JP2627666B2 - Antiallergic agent - Google Patents
Antiallergic agentInfo
- Publication number
- JP2627666B2 JP2627666B2 JP18116589A JP18116589A JP2627666B2 JP 2627666 B2 JP2627666 B2 JP 2627666B2 JP 18116589 A JP18116589 A JP 18116589A JP 18116589 A JP18116589 A JP 18116589A JP 2627666 B2 JP2627666 B2 JP 2627666B2
- Authority
- JP
- Japan
- Prior art keywords
- isotetrandrine
- antiallergic agent
- cepharanthin
- present
- agent
- 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.)
- Expired - Lifetime
Links
- 239000000043 antiallergic agent Substances 0.000 title claims description 10
- WTXHFWYAETTXNF-XZWHSSHBSA-N (+)-Isotetrandrine Natural products O(C)c1c(OC)cc2c3[C@H](N(C)CC2)Cc2cc(c(OC)cc2)Oc2cc(ccc2)C[C@@H]2N(C)CCc4c2cc(c(OC)c4)Oc13 WTXHFWYAETTXNF-XZWHSSHBSA-N 0.000 claims description 18
- WVTKBKWTSCPRNU-XZWHSSHBSA-N Isotetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-XZWHSSHBSA-N 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
- 230000002401 inhibitory effect Effects 0.000 description 13
- YVPXVXANRNDGTA-WDYNHAJCSA-N Cepharanthine Chemical compound C1C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@H](C2=C3)N(C)CCC2=CC(OC)=C3OC2=C(OCO3)C3=CC3=C2[C@H]1N(C)CC3 YVPXVXANRNDGTA-WDYNHAJCSA-N 0.000 description 11
- 229960001340 histamine Drugs 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229930013930 alkaloids Natural products 0.000 description 7
- 210000004027 cells Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 5
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- 230000001058 adult Effects 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000038129 antigens Human genes 0.000 description 3
- 108091007172 antigens Proteins 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- DFOCUWZXJBAUSQ-URLMMPGGSA-N Berbamine Chemical compound C([C@@H]1N(C)CCC=2C=C(C(OC=3C(OC)=C(OC)C=C4CCN(C)[C@@H](C=34)CC=3C=C(C(=CC=3)O)O3)=CC=21)OC)C1=CC=C3C=C1 DFOCUWZXJBAUSQ-URLMMPGGSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 210000003462 Veins Anatomy 0.000 description 2
- 201000005794 allergic hypersensitivity disease Diseases 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organs Anatomy 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000003449 preventive Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000001235 sensitizing Effects 0.000 description 2
- 230000001225 therapeutic Effects 0.000 description 2
- BJWWOUUGCAPHOV-UHFFFAOYSA-N 1,3-dibenzylisoquinoline Chemical class C=1C2=CC=CC=C2C(CC=2C=CC=CC=2)=NC=1CC1=CC=CC=C1 BJWWOUUGCAPHOV-UHFFFAOYSA-N 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N 2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000003455 Anaphylaxis Diseases 0.000 description 1
- 208000006673 Asthma Diseases 0.000 description 1
- 210000003651 Basophils Anatomy 0.000 description 1
- 210000000621 Bronchi Anatomy 0.000 description 1
- 210000000845 Cartilage Anatomy 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- -1 Dinitro phenyl Chemical group 0.000 description 1
- 208000005679 Eczema Diseases 0.000 description 1
- KBNIFDASRCWYGC-GXNXWABVSA-J Evans blue Chemical compound [Na+].[Na+].[Na+].[Na+].C\1=CC2=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C(N)=C2C(=O)C/1=N/NC(C(C)=C1)=CC=C1C1=CC=C(N\N=C/2C(C3=C(N)C(=CC(=C3C=C\2)S([O-])(=O)=O)S([O-])(=O)=O)=O)C(C)=C1 KBNIFDASRCWYGC-GXNXWABVSA-J 0.000 description 1
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 1
- 206010024324 Leukaemias Diseases 0.000 description 1
- 241001627404 Phasmahyla cruzi Species 0.000 description 1
- 241000218201 Ranunculaceae Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 210000003491 Skin Anatomy 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 240000004344 Tamarix gallica Species 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 206010046736 Urticarias Diseases 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 230000003266 anti-allergic Effects 0.000 description 1
- 230000003276 anti-hypertensive Effects 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 108090001123 antibodies Proteins 0.000 description 1
- 102000004965 antibodies Human genes 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 201000004624 dermatitis Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 231100001003 eczema Toxicity 0.000 description 1
- 230000001804 emulsifying Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 230000001035 methylating Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000002093 peripheral Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002522 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は抗アレルギー剤に関し、更に詳細には植物抽
出成分であるイソテトランドリンを有効成分とし、種々
のアレルギー性疾患の治療及び予防に利用することので
きる抗アレルギー剤に関する。Description: FIELD OF THE INVENTION The present invention relates to an antiallergic agent, and more particularly to isotetrandrine, which is a plant extract component, as an active ingredient and is used for treatment and prevention of various allergic diseases. It relates to an antiallergic agent that can be used.
ビスベンジルイソキノリンアルカロイドの１つである
セファランチンは、ツヅラフジ科タマサキツヅラフジの
塊根に含まれており、その薬理作用として、末梢血管拡
張作用、血流促進作用、鎮痛消炎作用、抗アレルギー作
用、降圧作用を有することが知られている。しかし、セ
ファランチンは、その化学構造が複雑であるため商業的
に化学合成を行なうことが困難であり、また、これを植
物体から直接得ようと試みても、タマサキツヅラフジの
塊根部から高収率で且つ高純度にセファランチンを単離
・精製して提供することは経済的な観点から問題があ
る。そのため、実際に市場に流通しているセファランチ
ン製剤は、タマサキツヅラフジの塊根部より回収された
複数のアルカロイド画分が含まれたものであり、セファ
ランチン以外に、ベルバミン、イソテトランドリン、セ
ファラノリン、ホモアロモリンなどの同属アルカロイド
が製剤中に60％以上含まれている場合もある。Cepharanthin, one of the bisbenzylisoquinoline alkaloids, is contained in the tuberous roots of the swelling family, Tamasaki tsutsudaji, and its pharmacological effects are peripheral vasodilation, blood flow promotion, analgesic anti-inflammatory, antiallergic, and antihypertensive. It is known to have However, cepharanthin is difficult to commercially synthesize due to its complex chemical structure, and even if it is attempted to obtain it directly from a plant, high yields from the tuberous roots of Tamafutsu rafuji are found. Isolating and providing cepharanthin with high efficiency and high purity is problematic from an economic viewpoint. Therefore, cepharanthin preparations that are actually distributed in the market are those containing a plurality of alkaloid fractions collected from the tuberous roots of T. cruzi, in addition to cepharanthin, berbamine, isotetrandrine, cephalanolin, In some cases, the preparation may contain at least 60% of a homologous alkaloid such as homoallomoline in the preparation.
ところがこれらの共存しているアルカロイドの薬理作
用については明確には知られておらず、単にセファラン
チンの作用の一部としてのみ認識されていた。そこで新
規有用な化合物を得るために、セファランチン類縁アル
カロイドを分離し、その薬理作用を明らかにすることに
大きな意味が生じていた。However, the pharmacological actions of these coexisting alkaloids were not clearly known, and were recognized only as a part of the action of cepharanthin. Therefore, in order to obtain a novel and useful compound, it has been very significant to separate alkaloids related to cepharanthin and clarify their pharmacological actions.
本発明者らは、先にタマサキツヅラフジの器官培養に
成功し、セファランチンを始めとするアルカロイドを実
験室内で多量に得ることができた。そして、これらのア
ルカロイドをそれぞれ単離し、そのヒスタミン遊離抑制
作用及び受身皮膚アナフィラキシー反応（PCA反応）抑
制作用について鋭意検討を重ねた結果、セファランチン
の類縁体アルカロイドである次の式（Ｉ） で表わされるイソテトラドリンが著しく強いヒスタミン
遊離抑制作用及びPCA反応抑制作用を有していることを
見出し、本発明を完成した。The present inventors have previously succeeded in organ cultivation of T. chinensis and obtained a large amount of alkaloids including cepharanthin in a laboratory. These alkaloids were isolated, and the histamine release inhibitory effect and the passive cutaneous anaphylaxis reaction (PCA reaction) inhibitory effect were studied intensively. As a result, the following formula (I) which is an alkaloid analogous to cepharanthin was obtained. The present inventors have found that isotetradrine represented by has a remarkably strong histamine release inhibitory action and a PCA reaction inhibitory action, and completed the present invention.
即ち、本発明は前記式（Ｉ）で表わされるイソテトラ
ンドリンを有効成分として含有することを特徴とする抗
アレルギー剤を提供するものである。That is, the present invention provides an antiallergic agent characterized by containing the isotetrandrine represented by the formula (I) as an active ingredient.
イソテトランドリンは、メギ科、ツヅラフジ科、キン
ポウゲ科植物等に含まれている化合物であり、その構造
は前記式（Ｉ）で表わされることが知られている。この
イソテトランドリンは上記植物から単離することもでき
るが、タマサキツヅラフジの培養物又は市販のセファラ
ンチン製剤から単離するか、あるいはベルバミンをメチ
ル化すること等によっても得ることができる。Isotetrandrine is a compound contained in plants of the family Barbitaceae, Betulae, Ranunculaceae and the like, and its structure is known to be represented by the above formula (I). This isotetrandrine can be isolated from the above-mentioned plants, but can also be isolated from a culture of P. cruzi or a commercially available cepharanthin preparation, or obtained by methylating belvamine.
本発明の抗アレルギー剤は、経口投与剤、注射剤、外
用剤及び吸入剤等の剤型とすることができる。The antiallergic agent of the present invention can be in the form of an oral agent, an injection, an external preparation, an inhalant, and the like.
経口投与剤は、常法に従い通常大人１日当り0.1〜500
mgのイソテトランドリンを乳糖、でんぷん等の担体と混
合し、必要により成型して錠剤、カプセル剤、顆粒剤、
散剤とするか、精製水、蒸留水等の水性担体に溶解ない
し分散させて液剤、シロップ剤、ドリンク剤等とするこ
とにより調製される。Oral dosage form is usually 0.1 to 500 per adult per day
lmg of isotetrandrine is mixed with carriers such as lactose and starch, and if necessary, formed into tablets, capsules, granules,
It is prepared by preparing a powder, or dissolving or dispersing in an aqueous carrier such as purified water or distilled water to prepare a liquid, syrup, drink or the like.
また注射剤は、通常大人１人当り0.1〜100mgのイソテ
トランドリンを注射用蒸留水等の水性担体に溶解、分
散、乳化等させることにより得られる。Injectables are usually obtained by dissolving, dispersing, emulsifying, etc., 0.1 to 100 mg of isotetrandrine per adult in an aqueous carrier such as distilled water for injection.
更に、本発明の抗アレルギー剤は湿疹、蕁麻疹、アト
ピー性皮膚炎などの治療を目的とする軟骨、クリーム、
液剤、乳剤等の外用製剤とすることができる。Further, the antiallergic agent of the present invention is eczema, hives, cartilage for the purpose of treating atopic dermatitis, cream,
External preparations such as solutions and emulsions can be prepared.
外用製剤中、有効成分であるイソテトランドリンは0.
1〜５重量％含有されることが好ましい。In the external preparation, isotetrandrine, which is the active ingredient, is contained in 0.
It is preferably contained in an amount of 1 to 5% by weight.
更にまた、本発明の抗アレルギー剤を吸入剤等の剤型
とすれば、直接気管支に作用させることができ、喘息等
の治療・予防効果を期待することも可能である。Furthermore, when the antiallergic agent of the present invention is in the form of an inhalant or the like, it can act directly on the bronchi, and can be expected to have a therapeutic / preventive effect on asthma and the like.
吸入剤としては、通常大人１人当りイソテトランドリ
ンとして0.1〜100mg用いる。As an inhalant, 0.1 to 100 mg of isotetrandrine is usually used per adult.
本発明の抗アレルギー剤は、有効成分であるイソテト
ランドリンが、強力なヒスタミン遊離抑制作用及びPCA
反応抑制作用を有するので、経口投与剤、注射剤、外用
剤、吸入剤等剤型を変化させることにより、様々なアレ
ルギー性疾患の治療・予防剤として利用することができ
る。The antiallergic agent of the present invention is characterized in that the active ingredient isotetrandrine has a strong histamine release inhibitory action and PCA.
Since it has a reaction-suppressing action, it can be used as a therapeutic / preventive agent for various allergic diseases by changing the dosage form such as an oral administration agent, an injection, an external preparation, and an inhalant.
以下に実施例を示して、本発明を更に具体的に説明す
る。Hereinafter, the present invention will be described more specifically with reference to examples.
実施例１ ヒスタミン遊離抑制作用： （実験方法） ラット好塩基球性白血病由来の細胞株である2H3細胞
を、24穴プレートに４×105個細胞／穴の割合で播き、
一晩、37℃にて５％炭酸ガス含有空気の下で培養した。
次いで、IgE抗体（抗DNP（Dinitro phenyl）マウスIgE
抗体）で細胞を感作し、被験試料で処理後、抗原である
DNP・BGG（DNP基結合 ウシガンマグロブリン）で刺激
し、遊離されるヒスタミン量を測定することにより、ヒ
スタミン遊離抑制能を調べた。Example 1 Histamine release inhibitory action: (Experimental method) 2H3 cells, a cell line derived from rat basophil leukemia, were seeded on a 24-well plate at a rate of 4 × 10 5 cells / well,
The cells were cultured overnight at 37 ° C. in air containing 5% carbon dioxide.
Next, an IgE antibody (anti-DNP (Dinitro phenyl) mouse IgE
Sensitize cells with antibody), treat with test sample,
The ability to inhibit histamine release was examined by stimulating with DNP / BGG (DNP group-bound bovine gamma globulin) and measuring the amount of histamine released.
尚、ヒスタミン量の測定はShoreらの方法（J.Pharmac
ol.Ther.,127,182（1959））に準じて行なった。The amount of histamine was measured by the method of Shore et al. (J. Pharmac.
ol. Ther., 127 , 182 (1959)).
（結果） ヒスタミン遊離に対する抑制率は下記第１表に示す通
りであった。(Results) The inhibition rate against histamine release was as shown in Table 1 below.
第１表から明らかな如く、本発明抗アレルギー剤の有
効成分であるイソテトランドリンは、10-3Ｍで70.5％と
いう顕著な抑制率を示し、かつ濃度依存性が認められ
た。これに対し、セファランチンは2H3細胞に対する膜
障害作用のため、細胞がプレート底より剥離して抑制活
性が認められない場合があり、かつ濃度依存性も認めら
れなかった。また、市販のリザベンはカプセル中のトラ
ニスト濃度10-3Ｍで抑制率は57％であり、イソテトラン
ドリンと比較して抑制活性は低かった。As is clear from Table 1, isotetrandrine, which is an active ingredient of the antiallergic agent of the present invention, showed a remarkable inhibition rate of 70.5% at 10 -3 M, and its concentration dependency was observed. On the other hand, cepharanthin has a membrane-damaging effect on 2H3 cells, so that cells may be detached from the plate bottom and no inhibitory activity may be observed, and no concentration dependency was observed. In addition, commercially available Rizaben had an inhibition rate of 57% at a Tranist concentration of 10 −3 M in the capsule, and the inhibitory activity was lower than that of isotetrandrine.
実施例２ PCA反応抑制作用： （実験方法） 体重200g前後のウィスター（Wister）系雄性ラット
に、PCA力価が10-6倍のIgE抗体（抗DNP（Dinitro pheny
l）マウスIgE抗体）の5,000倍希釈溶液0.075mlを側腹部
に皮内注射し、受動感作した。感作48時間後に抗原であ
るDNP・BGG（DNP基結合ウシガンマグロブリン）0.63mg/
0.28ml及び２％エバンスブルー色素液0.42mlを尾静脈よ
り注射し、PCA反応を惹起した。 Example 2 Inhibitory effect of PCA reaction: (Experimental method) An IgE antibody (anti-DNP (Dinitrophenypheny) having a PCA titer of 10 to 6 times was given to male Wistar rats weighing around 200 g.
l) 0.075 ml of a 5,000-fold diluted solution of mouse IgE antibody) was intradermally injected into the flank to carry out passive sensitization. 48 hours after sensitization, the antigen DNP / BGG (DNP group-bound bovine gamma globulin) 0.63 mg /
0.28 ml and 0.42 ml of 2% Evans blue dye solution were injected through the tail vein to elicit a PCA reaction.
抗原投与10分前にイソテトランドリン15mg/kg体重
を、また対照として生理食塩水を尾静脈より注射したラ
ットを抗原投与30分後に断頭、放血致死させ、側腹部皮
膚を剥離してPCA反応惹起部位の色素漏出量を測定し、
イソテトランドリンのPCA反応抑制率を算出した結果、5
5％であった。Rats injected with isotetrandrine 15 mg / kg body weight 10 minutes before antigen administration and saline as a control via the tail vein were decapitated and bled to death 30 minutes after antigen administration, and peeled the flank skin to induce a PCA reaction. Measure the amount of dye leakage at the site,
As a result of calculating the PCA reaction inhibition rate of isotetrandrine, 5
5%.
実施例３ 急性毒性： 本発明品イソテトランドリンをICR系雄性マウスに腹
腔内投与した結果、LD50値は180mg/kgであり、本発明化
合物の安全性が確認された。Example 3 Acute toxicity: Isotetrandrine of the present invention was administered intraperitoneally to male ICR mice, and as a result, the LD 50 value was 180 mg / kg, confirming the safety of the compound of the present invention.
参考例１ 既に確立した方法（Agric.Biol.Chem.,52,1495（198
8））に従いタマサキツヅラフジの根に器官培養を行な
い、根を収穫した。Reference Example 1 An already established method (Agric. Biol. Chem., 52 , 1495 (198
According to 8)), organ culture was carried out on the roots of T. samurai and the roots were harvested.
得られた乾燥根を磨砕し粉末とした。ここにメタノー
ルを加えて抽出を行ない、溶媒を留去してメタノール抽
出物を得た。これを３％クエン酸水溶液に溶解し、不溶
物を濾別後、溶液にアンモニア水を加えてアルカリ性と
した。クロロホルムを用いて抽出を行ない、塩基性画分
を得た。この画分を更にシリカゲルクロマトグラフィー
により分離し、イソテトランドリンを結晶として得た。The obtained dried root was ground to powder. Methanol was added thereto to perform extraction, and the solvent was distilled off to obtain a methanol extract. This was dissolved in a 3% aqueous citric acid solution, the insoluble matter was filtered off, and the solution was made alkaline by adding aqueous ammonia. Extraction was performed using chloroform to obtain a basic fraction. This fraction was further separated by silica gel chromatography to obtain isotetrandrine as crystals.
得られたイソテトランドリンの純度をHPLCを用いて測
定した結果、99％以上であった。また、マススペクトル
の結果は次に示す通りであった。As a result of measuring the purity of the obtained isotetrandrine using HPLC, it was found to be 99% or more. The results of the mass spectrum were as shown below.
Ms m/z（rel.int.）622〔Ｍ〕+（100.0）,395（52.2）,
199（57.3）,174（51.7）Ms m / z (rel.int.) 622 [M] + (100.0), 395 (52.2),
199 (57.3), 174 (51.7)
Claims (1)
する抗アレルギー剤。1. The following formula (I) An antiallergic agent comprising, as an active ingredient, isotetrandrine represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18116589A JP2627666B2 (en) | 1989-07-13 | 1989-07-13 | Antiallergic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18116589A JP2627666B2 (en) | 1989-07-13 | 1989-07-13 | Antiallergic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0344323A JPH0344323A (en) | 1991-02-26 |
| JP2627666B2 true JP2627666B2 (en) | 1997-07-09 |
Family
ID=16096024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18116589A Expired - Lifetime JP2627666B2 (en) | 1989-07-13 | 1989-07-13 | Antiallergic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2627666B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012031563A1 (en) * | 2010-09-10 | 2012-03-15 | 杭州本生药业有限公司 | Heterocyclic amino berbamine derivatives, preparation method and use thereof |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5627195A (en) * | 1995-04-11 | 1997-05-06 | Massachusetts Eye And Ear Infirmary | Treatment for ocular inflammation |
| EP1870426B1 (en) * | 2005-04-15 | 2010-10-27 | Zhou, Zhengming | Antiallergic production of latex or pvc and method for forming the same |
| CN103635475B (en) * | 2011-08-19 | 2016-06-08 | 杭州本生药业有限公司 | Tetrandrine derivant that 5-position carbon replaces, and its preparation method and application |
| CN104031057A (en) * | 2014-06-30 | 2014-09-10 | 施佩蓓 | Production method of berbamine |
-
1989
- 1989-07-13 JP JP18116589A patent/JP2627666B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012031563A1 (en) * | 2010-09-10 | 2012-03-15 | 杭州本生药业有限公司 | Heterocyclic amino berbamine derivatives, preparation method and use thereof |
| JP2013537171A (en) * | 2010-09-10 | 2013-09-30 | ハンジョウ ベンシェン ファーマシューティカル シーオー．， エルティーディー． | Heterocyclic aminoberbamine derivatives, their preparation and use |
| US8987288B2 (en) | 2010-09-10 | 2015-03-24 | Hangzhou Bensheng Pharmaceutical Co., Ltd. | Heterocyclic aminoberbamine derivatives, the preparation process and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0344323A (en) | 1991-02-26 |
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