JPS63255231A - Embolic agent - Google Patents
Embolic agentInfo
- Publication number
- JPS63255231A JPS63255231A JP62091374A JP9137487A JPS63255231A JP S63255231 A JPS63255231 A JP S63255231A JP 62091374 A JP62091374 A JP 62091374A JP 9137487 A JP9137487 A JP 9137487A JP S63255231 A JPS63255231 A JP S63255231A
- Authority
- JP
- Japan
- Prior art keywords
- hap
- sintered
- agent
- embolic
- calcium phosphate
- 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.)
- Granted
Links
- 230000003073 embolic effect Effects 0.000 title claims abstract description 19
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 17
- 239000011575 calcium Substances 0.000 claims abstract description 12
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 12
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 12
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 12
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 12
- 239000002245 particle Substances 0.000 claims description 10
- 238000010304 firing Methods 0.000 claims description 7
- 239000011859 microparticle Substances 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 abstract description 13
- 238000002560 therapeutic procedure Methods 0.000 abstract description 13
- 239000002246 antineoplastic agent Substances 0.000 abstract description 11
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 abstract description 8
- 229910052586 apatite Inorganic materials 0.000 abstract description 8
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 6
- KIZFHUJKFSNWKO-UHFFFAOYSA-M calcium monohydroxide Chemical compound [Ca]O KIZFHUJKFSNWKO-UHFFFAOYSA-M 0.000 abstract description 5
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 abstract description 4
- 229940009456 adriamycin Drugs 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 4
- 229960004857 mitomycin Drugs 0.000 abstract description 2
- 230000002195 synergetic effect Effects 0.000 abstract description 2
- 230000003327 cancerostatic effect Effects 0.000 abstract 2
- 238000005245 sintering Methods 0.000 abstract 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 229910000394 calcium triphosphate Inorganic materials 0.000 abstract 1
- 230000023597 hemostasis Effects 0.000 abstract 1
- 230000007794 irritation Effects 0.000 abstract 1
- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 abstract 1
- 230000000246 remedial effect Effects 0.000 abstract 1
- 230000010102 embolization Effects 0.000 description 14
- 229940041181 antineoplastic drug Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000002512 chemotherapy Methods 0.000 description 7
- 238000011282 treatment Methods 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010016717 Fistula Diseases 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000003890 fistula Effects 0.000 description 3
- 235000011178 triphosphate Nutrition 0.000 description 3
- 239000001226 triphosphate Substances 0.000 description 3
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000002583 angiography Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、癌のような悪性しゅように有効な塞栓療法に
用いる塞栓剤の発明である。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention is an embolic agent used for effective embolic therapy for malignant tumors such as cancer.
（従来技術およびその問題点）
癌による死亡者数は年々増加しており、Ｖ期発見ととも
に、切除不能例に対する有効な治療法の開発が望まれて
いる。(Prior art and its problems) The number of deaths from cancer is increasing year by year, and it is desired to develop effective treatment methods for unresectable cases as well as detection of stage V.
そこで、しゆよう局所に高濃度の制癌剤を作用させる目
的で、セルディンガ（Ｓｅｌｄｉｎｇｅｒ ） 法すど
の経皮的血管カテーテル術により、制癌剤の動脈内ワン
ショット動性療法が一般に行われるようになった。しか
し、ワンショ７ト勤注療法も、しゅよう局所での一過性
の高薬剤濃度は得られるが、血流による薬剤の流出が速
く、しゅよう局所で高濃度を長期に維持することはでき
ず、必ずしも効率の良い方法とはいえない。Therefore, one-shot intra-arterial kinetic therapy of anti-cancer drugs has become commonly performed by percutaneous vascular catheterization such as the Seldinger method in order to apply high-concentration anti-cancer drugs locally. However, although one-shot, seven-point intensive therapy can achieve a temporary high drug concentration in the local area of the tumor, the drug flows out through the bloodstream quickly, making it impossible to maintain a high concentration in the local area of the tumor for a long period of time. This is not necessarily an efficient method.
また、ゼラチンスポンジを用いた塞栓療法は有効な治療
法ではあるが、被膜外浸潤部、娘結節、門脈内しゅよ・
う栓には効果が乏しく、事実、長期の予後は不良である
。In addition, although embolization therapy using a gelatin sponge is an effective treatment, it is difficult to treat extracapsular infiltrates, daughter nodules, intraportal veins, etc.
It has little effect on cavities, and in fact, the long-term prognosis is poor.
このため、診断的有用性があり、ワンショット動性療法
の欠点を補い、塞栓療法の治療成績°を向上させるため
の塞栓効果を有する塞栓剤の開発が要望されている。Therefore, there is a need for the development of an embolic agent that is diagnostically useful and has an embolic effect to compensate for the shortcomings of one-shot kinetic therapy and improve the therapeutic results of embolic therapy.
（発明が解決しようとする問題点）
本発明の目的は、それ自体がしゅように対し診断的有用
性を発揮すると共に、他の制癌剤と併用することにより
制癌剤がしゅよう内で高濃度を保ち、制癌剤としゅよう
とが長時間接触し続けるような塞栓効果の高い塞栓剤を
提供することにある。(Problems to be Solved by the Invention) It is an object of the present invention to not only exhibit diagnostic usefulness against breast cancer by itself, but also to maintain a high concentration of the anticancer drug in the breast by using it in combination with other anticancer drugs. An object of the present invention is to provide an embolic agent with a high embolic effect that allows continued contact between the breast and the breast for a long period of time.
（問題点を解決するための手段）
本発明者は、上記目的を達成するため鋭意研究した結果
、特定のリン酸カルシウム焼結体が微小塞栓としてしゅ
よう内に停滞して血流を遮断し、併用する制癌剤を徐放
性にして著しい抗しゅよう効果を発揮することを見出し
、本発明を完成するに至った。(Means for Solving the Problems) As a result of intensive research to achieve the above object, the present inventor discovered that a specific calcium phosphate sintered body becomes a microembolus that stagnates in the breast and blocks blood flow. The present inventors have discovered that an anticancer drug can be made to have a sustained release property and exhibit remarkable anti-inflammatory effects, leading to the completion of the present invention.
すなわち１本発明の第１発明の塞栓剤は、／＼イドロキ
シ・カルシウム・アパタイト焼結体（ＨＡＰ）あるいは
３リン酸力ルシウム焼結体（ＴＣＰ）のようなリン酸カ
ルシウムの焼結微小粒体からなり、その焼成温度が６０
０〜１３５０℃で、平均粒径が１０〜１１０〜１０００
μｍで、且つ化学量論比Ｃａ ／ Ｐが１．０〜２．０
であることを特徴とする。That is, the embolic agent of the first aspect of the present invention is made of sintered fine particles of calcium phosphate such as sintered hydroxycalcium apatite (HAP) or sintered lucium triphosphate (TCP). , the firing temperature is 60
0-1350℃, average particle size 10-110-1000
μm, and the stoichiometric ratio Ca/P is 1.0-2.0
It is characterized by
また１本発明の第２発明の塞栓剤は、焼成温度が６００
〜１３５０℃で平均粒径１０〜１１０００ＪＬで且つ化
学量論比Ｃａ ／ Ｐが１．０〜２．０の、ハイドロキ
シ・カルシウム拳アパタイト焼結体（ＨＡＰ）あるいは
３リン酸力ルシウム焼結体（ＴＣＰ）のようなリン酸カ
ルシウムに、アドリアマイシンやマイトマイシンＣなど
の他の制癌剤を吸着させることを特徴とする。In addition, the embolic agent of the second invention of the present invention has a firing temperature of 600°C.
Hydroxy-calcium apatite sintered body (HAP) or lucium triphosphate sintered body (HAP) with an average particle size of 10-11000 JL at ~1350°C and a stoichiometric ratio Ca/P of 1.0-2.0. It is characterized by adsorbing other anticancer drugs such as adriamycin and mitomycin C to calcium phosphate such as TCP).
本発明で用いるハイドロキシ・カルシウム・アパタイト
焼結体あるいは３リン酸力ルシウム焼結体は、平均粒径
が１０〜１０００ｇｍである。平均粒径が１１０７℃未
満では、動性の際に血流に流され腎臓に詰まりやすいと
いう問題を生じ、平均粒径が１１０００ＪＬを超えると
、動性が困難であるという問題を生じる。The hydroxy calcium apatite sintered body or the lucium triphosphate sintered body used in the present invention has an average particle size of 10 to 1000 gm. If the average particle size is less than 1107°C, there will be a problem that it will be easily washed away in the bloodstream and clogged in the kidneys during mobilization, and if the average particle size exceeds 11000 JL, there will be a problem that mobilization will be difficult.
また、本発明で用いるリン酸カルシウム焼結体の組成に
おいて、ＣａとＰとの含有比は１．０≦Ｃａ／Ｐ＜２．
０とすることが好ましい、 Ｃａ ／ Ｐが上記の範囲
を外れると溶解度が増大し制癌剤の徐放性効果が減少す
るという問題を生じる。In addition, in the composition of the calcium phosphate sintered body used in the present invention, the content ratio of Ca and P is 1.0≦Ca/P<2.
It is preferable to set it to 0. If Ca/P is outside the above range, the problem arises that the solubility increases and the sustained release effect of the anticancer drug decreases.
さらに１本発明で用いるリン酸カルシウム焼結体の製造
に際して、その焼成温度は６００〜１３５０℃とするこ
とが好ましい、焼成温度が６００℃未満では充分に造粒
できず、マクロファージのようなモノサイトの吸着性が
低下するという問題を生じ、焼成温度が１３５０℃を超
えると７パタイト自身が分解して活性状態のセラミック
スが形成できないという問題を生じる。Furthermore, when producing the calcium phosphate sintered body used in the present invention, the firing temperature is preferably 600 to 1350°C. If the firing temperature is less than 600°C, sufficient granulation will not be possible, and monosites such as macrophages will be adsorbed. However, if the firing temperature exceeds 1350° C., heptapatite itself decomposes, resulting in a problem that ceramics in an active state cannot be formed.
（作用）
本発明の塞栓剤を癌のようなしゅよう局部に通ずる動脈
に注入すると、微小塞栓としてしゅよう内に停滞し、し
ゅようへの栄養補給を断つと共に、併用する制癌剤を局
部に長時間高濃度に保ち、しゅようの発育を抑制する。(Effect) When the embolic agent of the present invention is injected into the artery leading to the local area of a cancerous tumor, it stagnates within the tumor as a microembolus, cuts off nutritional supply to the tumor, and causes the anticancer drug used in combination to stay at a high concentration locally for a long time. to suppress the growth of cysts.
（実施例）
以下、本発明を実験しゅようやヒト肝悪性しゅように適
用した実施例を挙げる。(Example) Hereinafter, examples will be given in which the present invention was applied to experimental cases and human liver malignant cases.
実施例１
Ｂ Ａ Ｌ Ｂ ／ ｃマウスの右後肢筋肉内に移植し
たＭｅｔｈＡＬゆようを用い、第１及び第２発明の７パ
タイト塞栓化学療法の効果について検討した。Example 1 The effects of the 7patite embolization chemotherapy of the first and second inventions were investigated using MethAL cells transplanted into the right hind leg muscle of BAL B/c mice.
使用したリン酸カルシウムは、焼成温度７００〜８００
℃、化学量論比Ｃａ ／ Ｐ １．８Ｂ・−１平均粒径
５０ ＮＮ１００ｐのハイドロキシφカルシウム・アパ
タイト（純粋アパタイト；ＨＡＰ）である。The calcium phosphate used was fired at a temperature of 700 to 800.
℃, stoichiometric ratio Ca/P 1.8B·-1, average particle size 50 NN 100p, hydroxy φ calcium apatite (pure apatite; HAP).
しゅよう移植後２週目に同側のＩａＳ骨動脈よりアドリ
アマイシン（ＡＤＲｌ、５ ｍｇ／ｋｇ）を単独動性し
た群、アバタイ） （ＨＡ Ｐ ２０ｍ ｇ ／ｋｇ）
を単独動性した群、アバタイ） （ＨＡＰ）とアドリア
マイシン（ＡＤＨ）を吸着混合し・て動性した群につい
て、眼底静脈叢より経時的に採血した血清のＡＤＨ濃度
と動性後３０分間のしゅよう内ＡＤＨ濃度の測定（ＨＰ
ＬＣ法）、および抗しゅよう効果の判定を行い、各群を
比較検討した。A group in which adriamycin (ADRl, 5 mg/kg) was administered alone through the ipsilateral IaS bony artery 2 weeks after the transplantation of the fistula (Abatai) (HA P 20 mg/kg)
For the group subjected to mobilization by adsorption and mixing of (HAP) and adriamycin (ADH), the ADH concentration of serum collected over time from the fundus venous plexus and the 30-minute period after mobilization were determined. Measurement of internal ADH concentration (HP
LC method), and the anti-inflammatory effect was determined, and each group was compared and studied.
血清ＡＤＨ濃度は１両群とも動性後２分でピークを示し
たが、ＨＡＰによる塞栓化学療法群はＡＤＨ単独群に比
較して１０分まで有意（ｐ＜０．００５ ）に低値であ
った。（図１）。Serum ADH concentration peaked 2 minutes after mobilization in both groups, but the value was significantly (p<0.005) lower in the HAP embolization chemotherapy group up to 10 minutes than in the ADH alone group. Ta. (Figure 1).
またしゅよう内ＡＤＲ濃度はＨＡＰ−ＡＤＲ塞栓療法群
で有意（ｐ ＜０．００１ ）に高値を示した。In addition, the intra-synthesal ADR concentration was significantly (p<0.001) higher in the HAP-ADR embolization therapy group.
すなわちＨＡＰ塞栓化学療法を行うことで、しゅよう内
に、より高濃度のＡＤＨが捕捉されたと考えられた（表
１）。In other words, it was considered that a higher concentration of ADH was captured within the fistula by HAP embolization chemotherapy (Table 1).
しゅよう発育に対する塞栓療法の効果は、ＡＤＨ（１，
５ｍｇ／ｋｇ）注入のみでは、シュよう抑制効果が認め
られなかった。しかしＨＡＰ−ＡＤＲ塞栓化学療法群で
は著大なしゅよう発育抑制効果が見られた。またＨＡＰ
塞栓療法のみでもＡＤＨ単独に比べてしゅよう発育抑制
効果が認められた（図２）。The effect of embolization therapy on tumor growth is based on ADH (1,
5mg/kg) injection alone had no anti-inflammatory effect. However, in the HAP-ADR embolization chemotherapy group, a significant inhibitory effect on tumor growth was observed. Also HAP
Embolization therapy alone was more effective in suppressing tumor growth than ADH alone (Figure 2).
実施例２ 肝細胞癌切除不能例の１５例を対象とした。Example 2 The subjects were 15 cases of unresectable hepatocellular carcinoma.
使用したリン庸カルシウムは、実施例１と同様の純粋ア
パタイトＡＤＨである。The calcium phosphate used was the same pure apatite ADH as in Example 1.
肝癌取扱い規約に準じ、しゅようの拡がりを血管造影、
ＣＴより検討し、２区域以内５例、３区域以内３例、４
区域または遠隔転移を有する例７例で、これらは塊状型
７例、結節型６例、浸潤型２例に区別できた。In accordance with the liver cancer handling regulations, angiography is performed to check the spread of the tumor.
Examined from CT, 5 cases within 2 areas, 3 cases within 3 areas, 4 cases
There were 7 cases with regional or distant metastasis, which could be divided into 7 cases of massive type, 6 cases of nodular type, and 2 cases of invasive type.
薬剤はＡＤＨ（２０〜５０ｍｇ）をＨＡＰに混和、吸着
したものを用いた。The drug used was ADH (20 to 50 mg) mixed and adsorbed to HAP.
ＨＡＰ−ＡＤＨの投与は、胃十二指腸動脈への注入につ
いて安全性が確認されていないので、固有肝動脈または
それより計測に投与した。治療回数は１回であった。Administration of HAP-ADH was administered into the proper hepatic artery or beyond, as the safety of injection into the gastroduodenal artery has not been confirmed. The number of treatments was once.
治療効果の判定は、主に血管造影で行い、超音波所見も
参考にして、しゅようの面積縮小率について判定した。The treatment effect was mainly evaluated using angiography, and the reduction rate of the tumor area was also determined using ultrasound findings as a reference.
治療成績は、５０％以上のしゅよう縮小を認めたもの（
ｐａ）は７例、２０〜５０％縮小（ＭＲ）は４例、２５
％以下の縮小（Ｎ Ｃ）は４例で、２５％以上の増大（
ＦＤ）は認めなかった。すなわちＰＲ以上の奏効率は４
７％で、ＭＲ以上を含めたしゅよう縮小効果は７３％で
あった（図３）。The treatment results were those that showed a reduction of 50% or more (
pa) in 7 cases, 20-50% reduction (MR) in 4 cases, 25 cases.
There were 4 cases of reduction of less than % (N C) and increase of 25% or more (N C).
FD) was not accepted. In other words, the response rate of PR or higher is 4.
7%, and the tumor reduction effect including MR or higher was 73% (Figure 3).
（発明の効果）
以上説明したように、本発明によれば、特定粒径のハイ
ドロキシ・カルシウム・アパタイト焼結体もしくは、３
リン酸力ルシウム焼結体のようなリン酸カルシウム粒子
を、塞栓療法の塞栓剤として使用すると、生体を刺激す
ることなく、従来の塞栓療法に比し、ＨＡＰ塞栓療法で
は１回投与のみで治療効果に改善を認めた。ＨＡＰが微
小塞栓としてしゅよう内に停滞し、制癌剤は徐放性とな
り、またＨＡＰによる血流遮断との相乗作用によって著
しい抗しゅよう効果を認めた。さらに制癌剤の増量も可
能である。(Effects of the Invention) As explained above, according to the present invention, a hydroxy calcium apatite sintered body with a specific particle size or
When calcium phosphate particles such as sintered lucium phosphate are used as an embolic agent in embolization therapy, HAP embolization therapy achieves therapeutic effects with only one administration, without stimulating the living body, compared to conventional embolization therapy. Recognized improvement. HAP remained in the tumor as microemboli, the anticancer agent was released in a sustained manner, and a significant anti-inflammatory effect was observed due to the synergistic effect with blood flow blockage by HAP. Furthermore, it is possible to increase the amount of anticancer drug.
本発明の塞栓剤が生体親和性に優れ生体を刺激しないこ
とは１本発明におけるリン醜カルシウムが本来、を椎動
物の青成分と同一物質か極めてそれに近い物質であるこ
とに由来するものと考えられる。またこの物質は無毒性
で無抗原性であるから副作用もほとんどない、さらに、
造影作用を有するからしゅようの位置や大きさを知るこ
とができ、診断においても極めて有用である。The reason why the embolic agent of the present invention has excellent biocompatibility and does not irritate living organisms is believed to be that the phosphorus-ugly calcium of the present invention is originally the same substance as the blue component of vertebrates, or a substance very close to it. It will be done. In addition, this substance is non-toxic and non-antigenic, so there are almost no side effects.
It is extremely useful for diagnosis as it allows us to know the location and size of the cyst, which has a contrast effect.
第１図は、アトレアマイシン（ＡＤＨｌ、５ｍｇ／ｋｇ
）を用いた塞栓化学療法におけるマウスのＡＤＨ血中濃
度の時間的変化を示すグラフ。
第２図はアトレアマイシン（ＡＤＲｔ、５ ｍｇ／ｋｇ
）を用いた塞栓化学療法におけるしゅようの大きさの時
間的変化を示すグラフ、
ＷＩＪ３図は、ヒトの塞栓化学療法におけるしゅようの
大きさの時間的変化１５例を示すグラフ。
第４図はアトレアマイシン（ＡＤＨｌ、５ ｍｇ／ｋｇ
）を用いた塞栓化学療法１時間後におけるしゅよう内Ａ
ＤＨ濃度の表である。
特許出願人 株式会社 アルス・ジャパン（ほか１名
）
代 理 人 牧 骨部 （ほか２名）第２図
１は一晴間 ８
第３図
％Figure 1 shows atreamycin (ADHl, 5mg/kg).
) is a graph showing temporal changes in ADH blood concentration in mice during embolization chemotherapy. Figure 2 shows atreamycin (ADRt, 5 mg/kg).
WIJ3 is a graph showing temporal changes in the size of a fistula in human embolization chemotherapy using 15 cases. Figure 4 shows atreamycin (ADHl, 5 mg/kg).
) Intra-synthesis A 1 hour after chemotherapy embolization
It is a table of DH concentration. Patent applicant: Ars Japan Co., Ltd. (and 1 other person) Agent: Maki Kotsube (and 2 others) Figure 2 1 is Ichiharuma 8 Figure 3%
Claims (3)
を吸着させて成る塞栓剤。(2) An anti-plasty agent is added to the sintered microparticles of calcium phosphate at a firing temperature of 600 to 1350°C, a stoichiometric ratio Ca/P of 1.0 to 2.0, and an average particle size of 10 to 1000 μm. An embolic agent made by adsorbing
論比Ｃａ／Ｐが１．６６…であることを特徴とする塞栓
剤。(3) The embolic agent according to claim 1 or 2, characterized in that the stoichiometric ratio Ca/P is 1.66.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62091374A JPS63255231A (en) | 1987-04-14 | 1987-04-14 | Embolic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62091374A JPS63255231A (en) | 1987-04-14 | 1987-04-14 | Embolic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63255231A true JPS63255231A (en) | 1988-10-21 |
| JPH0151266B2 JPH0151266B2 (en) | 1989-11-02 |
Family
ID=14024598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62091374A Granted JPS63255231A (en) | 1987-04-14 | 1987-04-14 | Embolic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63255231A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04112832A (en) * | 1990-08-31 | 1992-04-14 | Sangi Co Ltd | Antiulcer agent |
| WO1998047532A1 (en) * | 1997-04-24 | 1998-10-29 | Nycomed Imaging As | Embolus therapy using insoluble microparticles or vesicles containing contrast agents |
| WO2006109635A1 (en) | 2005-04-06 | 2006-10-19 | Kabushiki Kaisha Sangi | Intestinal absorptive anti-tumor agent |
| JP2010126434A (en) * | 2008-11-25 | 2010-06-10 | Olympus Corp | Cancer cell inhibitor and cancer cell-inhibiting sheet |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005074991A1 (en) * | 2004-02-09 | 2005-08-18 | Kabushiki Kaisha Sangi | Antitumor agent |
-
1987
- 1987-04-14 JP JP62091374A patent/JPS63255231A/en active Granted
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04112832A (en) * | 1990-08-31 | 1992-04-14 | Sangi Co Ltd | Antiulcer agent |
| WO1998047532A1 (en) * | 1997-04-24 | 1998-10-29 | Nycomed Imaging As | Embolus therapy using insoluble microparticles or vesicles containing contrast agents |
| WO2006109635A1 (en) | 2005-04-06 | 2006-10-19 | Kabushiki Kaisha Sangi | Intestinal absorptive anti-tumor agent |
| US8293274B2 (en) | 2005-04-06 | 2012-10-23 | Kabushiki Kaisha Sangi | Intestinal absorptive anti-tumor agent |
| JP2010126434A (en) * | 2008-11-25 | 2010-06-10 | Olympus Corp | Cancer cell inhibitor and cancer cell-inhibiting sheet |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0151266B2 (en) | 1989-11-02 |
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