JPH0640947A - Composition for percutaneous absorption preparation and percutaneous absorption preparation - Google Patents
Composition for percutaneous absorption preparation and percutaneous absorption preparationInfo
- Publication number
- JPH0640947A JPH0640947A JP20156692A JP20156692A JPH0640947A JP H0640947 A JPH0640947 A JP H0640947A JP 20156692 A JP20156692 A JP 20156692A JP 20156692 A JP20156692 A JP 20156692A JP H0640947 A JPH0640947 A JP H0640947A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- percutaneous absorption
- absorption preparation
- carbon atoms
- salt
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000010521 absorption reaction Methods 0.000 title claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 150000007524 organic acids Chemical class 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 22
- 230000000052 comparative effect Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 239000004310 lactic acid Substances 0.000 description 11
- 235000014655 lactic acid Nutrition 0.000 description 11
- 210000003491 skin Anatomy 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 150000001733 carboxylic acid esters Chemical class 0.000 description 7
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 229960005195 morphine hydrochloride Drugs 0.000 description 5
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229960004194 lidocaine Drugs 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
- 235000021360 Myristic acid Nutrition 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SSVFMICWXDVRQN-UHFFFAOYSA-N ethanol;sodium Chemical compound [Na].CCO SSVFMICWXDVRQN-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229960004958 ketotifen Drugs 0.000 description 2
- 229960003630 ketotifen fumarate Drugs 0.000 description 2
- YNQQEYBLVYAWNX-WLHGVMLRSA-N ketotifen fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 YNQQEYBLVYAWNX-WLHGVMLRSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000005973 Carvone Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- KMISFPIWSMSMJD-GPKQSYPGSA-N Eptazocine hydrobromide Chemical compound Br.C1N(C)CC[C@@]2(C)C3=CC(O)=CC=C3C[C@@H]1C2 KMISFPIWSMSMJD-GPKQSYPGSA-N 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
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229960001889 buprenorphine hydrochloride Drugs 0.000 description 1
- UAIXRPCCYXNJMQ-RZIPZOSSSA-N buprenorphine hydrochlorie Chemical compound [Cl-].C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)C[NH+]2CC1CC1 UAIXRPCCYXNJMQ-RZIPZOSSSA-N 0.000 description 1
- GMTYREVWZXJPLF-AFHUBHILSA-N butorphanol D-tartrate Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O.N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 GMTYREVWZXJPLF-AFHUBHILSA-N 0.000 description 1
- 229960001590 butorphanol tartrate Drugs 0.000 description 1
- IVHBBMHQKZBJEU-UHFFFAOYSA-N cinchocaine hydrochloride Chemical compound [Cl-].C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCC[NH+](CC)CC)=C21 IVHBBMHQKZBJEU-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940045574 dibucaine hydrochloride Drugs 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
- 229960004207 fentanyl citrate Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- -1 poultices Substances 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、塩基性薬物またはその
塩を含む経皮吸収製剤用組成物および経皮吸収製剤に関
する。TECHNICAL FIELD The present invention relates to a composition for a percutaneous absorption preparation containing a basic drug or a salt thereof and a percutaneous absorption preparation.
【０００２】[0002]
【従来の技術】現在多くの薬物は主に注射剤または経口
剤の形で投与されている。しかし、注射剤は投与に技術
を要し、また投与にあたり生体に苦痛を与える。一方、
経口剤はこれを飲み込むことが困難な小児や老人に投与
するには不便であり、また胃腸障害を引き起こすことが
ある。さらに、これらの剤形では、１回の投与で長時間
の薬効の持続を期待することができない。そこで、近
年、投与時に生体に苦痛を与えることがなく、また胃腸
障害を引き起こすこともない、１回の簡単な適用で長時
間の薬効の持続が期待できる、皮膚を投与経路とする経
皮吸収製剤が注目されるようになった。2. Description of the Related Art Many drugs are currently administered mainly in the form of injections or oral preparations. However, injection requires a technique for administration, and causes pain to the living body upon administration. on the other hand,
Oral agents are inconvenient to administer to children and the elderly who have difficulty swallowing them, and may cause gastrointestinal disorders. Furthermore, with these dosage forms, it is not possible to expect a long-term sustained efficacy with a single administration. Therefore, in recent years, transdermal absorption using the skin as the route of administration, which does not cause any pain to the living body at the time of administration, and does not cause gastrointestinal disorders, can be expected to maintain a long-term medicinal effect with one simple application. Formulations have come to the fore.
【０００３】[0003]
【発明が解決しようとする課題】しかし、皮膚は生体を
外界から守るための防御膜でもあるので、一般に皮膚か
らの薬物の吸収は容易でなく、薬物の治療効果を薬物の
皮膚適用により得るためには、薬物の皮膚透過性を促進
する基剤を開発する必要がある。However, since the skin is also a protective film for protecting the living body from the external environment, it is generally not easy to absorb the drug from the skin and the therapeutic effect of the drug is obtained by applying the drug to the skin. Therefore, it is necessary to develop a base that promotes the skin permeability of the drug.
【０００４】[0004]
【課題を解決するための手段】本発明者は、上述の状況
に鑑みて種々研究を重ねた結果、塩基性薬物またはその
塩を有効成分とする経皮吸収製剤用組成物の基剤とし
て、炭素原子数２〜５のアルコール、炭素原子数２〜５
の有機酸および炭素原子数１６〜２０のカルボン酸エス
テルを併用すると、これらの薬物の高い皮膚透過速度が
得られることを見出した。Means for Solving the Problems The present inventor has conducted various studies in view of the above situation, and as a result, as a base of a composition for percutaneous absorption preparation containing a basic drug or a salt thereof as an active ingredient, Alcohol having 2 to 5 carbon atoms, 2 to 5 carbon atoms
It has been found that the combined use of the organic acid and the carboxylic acid ester having 16 to 20 carbon atoms provides a high skin permeation rate of these drugs.
【０００５】本発明は、上記知見に基づいて発明された
もので、塩基性薬物またはその塩を皮膚を通じて効果的
に投与できる経皮吸収製剤用組成物および経皮吸収製剤
を提供することを目的とし、 １． 塩基性薬物またはその塩、炭素原子数２〜５のア
ルコール、炭素原子数２〜５の有機酸および炭素原子数
１６〜２０のカルボン酸エステルを含有することを特徴
とする、経皮吸収製剤用組成物、および ２． 塩基性薬物またはその塩、炭素原子数２〜５のア
ルコール、炭素原子数２〜５の有機酸および炭素原子数
１６〜２０のカルボン酸エステルを含有することを特徴
とする、経皮吸収製剤に係るものである。The present invention was invented based on the above findings, and an object thereof is to provide a composition for transdermal absorption preparation and a transdermal preparation capable of effectively administering a basic drug or a salt thereof through the skin. And 1. A percutaneous absorption preparation comprising a basic drug or a salt thereof, an alcohol having 2 to 5 carbon atoms, an organic acid having 2 to 5 carbon atoms, and a carboxylic acid ester having 16 to 20 carbon atoms. A composition, and 2. A transdermal preparation containing a basic drug or a salt thereof, an alcohol having 2 to 5 carbon atoms, an organic acid having 2 to 5 carbon atoms, and a carboxylic acid ester having 16 to 20 carbon atoms. It is related.
【０００６】本発明に用いられる塩基性薬物またはその
塩としては、例えば、鎮痛薬、例えば、モルヒネまたは
その塩、クエン酸フェンタニール、ペンタゾシン、臭化
水素酸エプタゾシン、塩酸ブプレノルフィンまたは酒石
酸ブトルファノール；アレルギー性疾患治療薬、例え
ば、フマル酸ケトチフェン；あるいは局所麻酔薬、例え
ば、リドカインもしくはその塩、塩酸プロカインまたは
塩酸ジブカインが挙げられる。その配合量は、一般に、
本発明組成物１ｍｇあたり、０．００１〜０．５ｍｇ、
好ましくは０．００２〜０．１ｍｇ、特に０．００５〜
０．０５ｍｇである。Examples of the basic drug or a salt thereof used in the present invention include analgesics such as morphine or a salt thereof, fentanyl citrate, pentazocine, eptazocine hydrobromide, buprenorphine hydrochloride or butorphanol tartrate; allergic diseases. Therapeutic agents such as ketotifen fumarate; or local anesthetics such as lidocaine or its salts, procaine hydrochloride or dibucaine hydrochloride. The blending amount is generally
0.001 to 0.5 mg per 1 mg of the composition of the present invention,
Preferably 0.002-0.1 mg, especially 0.005-
It is 0.05 mg.
【０００７】本発明に用いられる炭素原子数２〜５のア
ルコールとしては、薬学的に許容される全ての炭素原子
数２〜５のアルコールを使用することができ、例えば、
エタノール、プロパノール、イソプロパノール、ブタノ
ール、好ましくは、エタノールまたはイソプロパノール
が挙げられる。その配合量は、一般に、本発明組成物１
ｍｇあたり、０．０１〜０．５ｍｇ、好ましくは０．０
５〜０．４ｍｇ、特に０．１〜０．３ｍｇである。As the alcohol having 2 to 5 carbon atoms used in the present invention, all pharmaceutically acceptable alcohols having 2 to 5 carbon atoms can be used.
Mention may be made of ethanol, propanol, isopropanol, butanol, preferably ethanol or isopropanol. The compounding amount is generally the composition 1 of the present invention.
0.01 to 0.5 mg per mg, preferably 0.0
5 to 0.4 mg, especially 0.1 to 0.3 mg.
【０００８】本発明に用いられる炭素原子数２〜５の有
機酸としては、薬学的に許容される全ての炭素原子数２
〜５の有機酸を使用することができ、例えば、乳酸また
は酢酸、好ましくは、乳酸が挙げられる。その配合量
は、一般に、本発明組成物１ｍｇあたり、０．００２〜
０．２ｍｇ、好ましくは０．００５〜０．１ｍｇ、特に
０．０１〜０．０５ｍｇである。As the organic acid having 2 to 5 carbon atoms used in the present invention, all pharmaceutically acceptable 2 carbon atoms can be used.
~ 5 organic acids can be used, for example lactic acid or acetic acid, preferably lactic acid. The amount thereof is generally 0.002 to 1 mg of the composition of the present invention.
0.2 mg, preferably 0.005-0.1 mg, especially 0.01-0.05 mg.
【０００９】本発明に用いられる炭素原子数１６〜２０
のカルボン酸エステルとしては、薬学的に許容される全
ての炭素原子数１６〜２０のカルボン酸エステルを使用
することができ、例えば、ミリスチン酸イソプロピルま
たはオレイン酸エチルが挙げられ、ミリスチン酸イソプ
ロピルが好ましい。その配合量は、一般に、本発明組成
物１ｍｇあたり、０．１〜０．９９ｍｇ、好ましくは
０．３〜０．９５ｍｇ、特に０．５〜０．９ｍｇであ
る。16 to 20 carbon atoms used in the present invention
As the carboxylic acid ester of, any pharmaceutically acceptable carboxylic acid ester having 16 to 20 carbon atoms can be used, and examples thereof include isopropyl myristate or ethyl oleate, and isopropyl myristate is preferred. . The amount thereof is generally 0.1 to 0.99 mg, preferably 0.3 to 0.95 mg, and particularly 0.5 to 0.9 mg per 1 mg of the composition of the present invention.
【００１０】これらの塩基性薬物またはその塩、炭素原
子数２〜５のアルコール、炭素原子数う２〜５の有機酸
および炭素原子数１６〜２０のカルボン酸エステルはい
ずれも、単独で、または２種以上合わせて用いることが
できる。Each of these basic drugs or salts thereof, alcohols having 2 to 5 carbon atoms, organic acids having 2 to 5 carbon atoms and carboxylic acid esters having 16 to 20 carbon atoms, either alone or Two or more kinds can be used in combination.
【００１１】本発明による経皮吸収製剤用組成物の代表
的な組成は次の通りである： 塩基性薬物またはその塩 ０．００５〜０．０５ｍｇ／ｍｇ 炭素原子数２〜５のアルコール ０．１ 〜０．３ ｍｇ／ｍｇ 炭素原子数２〜５の有機酸 ０．０１ 〜０．０５ｍｇ／ｍｇ 炭素原子数16〜18のカルボン酸エステル ０．５ 〜０．９ ｍｇ／ｍｇ 本発明による経皮吸収製剤用組成物は、例えば、塩基性
薬物またはその塩および有機酸を炭素原子数２〜５のア
ルコールに溶解または分散させ、得られた溶液または分
散物を炭素原子数１６〜２０のカルボン酸エステルに加
え、そして混合することによって製造することができ
る。The typical composition of the composition for percutaneous absorption preparation according to the present invention is as follows: basic drug or salt thereof 0.005-0.05 mg / mg alcohol having 2 to 5 carbon atoms 1 to 0.3 mg / mg C2 to C5 organic acid 0.01 to 0.05 mg / mg C16 to C18 carboxylic acid ester 0.5 to 0.9 mg / mg The composition for percutaneous absorption preparation is obtained by, for example, dissolving or dispersing a basic drug or a salt thereof and an organic acid in an alcohol having 2 to 5 carbon atoms, and preparing the obtained solution or dispersion with a carvone having 16 to 20 carbon atoms. It can be prepared by adding to the acid ester and mixing.
【００１２】本発明の組成物から製造される経皮吸収製
剤の剤形としては、例えば、液剤、パップ剤、クリーム
剤、軟膏剤、ゲル剤、プラスター剤またはテープ剤が挙
げられ、特に液剤およびゲル剤が好ましい。The dosage form of the percutaneous absorption preparation produced from the composition of the present invention includes, for example, solutions, poultices, creams, ointments, gels, plasters or tapes, especially liquids and Gels are preferred.
【００１３】本発明の経皮吸収製剤中の塩基性薬物また
はその塩の配合量は、薬物の種類、剤形、患者の症状、
年齢、体重などによって異なるが、一般に、製剤１ｍｇ
あたり０．００１〜０．５ｍｇ、好ましくは０．００２
〜０．１ｍｇ、特に０．００５〜０．０５ｍｇである。The compounding amount of the basic drug or its salt in the percutaneous absorption preparation of the present invention depends on the kind of drug, dosage form, patient's symptoms,
Although it depends on age, weight, etc., generally 1 mg of the preparation
Per 0.001 to 0.5 mg, preferably 0.002
~ 0.1 mg, especially 0.005-0.05 mg.
【００１４】本発明の製剤は、本発明の組成物を、製造
する剤形に必要な製剤成分、すなわち、基礎剤、補助剤
および／または添加剤と必要に応じて組み合わせること
により慣用の方法で製造することができる。The formulations according to the invention are prepared in the customary manner by optionally combining the compositions according to the invention with the formulation components necessary for the dosage form to be produced, ie bases, auxiliaries and / or additives. It can be manufactured.
【００１５】[0015]
【実施例】次いで、以下の実施例を参照して本発明をさ
らに詳細に説明するが、本発明はこれらの実施例に限定
されるものではない。EXAMPLES Next, the present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
【００１６】実施例１ 表１に示される組成で、塩基性薬物である塩酸モルヒ
ネ、フマル酸ケトチフェンまたはリドカイン、あるい
は、酸性薬物であるジクロロフェナックナトリウム、お
よび乳酸をエタノールに溶解し、得られた溶液をミリス
チン酸イソプロピルに添加し、そして混合して本発明組
成物１〜３および比較組成物７を調製するとともに、上
記の乳酸またはエタノールを用いない比較組成物１〜６
をそれぞれ調製した。Example 1 The composition shown in Table 1 was obtained by dissolving a basic drug, morphine hydrochloride, ketotifen fumarate or lidocaine, or an acidic drug, dichlorophenac sodium, and lactic acid in ethanol. The solutions are added to isopropyl myristate and mixed to prepare Inventive Compositions 1-3 and Comparative Composition 7, as well as Comparative Compositions 1-6 above without lactic acid or ethanol.
Were prepared respectively.
【００１７】 表１ 本発明 本発明 本発明 比 較 比 較 比 較 組成物 組成物 組成物 組成物 組成物 組成物 １ ２ ３ １ ２ ３ 塩酸モルヒネ 1 0 0 1 0 0 フマル酸 0 0.1 0 0 0.1 0 ケトチフェン リドカイン 0 0 5 0 0 5 ジクロフェナック 0 0 0 0 0 0 ナトリウム エタノール 10 10 10 10 10 10 乳酸 3 3 3 0 0 0 ミリスチン酸 86 86.9 82 89 89.9 85 イソプロピル 比 較 比 較 比 較 比 較 組成物 組成物 組成物 組成物 ４ ５ ６ ７ 塩酸モルヒネ 1 0 0 0 フマル酸 0 0.1 0 0 ケトチフェン リドカイン 0 0 5 0 ジクロフェナック 0 0 0 1 ナトリウム エタノール 0 0 0 10 乳酸 3 3 3 3 ミリスチン酸 96 96.9 92 86 イソプロピル 単位（ｇ） ヘアレスラット腹部摘出皮膚を横型拡散セル（有効透過
面積１ｃｍ2 ）に挟み、真皮側セルに水２．５ｍｌを入
れ、そして３７℃で攪拌しながら、角質層側に各組成物
を液剤として２．５ｇ入れた。経時的に真皮側に移行し
た薬物の累積透過量を測定した。結果を表２に示す。Table 1 Present Invention Present Invention Comparative Comparison Comparative Comparison Composition Composition Composition Composition Composition Composition 1 2 3 1 2 3 Morphine Hydrochloride 1 0 0 1 0 0 Fumaric Acid 0 0.1 0 0 0.1 0 Ketotifen Lidocaine 0 0 5 0 0 5 Diclofenac 0 0 0 0 0 0 Sodium Ethanol 10 10 10 10 10 10 Lactic acid 3 3 3 0 0 0 Myristic acid 86 86.9 82 89 89.9 85 Isopropyl ratio Comparative ratio Comparative composition Composition Composition Composition 4 5 6 7 Morphine Hydrochloride 1 0 0 0 Fumarate 0 0.1 0 0 Ketotifen Lidocaine 0 0 5 0 Diclofenac 0 0 0 1 Sodium Ethanol 0 0 0 10 Lactic acid 3 3 3 3 Myristic acid 96 96.9 92 86 Isopropyl unit (g) The hairless rat abdominal excised skin was sandwiched between horizontal diffusion cells (effective permeation area 1 cm 2 ), 2.5 ml of water was placed in the dermis side cell, and each composition was applied to the stratum corneum side while stirring at 37 ° C. Was added as a liquid agent. The cumulative amount of permeation of the drug transferred to the dermis side over time was measured. The results are shown in Table 2.
【００１８】 表２ 累積透過量* （μｇ／ｃｍ2 ） 本発明 本発明 本発明 比 較 比 較 比 較 組成物 組成物 組成物 組成物 組成物 組成物 時間 １ ２ ３ １ ２ ３ １ 105 85 130 12 10 19 ２ 501 332 652 26 32 45 ４ 823 595 996 40 162 98 ６ 1230 740 1352 84 299 126 ８ 1762 846 1892 123 536 166 比 較 比 較 比 較 比 較 組成物 組成物 組成物 組成物 時間 ４ ５ ６ ７ １ 2 1 5 1 ２ 5 3 11 2 ４ 12 9 23 3 ６ 18 14 34 4 ８ 26 23 47 5*) 塩を適用した場合の透過量は、透過した遊離塩基もし
くは遊離酸の量を、適用した塩の量に換算した値であ
る。Table 2 Cumulative Permeation Amount * (μg / cm 2 ) Present Invention Present Invention Present invention Comparative Comparison Comparative Composition Composition Composition Composition Composition Composition Time 1 2 3 1 2 3 1 105 85 130 12 10 19 2 501 332 652 26 32 45 4 4 823 595 996 40 162 98 6 1230 740 1352 84 299 126 818 762 846 1892 123 536 166 Comparative comparison Comparative composition Composition Comparative composition Time 45 6 7 1 2 1 5 1 2 5 3 11 2 4 12 9 23 3 6 18 14 34 4 8 26 23 47 5 *) Permeation amount when salt is applied is the amount of permeated free base or free acid. It is a value converted into the amount of applied salt.
【００１９】表２に示される結果から明らかなように、
エタノール、乳酸およびミリスチン酸イソプロピルを含
む本発明組成物１〜３は、エタノールまたは乳酸のいず
れかを含まない比較組成物１〜６よりも優れた、塩基性
薬物の皮膚透過促進作用を示すことがわかる。また、エ
タノール、乳酸およびミリスチン酸イソプロピルを併用
しても、薬物が酸性薬物の塩であるジクロフェナックナ
トリウムの場合には、比較組成物７で示されるように、
皮膚透過作用が全く促進されないこともわかる。As is clear from the results shown in Table 2,
Compositions 1 to 3 of the present invention containing ethanol, lactic acid and isopropyl myristate may exhibit a skin permeation promoting effect of a basic drug superior to comparative compositions 1 to 6 containing no ethanol or lactic acid. Recognize. Even when ethanol, lactic acid, and isopropyl myristate are used in combination, when the drug is diclofenac sodium, which is a salt of an acidic drug, as shown in Comparative Composition 7,
It can also be seen that the skin penetration effect is not promoted at all.
【００２０】実施例２ 表３に示される組成を有する経皮吸収製剤用組成物を、
実施例１と同様に調製した。Example 2 A composition for percutaneous absorption preparation having the composition shown in Table 3 was prepared.
Prepared as in Example 1.
【００２１】 表３ 本発明組成物１ 本発明組成物４ 塩酸モルヒネ 1 0 エタノール 10 10 乳酸 3 0 酢酸 0 3 ミリスチン酸イソプロピル 86 86 単位（ｇ） ヘアレスラット腹部摘出皮膚を横型拡散セル（有効透過
面積１ｃｍ2 ）に挟み、真皮側セルに水２．５ｍｌを入
れそして３７℃で攪拌しながら、角質層側に各組成物を
液剤として０．２ｇ入れた。経時的に真皮側に移行した
モルヒネの累積透過量を測定した。結果を表４に示す。Table 3 Inventive Composition 1 Inventive Composition 4 Morphine Hydrochloride 10 Ethanol 10 10 Lactic Acid 30 Acetic Acid 0 3 Isopropyl myristate 86 86 Units (g) Hairless rats Abdominal excised skin was placed in a horizontal diffusion cell (effective permeation area). sandwiched 1 cm 2), with stirring at put and 37 ° C. water 2.5ml dermal side cell, each composition was placed 0.2g as a solution to the stratum corneum side. The cumulative amount of permeation of morphine that migrated to the dermis side with time was measured. The results are shown in Table 4.
【００２２】 表４ 累積透過量* （μｇ／ｃｍ2 ） 時間 本発明組成物１ 本発明組成物４ １ 83 85 ２ 332 366 ４ 668 711 ６ 965 1002 ８ 1123 1199*) 透過量は、透過したモルヒネの量を、塩酸モルヒネの
量に換算した値である。Table 4 Cumulative Permeation Amount * (μg / cm 2 ) Time Inventive Composition 1 Inventive Composition 4 1 83 85 2 332 366 4 668 711 6 965 1002 8 1123 1199 *) Permeation amount is the amount of permeated morphine. Is the value converted into the amount of morphine hydrochloride.
【００２３】表４に示される結果から明らかなように、
有機酸として酢酸を用いた場合にも、乳酸を用いた場合
と同様の優れた、塩基性薬物の皮膚透過促進作用を示す
ことがわかる。As is clear from the results shown in Table 4,
It can be seen that when acetic acid is used as the organic acid, the same basic permeation-promoting action of the basic drug as in the case of using lactic acid is exhibited.
【００２４】[0024]
【発明の効果】以上述べた説明から明らかなように、本
発明によれば、塩基性薬物の薬効をもたらす遊離塩基の
高い皮膚透過性を示す、塩基性薬物またはその塩の経皮
吸収製剤用組成物および経皮吸収製剤が提供される。EFFECTS OF THE INVENTION As is clear from the above description, according to the present invention, a percutaneous absorption preparation of a basic drug or a salt thereof, which shows a high skin permeability of a free base which brings about the efficacy of the basic drug. Compositions and transdermal formulations are provided.
Claims (2)
〜５のアルコール、炭素原子数２〜５の有機酸および炭
素原子数１６〜２０のカルボン酸エステルを含有するこ
とを特徴とする、経皮吸収製剤用組成物。1. A basic drug or a salt thereof, having 2 carbon atoms.
A composition for percutaneous absorption preparation, which contains an alcohol having 5 to 5 carbon atoms, an organic acid having 2 to 5 carbon atoms and a carboxylic acid ester having 16 to 20 carbon atoms.
〜５のアルコール、炭素原子数２〜５の有機酸および炭
素原子数１６〜２０のカルボン酸エステルを含有する経
皮吸収製剤用組成物から製剤されることを特徴とする、
経皮吸収製剤。2. A basic drug or a salt thereof, having 2 carbon atoms.
~ 5 alcohol, an organic acid having 2 to 5 carbon atoms, and a carboxylic acid ester having 16 to 20 carbon atoms are prepared from a composition for percutaneous absorption preparation,
Percutaneous absorption preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20156692A JPH0640947A (en) | 1992-07-28 | 1992-07-28 | Composition for percutaneous absorption preparation and percutaneous absorption preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20156692A JPH0640947A (en) | 1992-07-28 | 1992-07-28 | Composition for percutaneous absorption preparation and percutaneous absorption preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0640947A true JPH0640947A (en) | 1994-02-15 |
Family
ID=16443186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20156692A Pending JPH0640947A (en) | 1992-07-28 | 1992-07-28 | Composition for percutaneous absorption preparation and percutaneous absorption preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0640947A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995024197A1 (en) * | 1994-03-11 | 1995-09-14 | Sekisui Chemical Co., Ltd. | Percutaneously absorbable plaster comprising acid-addition salt of morphine |
| JPH07267862A (en) * | 1994-03-29 | 1995-10-17 | Sekisui Chem Co Ltd | Transdermal patch |
| WO1997042952A1 (en) * | 1996-05-13 | 1997-11-20 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneous tape preparation containing fentanyl |
| WO1998016212A1 (en) * | 1996-10-14 | 1998-04-23 | Kowa Company, Ltd. | Local anesthetic for external use |
| WO2000061120A1 (en) * | 1999-04-13 | 2000-10-19 | Hisamitsu Pharmaceutical Co., Inc. | Preparations for percutaneous absorption |
| JP2002534460A (en) * | 1999-01-14 | 2002-10-15 | エルテーエス ローマン テラピー−ジステーメ アーゲー | Percutaneous absorption therapy system using self-adhesive substrate containing organic acid addition salt of morphine or morphinan type alkaloid |
| WO2009066457A1 (en) | 2007-11-22 | 2009-05-28 | Medrx Co., Ltd. | External preparation composition comprising fatty acid-based ionic liquid as active ingredient |
| JPWO2009060629A1 (en) * | 2007-11-11 | 2011-03-17 | 株式会社 メドレックス | Lidocaine tape |
| WO2011074567A1 (en) * | 2009-12-15 | 2011-06-23 | 帝國製薬株式会社 | Transdermal preparation containing basic anti-inflammatory agent |
| JP5780961B2 (en) * | 2009-09-07 | 2015-09-16 | ニプロパッチ株式会社 | Transdermal preparation |
-
1992
- 1992-07-28 JP JP20156692A patent/JPH0640947A/en active Pending
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995024197A1 (en) * | 1994-03-11 | 1995-09-14 | Sekisui Chemical Co., Ltd. | Percutaneously absorbable plaster comprising acid-addition salt of morphine |
| JPH07267862A (en) * | 1994-03-29 | 1995-10-17 | Sekisui Chem Co Ltd | Transdermal patch |
| WO1997042952A1 (en) * | 1996-05-13 | 1997-11-20 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneous tape preparation containing fentanyl |
| WO1998016212A1 (en) * | 1996-10-14 | 1998-04-23 | Kowa Company, Ltd. | Local anesthetic for external use |
| LT4585B (en) | 1996-10-14 | 1999-12-27 | Kowa Company, Ltd. | Local anesthetic for external use |
| US6429228B1 (en) | 1996-10-14 | 2002-08-06 | Kowa Company, Ltd. | Local anesthetic for external use |
| JP2002534460A (en) * | 1999-01-14 | 2002-10-15 | エルテーエス ローマン テラピー−ジステーメ アーゲー | Percutaneous absorption therapy system using self-adhesive substrate containing organic acid addition salt of morphine or morphinan type alkaloid |
| AU778011B2 (en) * | 1999-04-13 | 2004-11-11 | Hisamitsu Pharmaceutical Co. Inc. | Preparations for percutaneous absorption |
| WO2000061120A1 (en) * | 1999-04-13 | 2000-10-19 | Hisamitsu Pharmaceutical Co., Inc. | Preparations for percutaneous absorption |
| US7504114B1 (en) | 1999-04-13 | 2009-03-17 | Hisamitsu Pharmaceuticals | Preparations for percutaneous absorption |
| JP4643018B2 (en) * | 1999-04-13 | 2011-03-02 | 久光製薬株式会社 | Transdermal preparation |
| JPWO2009060629A1 (en) * | 2007-11-11 | 2011-03-17 | 株式会社 メドレックス | Lidocaine tape |
| EP2210599A4 (en) * | 2007-11-11 | 2012-12-19 | Medrx Co Ltd | PREPARATION OF LIDOCAINE BANDAGE |
| US8722065B2 (en) | 2007-11-11 | 2014-05-13 | Medrx Co., Ltd. | Lidocaine tape preparation |
| WO2009066457A1 (en) | 2007-11-22 | 2009-05-28 | Medrx Co., Ltd. | External preparation composition comprising fatty acid-based ionic liquid as active ingredient |
| EP3011954A1 (en) | 2007-11-22 | 2016-04-27 | Medrx Co., Ltd. | External preparation composition comprising fatty acid-based ionic liquid as active ingredient |
| JP5780961B2 (en) * | 2009-09-07 | 2015-09-16 | ニプロパッチ株式会社 | Transdermal preparation |
| US9168232B2 (en) | 2009-09-07 | 2015-10-27 | Nipro Patch Co., Ltd. | Transdermally absorbable preparation |
| WO2011074567A1 (en) * | 2009-12-15 | 2011-06-23 | 帝國製薬株式会社 | Transdermal preparation containing basic anti-inflammatory agent |
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