JPH07165610A - Blood pressure controlling agent - Google Patents
Blood pressure controlling agentInfo
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- JPH07165610A JPH07165610A JP34316193A JP34316193A JPH07165610A JP H07165610 A JPH07165610 A JP H07165610A JP 34316193 A JP34316193 A JP 34316193A JP 34316193 A JP34316193 A JP 34316193A JP H07165610 A JPH07165610 A JP H07165610A
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- Prior art keywords
- blood pressure
- pressure control
- ptio
- pressure controlling
- fatty acid
- Prior art date
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、血圧制御剤に関し、特
に、油剤製剤化した新規な血圧制御剤に関する。TECHNICAL FIELD The present invention relates to a blood pressure control agent, and more particularly to a novel blood pressure control agent formulated as an oil.
【０００２】[0002]
【従来の技術とその課題】血圧制御剤（血流制御剤）
は、疾病の治療に際し血管を拡張したり、収縮させた
り、あるいは血流を遮断する等の目的で用いられるもの
であるが、解決すべき課題も多い。2. Description of the Related Art Blood pressure control agents (blood flow control agents)
Is used for the purpose of dilating or contracting blood vessels or blocking blood flow when treating diseases, but there are many problems to be solved.
【０００３】例えば、血管拡張因子（血管拡張剤）であ
る一酸化窒素（ＮＯ）は、通常ガス体であり、心血管そ
の他の拡張による救命等に用いられるが、そのガスのボ
ンベからの流量（流速）の調整が困難であった。その理
由はこのＮＯは高濃度では猛毒であり、治療に際しては
１〜４０ｐｐｍの治療濃度を達成し、それを維持する必
要があるが、ガス体の厳密な流速制御は極めてデリケー
トであるからである。しかも、ＮＯガスは吸入を中止す
ると薬効が直ちに消失し、瞬間的〜短時間の単回投与
（吸入）で長時間の緩徐な薬理作用の維持が困難であっ
た。[0003] For example, nitric oxide (NO), which is a vasodilator (vasodilator), is usually a gas body and is used for lifesaving such as cardiovascular dilatation. The flow rate of the gas from the cylinder ( It was difficult to adjust the flow rate). The reason for this is that this NO is highly toxic at high concentrations, and it is necessary to achieve and maintain a therapeutic concentration of 1 to 40 ppm during treatment, but the strict flow rate control of the gas body is extremely delicate. . Moreover, the drug effect of NO gas immediately disappeared when the inhalation was stopped, and it was difficult to maintain a slow pharmacological action for a long time by a single administration (inhalation) for a moment to a short time.
【０００４】また、本発明者らの研究により、フェニル
テトラメチルイミダゾリン−Ｎオキシル−Ｎ’オキサイ
ド（ＰＴＩＯ）は、血管拡張因子（弛緩因子）である一
酸化窒素（ＮＯ）に対して中和作用を有することが見出
され（Biochemistry,32,827-832,1993）、血管収縮剤と
して期待されるが、このＰＴＩＯは水に難溶性であり水
溶性注射剤として使用できる可能性は極めて少なかっ
た。ＰＴＩＯをカルボキシ化すれば水に易溶化するが、
このような誘導体、すなわちカルボキシフェニルテトラ
メチルイミダゾリン−Ｎオキシル−Ｎ’オキサイドは尿
中への排泄が早すぎて血中濃度の維持が困難であるた
め、薬効を継続させるには持続的な注入を要する。Further, according to the studies by the present inventors, phenyltetramethylimidazoline-Noxyl-N'oxide (PTIO) has a neutralizing action on nitric oxide (NO) which is a vasodilator (relaxation factor). ( Biochemistry , 32 , 827-832, 1993), and is expected as a vasoconstrictor, but this PTIO is sparingly soluble in water and there was very little possibility that it could be used as a water-soluble injection. . If PTIO is carboxylated, it will be easily soluble in water,
Such a derivative, carboxyphenyl tetramethyl imidazoline-N oxyl-N 'oxide, is excreted in urine too early to maintain the blood concentration, and therefore, continuous infusion is required to continue the drug effect. It costs.
【０００５】その他、例えば、Ｓ−ニトロソアセチルペ
ニシリンアミンは、一酸化窒素遊離剤であり血管拡張薬
剤として期待されるが、水に難溶であるためにその有用
性が著しく減じられている。In addition, for example, S-nitrosoacetylpenicillinamine is a nitric oxide-releasing agent and is expected as a vasodilator, but its usefulness is significantly reduced because it is poorly soluble in water.
【０００６】[0006]
【課題を解決するための手段とその効果】本発明は、前
述したような各種の血圧制御成分の欠点をなくし、安定
で取扱い易く、各種の投与が可能な優れた血圧制御剤を
得ることを目的とする。Means for Solving the Problems and Effects Thereof The present invention eliminates the above-mentioned drawbacks of various blood pressure control components, and provides an excellent blood pressure control agent which is stable and easy to handle and can be administered in various ways. To aim.
【０００７】本発明者は、血圧制御薬剤の担体として数
多くの生体親和性を有する物質について研究したとこ
ろ、一連の脂質化合物、特に中鎖の脂肪酸トリグリセリ
ド類が血圧制御薬剤に対する溶媒として極めて優れた性
状を有し、上記の目的に合致し、生体に安全に投与でき
る薬剤となりうることを発見した。[0007] The present inventor has studied a number of substances having biocompatibility as carriers for blood pressure control agents. As a result, a series of lipid compounds, particularly medium-chain fatty acid triglycerides, have excellent properties as solvents for blood pressure control agents. It has been found that it has the above-mentioned characteristics and can meet the above-mentioned purpose, and can be a drug that can be safely administered to living bodies.
【０００８】かくして、本発明は、油性溶媒中に、ガス
状または水に難溶性の血圧制御成分（血流制御成分）を
溶解させた血圧制御剤を提供するものである。[0008] Thus, the present invention provides a blood pressure control agent in which a blood pressure control component (blood flow control component) which is hardly soluble in gas or water is dissolved in an oily solvent.
【０００９】本発明において用いられる油性溶媒として
は、中鎖の脂肪酸のモノグリセリド、ジグリセリド、ま
たはトリグリセリド、高級脂肪酸、オリーブ油、ゴマ油
その他の天然油脂、コレステロール誘導体、油脂とレシ
チンその他を用いたリボゾーム、エマルジョン、リピッ
ドマイクロスフェアさらに、油性造影剤（例えば、仏国
ゲルベ社製商品名リヒオドール）などが含まれる。ま
た、スクアレン、ＤＨＡ、その他の不飽和および飽和脂
肪酸を用いることもできる。Examples of the oily solvent used in the present invention include monoglycerides, diglycerides or triglycerides of medium chain fatty acids, higher fatty acids, olive oil, sesame oil and other natural fats and oils, cholesterol derivatives, ribosomes and fats containing lecithin and other fats, emulsions, and the like. Lipid microspheres Further, an oil-based contrast agent (eg, Lihiodol under the trade name of Guerbet in France) is included. It is also possible to use squalene, DHA and other unsaturated and saturated fatty acids.
【００１０】このように油脂溶媒中に血圧制御成分が溶
解された本発明の血圧制御剤は、安定性、徐放性のある
剤型で、経血管内投与、経口投与、エアゾルとして経気
道投与、経皮投与など各種の投与の可能性のある剤型を
形成することができる。As described above, the blood pressure control agent of the present invention in which the blood pressure control component is dissolved in the oil and fat solvent is a stable and sustained-release dosage form, and is intravascularly administered, orally administered, or administered as an aerosol through the respiratory tract. It is possible to form a dosage form having various administration possibilities such as transdermal administration.
【００１１】本発明の血圧制御剤において用いる油性溶
媒として特に好ましいのは、Ｃ6〜Ｃ10、すなわち炭素
数６〜１０の中鎖の脂肪酸（一般に飽和の脂肪酸である
が、不飽和の脂肪酸でもよい）のトリグリセリドであ
る。このような中鎖脂肪酸トリグリセリドを用いると、
特に、血管拡張剤ＮＯ、あるいは血管収縮剤フェニルテ
トラメチルイミダゾリン−Ｎオキシル−Ｎ’オキサイド
（ＰＴＩＯ）などを血圧制御成分とする優れた血圧制御
剤が得られる。炭素数が６より小さい低級脂肪酸のトリ
グリセリドを用いると溶血傾向があり、また１０より大
きい高級脂肪酸（例えばリノール酸）のグリセリドの使
用は毒性の点で問題を生じることがある。The oily solvent used in the blood pressure control agent of the present invention is particularly preferably C 6 to C 10 , that is, a medium-chain fatty acid having 6 to 10 carbon atoms (generally saturated fatty acid, but unsaturated fatty acid is also used). Good) triglyceride. With such a medium chain fatty acid triglyceride,
In particular, an excellent blood pressure control agent containing a vasodilator NO or a vasoconstrictor phenyltetramethylimidazoline-N oxyl-N 'oxide (PTIO) as a blood pressure control component can be obtained. Triglycerides of lower fatty acids with less than 6 carbons are prone to hemolysis, and the use of glycerides of higher fatty acids with greater than 10 (eg linoleic acid) can lead to toxicity problems.
【００１２】ＮＯガスを油剤化して本発明に従う血圧制
御剤を調製するには、ＮＯガスをボンベより中鎖脂肪酸
トリグリセリド中に導入し、バブリングにより中鎖脂肪
酸トリグリセリドにＮＯを溶解させる。必要に応じ、し
かるべき抗酸化剤等を適宜あらかじめ溶かしておく。こ
のようにして得られた液状の薬剤は、使用目的や投与形
態に応じて適宜、中鎖脂肪酸トリグリセリドその他の油
性溶媒で希釈され投与される。To prepare a blood pressure control agent according to the present invention by converting NO gas into an oil, NO gas is introduced into a medium chain fatty acid triglyceride from a cylinder and NO is dissolved in the medium chain fatty acid triglyceride by bubbling. If necessary, a suitable antioxidant or the like is appropriately dissolved in advance. The liquid drug thus obtained is appropriately diluted with a medium-chain fatty acid triglyceride or other oily solvent and administered depending on the purpose of use and administration form.
【００１３】例えば、心血管拡張剤として用いる場合に
は一酸化窒素濃度を１μＭ〜１０ｍＭの等油性溶媒に溶
解したものを経皮的、経口的あるいは経動脈的に投与す
ることができる。また、経静脈内投与にあたっては、油
性乳び懸濁補液（例えば商品名イントラリピッド）等の
１００ｍｌに対し、上記のようにして得られた油剤（液
状薬剤）０．１〜１ｍｌを添加し、よく振とうし分散さ
せたものを緩やかな経静脈内投与（例えば１００ｍｌを
３０〜４０分かけて注入する）する。本薬剤は主として
抹消循環改善薬として使用され、また、小児の先天性心
血流不全患者等にも使用できる。For example, when it is used as a cardiovascular dilator, it can be percutaneously, orally or transarterally administered by dissolving it in an oily solvent having a nitric oxide concentration of 1 μM to 10 mM. In the case of intravenous administration, 0.1 to 1 ml of the oil agent (liquid agent) obtained as described above is added to 100 ml of the oily milk suspension replacement liquid (for example, Intralipid). The well-shaken and dispersed product is gently intravenously administered (for example, 100 ml is infused over 30 to 40 minutes). This drug is mainly used as a peripheral circulation improving drug, and can also be used for pediatric patients with congenital heart blood flow insufficiency and the like.
【００１４】さらに、ＮＯを血管拡張成分とする本発明
の製剤（油剤）は、上記と同様の手技にて気管支の拡張
の目的、あるいは脳血管その他の血管に対する拡張剤と
して使用可能である。その対象疾患の例としては、成人
および新生児の呼吸促迫症候群や肺気腫、さらに脳梗塞
などが挙げられる。これらの製剤は血管内投与に加えエ
アロゾルにて吸入させることもできる。さらに一般的な
経皮吸収剤とすることもでき、その際、吸収助剤を加え
ることも可能である。Further, the preparation (oil) of the present invention containing NO as a vasodilator can be used for the purpose of dilating the bronchi by the same procedure as described above or as a dilator for cerebral blood vessels and other blood vessels. Examples of the target disease include respiratory distress syndrome and emphysema in adults and newborns, and cerebral infarction. In addition to intravascular administration, these preparations can be inhaled by aerosol. Further, it may be a general percutaneous absorption agent, and at this time, an absorption aid may be added.
【００１５】また、本発明に従えば、水に極めて難溶の
ＰＴＩＯを中鎖脂肪酸トリグリセリドに加温溶解するこ
とによって、安定で薬効の優れた血管収縮剤が得られ
る。ＰＴＩＯを含有する本発明の薬剤（油剤）は、例え
ば、抗ショック剤として（敗血症性、エンドトキシン性
のショック、出血性ショック剤として）、前述したよう
なＮＯを含有する本発明の血管拡張剤と同様に各種の投
与が可能である。また、この薬剤は、他の使用例として
血流抑制剤として抗癌効果も示す。Further, according to the present invention, a vasoconstrictor having a stable and excellent drug effect can be obtained by heating and dissolving PTIO, which is extremely sparingly soluble in water, in a medium-chain fatty acid triglyceride. The drug (oil) of the present invention containing PTIO is, for example, as an anti-shock agent (septic, endotoxin shock, hemorrhagic shock agent), the vasodilator of the present invention containing NO as described above. Similarly, various administrations are possible. Further, this drug also exhibits an anticancer effect as a blood flow suppressing agent as another use example.
【００１６】さらに、本発明に従う油剤化血圧制御剤の
例として、中鎖脂肪酸トリグリセリドその他の油性溶媒
に、水に難溶な一酸化窒素遊離剤、Ｓ−ニトロソアセチ
ルペニシルアミンを溶解（例えば、Ｓ−ニトロソアセチ
ルペニシルアミンの１％中鎖脂肪酸トリグリセリド溶液
とする）して得られた薬剤を前述のＮＯ含有油剤に準じ
た投与経路にて使用することができる。Further, as an example of the oiled blood pressure control agent according to the present invention, a nitric oxide releasing agent, S-nitrosoacetylpenicylamine, which is poorly soluble in water, is dissolved in a medium chain fatty acid triglyceride or other oily solvent (for example, S. -A 1% medium chain fatty acid triglyceride solution of nitrosoacetylpenicylamine) can be used in the administration route according to the above-mentioned NO-containing oil agent.
【００１７】以下、本発明の特徴をさらに明らかにする
ため実施例に沿って本発明を説明するが、本発明はこれ
らの実施例によって限定されるものではない。The present invention will be described below with reference to examples in order to further clarify the features of the present invention, but the present invention is not limited to these examples.
【００１８】[0018]
【実施例】実施例１：一酸化窒素（ＮＯ）の油剤化とその血管拡張
作用テスト １ｍｌの中鎖脂肪酸トリグリセリドに、市販のＮＯガス
ボンベから２００ｍｌ／分の割合でＮＯガスをバブリン
グしながら導入すると、約５分後に約１７ｍＭのＮＯ飽
和溶液を得た。このものの中鎖脂肪酸トリグリセリド中
の安定性を図１および表１に示す。なお、用いた中鎖脂
肪酸トリグリセリドは、日本油脂（株）製「商品名トリ
カプリリン」であり、Ｃ8脂肪鎖から成る。[Examples] Example 1: Conversion of nitric oxide (NO) into oil and its vasodilation
Action test When NO gas was introduced into a 1 ml medium chain fatty acid triglyceride from a commercially available NO gas cylinder while bubbling at a rate of 200 ml / min, a saturated NO solution of about 17 mM was obtained after about 5 minutes. The stability of this product in medium-chain fatty acid triglyceride is shown in FIG. 1 and Table 1. The medium-chain fatty acid triglyceride used is “trade name Tricaprylin” manufactured by NOF CORPORATION, and is composed of a C 8 fatty chain.
【００１９】[0019]
【表１】 ＊ ｐＨ7.0、0.15M NaCl入り0.01M燐酸緩衝液[Table 1] * PH 7.0, 0.01M phosphate buffer containing 0.15M NaCl
【００２０】このようにして得られた液状薬剤を適宜中
鎖脂肪酸トリグリセリドで希釈経口投与あるいは腹腔内
投与をし、血管拡張に基づく血圧低下作用をもたらすこ
とを観察した。すなわち、体重約２５０〜３００ｇのモ
ルモットの腎動脈の環流液にＮＯの油剤を一定量ずつ投
与し、その腎臓の血流の増加を公知の方法により測定し
た。その結果は図２の如く、ＮＯ量に比例して血流量は
増加した。即ち、このような剤型のＮＯによる血管拡張
作用を示している。一方、このものを腹腔内投与後の血
圧は図３のように、ＮＯ血管拡張作用により低下するこ
とが確認された。It was observed that the liquid drug thus obtained was appropriately diluted orally or intraperitoneally with a medium chain fatty acid triglyceride to bring about a blood pressure lowering action based on vasodilation. That is, a fixed amount of NO oil was administered to the perfusate of renal arteries of guinea pigs weighing about 250 to 300 g, and the increase in blood flow in the kidney was measured by a known method. As a result, as shown in FIG. 2, the blood flow increased in proportion to the NO amount. That is, it shows the vasodilatory action by NO of such a formulation. On the other hand, it was confirmed that the blood pressure after intraperitoneal administration of this substance was lowered by the NO vasodilatory action, as shown in FIG.
【００２１】実施例２：ＰＴＩＯの油剤化とその血管収
縮作用テスト ＰＴＩＯ（フェニルテトラメチルイミダゾリン−Ｎオキ
シル−Ｎ’オキサイド）を上記中鎖脂肪酸トリグリセリ
ドに加温溶解し、０．１Ｍ溶液とした。このものの安定
性は常温大気圧下で数カ月間は安定である。ただし空気
中の大気汚染酸化物質によって開放系では極めて緩やか
に分解する。このものを経口投与したときの血中への移
行を電子スピン共鳴装置により定量すると（方法は、Ak
aike T.他Biochemistry,32,827-832,1993による）、図
４の如くＰＴＩＯによるスペクトルが出現し１回の投与
で３時間は持続した。これに対し、水溶性のカルボキシ
ＰＴＩＯは１回の水溶性製剤の経口投与では３０分以内
に消失し、上記装置による検出は不可能であった（図
５）。即ち、本油剤の有用性を示している。 Example 2: Conversion of PTIO into an oil and its blood vessel yield
Contraction test PTIO (phenyl tetramethyl imidazoline-N oxyl-N 'oxide) was dissolved in the above-mentioned medium chain fatty acid triglyceride by heating to give a 0.1 M solution. The stability of this product is stable for several months at room temperature and atmospheric pressure. However, it decomposes extremely slowly in an open system due to atmospheric pollutants in the air. The transfer into blood when orally administered was quantified by an electron spin resonance apparatus (method: Ak
aike T. et al. Biochemistry , 32 , 827-832, 1993), and a spectrum by PTIO appeared as shown in FIG. 4, and it was maintained for 3 hours with one administration. On the other hand, the water-soluble carboxy PTIO disappeared within 30 minutes after one oral administration of the water-soluble preparation, and the detection by the above device was impossible (FIG. 5). That is, the usefulness of the present oil agent is shown.
【００２２】この薬剤を腫瘍血管における透過性抑制に
よって検討すると、図６の如く約６０％の抑制をみた。
この図は、ＰＴＩＯとして１０ｍＭの中鎖脂肪酸トリグ
リセリド溶液を用い、それを２時間ごとに１ｍｌを経口
的に３回投与し、６時間目の成績を示している。When this drug was examined by suppressing the permeability in tumor blood vessels, the suppression was found to be about 60% as shown in FIG.
This figure shows the results at 6 hours when 10 mM medium-chain fatty acid triglyceride solution was used as PTIO, and 1 ml was orally administered 3 times every 2 hours.
【００２３】また、本製剤がウサギ大動脈の５ｍｍの厚
さの輪状切片を用いアセチルコリンによる血管弛緩作用
を有することを検討したところ、図７に示した如く明ら
かにフニレフィリン前収縮後のアセチルコリンによる弛
緩を本薬剤が有意に抑制した。すなわち、ウサギの大動
脈輪状切片を酸素加リンゲル液につるし、あらかじめフ
ェニレフェリンにて収縮させたものにアセチルコリンを
添加し弛緩させ、このとき、ＰＴＩＯを油剤のまま添加
したところ、ＰＴＩＯ投与下ではアセチルコリンにより
遊離してくるＮＯが中和されるため、血管は弛緩しない
ことが確認された。Further, it was examined that this preparation has a vasorelaxation effect by acetylcholine using a rabbit aorta 5 mm-thick ring-shaped section, and as shown in FIG. 7, apparently the relaxation by acetylcholine after preconstriction of funirephilin was observed. This drug suppressed significantly. That is, a rabbit aortic ring-shaped section was hung in oxygenated Ringer's solution, and acetylcholine was added to and relaxed by contracting with phenylepherine in advance. At this time, PTIO was added as an oil solution, and under administration of PTIO, acetylcholine was used. It was confirmed that the blood vessels do not relax because the released NO is neutralized.
【００２４】さらに、本発明に従うＰＴＩＯ含有油剤が
血流遮断剤として癌患者において、固型悪性腫瘍に対す
る増殖抑制剤および癌転移抑制剤として使用することが
できることを示すため、癌組織における血流抑制テスト
を行った。結果を図８に示す。この図は、マウス固型癌
（Ｓ−１８０腫瘍）２×１０6個をｄｄＹマウス背部皮
下に移植後９日目に、油剤化ＰＴＩＯを経口投与したも
の（○）とキャリアーの油（中鎖脂肪酸トリグリセリ
ド）のみのもの（●）の血流の変化を示し、ＰＴＩＯで
血流は大幅に抑えられている。すなわち、血流の抑制を
受けた癌組織は自壊作用を示し、本薬剤による抗癌効果
を示している。Furthermore, since the PTIO-containing oil preparation according to the present invention can be used as a blood flow blocker in cancer patients as a growth inhibitor and a cancer metastasis inhibitor for solid malignant tumors, it suppresses blood flow in cancer tissues. I did a test. The results are shown in Fig. 8. This figure shows that 2 × 10 6 solid tumors of the mouse (S-180 tumor) were subcutaneously transplanted to the back of the ddY mouse on the 9th day after oral administration of the oiled PTIO (○) and the carrier oil (medium chain). Only fatty acid triglyceride) (●) shows changes in blood flow, and blood flow is significantly suppressed by PTIO. That is, the cancer tissue that has been suppressed in blood flow has a self-destructing action, and shows the anticancer effect of this drug.
【図１】本発明に従い中鎖脂肪酸トリグリセリドを用い
て油剤化した一酸化窒素製剤の安定性を示す。測定は室
温暗室放置後、電子スピン共鳴装置（ＥＳＲ）により行
った。FIG. 1 shows the stability of a nitric oxide preparation oiled with a medium-chain triglyceride according to the present invention. The measurement was carried out by using an electron spin resonance apparatus (ESR) after leaving it in a dark room at room temperature.
【図２】本発明に従う油剤化一酸化窒素製剤の投与量と
腎血流の増加の関係を示す。FIG. 2 shows the relationship between the dose of an oil-modified nitric oxide preparation according to the present invention and an increase in renal blood flow.
【図３】本発明に従う油剤化一酸化窒素製剤をラット腹
腔内投与したときの血圧の変化を示す。FIG. 3 shows changes in blood pressure when an oiled nitric oxide preparation according to the present invention is intraperitoneally administered to rats.
【図４】本発明に従う油剤化一酸化窒素製剤の血中への
移行を電子スピン共鳴装置で測定したものである。FIG. 4 is a graph showing the transfer of an oil-modified nitric oxide preparation according to the present invention into blood, which is measured by an electron spin resonance apparatus.
【図５】本発明に従う油剤化ＰＴＩＯ製剤をマウスに経
口投与した後の血中濃度変化を示す。FIG. 5 shows changes in blood concentration after oral administration of the oiled PTIO preparation according to the present invention to mice.
【図６】本発明に従う油剤化ＰＴＩＯ製剤をマウスに経
口投与後２時間後の血管の収縮に伴う肺動脈の血流抑制
効果を示す。FIG. 6 shows the effect of suppressing blood flow in the pulmonary artery associated with the contraction of blood vessels 2 hours after oral administration of the oiled PTIO preparation according to the present invention to mice.
【図７】本発明に従う油剤化ＰＴＩＯ製剤が、ウサギ大
動脈輪状切片を用いたアセチルコリン誘導性の血管弛緩
作用に対する中和効果を有することを示す。FIG. 7 shows that the oiled PTIO formulation according to the present invention has a neutralizing effect on acetylcholine-induced vasorelaxation using rabbit aortic ring sections.
【図８】マウス固型癌（Ｓ−１８０腫瘍）における油剤
化ＰＴＩＯによる腫瘍血流の抑制効果を示す。FIG. 8 shows the inhibitory effect on tumor blood flow by oil-treated PTIO in mouse solid cancer (S-180 tumor).
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 33/00 ＡＢＲ 47/14 Ｇ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification code Internal reference number FI technical display area A61K 33/00 ABR 47/14 G
Claims (5)
の血圧制御成分を溶解させたことから成ることを特徴と
する血圧制御剤。1. A blood pressure control agent comprising a gas or water-insoluble blood pressure control component dissolved in an oily solvent.
酸のトリグリセリドである請求項１の血圧制御剤。2. The blood pressure control agent according to claim 1, wherein the oily solvent is a triglyceride of a medium-chain fatty acid having 6 to 10 carbon atoms.
ある請求項２の血圧制御剤。3. The blood pressure control agent according to claim 2, wherein the blood pressure control component is nitric oxide (NO).
イミダゾリン−Ｎオキシル−Ｎ’オキサイドである請求
項２の血圧制御剤。4. The blood pressure control agent according to claim 2, wherein the blood pressure control component is phenyltetramethylimidazoline-Noxyl-N ′ oxide.
ペニシルアミンである請求項２の血圧制御剤。5. The blood pressure control agent according to claim 2, wherein the blood pressure control component is S-nitrosoacetylpenicylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34316193A JPH07165610A (en) | 1993-12-15 | 1993-12-15 | Blood pressure controlling agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34316193A JPH07165610A (en) | 1993-12-15 | 1993-12-15 | Blood pressure controlling agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07165610A true JPH07165610A (en) | 1995-06-27 |
Family
ID=18359392
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34316193A Pending JPH07165610A (en) | 1993-12-15 | 1993-12-15 | Blood pressure controlling agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07165610A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028810A1 (en) * | 1996-02-07 | 1997-08-14 | Schwarz Pharma Ag | Pharmaceutical composition containing nitric oxide |
| JP2005504070A (en) * | 2001-09-13 | 2005-02-10 | コリア・インスティテュート・オブ・サイエンス・アンド・テクノロジー | Oil-based paclitaxel composition and formulation for chemical embolization and method for producing the same |
| JP2007536351A (en) | 2004-05-04 | 2007-12-13 | ホルモス メディカル リミテッド | A new oral drug for Ospemifen |
| US8758821B2 (en) | 2004-05-04 | 2014-06-24 | Hormos Medical Ltd. | Oral formulations of ospemifene |
-
1993
- 1993-12-15 JP JP34316193A patent/JPH07165610A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028810A1 (en) * | 1996-02-07 | 1997-08-14 | Schwarz Pharma Ag | Pharmaceutical composition containing nitric oxide |
| JP2005504070A (en) * | 2001-09-13 | 2005-02-10 | コリア・インスティテュート・オブ・サイエンス・アンド・テクノロジー | Oil-based paclitaxel composition and formulation for chemical embolization and method for producing the same |
| JP2007536351A (en) | 2004-05-04 | 2007-12-13 | ホルモス メディカル リミテッド | A new oral drug for Ospemifen |
| US8758821B2 (en) | 2004-05-04 | 2014-06-24 | Hormos Medical Ltd. | Oral formulations of ospemifene |
| USRE47316E1 (en) | 2004-05-04 | 2019-03-26 | Quatrx Pharmaceuticals Company | Oral formulations of ospemifene |
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