JPH026326B2 - - Google Patents

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Publication number
JPH026326B2
JPH026326B2 JP8980682A JP8980682A JPH026326B2 JP H026326 B2 JPH026326 B2 JP H026326B2 JP 8980682 A JP8980682 A JP 8980682A JP 8980682 A JP8980682 A JP 8980682A JP H026326 B2 JPH026326 B2 JP H026326B2
Authority
JP
Japan
Prior art keywords
background background
animals
humans
infections
general formula
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
Application number
JP8980682A
Other languages
Japanese (ja)
Other versions
JPS58206517A (en
Inventor
Masakazu Yamamoto
Seiichi Araki
Hiroshi Yamamoto
Isao Yamatsu
Takeshi Suzuki
Shoji Kajiwara
Yoshikazu Suzuki
Masae Arai
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai Co Ltd
Original Assignee
Eisai Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd
Priority to JP57089806A priority Critical patent/JPS58206517A/en
Priority to DE3348500A priority patent/DE3348500C2/en
Priority to DE3318989A priority patent/DE3318989C2/en
Priority to DE3348492A priority patent/DE3348492C2/en
Priority to DE3348493A priority patent/DE3348493C2/en
Priority to GB08314419A priority patent/GB2122610B/en
Priority to CA000429108A priority patent/CA1310660C/en
Priority to BE2/60109A priority patent/BE896865A/en
Priority to NL8301892A priority patent/NL194300C/en
Priority to CH2902/83A priority patent/CH654823A5/en
Priority to SE8303013A priority patent/SE461650B/en
Priority to ES522789A priority patent/ES522789A0/en
Priority to DK239483A priority patent/DK171640B1/en
Priority to IT21364/83A priority patent/IT1164256B/en
Priority to AT0197283A priority patent/AT389871B/en
Priority to FR838308941A priority patent/FR2527597B1/en
Priority to FR8317170A priority patent/FR2532848B1/en
Priority to FR8317175A priority patent/FR2532846B1/en
Priority to FR8317171A priority patent/FR2532844B1/en
Priority to FR8317173A priority patent/FR2532845B1/en
Priority to FR8317176A priority patent/FR2532847B1/en
Priority to FR8317169A priority patent/FR2532843A1/en
Publication of JPS58206517A publication Critical patent/JPS58206517A/en
Priority to ES529754A priority patent/ES8507444A1/en
Priority to ES529753A priority patent/ES8506567A1/en
Priority to GB08508214A priority patent/GB2159054B/en
Priority to GB08508218A priority patent/GB2159711B/en
Priority to GB08508219A priority patent/GB2159712B/en
Priority to GB08508216A priority patent/GB2159055B/en
Priority to GB08508220A priority patent/GB2159713A/en
Priority to GB08508215A priority patent/GB2159709B/en
Priority to GB08508217A priority patent/GB2159710B/en
Priority to US06/760,221 priority patent/US4624966A/en
Priority to FR858513026A priority patent/FR2569108B1/en
Priority to SE8801515A priority patent/SE502924C2/en
Priority to SE8801513A priority patent/SE502922C2/en
Priority to SE8801514A priority patent/SE502923C2/en
Publication of JPH026326B2 publication Critical patent/JPH026326B2/ja
Priority to US08/011,197 priority patent/US5280048A/en
Priority to US08/584,145 priority patent/US6111131A/en
Priority to US08/599,944 priority patent/US5658958A/en
Priority to US08/601,489 priority patent/US6288128B1/en
Priority to NL9900009A priority patent/NL9900009A/en
Granted legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/02—Acyclic alcohols with carbon-to-carbon double bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
    • C07C43/14—Unsaturated ethers
    • C07C43/15—Unsaturated ethers containing only non-aromatic carbon-to-carbon double bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/203—Unsaturated compounds containing keto groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/03—Monocarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C07C69/14—Acetic acid esters of monohydroxylic compounds
    • C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

【発明の詳細な説明】[Detailed description of the invention]

本発明は、ヒトまたは動物の免疫機能不全によ
る疾患の予防・治療剤、特にヒトまたは動物の感
染症に対する防禦剤に関する。更に詳しく述べれ
ば、 一般式 （式中ａ、ｂは水素原子またはａ−ｂで結合手を
形成する。ｎは１〜10の整数を示す。）で表わさ
れるポリプレニルアルコール系化合物を有効成分
とするヒトまたは動物の免疫機能不全による疾患
の予防・治療剤、特にヒトまたは動物の感染症に
対する防禦剤に関する。 近年、免疫学の進歩が急速であり、種々の疾患
が免疫機能不全に起因しているものと考えられて
きている。例えば、癌、細菌感染症、喘息、関節
リウマチ、自己免疫疾患などが免疫機能不全に起
因している疾患としてあげられている。 細菌感染症は、単に病原菌の浸入のみによる単
純性感染症に加えて、各種重篤な基礎疾患を伴う
複雑性感染症の増加が深刻な問題となつてきてい
る。例えば癌に伴う感染症は臨床上最もわずらわ
しい問題である。癌を担うことによつて、全身
性、局所的な抵抗力低下を招き、易感染状態下で
感染症を合併、続発する。癌に伴う感染は、初期
においては呼吸器感染、尿路感染、胎道感染、皮
膚感染が多く、末期においては肺炎、敗血症が多
い。この腫瘍に伴う感染症併発の機序について
は、次のような過程が一般的である。 すなわち、白血病、悪性リンパ腫、癌の進展に
伴い、正常な組織、細胞の障害、特にリンパ系細
胞や、顆粒球細胞機能の低下をきたすので、易感
染性となり、感染症を併発すると考えられてい
る。このような場合、抗生剤投与による根治効果
が乏しく、反復感染、菌交代症、難治感染にいた
ることが多い。したがつて、従来の抗生剤、化学
療法剤のみでは根治がほとんど期待できず、生体
防禦機能の改善なくしては治療不可能であり、生
体の防禦機能を高める薬剤の開発が望まれてい
る。 一方、家蓄・家禽などの動物の細菌感染に対し
ては、抗性物質がその中心的存在となつており、
事実、各種の抗生物質の登場によつて病原細菌に
よる重篤な感染症は減少している。しかし、畜産
界では抗菌剤の乱用から、畜水産物中の残留・耐
性菌の増加、菌交代症などを引き起こし、社会問
題となつている。すなわち、宿主は感染防禦能が
著しく低下し、感染症に対する修復機能も障害さ
れているため、細菌感染症は直りにくく再感染し
易い状態を作つている。更に、自発性感染症（日
和見感染症）が家畜の生産性を低下させ、その損
失は大きい。そこで宿主の免疫能の活性を高め、
生体の防禦機能を高める必要がある。 本発明者らは、上述の実情に鑑み、免疫機能を
正常化し、生体の防禦機能を高める薬剤につい
て、長年鋭意研究してきたが、意外にも次の一般
式 （式中ａ、ｂは水素原子またはａ−ｂで結合手を
形成する。ｎは１〜10の整数を示す。）で表わさ
れるポリプレニルアルコールがヒトおよび動物の
免疫機能不全による疾患の予防・治療剤、特にヒ
トおよび動物の感染症に対する防禦剤として有効
であることを見い出し、本発明を完成したもので
ある。 すなわち、本発明化合物は、ヒトおよび動物の
免疫機能を正常化し感染抵抗性を高める作用を有
するので、ヒトおよび動物の免疫機能不全による
疾患の予防・治療剤、各種感染症に対する防禦剤
として有用である。 ヒトの場合の具体例をあげれば、関節リウマ
チ、自己免疫疾患、癌、喘息、および例えば敗血
症、肺炎、髄膜炎、各種ウイルス感染症などの各
種感染症などに有効である。 また動物の場合の具体例をあげれば、例えば豚
の下痢、肺炎（SEP、AR.ヘモフイルス、パスツ
レラ）、TGE、鶏の肺炎（マイクロプラズマ、ヘ
モフイルス）、マレツク病、牛の下痢、肺炎、乳
房炎などに有効である。 また、ヒトおよび動物の感染症に本発明化合物
を投与する場合、抗生物質との併用により著しく
その治療効果を高める。このことは、前述した畜
産業界で問題となつている抗生物質の乱用という
問題をも解決するものであり重要な意義がある。 更に、家畜・家禽などの動物の場合を例にとれ
ば、生体の感染抵抗性を高めるので、初生時のベ
ース薬として有用であること、多頭羽飼育、輸送
などに起因するストレスの緩和に有用であるこ
と、およびワクチン効果の増強に有用である。 したがつて、本発明の目的は、ヒトおよび動物
の免疫機能不全の新規な予防・治療剤を提供する
にある。 更に、本発明の目的は、ヒトおよび動物の感染
症に対する新規な防禦剤を提供するにある。 本発明におけるポリプレニルアルコールの代表
的化合物を以下に掲げるが、本発明がこれらのも
のに限定されることがないことはいうまでもな
い。 Γ３，７，11，15，19，23，27，31−オクタメチ
ル−２，６，10，14，18，22，26，30−ドトリ
アコンタオクタエン−１−オール Γ３，７，11，15，19，23，27，31，35−ノナメ
チル−２，６，10，14，18，22，26，30，34−
ヘキサトリコンタノナエン−１−オール Γ３，７，11，15，19，23，27，31，35，39−デ
カメチル−２，６，10，14，18，22，26，30，
34，38−テトラコンタデカエン−１−オール Γ３，７，11，15，19，23，27，31，35，39，43
−ウンデカメチル−２，６，10，14，18，22，
26，30，34，38，42−テトラテトラコンタウン
デカエン−１−オール Γ３，７，11，15，19，23，27−ヘプタメチル−
２，６，10，14，18，22，26−オクタコサヘプ
タエン−１−オール Γ３，７，11，15，19，23−ヘキサメチル−２，
６，10，14，18，22−テトラコサヘキサエン−
１−オール Γ３，７，11，15，19−ペンタメチル−２，６，
10，14，18−エイコサペンタエン−１−オール Γ３，７，11，15−テトラメチル−２，６，10，
14−ヘキサデカテトラエン−１−オール Γ３，７，11−トリメチル−２，６，10−ドデカ
トリエン−１−オール Γ３，７−ジメチル−２，６−オクタジエン−１
−オール Γ３，７，11，15，19，23，27，31，35−ノナメ
チル−６，10，14，18，22，26，30，34−ヘキ
サトリコンタオクタエン−１−オール Γ３，７，11，15，19，23，27，31，35，39−デ
カメチル−６，10，14，18，22，26，30，34，
38−テトラコンタノナエン−１−オール Γ３，７，11，15，19，23，27，31，35，39，43
−ウンデカメチル−６，10，14，18，22，26，
30，34，38，42−テトラテトラコンタデカエン
−１−オール Γ３，７，11，15，19−ペンタメチル−６，10，
14，18−エイコサテトラエン−１−オール Γ３，７，11，15−テトラメチル−６，10，14−
ヘキサデカトリエン−１−オール Γ３，７，11−トリメチル−６，10−ドデカジエ
ン−１−オール Γ３，７−ジメチル−６−オクタエン−１−オー
ル Γ３，７，11，15，19，23−ヘキサメチル−６，
10，14，18，22−テトラコサペンタエン−１−
オール Γ３，７，11，15，19，23，27−ヘプタメチル−
６，10，14，18，22，26−オクタコサヘキサエ
ン−１−オール Γ３，７，11，15，19，23，27，31−オクタメチ
ル−６，10，14，18，22，26，30−ドトリアコ
ンタヘプタエン−１−オール 本発明化合物は、種々の方法で製造されうる
が、一般式〔〕においてａ、ｂがａ−ｂで結合
手を形成している場合は、例えば、Burrell et
al.、J.Chem.Soc.(C)1966、2144に記載された方
法、Popjak et al.、J.Biol.Chem、237、56
（1962）記載された方法、O.Isler et al.、Helv.
Chim Acta、42、2616（1959）に記載された方
法、特開昭53−31610に記載された方法または特
開昭54−55506に記載された方法により製造する
ことが可能である。 またａ、ｂが水素原子である場合は、例えば特
開昭55−76829に記載された方法により製造する
ことが可能である。この方法を具体的に述べれば
以下のとおりである。 (イ) 次の一般式 （式中ｎは１〜10の整数を表わす） の化合物とシアノ酢酸低級アルキルエステルを
塩基の存在下に反応させて一般式 （式中ｎは前記の意味を有し、Ｒは低級アルキ
ル基を示す） で表わされる化合物を得、次に、 (ロ) 上記の一般式〔〕で表わされる化合物を例
えば水素化ホウ素ナトリウムなどの還元剤を用
いて還元して一般式 （式中ｎおよびＲは前記の意味を有する。） で表わされる化合物を得、次いで (ハ) 上記の一般式〔〕で表わされる化合物を、
例えば水酸化カリウムなどの強アルカリの存在
下に脱炭酸して次の一般式 （ｎは前記の意味を有する） で表わされる化合物を得、次いで (ニ) 上記の一般式〔〕で表わされる化合物を例
えば水酸化カリウムなどの強アルカリの存在下
に加水分解して次の一般式 で表わされる化合物を得、次いで (ホ) 上記の一般式〔〕で表わされる化合物を例
えばヴイトライト、リチウムアルミニウムハイ
ドライドなどの還元剤により還元して 目的物質〔〕 （式中ｎは前記の意味を有する） を得ることができる。 次に本発明化合物の効果を実験例にて詳述す
る。 実施例 １ 感染防禦効果 (1) 実験方法 slc：ICR雄性マウス（６〜７週令、体重
22〜30ｇ）に、下記に記載した被験化合物を
次表（表１）に示す量筋肉内投与し、24時間
後に臨床由来の大腸菌（Escherichia Coli）
を2.8×108／マウスを皮下接種し、感染後７
日目の生存数から生残率を求めた。 (2) 被験化合物 ３，７，11−トリメチル−６，10−ドデカ
ジエン−１−オール ３，７，11，15−テトラメチル−２，６，
10，14−ヘキサデカテトラエン−１−オール ３，７，11，15−テトラメチル−６，10，
14−ヘキサデカトリエン−１−オール ３，７，11，15，19−ペンタメチル−６，
10，14，18−エイコサテトラエン−１−オー
ル ３，７，11，15，19，23，27−ヘプタメチ
ル−２，６，10，14，18，22，26−オクタコ
サヘプタエン−１−オール ３，７−ジメチル−２，６−オクタジエン
−１−オール ３，７，11，15，19，23，27，31，35，39
−デカメチル−２，６，10，14，18，22，
26，30，34，38−テトラコンタデカエン−１
−オール ３，７，11，15，19，23，27，31，35，
39，43−ウンデカメチル−６，10，14，18，
22，26，30，34，38，42−テトラテトラコン
タデカエン−１−オール ３，７，11，15，19，23−ヘキサメチル−
６，10，14，18，22−テトラコサペンタエン
−１−オール ３，７，11，15，19，23，27−ヘプタメチ
ル−６，10，14，18，22，26−オクタコサヘ
キサエン−１−オール ３，７，11，15，19，23，27，31−オクタ
メチル−６，10，14，18，22，26，30−ドト
リアコンタヘプタエン−１−オール 対照化合物：MDP（AcMur−Ｌ−Ala−Ｄ
−Glu） (3) 実験結果 結果を表１に示す。 TECHNICAL FIELD The present invention relates to preventive and therapeutic agents for diseases caused by immune dysfunction in humans or animals, and particularly to agents for preventing infectious diseases in humans or animals. In more detail, the general formula (In the formula, a and b form a bond with a hydrogen atom or a-b. n represents an integer of 1 to 10.) Human or animal immune function using a polyprenyl alcohol compound as an active ingredient The present invention relates to preventive/therapeutic agents for diseases caused by malfunction, particularly to preventive agents against infectious diseases in humans or animals. In recent years, advances in immunology have been rapid, and various diseases are thought to be caused by immune dysfunction. For example, cancer, bacterial infections, asthma, rheumatoid arthritis, autoimmune diseases, and the like are listed as diseases caused by immune dysfunction. BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND BACKGROUND OF THE INVENTION Bacterial infections are becoming a serious problem, with an increase in complex infections accompanied by various serious underlying diseases, in addition to simple infections caused solely by infiltration of pathogenic bacteria. For example, infectious diseases associated with cancer are one of the most troublesome clinical problems. Carrying cancer leads to a decrease in systemic and local resistance, leading to complications and subsequent infections in immunocompromised conditions. Infections associated with cancer often include respiratory tract infections, urinary tract infections, fetal canal infections, and skin infections in the early stages, and pneumonia and sepsis in the late stages. The following process is the general mechanism of infection associated with this tumor. In other words, as leukemia, malignant lymphoma, and cancer progress, they cause damage to normal tissues and cells, especially lymphoid cells and granulocyte cell function, which makes them susceptible to infection and is thought to cause infections. There is. In such cases, antibiotic administration has little curative effect, often leading to repeated infections, bacterial replacement, and intractable infections. Therefore, conventional antibiotics and chemotherapeutic agents alone cannot be expected to provide a complete cure, and treatment is not possible without improving the body's defense function, and there is a desire for the development of drugs that enhance the body's defense function. On the other hand, antibiotics play a central role in preventing bacterial infections in animals such as livestock and poultry.
In fact, with the advent of various antibiotics, serious infections caused by pathogenic bacteria are decreasing. However, in the livestock industry, overuse of antibacterial agents has caused an increase in residual and resistant bacteria in livestock and marine products, as well as bacterial replacement disease, which has become a social problem. In other words, the host's ability to defend against infection is significantly reduced and its repair function against infection is impaired, creating a state in which bacterial infections are difficult to cure and reinfection is easy to occur. Furthermore, spontaneous infections (opportunistic infections) reduce the productivity of livestock, resulting in large losses. Therefore, it increases the activity of the host's immune system,
It is necessary to enhance the defense function of the living body. In view of the above-mentioned circumstances, the present inventors have been conducting intensive research for many years on drugs that normalize the immune function and enhance the defense function of the living body, but surprisingly, the following general formula (In the formula, a and b form a bond with a hydrogen atom or a-b. n represents an integer of 1 to 10.) Polyprenyl alcohol represented by the formula The present invention was completed based on the discovery that the present invention is effective as a therapeutic agent, particularly as a preventative against infectious diseases in humans and animals. That is, the compounds of the present invention have the effect of normalizing the immune function of humans and animals and increasing their resistance to infection, and therefore are useful as prophylactic and therapeutic agents for diseases caused by immune dysfunction in humans and animals, and as preventive agents against various infectious diseases. be. To give specific examples in humans, it is effective against rheumatoid arthritis, autoimmune diseases, cancer, asthma, and various infectious diseases such as sepsis, pneumonia, meningitis, and various viral infections. Specific examples for animals include diarrhea in pigs, pneumonia (SEP, AR. Haemophilus, Pasteurella), TGE, pneumonia in chickens (Microplasma, Haemophilus), Maretske's disease, diarrhea in cows, pneumonia, mastitis. It is effective for such things. Furthermore, when the compounds of the present invention are administered to treat infectious diseases in humans and animals, their therapeutic effects are significantly enhanced when used in combination with antibiotics. This is of great significance as it also solves the aforementioned problem of overuse of antibiotics in the livestock industry. Furthermore, in the case of animals such as livestock and poultry, it increases the organism's resistance to infection, so it is useful as a base drug at the beginning of life, and it is useful for alleviating stress caused by raising multiple birds and transporting them. and is useful for enhancing vaccine efficacy. Therefore, an object of the present invention is to provide a novel prophylactic/therapeutic agent for immune dysfunction in humans and animals. A further object of the present invention is to provide a novel protective agent against infectious diseases in humans and animals. Representative compounds of polyprenyl alcohol in the present invention are listed below, but it goes without saying that the present invention is not limited to these compounds. Γ3,7,11,15,19,23,27,31-octamethyl-2,6,10,14,18,22,26,30-dotriacontaoctaen-1-olΓ3,7,11,15 , 19, 23, 27, 31, 35-nonamethyl-2, 6, 10, 14, 18, 22, 26, 30, 34-
Hexatricontanonaen-1-ol Γ3,7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26,30,
34,38-tetracontadecaen-1-ol Γ3,7,11,15,19,23,27,31,35,39,43
-undecamethyl-2,6,10,14,18,22,
26,30,34,38,42-tetratetracontaunedecaen-1-ol Γ3,7,11,15,19,23,27-heptamethyl-
2,6,10,14,18,22,26-octacosaheptaen-1-ol Γ3,7,11,15,19,23-hexamethyl-2,
6,10,14,18,22-tetracosahexaene-
1-ol Γ3,7,11,15,19-pentamethyl-2,6,
10,14,18-eicosapentaen-1-ol Γ3,7,11,15-tetramethyl-2,6,10,
14-hexadecatetraen-1-ol Γ3,7,11-trimethyl-2,6,10-dodecatrien-1-ol Γ3,7-dimethyl-2,6-octadiene-1
-ol Γ3,7,11,15,19,23,27,31,35-nonamethyl-6,10,14,18,22,26,30,34-hexatriconetaoctaen-1-ol Γ3,7 , 11, 15, 19, 23, 27, 31, 35, 39-decamethyl-6, 10, 14, 18, 22, 26, 30, 34,
38-Tetracontanonaen-1-ol Γ3,7,11,15,19,23,27,31,35,39,43
-Undecamethyl-6, 10, 14, 18, 22, 26,
30,34,38,42-tetratetracontadecaen-1-ol Γ3,7,11,15,19-pentamethyl-6,10,
14,18-eicosatetraen-1-ol Γ3,7,11,15-tetramethyl-6,10,14-
Hexadecatrien-1-ol Γ3,7,11-trimethyl-6,10-dodecadien-1-ol Γ3,7-dimethyl-6-octaen-1-ol Γ3,7,11,15,19,23-hexamethyl -6,
10,14,18,22-tetracosapentaene-1-
All Γ3,7,11,15,19,23,27-heptamethyl-
6,10,14,18,22,26-octacosahexaen-1-ol Γ3,7,11,15,19,23,27,31-octamethyl-6,10,14,18,22,26, 30-dotriacontaheptaen-1-ol The compound of the present invention can be produced by various methods, but when a and b in the general formula [] form a bond with a-b, for example, Burrell et
al., J.Chem.Soc.(C)1966, 2144, Popjak et al., J.Biol.Chem, 237, 56
(1962) method described, O.Isler et al., Helv.
It can be produced by the method described in Chim Acta, 42, 2616 (1959), the method described in JP-A-53-31610, or the method described in JP-A-54-55506. When a and b are hydrogen atoms, it can be produced, for example, by the method described in JP-A-55-76829. This method will be specifically described as follows. (b) The following general formula (In the formula, n represents an integer of 1 to 10) and cyanoacetic acid lower alkyl ester are reacted in the presence of a base to form the general formula (In the formula, n has the above-mentioned meaning and R represents a lower alkyl group.) Next, (b) a compound represented by the above general formula [] is added to the compound, such as sodium borohydride, etc. The general formula is reduced using a reducing agent of (In the formula, n and R have the above-mentioned meanings.) Then, (c) obtain a compound represented by the above general formula [],
For example, decarboxylation in the presence of a strong alkali such as potassium hydroxide gives the following general formula: (n has the above-mentioned meaning), and then (d) the compound represented by the above general formula [] is hydrolyzed in the presence of a strong alkali such as potassium hydroxide to form the following general formula. formula A compound represented by is obtained, and then (e) the compound represented by the above general formula [] is reduced with a reducing agent such as Vuitrite or lithium aluminum hydride to obtain the target substance [] (wherein n has the meaning given above) can be obtained. Next, the effects of the compounds of the present invention will be explained in detail using experimental examples. Example 1 Infection prevention effect (1) Experimental method slc: ICR male mice (6-7 weeks old, body weight
The test compound described below was intramuscularly administered to the subjects (22 to 30 g) in the amount shown in the following table (Table 1), and 24 hours later, clinical Escherichia coli (Escherichia coli)
2.8 × 10 8 /mouse were inoculated subcutaneously, and 7 days after infection.
The survival rate was calculated from the number of survivors on the day. (2) Test compound 3,7,11-trimethyl-6,10-dodecadien-1-ol 3,7,11,15-tetramethyl-2,6,
10,14-hexadecatetraen-1-ol 3,7,11,15-tetramethyl-6,10,
14-hexadecatrien-1-ol 3,7,11,15,19-pentamethyl-6,
10,14,18-eicosatetraen-1-ol 3,7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-ol 3,7-dimethyl-2,6-octadien-1-ol 3, 7, 11, 15, 19, 23, 27, 31, 35, 39
-decamethyl-2,6,10,14,18,22,
26,30,34,38-tetracontadecaene-1
-all 3, 7, 11, 15, 19, 23, 27, 31, 35,
39,43-undecamethyl-6,10,14,18,
22,26,30,34,38,42-tetratetracontadecaen-1-ol 3,7,11,15,19,23-hexamethyl-
6,10,14,18,22-tetracosapentaen-1-ol 3,7,11,15,19,23,27-heptamethyl-6,10,14,18,22,26-octacosahexaen-1-ol 3,7,11,15,19,23,27,31-octamethyl-6,10,14,18,22,26,30-dotriacontaheptaen-1-ol Control compound: MDP (AcMur-L- Ala-D
-Glu) (3) Experimental results The results are shown in Table 1.

【表】【table】

【表】 ２ マクロフアージの貧食能の増大効果 (1) 実験方法および結果 slc：ICR系雄性マウス（８週令、体重22
〜30ｇ）に、前記した被験化合物を100mg／
Kg筋肉内投与し、24時間後にカーボン・クリ
アランステストをおこない、マクロフアージ
の貧食能を測定した。なおカーボン・クリア
ランステストは、G.BIOZZI、B.
BENACERRAF AND B.N.HALPERN、
Brit.J.exp.Path.、34、441−457に記載され
ている方法に準じておこなつた。 具体的に述べれば以下の方法で行つた。 カーボン・クリアランステストはコロイド
カーボンの血中からのクリアランスを指標と
して肝・脾のマクロフアージ機能を測定する
ものである。 Gu¨nter Wagner社製のカーボンを160mg／
Kgの割合でマウス尾静脈内に注入した。注入
後、１、４、７、10、13分後に後眼窩静脈叢
より20μを採血し、小試験管中で２mlの0.1
％炭酸ナトリウムと混合した。これについて
660nMの波長で吸光度を測定した。 横軸に時間（分）を、縦軸に吸光度の対数
値をとり、３分毎の値プロツトする。この直
線の勾配を求めて半減時間を算出した。
Control群の半減時間を100として、それに対
する各被験化合物の半減時間の割合を比較し
た（数値が小さくなつていればマクロフアー
ジの亢進を示す）。 その結果を表２に示す。 表２において、貧食能の変化（％）の数値
は、コントロールの半減時間を100とし、こ
れに対して変化した割合を示す。[Table] 2 Effect of macrophages on increasing poor eating ability (1) Experimental method and results slc: ICR male mice (8 weeks old, body weight 22
~30g) of the test compound described above at 100mg/
Kg was administered intramuscularly, and 24 hours later, a carbon clearance test was performed to measure the phagocytic ability of macrophages. The carbon clearance test was conducted by G.BIOZZI, B.
BENACERRAF AND BNHALPERN,
It was carried out according to the method described in Brit.J.exp.Path., 34, 441-457. Specifically, the following method was used. The carbon clearance test measures the macrophage function of the liver and spleen using the clearance of colloidal carbon from the blood as an indicator. 160 mg of Gunter Wagner carbon
Kg was injected into the mouse tail vein. 1, 4, 7, 10, and 13 minutes after injection, 20μ of blood was collected from the retroorbital venous plexus, and 2ml of 0.1
% sodium carbonate. about this
Absorbance was measured at a wavelength of 660 nM. The horizontal axis represents time (minutes), the vertical axis represents the logarithm of absorbance, and the values are plotted every 3 minutes. The half-life time was calculated by finding the slope of this straight line.
The half-life time of the control group was set as 100, and the ratio of the half-life time of each test compound to that was compared (a smaller value indicates enhancement of macrophages). The results are shown in Table 2. In Table 2, the numerical value of change (%) in hypophagia indicates the percentage of change relative to the half-life time of the control, which is set as 100.

【表】 表２において、貧食能力が高まつている場
合は、半減時間が減少するが、20（％）以上、
すなわちその数値が80より少い場合は強い貧
食能の促進を示す。したがつて、本発明化合
物のうち、化合物Ａ、Ｄ、Ｅ、Ｉ、Ｊ、Ｋは
非常に強い貧食能の促進効果があることが明
らかである。 上記の実施例により、本発明化合物は免疫機能
を正常化し、感染抵抗性を高めることが明らかと
なつた。 本発明化合物は、極めて毒性の低いものであ
り、安全性は非常に高いものであり、したがつて
長期連用投与が可能であり、この意味でも本発明
の価値は高い。 すなわち、SD系ラツト（体重約200ｇ）に前記
の化合物（化合物Ａ〜Ｋ）を500mg／Kgを経口投
与したが、死亡例、副作用は何ら観察されなかつ
た。 本発明化合物をヒトの免疫機能不全による疾患
の予防・治療剤あるいはヒトの感染症に対する防
禦剤として患者に投与する際の投与量は、疾患の
種類、症状の程度、化合物の種類などにより大き
く異なり特に限定されないが、成人１日あたり約
10mg〜4000mg、好ましくは50mg〜500mgを経口若
しくは非経口的に投与する。感染症に対する防禦
剤として投与する場合、抗生物質との併用はもち
ろんさしつかえない。投与剤型としては、例えば
散剤、細粒剤、顆粒剤、錠剤、カプセル剤、注射
剤などがあげられる。製剤化の際は、通常の製剤
担体を用い、常法により製造する。 すなわち、経口用固形製剤を調整する場合は主
薬に賦形剤、更に必要に応じて結合剤、崩壊剤、
滑沢剤、着色剤、矯味矯臭剤などを加えた後、常
法により錠剤、被覆錠剤、顆粒剤、散剤、カプセ
ル剤などとする。 賦形薬としては、例えば乳糖、コーンスター
チ、白糖、ブドウ糖、ソルビツト、結晶セルロー
スなどが、結合剤としては例えば、ポリビニルア
ルコール、ポリビニールエーテル、エチルセルロ
ース、メチルセルロース、アラビアゴム、トラガ
ント、ゼラチン、シエラツク、ヒドロキシプロピ
ルセルロース、ヒドロキシプロピルスターチ、ポ
リビニルピロリドンなどが、崩壊剤としては例え
ば、デンプン、寒天、ゼラチン末、結晶セルロー
ス、炭酸カルシウム、炭酸水素ナトリウム、クエ
ン酸カルシウム、デキストリン、ペクチン等が、
滑沢剤としては例えば、ステアリン酸マグネシウ
ム、タルク、ポリエチレングリコール、シリカ、
硬化植物油等が、着色剤としては医薬品に添加す
ることが許可されているものが、矯味矯臭剤とし
ては、ココア末、ハツカ脳、芳香酸、ハツカ油、
竜脳、桂皮末等が用いられる。これらの錠剤、顆
粒剤には糖衣、ゼラチン衣、その他必要により適
宜コーテイングすることはもちろんさしつかえな
い。 注射剤を調製する場合には、主薬に必要により
PH調整剤、緩衝剤、安定化剤、保存剤、可溶化剤
などを添加し、常法により皮下、筋肉内、静脈内
用注射剤とする。 家畜・家禽などの動物に投与する際も、経口投
与若しくは非経口投与により投与する。経口投与
は通常飼料に添加しておこなう。また非経口投与
の例をあげれば、常法により注射剤を調製し、皮
下、筋肉内、静脈内などに投与する。 次に本発明化合物の１つである３，７，11，
15，19，23，27，31−オクタメチル−２，６，
10，14，18，22，26，30−ドトリアコンタオクタ
エン−１−オール（以下主薬と称する）を有効成
分とした製剤例を示す。 製剤例 １ （カプセル剤） 主 薬 ５ｇ 微結晶セルローズ 80ｇ トウモロコシデンプン 20ｇ 乳 糖 22ｇ ポリビニルピロリドン ３ｇ 全量 130ｇ 上記成分を常法により顆粒化したのち、ゼラチ
ン硬カプセル1000カプセルに充填した。１カプセ
ル中に主薬５mgを含有する。 製剤例 ２ （散剤） 主 薬 50ｇ 微結晶セルローズ 400ｇ トウモロコシデンプン 550ｇ 全量 1000ｇ 主薬をアセトンに溶解し、次いでこれを微結晶
セルローズに吸着させたのち、乾燥した。これを
トウモロコシデンプンと混合し、常法により散剤
として、主薬の20倍散を調整した。 製剤例 ３ （錠剤） 主 薬 ５ｇ トウモロコシデンプン 10ｇ 乳 糖 20ｇ カルボキシメチルセルローズカルシウム 10ｇ 微結晶セルローズ 40ｇ ポリビニルピロリドン ５ｇ タルク 10ｇ 全量 100ｇ 主薬をアセトンに溶解し、次いでこれを微結晶
セルローズに吸着させたのち、乾燥した。これに
トウモロコシデンプン、乳糖、カルボキシメチル
セルローズカルシウムを混合し、次いでポリビニ
ルピロリドンの水溶液を結合剤として加えて常法
により顆粒化した。これに滑沢剤としてタルクを
加えて混合したのち、１錠100mgの錠剤に打錠し
た。１錠中には主薬５ｇを含有する。 製剤例 ４ （注射剤） 主 薬 10ｇ Nikkol HCO−60（日光ケミカル社製品名） 37ｇ ゴマ油 ２ｇ 塩化ナトリウム ９ｇ プロピレングリコール 40ｇ リン酸緩衝液（0.1M.PH6.0） 100ml 蒸留水 全量 1000ml 主薬、Nikkol HCO−60、ゴマ油および半量
のプロピレングリコールを混合して約80℃で加温
溶解し、これにリン酸緩衝液および塩化ナトリウ
ムとプロピレングリコールを予め溶解した蒸留水
を約80℃に加温して加え、全量1000mlの水溶液と
した。この水溶液を２mlのアンプルに分注して熔
閉したのち、加熱滅菌した。 １管中、主薬20mgを含有する。[Table] In Table 2, when the ability to eat poorly increases, the half-life time decreases;
In other words, if the value is less than 80, it indicates strong promotion of poor eating ability. Therefore, it is clear that among the compounds of the present invention, compounds A, D, E, I, J, and K have a very strong effect of promoting poor eating ability. The above examples revealed that the compounds of the present invention normalize immune function and increase resistance to infection. The compounds of the present invention have extremely low toxicity and are extremely safe, and therefore can be administered continuously over a long period of time, and in this sense, the value of the present invention is also high. That is, when 500 mg/Kg of the above-mentioned compounds (Compounds A to K) was orally administered to SD rats (body weight approximately 200 g), no deaths or side effects were observed. The dosage when administering the compound of the present invention to a patient as a prophylactic/therapeutic agent for diseases caused by human immune dysfunction or as a preventive agent against human infectious diseases varies greatly depending on the type of disease, severity of symptoms, type of compound, etc. Approximately, but not limited to, per day for an adult
10 mg to 4000 mg, preferably 50 mg to 500 mg, is administered orally or parenterally. When administered as a preventive agent against infectious diseases, it is of course possible to use it in combination with antibiotics. Examples of dosage forms include powders, fine granules, granules, tablets, capsules, and injections. When preparing a formulation, it is produced by a conventional method using a conventional pharmaceutical carrier. In other words, when preparing a solid preparation for oral use, excipients are added to the main drug, and if necessary, binders, disintegrants, and
After adding lubricants, coloring agents, flavoring agents, etc., it is made into tablets, coated tablets, granules, powders, capsules, etc. by conventional methods. Excipients include, for example, lactose, cornstarch, sucrose, glucose, sorbitol, crystalline cellulose, etc. Binders include, for example, polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, sierrac, and hydroxypropyl. Cellulose, hydroxypropyl starch, polyvinylpyrrolidone, etc., and disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, calcium citrate, dextrin, pectin, etc.
Examples of lubricants include magnesium stearate, talc, polyethylene glycol, silica,
Hydrogenated vegetable oils, etc. are permitted to be added to pharmaceuticals as coloring agents, but as flavoring agents, cocoa powder, peppermint, aromatic acids, peppermint oil,
Dragon brain, cinnamon powder, etc. are used. Of course, these tablets and granules may be coated with sugar coating, gelatin coating, or other coatings as appropriate. When preparing injections, add as necessary to the main drug.
Add PH regulators, buffers, stabilizers, preservatives, solubilizers, etc., and prepare subcutaneous, intramuscular, or intravenous injections using conventional methods. When administering to animals such as livestock and poultry, the drug is administered orally or parenterally. Oral administration is usually done by adding it to feed. As an example of parenteral administration, an injection is prepared by a conventional method and administered subcutaneously, intramuscularly, intravenously, etc. Next, 3,7,11, which is one of the compounds of the present invention,
15,19,23,27,31-octamethyl-2,6,
An example of a formulation containing 10,14,18,22,26,30-dotriacontaoctaen-1-ol (hereinafter referred to as the active ingredient) as an active ingredient is shown below. Formulation Example 1 (Capsule) Main drug 5g Microcrystalline cellulose 80g Corn starch 20g Lactose 22g Polyvinylpyrrolidone 3g Total amount 130g The above ingredients were granulated by a conventional method and then filled into 1000 hard gelatin capsules. Each capsule contains 5mg of the active ingredient. Formulation Example 2 (Powder) Main drug 50g Microcrystalline cellulose 400g Corn starch 550g Total amount 1000g The main drug was dissolved in acetone, then adsorbed on microcrystalline cellulose, and then dried. This was mixed with corn starch and prepared as a powder using a conventional method to prepare a 20-fold powder of the main drug. Formulation example 3 (tablet) Main drug 5g Corn starch 10g Lactose 20g Carboxymethyl cellulose calcium 10g Microcrystalline cellulose 40g Polyvinylpyrrolidone 5g Talc 10g Total amount 100g The main drug was dissolved in acetone, and then adsorbed on microcrystalline cellulose. Dry. Corn starch, lactose, and carboxymethyl cellulose calcium were mixed therein, and then an aqueous solution of polyvinylpyrrolidone was added as a binder to form granules in a conventional manner. After adding talc as a lubricant and mixing, the mixture was compressed into tablets each weighing 100 mg. One tablet contains 5g of the main drug. Formulation example 4 (injection) Main drug 10g Nikkol HCO-60 (Nikko Chemical Co., Ltd. product name) 37g Sesame oil 2g Sodium chloride 9g Propylene glycol 40g Phosphate buffer (0.1M.PH6.0) 100ml Distilled water Total volume 1000ml Main drug, Nikkol Mix HCO-60, sesame oil, and half the amount of propylene glycol, heat and dissolve at about 80℃, add phosphate buffer, sodium chloride, and distilled water with propylene glycol dissolved in advance, and heat to about 80℃. This was added to make a total volume of 1000 ml of an aqueous solution. This aqueous solution was dispensed into 2 ml ampoules, which were sealed and sterilized by heating. One tube contains 20mg of the main drug.

Claims (1)

【特許請求の範囲】 １ 一般式 （式中ａ、ｂは水素原子またはａ−ｂで結合手を
形成する。ｎは１〜10の整数を示す。）で表わさ
れるポリプレニルアルコール系化合物を有効成分
とするヒトまたは動物の免疫機能不全による疾患
の予防・治療剤。 ２ ヒトまたは動物の免疫機能不全による疾患の
予防・治療が、ヒトまたは動物の感染症に対する
防禦である特許請求の範囲第１項記載のヒトまた
は動物の免疫機能不全による疾患の予防・治療
剤。[Claims] 1. General formula (In the formula, a and b form a bond with a hydrogen atom or a-b. n represents an integer of 1 to 10.) Human or animal immune function using a polyprenyl alcohol compound as an active ingredient A preventive/therapeutic agent for diseases caused by malfunction. 2. The preventive/therapeutic agent for diseases caused by immune dysfunction in humans or animals according to claim 1, wherein the prevention/treatment of diseases caused by immune dysfunction in humans or animals is protection against infectious diseases in humans or animals.
JP57089806A 1982-05-28 1982-05-28 Preventive and remedy for disease caused by immunoinsufficiency Granted JPS58206517A (en)

Priority Applications (41)

Application Number Priority Date Filing Date Title
JP57089806A JPS58206517A (en) 1982-05-28 1982-05-28 Preventive and remedy for disease caused by immunoinsufficiency
DE3348500A DE3348500C2 (en) 1982-05-28 1983-05-25 beta, gamma-dihydropolyprenyl alcohol derivative
DE3318989A DE3318989C2 (en) 1982-05-28 1983-05-25 ß, gamma-dihydropolyprenyl alcohol derivatives and medicaments containing them and their use
DE3348492A DE3348492C2 (en) 1982-05-28 1983-05-25 Di:hydro-poly:prenyl alcohol and ester and ether derivs.
DE3348493A DE3348493C2 (en) 1982-05-28 1983-05-25 Di:hydro-poly:prenyl alcohol and ester and ether derivs.
GB08314419A GB2122610B (en) 1982-05-28 1983-05-25 A polyprenyl compound and a pharmaceutical composition containing a polyprenyl compound
CA000429108A CA1310660C (en) 1982-05-28 1983-05-27 B, -dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
BE2/60109A BE896865A (en) 1982-05-28 1983-05-27 ALCOHOL BETA DERIVATIVES, ALPHA-DIHYDROPOLYPRENYLIC AND PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYL COMPOUND.
NL8301892A NL194300C (en) 1982-05-28 1983-05-27 Pharmaceutical composition containing a polyprenol as an active ingredient and polyprenols suitable for use therein.
CH2902/83A CH654823A5 (en) 1982-05-28 1983-05-27 ALCOHOL DERIVATIVES BETA, GAMMA-DIHYDROPOLYPRENYLIQUE AND PHARMACEUTICAL COMPOSITIONS CONTAINING A POLYPRENYLIC COMPOUND.
SE8303013A SE461650B (en) 1982-05-28 1983-05-27 B-DIHYDROPOLYPRENYL ALCOHOL DERIVATIVES AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
ES522789A ES522789A0 (en) 1982-05-28 1983-05-27 A DERIVATIVE OF ALCOHOL B, V-DIHIDROPOLIPRENILICO.
DK239483A DK171640B1 (en) 1982-05-28 1983-05-27 Analogous Process for Preparation of Beta, Gamma-dihydro-polyprenyl Alcohol Derivatives
IT21364/83A IT1164256B (en) 1982-05-28 1983-05-30 BETA DERIVATIVES, ALPHA DIHYDROPOLIPRENYL ALCOHOL AND PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYL COMPOUND
AT0197283A AT389871B (en) 1982-05-28 1983-05-30 METHOD FOR PRODUCING BETA, GAMMA -DIHYDROPOLYPRENYL ALCOHOL DERIVATIVES
FR838308941A FR2527597B1 (en) 1982-05-28 1983-05-30 ALCOHOL B DERIVATIVES, G-DIHYDROPOLYPRENYLIC AND PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYLIC COMPOUND
FR8317169A FR2532843A1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION COMPRISING PHYTOL OR ISOPHYTOL AS ACTIVE INGREDIENT
FR8317175A FR2532846B1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION COMPRISING AS ACTIVE INGREDIENT 3,7,11,15 - TETRAMETHYL -1,6,10,14-HEXADECATETRAENE-3-OL
FR8317171A FR2532844B1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYL COMPOUND
FR8317173A FR2532845B1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION COMPRISING DOCOSANOL AS ACTIVE INGREDIENT
FR8317176A FR2532847B1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION COMPRISING AS ACTIVE INGREDIENT 3,7,11,15-TETRAMETHYLHEXADECA-1-ENE-3-OL
FR8317170A FR2532848B1 (en) 1982-05-28 1983-10-27 PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYL DERIVATIVE
ES529754A ES8507444A1 (en) 1982-05-28 1984-02-15 Beta, gamma-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
ES529753A ES8506567A1 (en) 1982-05-28 1984-02-15 Beta, gamma-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
GB08508217A GB2159710B (en) 1982-05-28 1985-03-29 Containing a polyprenyl compound
GB08508220A GB2159713A (en) 1982-05-28 1985-03-29 Containing a polyprenyl compound
GB08508218A GB2159711B (en) 1982-05-28 1985-03-29 Containing a polyprenyl compound
GB08508219A GB2159712B (en) 1982-05-28 1985-03-29 Containing a polyprenyl compound
GB08508216A GB2159055B (en) 1982-05-28 1985-03-29 Pharmaceutical compositions of 3,7,11,15-tetra-methylhexadec-1-en-3-ol
GB08508214A GB2159054B (en) 1982-05-28 1985-03-29 Pharmaceutical compositions of polyprenyl alcohols
GB08508215A GB2159709B (en) 1982-05-28 1985-03-29 Containing a polyprenyl compound
US06/760,221 US4624966A (en) 1982-05-28 1985-07-29 β,γ-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
FR858513026A FR2569108B1 (en) 1982-05-28 1985-09-02 PHARMACEUTICAL COMPOSITION CONTAINING A POLYPRENYL COMPOUND
SE8801514A SE502923C2 (en) 1982-05-28 1988-04-22 Use of a polyprenyl compound for the preparation of protylactic / therapeutic agent for human and animal diseases due to defective immune system
SE8801515A SE502924C2 (en) 1982-05-28 1988-04-22 Pharmaceutical composition containing an effective amount of 3,7,11,15-tetramethyl-hexadeca-1-en-3-ol or 3,7,11,15-tetramethyl-1,6,10,14-hexadecatetraen-3-ol
SE8801513A SE502922C2 (en) 1982-05-28 1988-04-22 Use of a polyprenyl compound for the preparation of prophylactic / therapeutic agent for human and animal diseases due to defective immune system
US08/011,197 US5280048A (en) 1982-05-28 1993-01-29 β,γ-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
US08/584,145 US6111131A (en) 1982-05-28 1996-01-11 Beta, gamma-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
US08/599,944 US5658958A (en) 1982-05-28 1996-02-14 β, γ-dihydropolyprenyl alcohol derivatives effective at mitigating stress in animals
US08/601,489 US6288128B1 (en) 1982-05-28 1996-02-14 β,γ-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
NL9900009A NL9900009A (en) 1982-05-28 2000-12-05 Di:hydro-poly:prenyl alcohol and ester and ether derivs.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP57089806A JPS58206517A (en) 1982-05-28 1982-05-28 Preventive and remedy for disease caused by immunoinsufficiency

Publications (2)

Publication Number Publication Date
JPS58206517A JPS58206517A (en) 1983-12-01
JPH026326B2 true JPH026326B2 (en) 1990-02-08

Family

ID=13980959

Family Applications (1)

Application Number Title Priority Date Filing Date
JP57089806A Granted JPS58206517A (en) 1982-05-28 1982-05-28 Preventive and remedy for disease caused by immunoinsufficiency

Country Status (2)

Country Link
JP (1) JPS58206517A (en)
BE (1) BE896865A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5973533A (en) * 1982-10-21 1984-04-25 Eisai Co Ltd Beta,gamma-dihydropolyprenyl alcohol derivative

Also Published As

Publication number Publication date
BE896865A (en) 1983-11-28
JPS58206517A (en) 1983-12-01

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