JP2001002591A - Percutaneous absorbefacient - Google Patents
Percutaneous absorbefacientInfo
- Publication number
- JP2001002591A JP2001002591A JP11175222A JP17522299A JP2001002591A JP 2001002591 A JP2001002591 A JP 2001002591A JP 11175222 A JP11175222 A JP 11175222A JP 17522299 A JP17522299 A JP 17522299A JP 2001002591 A JP2001002591 A JP 2001002591A
- Authority
- JP
- Japan
- Prior art keywords
- alkylene oxide
- absorption enhancer
- oxide
- percutaneous
- molecular weight
- 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
- 238000010521 absorption reaction Methods 0.000 claims abstract description 30
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 17
- 239000004721 Polyphenylene oxide Substances 0.000 claims abstract description 12
- 229920000570 polyether Polymers 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 229920001577 copolymer Polymers 0.000 claims abstract description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229920001400 block copolymer Polymers 0.000 claims abstract description 4
- 239000003623 enhancer Substances 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 230000017531 blood circulation Effects 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 8
- 230000001965 increasing effect Effects 0.000 abstract description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 235000019256 formaldehyde Nutrition 0.000 abstract 1
- 229920000642 polymer Polymers 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 7
- 210000002615 epidermis Anatomy 0.000 description 5
- 210000004207 dermis Anatomy 0.000 description 4
- 230000008326 skin blood flow Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は経皮吸収促進剤に関
し、詳しくは、皮膚外用剤として適用した箇所の血行を
促して、前記皮膚外用剤に含まれ経皮投与される薬物の
体内吸収を促進するための経皮吸収促進剤である。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a percutaneous absorption enhancer, and more particularly, it promotes blood circulation at a site applied as an external preparation for skin, and enhances the absorption of a drug contained in the external preparation for skin and administered transdermally. It is a transdermal absorption enhancer for accelerating.
【０００２】[0002]
【従来の技術と発明が解決しようとする課題】皮膚への
薬物投与は古くから行なわれているが、その大部分は皮
膚表面に対する殺菌や局所作用を目的としたものであっ
た。しかし、最近において、制御された速度で長時間
投与が可能である。投与が確実である。肝臓での初
回通過効果が回避できる（代謝を受けにくい）。必要
に応じて投与を中止できる。などの理由から、皮膚は全
身的な薬物治療を目的とした投与部位として注目されて
いる。2. Description of the Related Art Drug administration to the skin has been performed for a long time, but most of them have been aimed at sterilization and local action on the skin surface. However, recently, long-term administration at a controlled rate is possible. Administration is assured. Avoids first-pass effects in the liver (less susceptible to metabolism). Administration can be discontinued if necessary. For such reasons, the skin has been attracting attention as an administration site for systemic drug treatment.
【０００３】そもそも皮膚は、表皮、真皮、皮下組織の
三層からなり、さらに、汗腺や毛嚢といった付属器官が
表皮から真皮までを貫いて存在し、そして真皮側の表皮
側に毛細血管が存在しているので皮膚表面に適用された
薬物が血管系に移行するためには、表皮層、真皮層内を
移動しさらに毛細血管壁を透過しなければならない。ま
た、表皮の最も外側は角質層と呼ばれるケラチンマトリ
ックスで満たされた古い細胞層で覆われ、外部からの物
質侵入に対する強固なバリアーになっている。上記した
実情に鑑み、皮膚（特に角質層）に作用し、そのバリア
ーとしての性質を変えることによって薬物の皮膚透過性
を増大させる機能をもつ経皮吸収促進剤の開発が盛んに
行なわれている。[0003] In the first place, the skin consists of three layers: the epidermis, the dermis, and the subcutaneous tissue. Further, accessory organs such as sweat glands and hair follicles penetrate from the epidermis to the dermis, and capillaries exist on the dermis side of the epidermis. Therefore, in order for the drug applied to the skin surface to move into the vascular system, it must move in the epidermis and dermis and penetrate the capillary wall. The outermost part of the epidermis is covered with an old cell layer filled with a keratin matrix called the stratum corneum, providing a strong barrier to invasion of substances from the outside. In view of the above circumstances, transdermal absorption enhancers that act on the skin (especially the stratum corneum) and increase the skin permeability of drugs by changing their barrier properties have been actively developed. .
【０００４】そこで、本発明者らは、ある特定の化合物
を含有する皮膚外用剤を適用することにより、当該適用
箇所の血流量が増加して薬物の吸収が促進されることを
見い出し、そして本発明に至った。[0004] The present inventors have found that by applying a skin external preparation containing a specific compound, the blood flow at the site of application is increased and the absorption of the drug is promoted. Invented the invention.
【０００５】[0005]
【課題を解決するための手段】請求項１記載の経皮吸収
促進剤は、ポリエーテル化合物を含有する経皮吸収促進
剤であって、前記ポリエーテル化合物が、エチレンオキ
サイドと、炭素数４以上のアルキレンオキサイドとの共
重合体を主鎖として備え、かつ前記アルキレンオキサイ
ド構造単位の分子量が４００以上であることを特徴とす
る。A transdermal absorption enhancer according to claim 1 is a transdermal absorption enhancer containing a polyether compound, wherein said polyether compound is composed of ethylene oxide and at least 4 carbon atoms. Wherein the copolymer with an alkylene oxide is used as a main chain, and the molecular weight of the alkylene oxide structural unit is 400 or more.
【０００６】請求項２記載の経皮吸収促進剤は、請求項
１に記載の経皮吸収促進剤において、エチレンオキサイ
ド（ＥＯ）と炭素数４以上のアルキレンオキサイド（Ａ
Ｏ）の共重合体が、（ＥＯ）（ＡＯ）（ＥＯ）型のブロ
ック共重合体であることを特徴とする。The percutaneous absorption enhancer according to claim 2 is the same as the percutaneous absorption enhancer according to claim 1, except that ethylene oxide (EO) and alkylene oxide (A) having 4 or more carbon atoms are used.
The copolymer (O) is a (EO) (AO) (EO) type block copolymer.
【０００７】請求項３記載の経皮吸収促進剤は、下記一
般式（１）で表されるポリエーテルを含有することを特
徴とする。[0007] The transdermal absorption enhancer according to claim 3 is characterized by containing a polyether represented by the following general formula (1).
【０００８】[0008]
【化２】 （但し、式中、２ｎは６以上の整数であり、２つのｎは
同じであっても良いし、互いに異なっていても良い、
（ＡＯ）ｍは炭素数４以上のアルキレンオキサイドの繰
り返し単位であって、この単位の分子量は４００以上。)。 請求項４記載の経皮吸収促進剤は、請求項１〜３のいず
れか１項に記載の経皮吸収促進剤において、前記アルキ
レンオキサイドがブチレンオキサイド（ＢＯ）またはテ
トラハイドロフラン（テトラヒドロフラン）であること
を特徴とする。Embedded image (Where 2n is an integer of 6 or more, and two n's may be the same or different from each other;
(AO) m is a repeating unit of an alkylene oxide having 4 or more carbon atoms, and the molecular weight of this unit is 400 or more. ). The transdermal absorption enhancer according to claim 4 is the transdermal absorption enhancer according to any one of claims 1 to 3, wherein the alkylene oxide is butylene oxide (BO) or tetrahydrofuran (tetrahydrofuran). It is characterized by the following.
【０００９】[0009]
【発明の実施の形態】ポリエーテル化合物におけるエチ
レンオキサイド構造（ＥＯ）の繰り返し数（ｎ）として
は特に限定はないが、１分子中に６個以上存在すること
が好適である。５個未満の場合、本発明の十分な効果が
得られないという問題が生じる可能性がある。なお、
（ＥＯ）（ＡＯ）（ＥＯ）型のブロック共重合体である
場合において、一方の（ＥＯ）と他方の（ＥＯ）の数は
同じであってよく、異なっていてもよいが、その合計が
６個以上存在していることが好適である。BEST MODE FOR CARRYING OUT THE INVENTION The number of repetitions (n) of an ethylene oxide structure (EO) in a polyether compound is not particularly limited, but it is preferable that six or more are present in one molecule. If the number is less than 5, there is a possibility that a problem that a sufficient effect of the present invention cannot be obtained may occur. In addition,
In the case of the (EO) (AO) (EO) type block copolymer, the number of one (EO) and the other (EO) may be the same or different, but the total is Preferably, there are six or more.
【００１０】また、炭素数４以上のアルキレンオキサイ
ドとしては、例えばブチレンオキサイド（ＢＯ）、テト
ラハイドロフランなどが挙げられる。その繰返し数とし
ては特に限定はないが、当該アルキレンオキサイド構造
単位の分子量が４００以上となるようにする必要があ
る。この分子量が４００未満であれば、適用箇所の血流
量を充分に増加させることができない。なお、好ましく
は６００以上である。The alkylene oxide having 4 or more carbon atoms includes, for example, butylene oxide (BO), tetrahydrofuran and the like. The number of repetitions is not particularly limited, but it is necessary that the molecular weight of the alkylene oxide structural unit be 400 or more. If the molecular weight is less than 400, the blood flow at the application site cannot be sufficiently increased. In addition, it is preferably 600 or more.
【００１１】また、ポリエーテル化合物の１分子内にお
いて、前記アルキレンオキサイド構造単位が、２つのエ
チレンオキサイド構造単位に間に存することが、血流量
増加の点で好適である。In one molecule of the polyether compound, it is preferable that the alkylene oxide structural unit exists between two ethylene oxide structural units from the viewpoint of increasing blood flow.
【００１２】本発明の経皮吸収促進剤の有効成分である
ポリエーテル化合物の数平均分子量としては、本発明の
効果が顕著に得られるという点で、７００〜６，０００
であることが好ましく、７００〜４，０００であること
がさらに好ましい。The number average molecular weight of the polyether compound which is an active ingredient of the percutaneous absorption enhancer of the present invention is 700 to 6,000 in that the effect of the present invention is remarkably obtained.
, And more preferably 700 to 4,000.
【００１３】経皮吸収促進剤と併用する薬効成分として
は、通常の皮膚外用剤に使用されるものであれば特に限
定はなく、例えば鎮痛消炎剤、副腎皮質ホルモンなどの
ホルモン剤、抗ヒスタミン剤、抗狭心症剤、催眠鎮静
剤、抗真菌剤等が挙げられる。また、剤形としては軟膏
剤、クリーム剤、パップ剤、テープ剤、ローション剤、
パッチ剤等が挙げられる。The medicinal component used in combination with the percutaneous absorption enhancer is not particularly limited as long as it is used in ordinary skin external preparations. For example, hormone agents such as analgesic anti-inflammatory agents, corticosteroids, antihistamines, antihistamines, Angina pectoris, hypnotic sedatives, antifungals and the like. Ointments, creams, cataplasms, tapes, lotions,
Patches and the like can be mentioned.
【００１４】これらの薬効成分は、本発明の経皮吸収促
進剤中に混合して用いて皮膚に適用することにより、速
やかに、かつ効率よく皮膚に吸収される。しかも、経皮
吸収促進剤自身は皮膚への透過浸透性が少ない。また、
パップ剤、テープ剤に適応した場合において、当該経皮
吸収促進剤を混合することにより、貼り付け部位への優
れた密着性を発揮するとともに、剥離時の痛みや角質損
傷を抑える物性にも優れた性能を発揮する。These medicinal components are absorbed into the skin promptly and efficiently by being mixed with the transdermal absorption enhancer of the present invention and applied to the skin. In addition, the percutaneous absorption enhancer itself has low permeability to the skin. Also,
When applied to cataplasms and tapes, by mixing the percutaneous absorption enhancer, it exhibits excellent adhesion to the application site and has excellent physical properties to suppress pain and exfoliation damage when peeling. Demonstrated performance.
【００１５】本発明の経皮吸収促進剤において、ポリエ
ーテル化合物１重量部に対する薬効成分の配合割合とし
ては、使用する薬剤の種類や剤形によって変わるので一
概には言えないが、およそのところ０．０１〜４０重量
部である。In the percutaneous absorption enhancer of the present invention, the ratio of the pharmaceutically active ingredient to 1 part by weight of the polyether compound cannot be unconditionally determined because it varies depending on the kind and dosage form of the drug to be used. 0.01 to 40 parts by weight.
【００１６】また、皮膚外用剤全量中の経皮吸収促進剤
の含有割合としては、およそのところ３〜１０重量％で
ある。The content of the transdermal absorption enhancer in the total amount of the external preparation for skin is about 3 to 10% by weight.
【００１７】[0017]
【実施例】実施例、及び比較例 下記［表１］に示すローション製剤（実施例、比較例）
を調製して経皮吸収促進剤を得た。 Examples and Comparative Examples Lotion preparations shown in Table 1 below (Examples and Comparative Examples)
Was prepared to obtain a transdermal absorption enhancer.
【００１８】[0018]
【表１】 [Table 1]
【００１９】皮膚血流量試験法を下記に示す方法で実施
し、経皮吸収促進効果を血流量増加作用の程度から判定
した。The skin blood flow test was carried out in the following manner, and the effect of promoting percutaneous absorption was determined from the degree of blood flow increasing effect.
【００２０】（皮膚血流量試験方法）２５歳〜４０歳の
健康な成人３０人を対象にし、安静時、対象者の腕部の
皮膚血流量の値を血流計により測定した。続いて、皮膚
血流量を測定した腕部に試料溶液を均一に塗布し、血流
量の経時的変化を測定した。(Skin Blood Flow Test Method) The skin blood flow in the arm of the subject was measured using a blood flow meter at rest in 30 healthy adults 25 to 40 years old. Subsequently, the sample solution was uniformly applied to the arm part where the skin blood flow was measured, and the change over time in the blood flow was measured.
【００２１】試料塗布前の血流量（Ｘ）（単位：ｍＶ）
と試料塗布後、一定時間後の血流量（Ｙ）（単位：ｍ
Ｖ）を測定し、次の式によって血流増加率を算出した。Blood flow before application of sample (X) (unit: mV)
And blood flow (Y) after a certain time after sample application (unit: m)
V) was measured, and the blood flow increase rate was calculated by the following equation.
【００２２】[0022]
【数１】 (Equation 1)
【００２３】上記測定により得た血流増加率の経時変化
を図１に示す。図１から明らかなように、本発明の経皮
吸収促進剤を含有する試料溶液を使用することで血流量
は増加した。FIG. 1 shows the change over time in the blood flow increase rate obtained by the above measurement. As is clear from FIG. 1, the blood flow increased by using the sample solution containing the transdermal absorption enhancer of the present invention.
【００２４】[0024]
【発明の効果】本発明の経皮吸収促進剤は、これを皮膚
外用剤に含ませることによって適用箇所の血流量を増加
せしめ、延いては当該薬剤の経皮吸収率を向上させるこ
とができる。The percutaneous absorption enhancer of the present invention can increase the blood flow rate at the application site by including it in the external preparation for skin, and can further improve the percutaneous absorption rate of the drug. .
【図１】血流量の経時的増加を示すグラフ図である。FIG. 1 is a graph showing an increase in blood flow over time.
Claims (4)
進剤であって、 前記ポリエーテル化合物が、エチレンオキサイドと、炭
素数４以上のアルキレンオキサイドとの共重合体を主鎖
として備え、かつ前記アルキレンオキサイド構造単位の
分子量が４００以上であることを特徴とする経皮吸収促
進剤。A percutaneous absorption enhancer containing a polyether compound, wherein the polyether compound has, as a main chain, a copolymer of ethylene oxide and an alkylene oxide having 4 or more carbon atoms, and A transdermal absorption enhancer, wherein the molecular weight of the alkylene oxide structural unit is 400 or more.
上のアルキレンオキサイド（ＡＯ）の共重合体が、（Ｅ
Ｏ）（ＡＯ）（ＥＯ）型のブロック共重合体であること
を特徴とする請求項１に記載の経皮吸収促進剤。2. The copolymer of ethylene oxide (EO) and an alkylene oxide (AO) having 4 or more carbon atoms is (E)
The percutaneous absorption enhancer according to claim 1, which is a block copolymer of the type O) (AO) (EO).
を含有することを特徴とする経皮吸収促進剤。 【化１】 （但し、式中、２ｎは６以上の整数であり、２つのｎは
同じであっても良いし、互いに異なっていても良い、
（ＡＯ）ｍは炭素数４以上のアルキレンオキサイドの繰
り返し単位であって、この単位の分子量は４００以上。)3. A transdermal absorption enhancer containing a polyether represented by the following general formula (1). Embedded image (Where 2n is an integer of 6 or more, and two n's may be the same or different from each other;
(AO) m is a repeating unit of an alkylene oxide having 4 or more carbon atoms, and the molecular weight of this unit is 400 or more. )
キサイド（ＢＯ）またはテトラハイドロフランであるこ
とを特徴とする請求項１〜３のいずれか１項に記載の経
皮吸収促進剤。4. The transdermal absorption enhancer according to claim 1, wherein the alkylene oxide is butylene oxide (BO) or tetrahydrofuran.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11175222A JP2001002591A (en) | 1999-06-22 | 1999-06-22 | Percutaneous absorbefacient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11175222A JP2001002591A (en) | 1999-06-22 | 1999-06-22 | Percutaneous absorbefacient |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001002591A true JP2001002591A (en) | 2001-01-09 |
Family
ID=15992435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11175222A Pending JP2001002591A (en) | 1999-06-22 | 1999-06-22 | Percutaneous absorbefacient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001002591A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006038724A1 (en) * | 2004-10-06 | 2006-04-13 | Nof Corporation | Cosmetic bases and cosmetics containing the same |
| WO2007136067A1 (en) * | 2006-05-23 | 2007-11-29 | Shiseido Company Ltd. | External preparation for skin |
-
1999
- 1999-06-22 JP JP11175222A patent/JP2001002591A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006038724A1 (en) * | 2004-10-06 | 2006-04-13 | Nof Corporation | Cosmetic bases and cosmetics containing the same |
| JPWO2006038724A1 (en) * | 2004-10-06 | 2008-05-15 | 日油株式会社 | Cosmetic base and cosmetic comprising the same |
| CN100508939C (en) * | 2004-10-06 | 2009-07-08 | 日油株式会社 | Cosmetic substrate and cosmetics containing the same |
| JP4736134B2 (en) * | 2004-10-06 | 2011-07-27 | 日油株式会社 | Cosmetic base and cosmetic comprising the same |
| US9193654B2 (en) | 2004-10-06 | 2015-11-24 | Nof Corporation | Cosmetic bases and cosmetics containing the same |
| WO2007136067A1 (en) * | 2006-05-23 | 2007-11-29 | Shiseido Company Ltd. | External preparation for skin |
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