JPS61225122A - Composition containing quinazoline compound - Google Patents
Composition containing quinazoline compoundInfo
- Publication number
- JPS61225122A JPS61225122A JP6500485A JP6500485A JPS61225122A JP S61225122 A JPS61225122 A JP S61225122A JP 6500485 A JP6500485 A JP 6500485A JP 6500485 A JP6500485 A JP 6500485A JP S61225122 A JPS61225122 A JP S61225122A
- Authority
- JP
- Japan
- Prior art keywords
- lecithin
- compound
- absorption
- sample
- results
- 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 19
- -1 quinazoline compound Chemical class 0.000 title claims abstract description 7
- 239000000787 lecithin Substances 0.000 claims abstract description 24
- 235000010445 lecithin Nutrition 0.000 claims abstract description 24
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 22
- 229940067606 lecithin Drugs 0.000 claims abstract description 22
- 238000010521 absorption reaction Methods 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 230000007704 transition Effects 0.000 claims abstract description 9
- IUGQFMIATSVYLK-UHFFFAOYSA-N benzyl 2-(4-hydroxyphenyl)acetate Chemical compound C1=CC(O)=CC=C1CC(=O)OCC1=CC=CC=C1 IUGQFMIATSVYLK-UHFFFAOYSA-N 0.000 claims description 5
- 229960003612 bunazosin hydrochloride Drugs 0.000 claims description 5
- 230000037384 skin absorption Effects 0.000 claims description 4
- 231100000274 skin absorption Toxicity 0.000 claims description 4
- WFXFYZULCQKPIP-UHFFFAOYSA-N prazosin hydrochloride Chemical compound [H+].[Cl-].N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 WFXFYZULCQKPIP-UHFFFAOYSA-N 0.000 claims description 3
- 229960002386 prazosin hydrochloride Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 5
- 230000001737 promoting effect Effects 0.000 abstract description 4
- 239000000829 suppository Substances 0.000 abstract description 4
- 244000068988 Glycine max Species 0.000 abstract description 2
- 235000010469 Glycine max Nutrition 0.000 abstract description 2
- 206010020772 Hypertension Diseases 0.000 abstract description 2
- 239000002674 ointment Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 16
- 239000012528 membrane Substances 0.000 description 10
- 150000003904 phospholipids Chemical class 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000008280 blood Substances 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000013068 control sample Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- RHLJLALHBZGAFM-UHFFFAOYSA-N Bunazosinum Chemical compound C1CN(C(=O)CCC)CCCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 RHLJLALHBZGAFM-UHFFFAOYSA-N 0.000 description 6
- 229960002467 bunazosin Drugs 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229960001289 prazosin Drugs 0.000 description 4
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 3
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 150000003246 quinazolines Chemical class 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- JEYCTXHKTXCGPB-UHFFFAOYSA-N Methaqualone Chemical compound CC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C JEYCTXHKTXCGPB-UHFFFAOYSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000002315 glycerophosphates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229960002803 methaqualone Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 229940070673 prazosin 5 mg Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 本発明は、キナツオリン系化合物含有組成物に関する。[Detailed description of the invention] The present invention relates to a composition containing a quinatuolin compound.
さらに詳しくはギナッオリン系化合物の吸収促進を目的
とするキナツオリン系化合物含有組成物に関する。More specifically, the present invention relates to a composition containing a quinazoline compound for the purpose of promoting absorption of the quinazoline compound.
医薬品の分野においてキナツオリン系化合物には有用な
物質があり１例えば高血圧治療剤としてのプラゾシンあ
るいは催眠剤としてのメタカロン等を挙げることができ
る。通常これらの物質は経口によって投与され腸管より
吸収されて所定の血中濃度を示すに至っている。しかし
ながらこれらの物質が直接に皮１ｔ’ｈに投与され皮膚
吸収によって所定の血中濃度を示すに至ったり、あるい
は直腸に投与され直腸吸収によって所定の血中濃度を示
すに至ることができるならば、キナツオリン系化合物を
より安全に使用することができる。In the pharmaceutical field, quinatuolin compounds are useful substances, such as prazosin as a therapeutic agent for hypertension and methaqualone as a hypnotic agent. Usually, these substances are administered orally and absorbed through the intestinal tract to reach a predetermined blood concentration. However, if these substances can be administered directly to the skin and reach a specified blood concentration through skin absorption, or if they are administered to the rectum and can reach a specified blood concentration through rectal absorption. , quinatuolin-based compounds can be used more safely.
本発明者は、キナツオリン系化合物、とりわけ高血圧治
療剤としてのキナツオリン系化合物の安全な使用を目的
として該化合物の皮膚投与および直腸投与を中心に該化
合物の吸収について研究をおこなってきた。その結果、
該化合物はレシチンと共に投与された場合に吸収が促進
されることを見出し２本発明を完成するに至った。The present inventors have conducted research on the absorption of quinatuolin compounds, particularly through dermal and rectal administration of the compounds, with the aim of safe use of quinatuolin compounds, particularly as antihypertensive agents. the result,
The inventors discovered that the absorption of this compound is promoted when it is administered together with lecithin, leading to the completion of the present invention.
すなわち２本発明の目的はギナツォリン系化合物の吸収
促進であり２本発明は該目的の達成のために、レシチン
を必須成分とすることを特徴とするキナツオリン系化合
物含有組成物を開示する。That is, the object of the present invention is to promote the absorption of guinazoline compounds, and in order to achieve the object, the present invention discloses a composition containing a quinazoline compound characterized in that it contains lecithin as an essential component.
医薬品の分野において薬剤の作用を有効に発現させるた
めにレシチンを添加する技術は従来から知られている。In the field of pharmaceuticals, techniques for adding lecithin to effectively express the effects of drugs have been known.
例えば特開昭５６−１３５４１６． 同５８−１５０
５０８ 、同５５−４７６０８．同５７−７５９１６に
係る発明に見られること（である。しかしながらキナツ
オリン系化合物においてレシチンを添加することによっ
て吸収が大幅に増大することは知られていなかった。す
なわち、ギナツォリン系化合物にレシチンを添加するこ
と、特に相転移温度が３７℃以下のレシチンを添加する
ことは新規であり、従来知見から想到することのできな
い技術であり、その効果は予見することのできない効果
である。For example, JP-A-56-135416. 58-150
508, 55-47608. What is seen in the invention related to No. 57-75916 (However, it was not known that adding lecithin to quinazoline compounds greatly increases absorption. In other words, adding lecithin to quinazoline compounds In particular, the addition of lecithin having a phase transition temperature of 37° C. or lower is new, a technique that could not be imagined based on conventional knowledge, and its effects are unpredictable.
以下に本発明の詳細な説明する。The present invention will be explained in detail below.
本発明においてギナツオリン系化合物とは、ギナツオリ
ン骨格を有する化合物であるが、特に医薬品分野におい
て重要なものは高血圧治療剤であり、その代表例はそれ
ぞれ下記４１１４造式で示されるプラゾシンおよびブナ
ゾシンである。In the present invention, a guinatuolin-based compound is a compound having a guinatuolin skeleton, and those that are particularly important in the pharmaceutical field are antihypertensive agents, representative examples of which are prazosin and bunazosin, each represented by the following formula 4114.
これらの物質は一般に塩酸塩として入手される。These substances are generally available as hydrochloride salts.
従ってこれらの物質の塩酸塩を使用することは本発明の
具体的な実施態様である。The use of the hydrochloride salts of these substances is therefore a specific embodiment of the invention.
本発明に係るレシチンは卵黄あるいは大豆等から抽出さ
れ、場合によってはさらに精製されたリン脂質含有物ま
たはその水素添加物あるいは合成グリセロリン酸エステ
ル等を使用することができる。レシチンのうち特に相転
移温度が３７℃以下のレシチンが好ましい。ここで相転
移温度とは固相から液相に転移する際の温度であり、レ
シチンにおいてはレシチンの炭化水素部分の炭素数およ
び不飽和度によって定まる。後記実験例によれば。The lecithin according to the present invention is extracted from egg yolk or soybean, and in some cases, further purified phospholipid-containing substances, hydrogenated products thereof, or synthetic glycerophosphate esters can be used. Among lecithins, lecithins having a phase transition temperature of 37° C. or lower are particularly preferred. Here, the phase transition temperature is the temperature at which the solid phase transitions to the liquid phase, and in lecithin, it is determined by the number of carbon atoms and the degree of unsaturation of the hydrocarbon moiety of lecithin. According to the experimental example described later.
炭化水素部分が飽和しているレシチンについて検討をお
こなったところ炭化水素部分の炭素数が少ないほど薬剤
の膜透過速度は大きくなり、従って吸収が促進されるこ
とが判明した。当該実験例の結果から相転移温度が３７
℃以下のレシチンが使用される場合に好ましい実施態様
が得られることが知られた。A study of lecithin in which the hydrocarbon moiety is saturated revealed that the lower the number of carbon atoms in the hydrocarbon moiety, the higher the membrane permeation rate of the drug, and therefore the absorption is promoted. From the results of this experimental example, the phase transition temperature is 37
It has been found that preferred embodiments are obtained when lecithin below 0.degree. C. is used.
本発明組成物はキナツオリン系化合物が膜透過によって
吸収される製剤形態の組成物であれば特に限定はない。The composition of the present invention is not particularly limited as long as it is a composition in the form of a preparation in which the quinatuolin compound is absorbed through membrane permeation.
しかし皮膚吸収を目的とする投与形態および直腸吸収を
目的とする投与形態は特に好ましい製剤形態であり、従
って軟付剤および坐剤は本発明の好ましい実施態様であ
る。However, dosage forms intended for dermal absorption and dosage forms intended for rectal absorption are particularly preferred formulation forms, and therefore emollients and suppositories are preferred embodiments of the invention.
本発明組成物を製造するために必要な賦形剤等の成分は
任意に選択して添加することができ９本発明はこれらに
よって限定されない。また本発明組成物は選択した製剤
形態に応じて常法に従って製造すればよい。Components such as excipients necessary for producing the composition of the present invention can be arbitrarily selected and added, and the present invention is not limited thereto. Moreover, the composition of the present invention may be manufactured according to a conventional method depending on the selected formulation form.
以下の実施例によって本発明を具体的に説明する。The present invention will be specifically explained by the following examples.
実施例１
塩酸ブナゾシン１０ｇ、卵黄レシチン１５ｇをプロピレ
ングリコール５００ｇに溶解し、皮膚吸収用の本発明薬
液とした。Example 1 10 g of bunazosin hydrochloride and 15 g of egg yolk lecithin were dissolved in 500 g of propylene glycol to prepare a drug solution of the present invention for skin absorption.
実施例２
塩酸ブナゾシン３ＩＩ、卵黄レシチン１５．９をカカオ
脂５００ｇに混和し、直腸吸収用の本発明坐剤とした。Example 2 Bunazosin hydrochloride 3II and egg yolk lecithin 15.9 g were mixed with 500 g of cocoa butter to prepare a suppository of the present invention for rectal absorption.
実施例３
実施例１において塩酸ブナゾシンの代わりに塩酸プラゾ
シンを使用した点を除いて実施例１と同様におこない２
本発明薬液とした。Example 3 The procedure was carried out in the same manner as in Example 1 except that prazosin hydrochloride was used instead of bunazosin hydrochloride in Example 1.
The chemical solution of the present invention was prepared.
以下の実験例をもって本発明の詳細な説明する。The present invention will be explained in detail using the following experimental examples.
実験例１
試料と方法
実施例１の薬液を検体試料とした。別に実施例１におい
て卵黄レシチンを除いた薬液を調製し。Experimental Example 1 Sample and Method The chemical solution of Example 1 was used as a specimen sample. Separately, a drug solution was prepared in Example 1 except that the egg yolk lecithin was removed.
対照試料として用意した。家兎背部を除毛し、−目抜に
検体または対照の各試料を５ｇづつ投与し。This was prepared as a control sample. The hair on the back of the rabbit was removed, and 5 g of each specimen or control sample was randomly administered.
血中のブナゾシン濃度を経時的に測定した。なお。Bunazosin concentration in blood was measured over time. In addition.
定量は蛍光光度法によっておこなった。Quantification was performed by fluorometry.
結果
対照試料については投与後いづれの時間においても血中
ブナゾシン濃度はブナゾシンの定量検出限界以下であっ
た。これに対し検体試料については図１のどと（であっ
た。なお図１はｎ ＝ ３の平均値の結果を示す。図１
より本発明薬液が著しい吸収促進をもたらす効果を発揮
することが判明する。Results Regarding the control sample, the blood bunazosin concentration was below the quantitative detection limit of bunazosin at any time after administration. On the other hand, for the specimen sample, it was (Figure 1). Figure 1 shows the results of the average value of n = 3. Figure 1
It is clear from these results that the drug solution of the present invention exhibits the effect of significantly promoting absorption.
実験例２
試料と方法
実施例２の止剤を検体試料とした。別に実施例２におい
て卵黄レシチンを除いた止剤を調製し。Experimental Example 2 Sample and Method The inhibitor of Example 2 was used as a test sample. Separately, a detergent was prepared in Example 2 except that egg yolk lecithin was removed.
対照試料として用意した。約３００ｇの雄ラットの直腸
に検体または対照の各試料を５００ ＋ｎｇづつ投与し
、血中のブナゾシン濃度を経時的に測定した。This was prepared as a control sample. 500+ng of each test sample or control sample was administered into the rectum of male rats weighing approximately 300 g, and the bunazosin concentration in the blood was measured over time.
なお、定量は蛍光光度法によっておこなった。Note that quantification was performed by fluorescence photometry.
結果
結果を図２に示す。図２はｎ−２の平均値の結果を示す
。図中ｅ印線は検体試料についての結果を、また○印線
は対照試料についての結果を示す。The results are shown in Figure 2. Figure 2 shows the results of the average value of n-2. In the figure, the e-marked line shows the results for the specimen sample, and the ○ mark line shows the results for the control sample.
図２より本発明坐剤が吸収促進をもたらす効果を発揮す
ることが判明する。It is clear from FIG. 2 that the suppository of the present invention exhibits the effect of promoting absorption.
実験例３
試料
塩酸ブナゾシン２０ ｍｇおよび下記表１のリン脂質８
欄に記載のリン脂質５ｎ９をプロピレングリコール０．
５ｇに溶解した薬液を調製し、試料とした。Experimental Example 3 Sample bunazosin hydrochloride 20 mg and phospholipid 8 in Table 1 below
The phospholipid 5n9 described in the column was mixed with propylene glycol 0.
A drug solution dissolved in 5 g was prepared and used as a sample.
表１
方法
ヘアレスマウスより摘出した皮膚を膜透過実験装置に装
着し２表皮側に試料を、また真皮側に水を入れ、水相を
撹拌しなから水相中のブナゾシンを測定し、膜透過速度
を求めた。Table 1 Method: The skin removed from a hairless mouse was attached to a membrane permeation test device, and the sample was placed on the epidermis side and water was placed on the dermis side.The aqueous phase was stirred and bunazosin in the aqueous phase was measured. I found the speed.
結果
結果を図３に示す。図３よりレシチンを構成するリン脂
質の炭化水素部分の炭素数が増加するに従って膜透過速
度は減少し、相転移温度が通常の動物体温である３７℃
を越えるリン脂質を使用する場合には著しく低くなるこ
とが知られる。従って相転移温度が３７℃以下のレシチ
ンが使用されることが好ましいことが判明する。The results are shown in Figure 3. Figure 3 shows that as the number of carbon atoms in the hydrocarbon moiety of the phospholipids that make up lecithin increases, the membrane permeation rate decreases, and the phase transition temperature is 37°C, which is the normal body temperature of animals.
It is known that when using phospholipids exceeding Therefore, it has been found that it is preferable to use lecithin having a phase transition temperature of 37° C. or lower.
実験例４
実験例３の試料においてリン脂質５ ｒｎ９の代わりに
卵黄レシチンを０．１％〜３．０％となるように使用し
た点を除いて実験例３の試料と同様にして試料を用意し
、同実験例の方法と同様にして膜透過速度を求めた。結
果を図４に示す。図４よりレシチン濃度の上昇に伴ない
、一定濃度までは膜透過速度が増大することが判明する
。この一定濃度は組成物中におけるレシチンのミセル形
成濃度と関係があると推定される。従ってレシチンは、
特別な濃度限定をすることなく配合してよいが、実用的
には５％までで十分であると考えられる。Experimental Example 4 A sample was prepared in the same manner as in Experimental Example 3, except that egg yolk lecithin was used at a concentration of 0.1% to 3.0% instead of phospholipid 5 rn9 in the sample of Experimental Example 3. Then, the membrane permeation rate was determined in the same manner as in the same experimental example. The results are shown in Figure 4. It is clear from FIG. 4 that as the lecithin concentration increases, the membrane permeation rate increases up to a certain concentration. It is presumed that this constant concentration is related to the micelle-forming concentration of lecithin in the composition. Therefore, lecithin is
Although it may be blended without any particular concentration limitation, it is considered that up to 5% is practically sufficient.
実験例５
試料と方法
塩酸プラゾシン２０ｍｇおよびリン脂質５ｍｇをプロピ
レングリコール０．５ｇに溶解した薬液を調製し。Experimental Example 5 Sample and Method A drug solution was prepared by dissolving 20 mg of prazosin hydrochloride and 5 mg of phospholipid in 0.5 g of propylene glycol.
検体試料とした。別にリン脂質を配合しない点を除いて
検体試料と同様に調製した薬液を用意し。It was used as a specimen sample. Prepare a drug solution prepared in the same way as the test sample, except that phospholipids are not added.
対照試料とした。実験例３の方法と同様にして膜透過実
験をおこない、プラゾシンの累積透過量の経時的変化を
求めた。This was used as a control sample. A membrane permeation experiment was conducted in the same manner as in Experimental Example 3, and changes over time in the cumulative amount of prazosin permeated were determined.
結果
結果を図５に示す。図中・印線は検体試料についての結
果を、また○印線は対照試料についての結果を示す。図
５よりレシチンを構成するリン脂質がプラゾシンの吸収
のための膜透過を促進することが判明する。The results are shown in FIG. In the figure, the marked lines indicate the results for the specimen sample, and the ○ marked lines indicate the results for the control sample. It is clear from FIG. 5 that the phospholipids constituting lecithin promote membrane permeation for absorption of prazosin.
図１は、実験例１の結果の項に記載の回１であり、皮膚
投与における血中濃度の経時変化を示すグラフである。
図２は実験例２の結果の項に記載の図２であり。
直腸投与における血中濃度の経時変化を示すグラフであ
る。
図３は、実験例３の結果の項に記載の図３であり、リン
脂質の炭化水素部分の炭素数と膜透過速度との関係を示
すグラフである。
図４は、実験例４に記載の図４であり、レシチン濃度と
膜透過速度との関係を示すグラフである。
図５は、実験例５の結果の項に記載の図５であり、薬剤
の累積透過量の経時的変化を示すグラフである。FIG. 1 is Time 1 described in the results section of Experimental Example 1, and is a graph showing the change over time in blood concentration in skin administration. FIG. 2 is the one described in the section of results of Experimental Example 2. It is a graph showing the change in blood concentration over time during rectal administration. FIG. 3 is shown in the section of results of Experimental Example 3, and is a graph showing the relationship between the number of carbon atoms in the hydrocarbon portion of a phospholipid and the membrane permeation rate. FIG. 4 is described in Experimental Example 4, and is a graph showing the relationship between lecithin concentration and membrane permeation rate. FIG. 5 is described in the section of results of Experimental Example 5, and is a graph showing the change over time in the cumulative amount of drug permeation.
Claims (4)
含有組成物(1) Quinatuolin-based compound-containing composition containing lecithin as an essential component
酸ブナゾシンである特許請求の範囲第１項記載のキナツ
オリン系化合物含有組成物(2) The quinazoline compound-containing composition according to claim 1, wherein the quinazoline compound is prazosin hydrochloride or bunazosin hydrochloride.
物である特許請求の範囲第１項または第２項記載のキナ
ツオリン系化合物含有組成物(3) The quinatuolin compound-containing composition according to claim 1 or 2, wherein the composition is a composition for skin absorption or a composition for rectal absorption.
ンである特許請求の範囲第１項乃至第３項記載のキナツ
オリン系化合物含有組成物(4) The quinatuolin compound-containing composition according to claims 1 to 3, wherein the lecithin has a phase transition temperature of 37°C or lower.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6500485A JPS61225122A (en) | 1985-03-30 | 1985-03-30 | Composition containing quinazoline compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6500485A JPS61225122A (en) | 1985-03-30 | 1985-03-30 | Composition containing quinazoline compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61225122A true JPS61225122A (en) | 1986-10-06 |
Family
ID=13274414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6500485A Pending JPS61225122A (en) | 1985-03-30 | 1985-03-30 | Composition containing quinazoline compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61225122A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02131426A (en) * | 1988-11-11 | 1990-05-21 | Sansei Seiyaku Kk | Percutaneous administrative preparation containing bunazosin or its salt |
-
1985
- 1985-03-30 JP JP6500485A patent/JPS61225122A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02131426A (en) * | 1988-11-11 | 1990-05-21 | Sansei Seiyaku Kk | Percutaneous administrative preparation containing bunazosin or its salt |
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