JPH11171794A - Arterial parenteral injection preparation - Google Patents
Arterial parenteral injection preparationInfo
- Publication number
- JPH11171794A JPH11171794A JP9334602A JP33460297A JPH11171794A JP H11171794 A JPH11171794 A JP H11171794A JP 9334602 A JP9334602 A JP 9334602A JP 33460297 A JP33460297 A JP 33460297A JP H11171794 A JPH11171794 A JP H11171794A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- saturated fatty
- drug
- brain
- injection preparation
- 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.)
- Withdrawn
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】この発明は動脈注射製剤、詳
細には薬物を脳の疾患部位に高濃度に送るための動脈に
注射する製剤に関するもので、医療の分野で利用される
ものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a preparation for arterial injection, and more particularly to a preparation for injecting a drug into an artery for delivering a drug to a diseased part of the brain at a high concentration, which is used in the medical field.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】薬物
のなかには抗腫瘍剤や抗痴呆剤のように直接脳の疾患部
位に作用させることによって、脳腫瘍や痴呆に対して高
い薬効をあらわすものがある。そして、これらの薬物は
通常静脈注射や動脈注射によって生体内に投与される
が、血液と脳との間には血液−脳関門（Blood-brain ba
rrier)と呼ばれる障壁が存在し、水溶性の高い薬物や分
子量の大きいポリペプタイドのような薬物は、この障壁
を通過して脳内に移行することが困難であり、十分な薬
効をあげることができない。そのため、血液−脳関門を
通過させてこれらの薬物を高濃度に脳の疾患部位に送り
こめる製剤の開発が必要とされている。2. Description of the Related Art Some drugs, such as antitumor agents and anti-dementia agents, exhibit high efficacy against brain tumors and dementia by directly acting on diseased parts of the brain, such as antitumor agents and anti-dementia agents. . These drugs are usually administered into a living body by intravenous injection or arterial injection, but a blood-brain barrier (Blood-brain barrier) exists between blood and brain.
There is a barrier called rrier), and it is difficult for drugs such as highly water-soluble drugs and high-molecular-weight polypeptides to pass through this barrier and move into the brain. Can not. Therefore, there is a need for the development of preparations that can pass these drugs at high concentrations to diseased parts of the brain by passing through the blood-brain barrier.
【０００３】[0003]
【課題を解決するための手段】この発明の発明者らは鋭
意検討の結果、炭素数１０以上の飽和脂肪酸、その塩ま
たはそのエステルが薬物の血液−脳関門通過を促進し、
注射剤として動脈に投与することにより、薬物を高濃度
に脳の疾患部位に送れることを見出した。Means for Solving the Problems As a result of intensive studies, the inventors of the present invention have found that saturated fatty acids having 10 or more carbon atoms, salts or esters thereof promote the passage of drugs through the blood-brain barrier,
It has been found that a drug can be sent to a diseased part of the brain at a high concentration by administering it to an artery as an injection.
【０００４】この発明の動脈注射製剤は、（ａ）脳の疾
患部位に作用させることにより薬効を発揮する薬物およ
び（ｂ）炭素数１０以上の飽和脂肪酸、その塩またはそ
のエステル（以下、「飽和脂肪酸など」ということもあ
る）を含有するものである。The arterial injection preparation of the present invention comprises (a) a drug which exerts its medicinal properties by acting on a diseased site in the brain and (b) a saturated fatty acid having 10 or more carbon atoms, a salt or ester thereof (hereinafter referred to as "saturated"). Fatty acids, etc. ").
【０００５】この発明に用いられる薬物は、血液−脳関
門を通過させることにより脳の疾患部位に作用させて薬
効を発揮するものであつて、例えば、抗腫瘍剤（例え
ば、５−フルオロウラシル、メトトレキセートなど）、
抗痴呆剤（例えば、メラトニン、神経成長因子など）な
どが挙げられる。この発明の製剤における薬物の含量お
よびその投与量は、薬物の種類や疾患の種類などによっ
て適宜定められる。[0005] The drug used in the present invention is a drug which acts on a diseased part of the brain by passing through the blood-brain barrier and exerts a drug effect. Examples thereof include antitumor agents (eg, 5-fluorouracil, methotrexate). Such),
Anti-dementia agents (eg, melatonin, nerve growth factor, etc.) and the like. The content of the drug and the dose of the drug in the preparation of the present invention are appropriately determined depending on the type of the drug, the type of the disease and the like.
【０００６】この発明に用いられる炭素数１０以上の飽
和脂肪酸としては、例えば、カプリン酸、ウンデシル
酸、ラウリン酸、トリデシル酸、ミリスチン酸、ペンタ
デシル酸、パルミチン酸、ヘプタデシル酸、ステアリン
酸、ノナデカン酸、アラキン酸、ベヘン酸などが挙げら
れる。これらの飽和脂肪酸の中では、上記カプリン酸か
らアラキン酸までの炭素数１０以上２０以下の飽和脂肪
酸が好ましく、カプリン酸およびパルミチン酸がより好
ましい。The saturated fatty acids having 10 or more carbon atoms used in the present invention include, for example, capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, heptadecylic acid, stearic acid, nonadecanoic acid, Arachiic acid, behenic acid and the like can be mentioned. Among these saturated fatty acids, a saturated fatty acid having 10 to 20 carbon atoms from capric acid to arachinic acid is preferable, and capric acid and palmitic acid are more preferable.
【０００７】これらの飽和脂肪酸の塩としては、例え
ば、アルカリ金属塩（例えば、ナトリウム塩、カリウム
塩など）などが挙げられる。これらの飽和脂肪酸のエス
テルとしては、例えば、カルニチンとのエステル（例え
ば、パルミチン酸とカルニチンとのエステルであるパル
ミトイルカルニチンなど）などが挙げられる。The salts of these saturated fatty acids include, for example, alkali metal salts (eg, sodium salt, potassium salt, etc.). Examples of the esters of these saturated fatty acids include esters with carnitine (for example, palmitoyl carnitine, which is an ester of palmitic acid and carnitine).
【０００８】これらの飽和脂肪酸、その塩およびそのエ
ステルは製剤中に０．０１ｍｍｏｌ〜１００ｍｍｏｌ／
ｌ、好ましくは、０．１ｍｍｏｌ〜５０ｍｍｏｌ／ｌ含
有される。[0008] These saturated fatty acids, salts and esters thereof are contained in the preparation in an amount of 0.01 mmol to 100 mmol /
l, preferably 0.1 to 50 mmol / l.
【０００９】この発明の製剤は、前記薬物および飽和脂
肪酸などを、生理食塩水、注射用蒸留水、５％ブドウ糖
液などに溶解して自体公知の方法により製造する。製造
の際、必要に応じてリン酸二水素ナトリウムなどの緩衝
剤、食塩などの等張化剤、パラオキシ安息香酸などの防
腐剤などを加えてもよい。The preparation of the present invention is prepared by dissolving the above-mentioned drug and saturated fatty acid in physiological saline, distilled water for injection, 5% dextrose solution and the like by a method known per se. During production, a buffer such as sodium dihydrogen phosphate, a tonicity agent such as salt, a preservative such as paraoxybenzoic acid, and the like may be added as necessary.
【００１０】[0010]
【発明の効果】このようにして製造されたこの発明の製
剤は、動脈、例えば頚動脈などから生体に注射投与さ
れ、血液−脳関門を通過して脳の疾患部位に大量の薬物
を送り込むことができる。以下に示す試験例により、こ
の発明の動脈注射製剤の効果を説明する。The preparation of the present invention thus produced can be injected into a living body through an artery, for example, a carotid artery, and can deliver a large amount of drug to a diseased site in the brain through the blood-brain barrier. it can. The effects of the arterial injection preparation of the present invention will be described with reference to the following test examples.
【００１１】試験例１ 試験方法 ラット外頚動脈にポリエチレンチューブをタカサト等の
方法に従い挿入する。挿入したチューブより、試験物質
として正常な脳毛細血管を透過することのできないショ
糖を14Ｃで標識した化合物（分子量３４２）、ポリエチ
レングリコール４０００を3Ｈで標識した化合物（分子
量４０００）またはデキストランを蛍光標識したＦＤ−
７０Ｋ（分子量７１２００）と、吸収促進剤としてカプ
リン酸ナトリウムとを溶解した等張の緩衝液（ｐＨ７．
４）を、１ｍｌ／分の速度で５分間かん流する。かん流
開始から一定時間後に断頭し、かん流を停止する。大脳
を摘出し、回収した試験物質の量を常法により測定す
る。試験結果Test Example 1 Test Method A polyethylene tube is inserted into a rat external carotid artery according to Takasato et al. From the inserted tube, a compound labeled with 14 C as sucrose that cannot penetrate normal brain capillaries (molecular weight 342), a compound labeled with 3 H as polyethylene glycol 4000 (molecular weight 4000), or dextran was used as a test substance. Fluorescently labeled FD-
70K (molecular weight 71200) and an isotonic buffer (pH 7.0) in which sodium caprate is dissolved as an absorption promoter.
4) Perfuse at a rate of 1 ml / min for 5 minutes. Decapitation is performed after a certain period of time from the start of perfusion, and perfusion is stopped. The cerebrum is excised and the amount of the test substance collected is measured by a conventional method. Test results
【表１】 [Table 1]
【００１２】試験例２ 試験方法 試験例１と同様にして、試験物質として14Ｃ標識ショ
糖、吸収促進剤としてパルミトイルカルニチンを溶解し
た緩衝液（ｐＨ３．０）を用いて試験した。試験結果Test Example 2 Test method Tests were carried out in the same manner as in Test Example 1, using 14 C-labeled sucrose as a test substance and a buffer solution (pH 3.0) in which palmitoylcarnitine was dissolved as an absorption enhancer. Test results
【表２】 [Table 2]
【００１３】これらの試験結果から、この発明の動脈注
射製剤は、通常血液−脳関門を通過しにくい化合物の通
過を促進することがわかり、これまで血液−脳関門を通
過しにくいために用いられなかった水溶性薬物やポリペ
プタイドなどの投与に好適である。From the results of these tests, it was found that the arterial injection preparation of the present invention promotes the passage of compounds that normally do not easily pass through the blood-brain barrier. It is suitable for administration of undissolved water-soluble drugs and polypeptides.
【００１４】[0014]
【実施例】実施例１ ５−フルオロウラシル（２ μ ｍｏｌ）およびカプリン
酸ナトリウム（２ｍｍｏｌ）を生理食塩水（１００ｍ
ｌ）に溶解して、動脈注射製剤を得た。EXAMPLES Example 1 5-Fluorouracil (2 μmol) and sodium caprate (2 mmol) were added to physiological saline (100 ml).
l) to give an arterial injection formulation.
【００１５】実施例２ 神経成長因子（１ｎｍｏｌ）およびパルミトイルカルニ
チン（１０μ ｍｏｌ）を生理食塩水（１００ｍｌ）に
溶解して、動脈注射製剤を得た。Example 2 Nerve growth factor (1 nmol) and palmitoylcarnitine (10 μmol) were dissolved in physiological saline (100 ml) to obtain an arterial injection preparation.
───────────────────────────────────────────────────── フロントページの続き (71)出願人 000005245 藤沢薬品工業株式会社 大阪府大阪市中央区道修町３丁目４番７号 (72)発明者 粟津 荘司 埼玉県川口市芝中田１−23−23 (72)発明者 大西 俊正 東京都八王子市長沼町205−７ ベラフロ ール201 (72)発明者 間 和之助 東京都日野市平山３−５−11 コーポ下村 106 (72)発明者 大西 倫夫 京都府京都市右京区嵯峨天龍寺北造路町10 (72)発明者 伊吹 リン太 京都府京都市北区小山東広以町７ (72)発明者 豊田 俊彦 大阪府箕面市桜井３−11−３ ルネス桜井 201 ──────────────────────────────────────────────────続 き Continued on the front page (71) Applicant 000005245 Fujisawa Pharmaceutical Co., Ltd. 3-4-7 Doshomachi, Chuo-ku, Osaka-shi, Osaka (72) Inventor Soji Awazu 1-2-23-23, Shibatanata, Kawaguchi-shi, Saitama (72) Inventor Toshimasa Onishi Beraflor 201, 205-7 Naganuma-cho, Hachioji-city, Tokyo (72) Kazunosuke Ma 3-5-11 Hirayama, Hino-shi, Tokyo Corp. Shimomura 106 (72) Inventor Toshio Onishi Kyoto Rinta Ibuki 10 (72) Inventor Rinta, Kyoto 7-72 Koyama Higashihiroi-cho, Kita-ku, Kyoto-shi, Kyoto (72) Inventor Toshihiko 3-11-3 Sakurai, Minoh-shi, Osaka Lunez Sakurai 201
Claims (5)
より薬効を発揮する薬物および（ｂ）炭素数１０以上の
飽和脂肪酸、その塩またはそのエステルを含有する動脈
注射製剤。1. An arterial injection preparation containing (a) a drug which exerts a medicinal effect by acting on a diseased site in the brain and (b) a saturated fatty acid having 10 or more carbon atoms, a salt or an ester thereof.
飽和脂肪酸である請求項１記載の動脈注射製剤。2. The arterial injection preparation according to claim 1, wherein the saturated fatty acid is a saturated fatty acid having 10 to 20 carbon atoms.
ン酸である請求項２記載の動脈注射製剤。3. The arterial injection preparation according to claim 2, wherein the saturated fatty acid is capric acid or palmitic acid.
り、飽和脂肪酸のエステルがカルニチンとのエステルで
ある請求項１〜３のいずれか一つに記載の動脈注射製
剤。4. The arterial injection preparation according to claim 1, wherein the salt of the saturated fatty acid is an alkali metal salt, and the ester of the saturated fatty acid is an ester with carnitine.
請求項１〜４のいずれか一つに記載の動脈注射製剤。5. The arterial injection preparation according to any one of claims 1 to 4, wherein the drug is an antitumor agent or an anti-dementia agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9334602A JPH11171794A (en) | 1997-12-04 | 1997-12-04 | Arterial parenteral injection preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9334602A JPH11171794A (en) | 1997-12-04 | 1997-12-04 | Arterial parenteral injection preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11171794A true JPH11171794A (en) | 1999-06-29 |
Family
ID=18279234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9334602A Withdrawn JPH11171794A (en) | 1997-12-04 | 1997-12-04 | Arterial parenteral injection preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11171794A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005506992A (en) * | 2001-10-19 | 2005-03-10 | アイデックス ラボラトリーズ インコーポレイテッド | Injectable composition for controlled delivery of pharmacologically active compounds |
| JP2006523723A (en) * | 2003-04-18 | 2006-10-19 | アイデックス ラボラトリーズ，インコーポレイティド | Method of modulating and introducing pharmaceutically active compounds |
-
1997
- 1997-12-04 JP JP9334602A patent/JPH11171794A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005506992A (en) * | 2001-10-19 | 2005-03-10 | アイデックス ラボラトリーズ インコーポレイテッド | Injectable composition for controlled delivery of pharmacologically active compounds |
| JP4850390B2 (en) * | 2001-10-19 | 2012-01-11 | アイデックス ラボラトリーズ インコーポレイテッド | Injectable composition for controlled delivery of pharmacologically active compounds |
| JP2006523723A (en) * | 2003-04-18 | 2006-10-19 | アイデックス ラボラトリーズ，インコーポレイティド | Method of modulating and introducing pharmaceutically active compounds |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A300 | Withdrawal of application because of no request for examination |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 20050301 |