bladder dysfunction such as urinary incontinence, urinary urgency, and frequent urination. More specifically, the present invention relates to a transdermal preparation characterized by containing terodiline, oxyputinin, salts thereof, or a mixture thereof as an active ingredient.
【０００２】0002
【従来の技術】尿失禁、頻尿などの膀胱機能障害の治療
剤としてテロジリン製剤、オキシブチニン製剤等が用い
られるが、いずれも経口投与剤であり、これらの治療剤
の経皮投与製剤は未だ開発されていない。[Prior Art] Terodiline preparations, oxybutynin preparations, etc. are used as therapeutic agents for bladder dysfunction such as urinary incontinence and frequent urination, but both are orally administered preparations, and transdermal administration preparations for these therapeutic agents have not yet been developed. It has not been.
【０００３】0003
【発明が解決しようとする課題】高齢化社会を迎え、老
人人口の増大から医療上重要課題の一つとなった尿失禁
、頻尿等の膀胱機能障害対策が不可欠になってきた。
６０歳以上の老人入院患者を対象にした調査でも５０％
以上の老人がさまざまな程度の失禁を有しておりその対
策が必要とされている。[Problems to be Solved by the Invention] As we enter an aging society, it has become essential to take measures against bladder dysfunction such as urinary incontinence and frequent urination, which have become important medical issues due to the increase in the elderly population. 50% in a survey targeting geriatric inpatients aged 60 and over.
The elderly people mentioned above have various degrees of incontinence, and countermeasures are needed.
【０００４】尿失禁等の治療薬としてすでに塩酸テロジ
リン、塩酸オキシブチニン等の経口投与製剤が用いられ
ている。これらの経口投与製剤は１日に２〜３回服用さ
れており、吸収も良好であることが知られているが、一
方、肝での代謝の多いことが報告されている（薬局、４
１（５），４５〜５３（１９９０））。Orally administered preparations such as terodiline hydrochloride and oxybutynin hydrochloride have already been used as therapeutic agents for urinary incontinence and the like. These orally administered preparations are taken two to three times a day and are known to be well absorbed, but on the other hand, it has been reported that they are heavily metabolized in the liver (Pharmacy, 4
1(5), 45-53 (1990)).
【０００５】また、これらの治療剤の適用対象となる老
人の中には経口剤の投薬においても介添えを要する患者
も少なくないことから、より簡便でしかも肝での代謝を
受けにくい製剤の開発が望まれていた。[0005] Furthermore, among the elderly patients to whom these therapeutic agents are applied, there are many patients who require assistance even when administering oral preparations, so it is necessary to develop preparations that are simpler and less susceptible to metabolism in the liver. It was wanted.
【０００６】[0006]
【課題を解決するための手段】本発明者は上述した課題
を解決すべく鋭意研鑽を重ねた結果、投与が簡便であり
、患者に受け入れられ易く、また、持続性にすぐれ、し
かも肝での代謝を受けにくい膀胱機能障害治療用経皮投
与製剤を開発することに成功し、本発明を成すに至った
。[Means for Solving the Problems] As a result of intensive research in order to solve the above-mentioned problems, the present inventor has developed a drug that is easy to administer, easily accepted by patients, has excellent long-lasting effects, and has a high level of efficacy in the liver. We have succeeded in developing a transdermal preparation for treating bladder dysfunction that is not easily metabolized, and have come to form the present invention.
【０００７】経皮吸収剤は一般に医薬の作用が持続的と
なり、１回適用で１日から数日間有効である。しかも肝
での代謝を減ずることができるので、肝代謝の大きい薬
物に適する投与剤形である。また、投与方法が簡便であ
るので老人に対する治療薬としてはきわめて有用性が高
い。[0007] Transdermal absorption agents generally have a long-lasting medicinal effect, and are effective for one to several days after a single application. Moreover, since it can reduce hepatic metabolism, it is a dosage form suitable for drugs that are highly metabolized in the liver. Furthermore, since the method of administration is simple, it is extremely useful as a therapeutic agent for the elderly.
【０００８】しかしながら、経皮投与製剤は、経口剤、
注射剤と異なり、媒体として使用する溶剤、軟膏基剤、
ゲル化剤などの医薬品添加物により吸収率が大きく左右
されることが知られている。[0008] However, transdermal preparations include oral preparations,
Unlike injections, the solvent used as a vehicle, ointment base,
It is known that the absorption rate is greatly influenced by pharmaceutical additives such as gelling agents.
【０００９】本発明者は、テロジリン、オキシブチニン
またはそれらの塩を有効成分として含有する経皮投与製
剤について研究した結果、きわめて吸収率が高く、皮膚
刺激も少ない経皮投与製剤を開発することに成功した。As a result of research into transdermal preparations containing terodiline, oxybutynin, or their salts as active ingredients, the present inventor succeeded in developing a transdermal preparation with extremely high absorption rate and minimal skin irritation. did.
【００１０】本発明の経皮投与製剤の有効成分として用
いられるテロリジンおよびオキシブチニンはフリー体で
も塩でも用いることができるが、フリー体の方が吸収効
率が高い。有効成分として塩を用いる場合は、適当な塩
基または緩衝液を用いて中和して使用する方が好ましい
。Telolidine and oxybutynin, which are used as active ingredients in the transdermal preparation of the present invention, can be used in either free form or salt form, but absorption efficiency is higher in free form. When using a salt as an active ingredient, it is preferable to neutralize it with an appropriate base or buffer before use.
【００１１】本発明の経皮投与製剤は有効成分のテロジ
リン、オキシブチニンおよびそれらの塩のいずれかある
いはそれらの混合物を０．５〜１０重量％含有する。The transdermal preparation of the present invention contains 0.5 to 10% by weight of any one of the active ingredients terodiline, oxybutynin and their salts, or a mixture thereof.
【００１２】本発明の経皮投与製剤を製造するにあたり
、通常の経皮剤の調製に使用される医薬品添加物を適宜
選択して使用することができる。[0012] In producing the transdermal preparation of the present invention, pharmaceutical additives commonly used in the preparation of transdermal preparations can be appropriately selected and used.
【００１３】本発明の経皮投与製剤はさらに常法に従い
、軟膏、クリーム製剤、テープ製剤およびパッチ剤等の
貼付剤ならびに溶液剤、乳剤及び懸濁剤などの経皮投与
用液剤など種々の経皮投与用製剤に調製して使用するこ
とができる。[0013] The transdermal preparation of the present invention can be further applied to various transdermal preparations such as patches such as ointments, cream preparations, tape preparations, and patches, and liquid preparations for transdermal administration such as solutions, emulsions, and suspensions. It can be prepared and used as a preparation for skin administration.
【００１４】さらに有効成分の持続性を延長させるため
に、徐放性の基剤を使用して徐放註製剤としてもよいが
、通常の手法により調製された組成物を特殊な膜を介し
て貼付する膜放出制御による持続性製剤とすることもで
きる。このような膜放出制御経皮投与製剤に用いられる
膜として０．１ないし０．８５の多孔性を有する微孔性
膜をあげることができる。微孔性膜の材質としてはポリ
プロピレン、ポリオレフィン、ポリエチレンなどが使用
される。また１ないし１０の蛇行性を有するものがよく
、厚さは１０−３ないし１０−２ｃｍ程度が好ましい。[0014] In order to further extend the duration of the active ingredient, a sustained release preparation may be prepared using a sustained release base. It can also be made into a sustained-release preparation by applying a membrane to control release. A microporous membrane having a porosity of 0.1 to 0.85 can be used as a membrane for use in such membrane-controlled release transdermal preparations. Polypropylene, polyolefin, polyethylene, etc. are used as the material for the microporous membrane. Also, it is preferable to have a meandering property of 1 to 10, and a thickness of about 10-3 to 10-2 cm.
【００１５】軟膏およびクリーム製剤の基剤としては、
一般にポリエチレングリコール、カルボキシビニルポリ
マー、ミツロウ、油脂、白色ワセリン、プラスチベ−ス
、高級脂肪酸または高級アルコールなどを用いることが
できる。具体的な例としては、ポリエチレングリコール
類では、マクロゴール４００、マクロゴール１５００、
マグロゴール４０００およびマグロゴール６０００（米
国グットリッチケミカル社製）などがあり、カルボキシ
ビニルポリマー類としては、カーボポール９３４、カー
ボポール９４０、カーボポール９４１（米国グットリッ
チケミカル社製）、ハイビスワコー１０３、ハイビスワ
コー１０４、ハイビスワコー１０５およびハイビスワコ
ー１０６（和光純薬工業（株）製）などをあげることが
できる。[0015] As a base for ointment and cream preparations,
In general, polyethylene glycol, carboxyvinyl polymer, beeswax, fats and oils, white vaseline, plastibase, higher fatty acids or higher alcohols can be used. Specific examples of polyethylene glycols include Macrogol 400, Macrogol 1500,
Examples of carboxyvinyl polymers include Magrogol 4000 and Magrogol 6000 (manufactured by Goodrich Chemical Co., USA), Carbopol 934, Carbopol 940, Carbopol 941 (manufactured by Goodrich Chemical Co., USA), Hivis Wako 103, Examples include Hivis Wako 104, Hibis Wako 105, and Hibis Wako 106 (manufactured by Wako Pure Chemical Industries, Ltd.).
【００１６】テープ剤およびパッチ剤の薬物含有層に用
いられる基剤としては、アクリル酸、アクリル酸エステ
ルまたはアクリルアミドを原料とする重合体、天然ゴム
、合成イソプレンゴム、スチレン−ブタジエンゴム、ス
チレン−イソブチレン共重合体、ポリビニールエーテル
およびシリコンゴムなどが用いられる。The base material used in the drug-containing layer of tapes and patches includes polymers made from acrylic acid, acrylic esters, or acrylamide, natural rubber, synthetic isoprene rubber, styrene-butadiene rubber, and styrene-isobutylene. Copolymers, polyvinyl ether, silicone rubber, etc. are used.
【００１７】これらの基剤は単独で用いても適宜混合し
て用いてもよいが、さらに、ロジン、ロジン誘導体、ポ
リテルペン樹脂、クマロン−インデン樹脂、石油系樹脂
およびテルペンフェノール樹脂等を必要に応じて添加し
、薬物含有層の粘性を増大させることもできる。[0017] These bases may be used alone or in an appropriate mixture, but in addition, rosin, rosin derivatives, polyterpene resins, coumaron-indene resins, petroleum resins, terpene phenol resins, etc. may be used as necessary. It can also be added to increase the viscosity of the drug-containing layer.
【００１８】貼付剤の支持体としては、一般に貼付剤の
支持体として使用されているものを使用することができ
る。この支持体の素材としては、例えば、酢酸セルロー
ス、エチルセルロース、ポリエチレンテレフタレート、
酢酸ビニル−塩化ビニル共重合体、可塑性ポリ塩化ビニ
ル、ポリウレタン、ポリオレフィン、ポリ塩化ビニリデ
ンおよびアルミニウムなどをあげることができる。これ
らは、例えば単層シート（フィルムも含有される）およ
び積層シートとして用いられる。また、これらを使用し
た繊維で作られた織布および不織布ならびに抄紙もそれ
ぞれ使用することができる。アルミニウムはその箔が使
用される。As the support for the patch, those commonly used as supports for patches can be used. Examples of materials for this support include cellulose acetate, ethyl cellulose, polyethylene terephthalate,
Examples include vinyl acetate-vinyl chloride copolymer, plastic polyvinyl chloride, polyurethane, polyolefin, polyvinylidene chloride, and aluminum. These are used, for example, as monolayer sheets (films are also included) and laminated sheets. Furthermore, woven and nonwoven fabrics and paper made from fibers using these materials can also be used. Aluminum foil is used.
【００１９】本発明の経皮投与製剤において、所望によ
り適宜、防腐剤、芳香剤、保湿剤、安定剤、その他の添
加剤を含有させることができる。The transdermal preparation of the present invention may contain preservatives, fragrances, humectants, stabilizers, and other additives, if desired.
【００２０】また、本発明の経皮投与製剤における吸収
促進剤の濃度は、製剤の種類により異なり、一概に特定
できないが、通常は、例えば、当該組成物において０．
１〜１５重量％程度であればよい。Further, the concentration of the absorption enhancer in the transdermal preparation of the present invention varies depending on the type of preparation and cannot be unconditionally specified, but usually, for example, the concentration of the absorption enhancer in the composition is 0.
It may be about 1 to 15% by weight.
【００２１】本発明の経皮投与製剤の軟膏、クリーム剤
および貼付剤等の薬物含有層に含まれる薬物の濃度は、
０．１〜１０重量％が好ましく、投与回数は１日１回ま
たは２日に１回が適当である。The concentration of the drug contained in the drug-containing layer of the ointment, cream, patch, etc. of the transdermal preparation of the present invention is as follows:
The amount is preferably 0.1 to 10% by weight, and the appropriate frequency of administration is once a day or once every two days.
【００２２】[0022]
【実施例】本発明を実施例によってさらに具体的に説明
する。なお、本発明は実施例によって限定されるもので
はない。EXAMPLES The present invention will be explained in more detail by way of examples. Note that the present invention is not limited to the examples.
【００２３】〔実施例１〕
グリセリン
６３．３ｇ
プロピレングリコール
３０．０ｇ ハイビスワコー１０
４（和光純薬工業（株）製） ２．０ｇ
トリエタノールアミン
２．７３ｇ テロジリン
２．０ｇハイビスワコー１０４にグリセリンを加
え、６５℃で加熱しながら激しく攪拌した。冷後トリエ
タノールアミンを加え、中和（ｐＨ６．５〜７．０）す
る。プロピレングリコールに溶解したテロジリンを加え
、よく混和して経皮吸収用軟膏組成物を得た。[Example 1] Glycerin
63.3g
Propylene glycol
30.0g Hibis Wako 10
4 (manufactured by Wako Pure Chemical Industries, Ltd.) 2.0g
triethanolamine
2.73g Terodiline
Glycerin was added to 2.0 g Hibis Wako 104, and the mixture was stirred vigorously while heating at 65°C. After cooling, triethanolamine is added to neutralize (pH 6.5 to 7.0). Terodiline dissolved in propylene glycol was added and mixed well to obtain an ointment composition for transdermal absorption.
【００２４】〔実施例２〕シリコンゴム（ＳＲ−５０、
厚さ１ｍｍ、タイガースポリマー株式会社製）を円形に
切り抜き（外径５．５ｃｍ、内径４ｃｍ）、シリコンゴ
ムの片面に酢酸セルロース膜とアルミニウム箔を重ねて
接着した。そのシリコンゴムの内部に、実施例１の軟膏
組成物１．９ｇを均一に塗布した。軟膏組成物面にポリ
オレフィン製の微孔性膜を貼付した。さらに微孔性膜の
上に離型ライナーを貼付して貼付剤を得た。なお貼付剤
の使用に際しては離型ライナーを剥離して使用した。[Example 2] Silicone rubber (SR-50,
(1 mm thick, manufactured by Tigers Polymer Co., Ltd.) was cut out into a circular shape (outer diameter 5.5 cm, inner diameter 4 cm), and a cellulose acetate membrane and aluminum foil were layered and adhered to one side of the silicone rubber. 1.9 g of the ointment composition of Example 1 was uniformly applied inside the silicone rubber. A microporous membrane made of polyolefin was attached to the ointment composition surface. Furthermore, a release liner was pasted onto the microporous membrane to obtain a patch. When using the adhesive patch, the release liner was peeled off.
【００２５】〔実施例３〕
エチルヘキシルアクリレート
９０ｇ（ドイツ、ロームファーム社製）
プロピレングリコール
８ｇテロジリン
２ｇエチルヘキシルアクリレート懸濁液（７９２７／８
０、ロームファーム製）を１２０℃で３０分加熱し、粘
着層を得た。冷後、これにプロピレングリコールに溶解
したテロジリンを混合して経皮吸収用粘着剤を得た。こ
の粘着剤を離型ライナーであるポリエチレン加工紙表而
に厚み５０μｍとなるよう塗布して、テロジリンを含有
する貼付剤の薬物含有層を得た。次いで支持体である、
酸化処理加工を表面に施した多孔性ポリエチレンフィル
ム（孔径約０．２ｍｍ、孔間距離１．５ｍｍ）の処理面
に前記の薬物層を、その離型ライナーの反対側の面が接
するように貼り合わせて貼付剤を得た。[Example 3] Ethylhexyl acrylate
90g (manufactured by Rohm Farm, Germany) Propylene glycol
8g terodiline
2g ethylhexyl acrylate suspension (7927/8
0, manufactured by Rohm Farm) was heated at 120° C. for 30 minutes to obtain an adhesive layer. After cooling, terodiline dissolved in propylene glycol was mixed therewith to obtain an adhesive for transdermal absorption. This adhesive was applied to a polyethylene-treated paper surface serving as a release liner to a thickness of 50 μm to obtain a drug-containing layer of a patch containing terodiline. Next is the support,
The drug layer was applied to the treated surface of a porous polyethylene film (pore diameter: approximately 0.2 mm, distance between pores: 1.5 mm) that had been subjected to oxidation treatment, so that the surface opposite to the release liner was in contact with the treated surface. A patch was also obtained.
【００２６】〔実施例４〕
カーボポール９３４（米国グッドリッチケミカ
ル社製） ２．０ｇ プロピレングリコール
２０．０ｇ ｎ−オクチル−β−Ｄ−チオグ
ルコピラノシド １．５ｇ タウ
ロコール酸ナトリウム
１．０ｇ 塩酸テロジリ
ン
３．０ｇ 精製水（全
量）
１００．０ｇカーボポール９３
４に水２０ｇを加えて膨潤させ、ついで５重量％苛性ソ
ーダ水溶液で中和（ｐＨ６．５〜７．０）した。これに
精製水３０ｇに溶解した塩酸テロジリンを加えよく混和
した。さらにｎ−オクチル−β−Ｄ−チオグルコピラノ
シドおよびタウロコール酸ナトリウムを精製水に溶解し
た液を混合した後、プロピレングリコールを加え混合し
て経皮吸収用軟膏組成物を得た。[Example 4] Carbopol 934 (manufactured by Goodrich Chemical Co., USA) 2.0 g Propylene glycol
20.0g n-octyl-β-D-thioglucopyranoside 1.5g Sodium taurocholate
1.0g Terodiline hydrochloride
3.0g purified water (total amount)
100.0g Carbopol 93
4 was added with 20 g of water to swell it, and then neutralized (pH 6.5 to 7.0) with a 5% by weight aqueous solution of caustic soda. Terodiline hydrochloride dissolved in 30 g of purified water was added to this and mixed well. Further, a solution of n-octyl-β-D-thioglucopyranoside and sodium taurocholate dissolved in purified water was mixed, and then propylene glycol was added and mixed to obtain an ointment composition for transdermal absorption.
【００２７】〔実施例５〕塩酸テロジリンの代わりに塩
酸オキシブチニン３．０ｇを用いたほか、実施例４と同
様に行って経皮吸収用軟膏組成物を得た。[Example 5] An ointment composition for transdermal absorption was obtained in the same manner as in Example 4 except that 3.0 g of oxybutynin hydrochloride was used instead of terodiline hydrochloride.
【００２８】〔試験例１〕雄性ウィスタ ラット（体
重２００〜２５０ｇ）の腹部皮膚を電気バリカンとシェ
ーバーで前日に除毛した。実験当日、ラットを断首によ
り殺し、その腹部皮膚を切り取り、皮膚に付着する脂肪
等を除去した。切除した皮膚を真皮側を下にしてフラン
ツセル（内径１ｃｍ、受器の容積１３ｍｌ）に装着した
。
受器には０．９％塩化ナトリウム−１０ｍＭリン酸緩衝
液（ｐＨ７．４）を満たし、さらに防腐剤としてゲンタ
マイシン液を１００分の１容加えた。皮膚の表面に実施
例１の軟膏組成物０．２５ｇを均一に塗布し、その上面
をアルミ箔で被覆した。このフランツセルを３７℃に加
温しながら、皮膚を透過するテロジリン量をガスクロマ
トグラフィ（熱伝導度検出器）を用いて定量した。この
試験におけるテロジリン透過量の変化を、吸収促進剤ラ
ウロカプラム（ネルソン リサーチ ディベロップ
メント社製）を含有する軟膏組成物（実施例１の組成物
にラウロカプラムを５重量％配合）のそれと比較して図
１に示した。[Test Example 1] The abdominal skin of male Wista rats (weight 200-250 g) was removed using electric clippers and a shaver the previous day. On the day of the experiment, the rats were killed by decapitation, their abdominal skin was cut off, and fat etc. adhering to the skin were removed. The excised skin was placed in a Franz cell (inner diameter 1 cm, receiver volume 13 ml) with the dermal side facing down. The receiver was filled with 0.9% sodium chloride-10mM phosphate buffer (pH 7.4), and 1/100 volume of gentamicin solution was added as a preservative. 0.25 g of the ointment composition of Example 1 was evenly applied to the surface of the skin, and the upper surface was covered with aluminum foil. While heating this Franz cell to 37° C., the amount of terodiline permeating the skin was determined using gas chromatography (thermal conductivity detector). Figure 1 compares the changes in the amount of terodiline permeation in this test with that of an ointment composition (5% by weight of laurocapram in the composition of Example 1) containing the absorption enhancer laurocapram (manufactured by Nelson Research Development). It was shown to.
【図１】[Figure 1]
【００２９】〔試験例２〕雄性ウィスタ ラット（体
重２５０〜３００ｇ）の腹部を前日除毛した。実験当日
にラットの除毛した腹部に実施例１で得られた経皮吸収
用軟膏組成物０．９ｇを、前記の腹部６ｃｍ２に均一に
塗布し、その上をアルミ箔、さらにガムテープで被覆し
た。経皮投与時間は４８時間とした。経皮投与開始後１
時間から４８時間まで、頸静脈カニュレーションチュー
ブより血液０．２ｍｌずつを経時的に採取し、この血液
を直ちに遠心分離に付して血漿０．１ｍｌを採取した。
この血液０．１ｍｌについて、テロジリンを抽出後、ガ
スクロマトグラフィー（熱伝導度検出器）を使用して定
量した。この試験における血漿テロジリン濃度の経時変
化を図２に示した。[Test Example 2] The abdomen of a male Wista rat (body weight 250-300 g) was shaved the day before. On the day of the experiment, 0.9 g of the ointment composition for transdermal absorption obtained in Example 1 was uniformly applied to the abdomen of the rat from which hair had been removed (6 cm2), and the top was covered with aluminum foil and duct tape. . The transdermal administration time was 48 hours. After starting dermal administration 1
From time to time until 48 hours, 0.2 ml of blood was collected from the jugular cannulation tube over time, and the blood was immediately centrifuged to collect 0.1 ml of plasma. After extracting terodiline from 0.1 ml of this blood, it was quantified using gas chromatography (thermal conductivity detector). Figure 2 shows the time course of plasma terodiline concentration in this test.
【図２】[Figure 2]
【００３０】〔試験例３〕前記試験例２と同様の方法で
、実施例３で得られた経皮吸収用貼付剤（粘着剤０．４
ｇ、８ｃｍ２）をラット腹部に貼付して測定した血漿テ
ロジリン濃度の経時変化を図３に示した。[Test Example 3] The transdermal patch obtained in Example 3 was prepared in the same manner as in Test Example 2 (adhesive: 0.4
Fig. 3 shows the time course of the plasma terodiline concentration measured by attaching the tablet (g, 8 cm2) to the abdomen of a rat.
【図３】[Figure 3]
【００３１】[0031]
【発明の効果】本発明の経皮投与製剤は、投与が簡便で
あり、患者に受け入れられ易く、しかも活性成分のテロ
ジリン、オキシブチニンが皮膚から容易に吸収され、高
い血漿濃度と持続性を示すので、生体内利用が良好で、
老人の尿失禁、頻尿等の治療に適する簡便な製剤として
有用である。[Effects of the Invention] The transdermal preparation of the present invention is easy to administer and easily accepted by patients, and the active ingredients terodiline and oxybutynin are easily absorbed through the skin and exhibit high plasma concentrations and persistence. , good bioavailability,
It is useful as a simple preparation suitable for treating urinary incontinence, frequent urination, etc. in the elderly.
【００３２】[0032]
【図１】 剥離したラッ卜腹部皮膚を透過するテロジ
リン量の変化を示すグラフであり、縦軸は透過したテロ
ジリン量（μｇ／ｃｍ２）、横軸は経過時間（時間）を
表す。FIG. 1 is a graph showing changes in the amount of terodiline permeated through exfoliated rat abdominal skin, where the vertical axis represents the amount of terodiline permeated (μg/cm2), and the horizontal axis represents elapsed time (hours).
【００３３】[0033]
○―○： 実施例１の組成物
●―●： 実施例１の組成物＋ラウロカプラム ５
重量％○-○: Composition of Example 1 ●-●: Composition of Example 1 + Laurocapram 5
weight%
【００３４】[0034]
【図２】 ラット腹部に実施例１の組成物を塗布した
時の血漿中のテロジリンの濃度変化を示すグラフであり
、縦軸は血漿中のテロジリン濃度（μｇ／ｍｌ）、横軸
は適用時間（時間）を表す。FIG. 2 is a graph showing changes in the concentration of terodiline in plasma when the composition of Example 1 is applied to the abdomen of a rat, where the vertical axis is the concentration of terodiline in plasma (μg/ml) and the horizontal axis is the application time. (time).
【００３５】[0035]
【図３】 ラット腹部に実施例３の貼付剤を適用した
時の血漿中のテロジリンの濃度変化を示すグラフであり
、縦軸は血漿中のテロジリン濃度（μｇ／ｍｌ）、横軸
は適用時間（時間）を表す。FIG. 3 is a graph showing changes in the concentration of terodiline in plasma when the patch of Example 3 is applied to the abdomen of a rat, where the vertical axis is the concentration of terodiline in plasma (μg/ml) and the horizontal axis is the application time. (time).
Claims (5)
れらの塩のいずれかまたはそれらの混合物を活性成分と
して含有することを特徴とする経皮投与製剤。1. A transdermal preparation comprising terodiline, oxybutynin, a salt thereof, or a mixture thereof as an active ingredient.
％である請求項１記載の経皮投与製剤2. The transdermal preparation according to claim 1, wherein the content of the active ingredient is 0.1 to 10% by weight.
ジエチル−ｍ−トルアミド類、アルキル−Ｄ−グルコシ
ド類、アルキル−β−Ｄ−チオグルコシド類および１−
アルキルピロリドン類の中から選択されるいずれかまた
はそのいくつかの混合物を吸収促進剤として含有する請
求項１記載の経皮投与製剤。[Claim 3] Fatty acids having 8 to 18 carbon atoms, N,N-
Diethyl-m-toluamides, alkyl-D-glucosides, alkyl-β-D-thioglucosides and 1-
2. The transdermal preparation according to claim 1, which contains one selected from alkylpyrrolidones or a mixture of some thereof as an absorption enhancer.
ールおよび水のいずれかまたはいくつかを混合してなる
媒体に加え、これにゲル化剤、さらに所望により、これ
に吸収助剤、吸収促進剤を添加しゲル化せしめてなる請
求項１記載の経皮投与製剤。4. The active ingredient is added to a medium consisting of a mixture of glycols, lower alcohols, and/or water, and a gelling agent is added thereto, and if desired, an absorption aid or an absorption enhancer is added thereto. 2. The transdermal administration preparation according to claim 1, which is formed by adding and gelling.
ステルまたはアクリルアミドを原料とする重合体、天然
ゴム、合成ゴム、ポリビニルエーテルおよびシリコンゴ
ムの中から選択される粘着剤に含有させてなる請求項１
記載の経皮投与製剤。5. Claim 1, wherein the active ingredient is contained in an adhesive selected from polymers made from acrylic acid, acrylic esters, or acrylamide, natural rubber, synthetic rubber, polyvinyl ether, and silicone rubber.
The transdermal formulation described.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11964491A JPH04273818A (en) | 1991-02-28 | 1991-02-28 | Percutaneous administration preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11964491A JPH04273818A (en) | 1991-02-28 | 1991-02-28 | Percutaneous administration preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04273818A true JPH04273818A (en) | 1992-09-30 |
Family
ID=14766552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11964491A Pending JPH04273818A (en) | 1991-02-28 | 1991-02-28 | Percutaneous administration preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04273818A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5411740A (en) * | 1992-05-13 | 1995-05-02 | Alza Corporation | Transdermal administration of oxybutynin |
| WO1995031190A1 (en) * | 1994-05-18 | 1995-11-23 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneously administrable preparation for treating urination disorder |
| WO2000064434A1 (en) * | 1999-04-26 | 2000-11-02 | Lead Chemical Co., Ltd. | Percutaneous preparations containing oxybutynin |
| WO2000076490A3 (en) * | 1999-06-10 | 2002-03-21 | Sepracor Inc | Methods and compositions for treating urinary frequency and urgency using optically pure (s)-oxybutynin |
| CN1111404C (en) * | 1994-03-04 | 2003-06-18 | 潘威斯脱药物公司 | The oxybutynin formulations of controlled release |
| WO2006082888A1 (en) * | 2005-02-03 | 2006-08-10 | Kyorin Pharmaceutical Co., Ltd. | Percutaneous absorption preparation |
| WO2010013423A1 (en) * | 2008-07-28 | 2010-02-04 | 花王株式会社 | External preparation for skin, and wrinkle-repairing agent |
| WO2010109913A1 (en) * | 2009-03-27 | 2010-09-30 | トーアエイヨー株式会社 | Transdermal preparation |
| JP2010229088A (en) * | 2009-03-27 | 2010-10-14 | Toa Eiyo Ltd | Transdermal preparation |
-
1991
- 1991-02-28 JP JP11964491A patent/JPH04273818A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5500222A (en) * | 1992-05-13 | 1996-03-19 | Alza Corporation | Transdermal administration of oxybutynin |
| US5411740A (en) * | 1992-05-13 | 1995-05-02 | Alza Corporation | Transdermal administration of oxybutynin |
| CN1111404C (en) * | 1994-03-04 | 2003-06-18 | 潘威斯脱药物公司 | The oxybutynin formulations of controlled release |
| WO1995031190A1 (en) * | 1994-05-18 | 1995-11-23 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneously administrable preparation for treating urination disorder |
| US5770221A (en) * | 1994-05-18 | 1998-06-23 | Hisamitsu Pharmaceutical Co., Inc. | Formulation for percutaneous administration for treating disturbance in micturition |
| WO2000064434A1 (en) * | 1999-04-26 | 2000-11-02 | Lead Chemical Co., Ltd. | Percutaneous preparations containing oxybutynin |
| EP1174132A1 (en) * | 1999-04-26 | 2002-01-23 | Lead Chemical Co. Ltd. | Percutaneous absorption preparations containing oxybutynin |
| EP1174132A4 (en) * | 1999-04-26 | 2002-08-07 | Lead Chem Co Ltd | Percutaneous absorption preparations containing oxybutynin |
| WO2000076490A3 (en) * | 1999-06-10 | 2002-03-21 | Sepracor Inc | Methods and compositions for treating urinary frequency and urgency using optically pure (s)-oxybutynin |
| WO2006082888A1 (en) * | 2005-02-03 | 2006-08-10 | Kyorin Pharmaceutical Co., Ltd. | Percutaneous absorption preparation |
| WO2010013423A1 (en) * | 2008-07-28 | 2010-02-04 | 花王株式会社 | External preparation for skin, and wrinkle-repairing agent |
| WO2010109913A1 (en) * | 2009-03-27 | 2010-09-30 | トーアエイヨー株式会社 | Transdermal preparation |
| JP2010229088A (en) * | 2009-03-27 | 2010-10-14 | Toa Eiyo Ltd | Transdermal preparation |
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