JP3652865B2

JP3652865B2 - Mixture of lactic acid condensate and composition containing the same

Info

Publication number: JP3652865B2
Application number: JP34767697A
Authority: JP
Inventors: 久雄曽根; 正記坂入; 典子吉澤; 悦子伊佐
Original assignee: 株式会社Ｇｌａｒｔ
Priority date: 1997-12-17
Filing date: 1997-12-17
Publication date: 2005-05-25
Anticipated expiration: 2017-12-17
Also published as: JPH11180865A

Description

【０００１】
【発明の属する技術分野】
本発明は、生体の内分泌異常、代謝異常および免疫異常を改善、治癒または予防する作用を有する乳酸縮合物の混合物および当該混合物を含有する医薬品や機能性食品等の組成物に関する。
【０００２】
【従来の技術】
今までの内分泌異常、代謝異常および免疫異常疾患の治療に用いられている薬剤の多くは、ホルモン、ビタミン、酵素または免疫性物質であり、生体にとっての不足分または欠損分を補うか、生体の過剰反応に拮抗させるために用いられる。これらの薬剤の効果は顕著であるが、長期に渡って使用することによる副作用も強く、使用に際しては多大な注意カと慎重さが要求される。
【０００３】
一方、近年、現代医療の「適応」と「限界」が次第に明らかになるにつれ、医療現場においても様々な方法により患者の持つ治癒力（免疫能力、ホルモンバランス維持能力等）を高めて治療に役立てようとする試みが数多くおこなわれている。
【０００４】
また、これまでに種々の乳酸縮合物が知られているが、そのほとんどが生分解性プラスティックとしての工業的利用や、徐放性薬剤用基材としての利用や、縫合糸などの医療用材料としての利用が提案されているにすぎず、乳酸縮合物自体の薬効については詳しく研究されていないのが現状である。
【０００５】
【発明が解決しようとする課題】
かかる状況に鑑み、本発明者が鋭意研究を重ねた結果、生体成分である乳酸を加熱し脱水縮合することにより得られる乳酸縮合物の混合物を、経口経路或いはその他の経路を通じて生体に摂取させると、腸内細菌増殖促進、免疫賦活および免疫調整等の種々の薬理効果が発揮されることを見出し、本発明を完成するに至つた。
【０００６】
すなわち、本発明は、経口、塗布、貼布、挿入、包埋などの経路を通じて生体に摂取させることにより、内分泌異常、代謝異常および免疫異常を改善、治癒または予防する効果を発揮する乳酸縮合物の混合物および当該混合物を含有する医薬品や機能性食品等の組成物を提供することを目的とする。
【０００７】
【課題を解決するための手段】
前記の課題を解決するために本発明が提供する乳酸縮合物の混合物とは、乳酸を加熱縮合することにより得られ、下記の条件で高速液体クロマトグラフィーを行なった時に総ピーク面積に対して乳酸のピーク面積が２０％以下となり、且つ、溶出開始後３分経過する時点から２０分経過する時点までの間に現れる全分画のピーク面積が３０％以上となる組成を有し、腸内細菌増殖促進の薬理作用を有することを特徴とする乳酸縮合物の混合物である。
【０００８】
［高速液体クロマトグラフィーの条件］
（１）カラム：内径４．６ｍｍ、長さ１５ｃｍのＯＤＳカラムを用いる。
【０００９】
（２）溶離液：トリフルオロ酢酸を０．００２重量％の割合で溶解した蒸留水（Ａ液）とアセトニトリル（Ｂ液）を組み合わせて用いる。
【００１０】
（３）溶出プログラム：溶出開始（０分）から５分経過する時点まではＡ液／Ｂ液＝７５容量％／２５容量％の一定比率で溶離液を流し、溶出開始後５分経過する時点から３５分経過する時点まではＡ液／Ｂ液＝７５容量％／２５容量％からＡ液／Ｂ液＝０容量％／１００容量％に変化するリニアグラジュエント溶出を行ない、溶出開始後３５分経過する時点から４０分経過する時点まではＡ液／Ｂ液＝０容量％／１００容量％の一定比率で溶離液を流す。
【００１１】
（４）溶離液の流量：１．０ｍｌ／ｍｉｎ
（５）検出：２１０ｎｍの紫外波長を用いた紫外吸光法により検出する。
【００１２】
本発明にかかる乳酸縮合物の混合物は、分子量が比較的小さい各種の乳酸縮合物を多量に含有する混合物であり、これを様々な経路（例えば、経口、塗布、貼布、挿入、包埋など）を通じて生体に摂取させると、特異的に腸内細菌増殖促進、免疫賦活および免疫調節等の薬理効果を発揮し、しかも毒性をほとんど示さない。本発明にかかる乳酸縮合物の混合物は、粘度の高い液体又は硬度の低い固体であるが、対象疾患、適用部位に応じて様々な成分、材料または添加剤を加え、物理的性質を改変したり、様々な形態の組成物にしたりすることができる。例えば、取り扱い性を良くするために中和塩の粉末にしたり、希釈したり、経口投与可能な剤型にしたり、塗布可能な剤型にしたり、不織布等に塗布して貼付可能な剤型にしたりしてもよい。
【００１３】
また、本発明にかかる乳酸縮合物の混合物は、生体の内分泌異常、代謝異常および免疫異常を改善、治癒または予防することを期待して用いるものであるから、医薬品として利用されることは勿論であるが、そのほかにも、いわゆる健康食品のような機能性食品、化粧品、医薬部外品、医療用品、衛生用品などの形態で利用してもよい。
【００１４】
【発明の実施の形態】
次に本発明の実施の形態について、具体的に説明する。本発明にかかる乳酸縮合物の混合物は、Ｌ−乳酸、Ｄ−乳酸又はＤＬ−乳酸のうちの少なくともひとつを含有する乳酸を加熱縮合することにより得られ、下記の条件で高速液体クロマトグラフィーを行なった時に総ピーク面積に対して乳酸のピーク面積が２０％以下となり、且つ、溶出開始後３分経過する時点から２０分経過する時点までの間に現れる全分画のピーク面積が３０％以上となる組成を有する。
【００１５】
［高速液体クロマトグラフィーの条件］
（１）カラム：内径４．６ｍｍ、長さ１５ｃｍのＯＤＳカラムを用いる。カラム内のＯＤＳゲルとしては、通常は、孔径が８０オングストローム（Å）以上のものを用いる。
【００１６】
（２）溶離液：トリフルオロ酢酸を０．００２重量％の割合で溶解した蒸留水（Ａ液）とアセトニトリル（Ｂ液）を組み合わせて用いる。
【００１７】
（３）溶出プログラム：溶出開始（０分）から５分経過する時点まではＡ液／Ｂ液＝７５容量％／２５容量％の一定比率で溶離液を流し、溶出開始後５分経過する時点から３５分経過する時点まではＡ液／Ｂ液＝７５容量％／２５容量％からＡ液／Ｂ液＝０容量％／１００容量％に変化するリニアグラジュエント溶出を行ない、溶出開始後３５分経過する時点から４０分経過する時点まではＡ液／Ｂ液＝０容量％／１００容量％の一定比率で溶離液を流す。
【００１８】
（４）溶離液の流量：１．０ｍｌ／ｍｉｎ
（５）検出：２１０ｎｍの紫外波長を用いた紫外吸光法により検出する。
【００１９】
上記したような条件を満たす乳酸縮合物の混合物を製造するには、反応条件を適切に制御しなければならない。
【００２０】
原料とされる乳酸としては、Ｌ−乳酸、Ｄ−乳酸、ＤＬ−乳酸、又は、これらの混合物を使用する。乳酸は、試薬級のグレードである必要はなく、例えば、食品添加用の乳酸であってもよい。原料中の乳酸濃度は、作業効率から見れば高濃度のものが好ましいが、低濃度でもなんら差し支えない。
【００２１】
乳酸を脱水縮合させる際の加熱温度は、通常、１００〜１８０℃であり、好ましくは１２０〜１５０℃である。加熱温度が１００℃よりも低いと、脱水縮合が十分に行われないことがある。一方、加熱温度１８０℃よりも高いと、目的とする比較的低分子の乳酸縮合物が少なくなってしまう。
【００２２】
脱水縮合の際の圧力は、目的の縮合物を得るためには常圧でもなんら差し支えないが、効率の点から見ると減圧した方が反応時間を短縮することができる。減圧する場合、通常、３０〜１ｍｍＨｇ、好ましくは１０〜１ｍｍＨｇとする。この圧力が３０ｍｍＨｇより高いと脱水縮合反応が進行しにくく、時間がかかってしまう。反応時間は、減圧条件にもよるが、通常は１時間以上であり、好ましくは２〜８時間である。脱水縮合を行なう際には、必要に応じて窒素ガス等の不活性ガスを通気してもよい。
【００２３】
本発明の乳酸縮合物の混合物を得る場合の具体的な操作は、例えば次の手順で行えばよい。先ず、原科である乳酸を用意する。乳酸としては、Ｌ体、Ｄ体またはＤＬ体を用いる。これらは、単独で用いてもよいし、２種以上を組み合わせて用いてもよい。なお、作業効率の点から乳酸濃度は高いことが好ましい。次いで、この乳酸を、温度１００℃以上、圧力７６０ｍｍＨｇ〜３００ｍｍＨｇの条件下で１時間以上、例えば、１４０℃／７６０ｍｍＨｇから１４０℃／３００ｍｍＨｇまで段階的に減圧度を変えながら１〜２時間減圧下で加熱することにより、水分を除去する。その後、温度１００℃以上、圧力１０〜１ｍｍＨｇの条件下で１時間以上、例えば１４０℃／１０ｍｍＨｇで１〜４時間縮合反応させて反応液を得る。
【００２４】
本発明にかかる乳酸縮合物の混合物は、高速液体クロマトグラフィーにより上記の条件で分析した時に、溶出開始後３分経過する時点から２０分経過する時点までの間に現れる全分画のピーク面積の合計が、総ピーク面積の３０％以上に達するものであり、比較的低分子の乳酸縮合物を多量に含有している。従来、乳酸を加熱脱水することにより得られる乳酸縮合物の混合物としては、低分子分画が多いのものから高分子分画が多いのものまで知られているが、本発明にかかる乳酸縮合物の混合物は、従来公知のものと比べて低分子分画を極めて多量に含んでいる。しかしながら、本発明にかかる乳酸縮合物の混合物の中にどのような乳酸縮合物が含有されているかの詳細は不明である。
【００２５】
本発明にかかる乳酸縮合物の混合物は、生体に対し特異的に腸内細菌増殖促進、免疫賦活および免疫調節等の薬理効果を発揮し、しかも毒性をほとんど示さない。より具体的には、例えば、経口摂取によって、制癌剤副作用の抑制、リュウマチ、前立腺疾患、糖尿病、高血圧、ウイルス性肝炎、自己免疫疾患、アレルギー性疾患、新生物、自律神経失調症などの各種疾患の改善および治癒、術前術後の創傷回復および体力回復、更年期障害または生理痛などの婦人病の改善および治癒、或いは前記以外の成人病の改善および治癒などの薬理効果が認められる。また、患部へ塗布、貼付、挿入、包埋などの方法で直接的に適用することにより、アトピー性皮膚炎、火傷、あかぎれ、痔、にきび、いぼ、魚の目、たこ等の改善や治癒にも有効である。
【００２６】
従って、本発明にかかる乳酸縮合物の混合物を様々な経路で生体に適用することにより、生体の内分泌異常、代謝異常および免疫異常を改善、治癒または予防する効果を期待できる。なお、本発明にかかる乳酸縮合物の混合物は、前記のような薬理効果を期待して用いるものであるから、医薬品として利用されることは勿論であるが、そのほかにも、いわゆる健康食品のような機能性食品、化粧品、医薬部外品、医療用品、衛生用品などの形態で利用することができる。
【００２７】
本発明にかかる乳酸縮合物の混合物を製造する際には、縮合反応のための加熱温度、圧力、反応時間などを適切に調節する必要はあるが、反応過程において触媒、添加物、反応除剤のような原料以外の成分を添加する必要はない。従って、加熱脱水反応により得られた反応液または反応物を、そのまま本発明にかかる乳酸縮合物の混合物として使用することができる。しかしながら、加熱脱水反応により得られる乳酸縮合物の混合物は粘度の高い液体若しくは硬度の低い固体であるから、そのままでは実用に供しにくいことが多い。そこで、本発明にかかる乳酸縮合物の混合物に、対象疾患、適用部位に応じて様々な成分、材料または添加剤を加え、物理的性質を改変したり、様々な形態の組成物にしたりすることができる。
【００２８】
例えば、乳酸縮合物の混合物を、グリセリンやプロピレングリコールなどの溶媒に溶解し用いても良い。また、必要に応じ、加熱脱水反応の終了後に得られた反応液に水やエタノールなどの有機溶媒を加え、さらに炭酸カルシウム、炭酸水素ナトリウム等の金属塩を加えて希望のｐＨに中和することもできる。中和した場合には、凍結乾燥、減圧乾燥、噴霧乾燥などの種々の乾燥方法により乾燥を行なう。様々な乾燥法の中から乳酸縮合物の混合物の使用目的を考慮して適切な方法が選ばれるが、粉末化するのであれば凍結乾燥法が最も効果的である。
【００２９】
乳酸縮合物の混合物に希釈、中和、粉末化などの予備的調製を施した後に、さらに高度な加工を施して使用目的に適合した組成物に作り上げてもよい。例えば、生体での摂取や吸収を容易にするために賦形剤や食品添加物等を加えて機能性食品（例えば健康食品等）としたり、また、他の賦形剤や安定剤等を加え薬剤（例えば経口剤や経皮吸収剤等）の原料としたり、不織布等の支持体に本発明の乳酸縮合物の混合物を塗布して貼付可能な剤型とすることができる
【実施例】
次に、本発明の実施例を挙げ、本発明をさらに具体的に説明する。以下に示す実施例のうち、実施例１〜３は本発明にかかる乳酸縮合物の混合物の製造例であり、実施例４と５は乳酸縮合物の混合物の免疫に関与する性質を明らかにする実験例であり、実施例６と７は乳酸縮合物の混合物の腸内細菌増殖促進作用を明らかにする実験例であり、実施例８〜３５は乳酸縮合物の混合物の適用例である。
【００３０】
（実施例１）
Ｌ−乳酸５００ｍｌを窒素気流下にて１２０℃／７６０ｍｍＨｇの条件で１２時間加熱し、乳酸縮合物の混合物を約４００ｇ得た。次いで、前記の条件で高速液体クロマトグラフィー（ＨＰＬＣ）を行なうことにより、得られた乳酸縮合物の混合物を分析した。その結果、原料である乳酸のピーク面積は、総ピーク面積の１４％であり、また、溶出開始から３分を経過した時点〜２０分に到達した時点の間に出現した全分画のピーク面積は５６％であった。それから、乳酸縮合物の混合物に水を適当量加えて攪件し、炭酸水素カルシウムを６８ｇ加えて中和した後、凍結乾燥し、白色粉末を得た。
【００３１】
（実施例２）
Ｌ一乳酸５００ｍｌを窒素気流下にて１４０℃／７６０〜３０ｍｍＨｇの条件で段階的に２時間加熱し、さらに１４０℃／ｌ０ｍｍＨｇにて３時問加熱することにより、乳酸縮合物の混合物を約３５０ｇ得た。次いで、前記の条件で高速液体クロマトグラフィー（ＨＰＬＣ）を行なうことにより、得られた乳酸縮合物の混合物を分析した。その結果、原料である乳酸のピーク面積は、総ピーク面積の１８％であり、また、溶出開始から３分を経過した時点〜２０分に到達した時点の間に出現した全分画のピーク面積は５６％であった。それから、乳酸縮合物の混合物に水を適当量加えて攪件し、炭酸水素カルシウムを６０ｇ加えて中和した後、凍結乾燥し、白色粉末を得た。
【００３２】
（実施例３）
ＤＬ−乳酸５００ｍ１を窒素気流下にて１４０℃／７６０ｍｍＨｇの条件で３時間加熱し、さらにｌ４０℃／１５０ｍｍＨｇにて２時間加熱することにより、乳酸縮合物の混合物を約４００ｇ得た。次いで、前記の条件で高速液体クロマトグラフィー（ＨＰＬＣ）を行なうことにより、得られた乳酸縮合物の混合物を分析した。その結果、原料である乳酸のピーク面積は、総ピーク面積の１２％であり、また、溶出開始から３分を経過した時点〜２０分に到達した時点の間に出現した全分画のピーク面積は６２％であった。それから、乳酸縮合物の混合物に水を適当量加えて攪件し、炭酸水素カルシウムを６８ｇ加えて中和した後、凍結乾燥し、白色粉末を得た。
【００３３】
（実施例４）
実施例２で得られた乳酸縮合物の混合物を被験物として用い、ＳＤラットに４ｍｇ／ｋｇ／ｄａｙで４週間経口投与した。投与終了後、各ラットの腹腔内に流動パラフインを投与し、３日後、腹腔浸出細胞を採取した。この腹腔浸出細胞から調製したマクロファージについて、遊走能試験をガラス毛細管法により行った。２４時間後にマクロファージの遊走面積を測定し、乳酸縮合物の混合物を投与しなかったＣｏｎｔｒｏｌ群との面積比を算出した。その結果を第１表に示す。
【００３４】
【表１】

以上の結果から、乳酸縮合物の混合物は、ｉｎｖｉｖｏ試験においてラットのマクロファージ遊走能を向上させている。
【００３５】
（実施例５）
無処置ＳＤラットの腹腔内に流動パラフィンを投与し、３日後、腹腔浸出細胞を採取した。この腹腔浸出細胞から調製したマクロファージに乳酸縮合物の混合物を含有する培地を加えて２４時間放置した後、遊走能試験をガラス毛細管法により行った。実施例２で得られた乳酸縮合物の混合物を被験物として用い、培地１ｍｌあたり当該乳酸縮合物の混合物を０．４ｍｇ溶解した。マクロファージの遊走面積を測定し、乳酸縮合物の混合物を含まない培地を用いたＣｏｎｔｒｏｌ群との面積比を算出した。その結果を第２表に示す。
【００３６】
【表２】

以上の結果から、乳酸縮合物の混合物は、ｉｎｖｉｔｒｏにおいてもラットのマクロファージ遊走能を向上させている。
【００３７】
（実施例６）
実施例２で得られた乳酸縮合物の混合物を被験物として用い、ＳＤラットに４ｍｇ／ｋｇ／ｄａｙで４週間経口投与した。投与終了後、各ラットの腸管内容物を採取し、一定倍率で希釈した後、ＭＲＳ寒天培地に接種し、腸内乳酸菌数を調べた。その結果を第３表に示す。第３表では、乳酸縮合物の混合物を投与しなかったＣｏｎｔｒｏｌ群の腸内乳酸菌数を１とした場合の比を示す。
【００３８】
【表３】

以上の結果から、乳酸縮合物の混合物は、ｉｎｖｉｖｏ試験においてラットの腸内乳酸菌を増殖させている。
【００３９】
（実施例７）
実施例２で得られた乳酸縮合物の混合物を、ラクトバチラス・カゼイ菌を含有する培養液に０．１２５ｍｇ混合物／５ｍｌ倍溶液の濃度で加え、４８時間培養し、一定倍率で希釈した後、ＭＲＳ寒天培地に接種し、ラクトバチラス・カゼイ菌の数を調べた。その結果を第４表に示す。第４表では、乳酸縮合物の混合物を含有しない培養液を添加したＣｏｎｔｒｏｌ群のラクトバチラス・カゼイ菌数を１とした場合の比を示す。
【００４０】
【表４】

以上の結果から、乳酸縮合物の混合物は、ｉｎｖｉｔｒｏ試験においても乳酸菌を増殖させている。
【００４１】
（実施例８）
前記実施例２で得られた乳酸縮合物の混合物を、骨髄癌の患者（６５才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、１週間ほどで体調が良好になり、１〜２ヶ月ほどで、手術後に肺に転移していた腫瘍の縮小が認められた。
【００４２】
（実施例９）
前記実施例２で得られた乳酸縮合物の混合物を、腎臓癌、膀胱癌の患者（６５才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、２〜３週間ほどで体調が良好になり、約２〜３ヶ月経過後、血液検査、ＣＴ検査等の検査で異常は認められなくなった。
【００４３】
（実施例１０）
前記実施例２で得られた乳酸縮合物の混合物を、脳腫瘍の患者（５４才、男性）が２ｇ／Ｄａｙで経口経路にて連日服用したところ、放射線治療、化学療法による白血球の減少が抑えられた。また、副作用による頭髪の脱毛も短期間のうちに回復した。
【００４４】
（実施例１１）
前記実施例２で得られた乳酸縮合物の混合物を、原因不明の危篤患者（８９才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、１週間ほどで体調が良好になり、１〜２ヶ月ほどで健常人と変わらないほどになった。
【００４５】
（実施例１２）
前記実施例２で得られた乳酸縮合物の混合物を、ポリープを持つ患者（６６才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、３年前の手術で取りきれなかったＳ字結腸のポリープがあったにもかかわらず、服用開始から２〜３週間ほどでレントゲン検査による異常が認められなくなり、消失した。
【００４６】
（実施例１３）
前記実施例２で得られた乳酸縮合物の混合物を、Ｃ型肝炎の患者（５１才、男性）が２ｇ／Ｄａｙで経口経路にて連日服用したところ、３〜４日ほどで自覚症状（黄疽等）が改善し、その後、血液検査でもＧＯＴ、γ一ＧＰＴ値が下がった。
【００４７】
（実施例１４）
前記実施例２で得られた乳酸縮合物の混合物を、前立腺肥大の患者（５２才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、３年間通院治療して治らなかったものが２日で痛みが消え、２週問ほどで頻尿、残尿感が解消された。
【００４８】
（実施例１５）
前記実施例２で得られた乳酸縮合物の混合物を、糖尿病の患者（６０才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、１ヶ月ほどで自覚症状（手足のしびれ、頻尿、疲労感等）が改善し、血糖値も２００〜２２０あったものが９３にまで下がった。
【００４９】
（実施例１６）
前記実施例２で得られた乳酸縮合物の混合物を、高血圧の患者（５９才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、２ヶ月ほどで自覚症状（耳鳴り、疲労感、関節痛等）が改善した。
【００５０】
（実施例１７）
前記実施例２で得られた乳酸縮合物の混合物を、リュウマチの患者（５３才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、７年間の通院でも改善しなっかたものが、３〜４日ほどで体が動かせるようになり、２週間ほどで外出できるほどに改善した。
【００５１】
（実施例１８）
前記実施例２で得られた乳酸縮合物の混合物を、リュウマチの患者（７０才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、３〜４日で痛みが消え、手足の動きが楽になった。１ケ月後も経過は良好であり、散歩ができるほどに改善した。
【００５２】
（実施例１９）
前記実施例２で得られた乳酸縮合物の混合物を、関節痛の患者（６７才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、それまでは７年間寝たきりであったものが、３〜４日で歩行できるほどに改善した。
【００５３】
（実施例２０）
前記実施例２で得られた乳酸縮合物の混合物を、膠原病の患者（５０才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、２〜３日で痛みが軽減し、１週間ほどで体の痛みがなくなり、他の薬剤は使用する必要がなくなった。
【００５４】
（実施例２１）
前記実施例２で得られた乳酸縮合物の混合物を、アトピー性皮膚炎の患者（５０才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、３〜４日ほどで痒みが軽減した。服用を中止したところ症状が再発し、再度服用したところ症状が治まった。また、この患者には軽度の更年期障害もあったが、乳酸縮合物の混合物の服用により、その症状も治まってきた。
【００５５】
（実施例２２）
前記実施例２で得られた乳酸縮合物の混合物を、紫外線過敏症の患者（８才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、１０日ほどで症状が軽減した。
【００５６】
（実施例２３）
前記実施例２で得られた乳酸縮合物の混合物を、花粉症の患者（５０才、男性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、５日ほどで鼻水が軽減し、１ヶ月後には、それまで必要としていた保護メガネ、マスクをしなくても良いほどに改善した。
【００５７】
（実施例２４）
前記実施例２で得られた乳酸縮合物の混合物を、蓄膿症の患者（５４才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、１０日ほどでそれまでの症状が改善した。
【００５８】
（実施例２５）
前記実施例２で得られた乳酸縮合物の混合物を、白内障の患者（６５才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、医師により治らないと言われていたものが１ヶ月ほどで改善し、通院する必要もなくなった。
【００５９】
（実施例２６）
前記実施例２で得られた乳酸縮合物の混合物を、ホルモン分泌異常の患者（３３才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、３ヶ月ほどで、年１回だった月経が正常に戻った。
【００６０】
（実施例２７）
前記実施例２で得られた乳酸縮合物の混合物を、生理不順の患者（２６才、女性）が０．５ｇ／Ｄａｙで経口経路にて連日服用したところ、１ヶ月ほどで正常に戻った。
【００６１】
（実施例２８）
前記実施例２で得られた乳酸縮合物の混合物を、自律神経失調症の患者（４２才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、４〜５日経過後には２３年間治らなかった自覚症状（疲労感、頭痛、低血圧、虚弱体質、めまい等）が改善した。
【００６２】
（実施例２９）
前記実施例２で得られた乳酸縮合物の混合物を、パーキンソン病の患者（５０才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、それまで３年間寝たきりであったものが、１ヶ月ほどで普通の生活が送れるほどに改善した。
【００６３】
（実施例３０）
前記実施例２で得られた乳酸縮合物の混合物を、アルコール拒絶症の患者（５３才、男性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、１ヶ月ほどでアルコールに対し拒絶反応を起こさないようになった。
【００６４】
（実施例３１）
前記実施例２で得られた乳酸縮合物の混合物を、腰痛の患者（６５才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、２〜３日ほどで自覚症状が改善した。また、それまであった便秘症も改善した。
【００６５】
（実施例３２）
前記実施例２で得られた乳酸縮合物の混合物を、むち打ち症の患者（４５才、女性）が１ｇ／Ｄａｙで経口経路にて連日服用したところ、２〜３日ほどでそれまで回らなかった首が回るようになった。
【００６６】
（実施例３３）
痔疾の患者（６６才、男性）が、前記実施例２で得られた乳酸縮合物の混合物の適当量を水に溶解し患部に塗布したところ、１〜２日ほどで患部の痛みが取れた。
【００６７】
（実施例３４）
魚の目のひどい患者（３４才、女性）が、前記実施例２で得られた乳酸縮合物の混合物の適当量を市販の軟膏に溶解し患部に塗布したところ、１〜２日で痛みが緩和し、２〜３週間で症状が緩和された。
【００６８】
（実施例３５）
ヒビ、あかぎれのひどい患者（５８才、女性）が、前記実施例２で得られた乳酸縮合物の混合物の適当量を水５〜６ｍｌに溶解し、患部に塗布したところ、１〜３日で症状が改善された。
【００６９】
【発明の効果】
以上に詳述した通り、本発明の乳酸縮合物の混合物は、生体に対し特異的に腸内細菌増殖促進、免疫賦活および免疫調節等の薬理効果を発揮し、しかも毒性をほとんど示さないことから、生体に様々な経路で摂取させることにより、内分泌異常、代謝異常、免疫異常等の疾患またはその症状を改善、治癒または予防することができる。
【００７０】
そして、例えば、経口摂取によって、制癌剤副作用の抑制、リュウマチ、前立腺疾患、糖尿病、高血圧、ウイルス性肝炎、自己免疫疾患、アレルギー性疾患、新生物、自律神経失調症等の改善および治癒、術前術後の創傷回復および体力回復、更年期障害または生理痛等の婦人病の改善および治癒、或いはその他の成人病の改善および治癒に極めて有効である。また、患部への塗布、貼布、挿入および包埋によって、アトピー性皮膚炎、火傷、あかぎれ、痔、にきび、いぼ、魚の目、たこ等の改善および治癒に対し極めて有効である。
【００７１】
本発明の乳酸縮合物の混合物は、人間以外の動物の疾患に対する予防および治療にも有効である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a mixture of lactic acid condensates having an action of improving, curing or preventing endocrine abnormalities, metabolic abnormalities and immune abnormalities in a living body, and compositions such as pharmaceuticals and functional foods containing the mixtures.
[0002]
[Prior art]
Many of the drugs used to treat endocrine disorders, metabolic disorders and immune disorders so far are hormones, vitamins, enzymes or immunological substances, which make up for shortages or deficiencies in the body, Used to antagonize over reaction. Although the effects of these drugs are remarkable, there are strong side effects due to long-term use, and great care and carefulness are required for use.
[0003]
On the other hand, as the “adaptation” and “limits” of modern medical care have become increasingly clear in recent years, the therapeutic power (immunity ability, ability to maintain hormone balance, etc.) of patients can be enhanced by various methods even in the medical field and used for treatment. Many attempts have been made.
[0004]
Various lactic acid condensates have been known so far, most of which are industrially used as biodegradable plastics, used as substrates for sustained-release drugs, and medical materials such as sutures. However, the pharmacological effect of the lactic acid condensate itself has not been studied in detail.
[0005]
[Problems to be solved by the invention]
In view of such a situation, as a result of intensive studies by the present inventors, when a living body ingests a mixture of lactic acid condensates obtained by heating and dehydrating condensation of lactic acid, which is a biological component, to the living body through the oral route or other routes. The present inventors have found that various pharmacological effects such as promotion of intestinal bacterial growth, immunostimulation, and immune regulation are exhibited, and the present invention has been completed.
[0006]
That is, the present invention provides a lactic acid condensate that exhibits an effect of improving, curing, or preventing endocrine abnormalities, metabolic abnormalities, and immune abnormalities by ingesting the living body through routes such as oral, application, patching, insertion, and embedding. It is an object of the present invention to provide a mixture of the above and a composition such as a pharmaceutical or a functional food containing the mixture.
[0007]
[Means for Solving the Problems]
The mixture of lactic acid condensates provided by the present invention to solve the above-mentioned problems is obtained by heat condensation of lactic acid, and the lactic acid condensate with respect to the total peak area when performing high performance liquid chromatography under the following conditions: peak area becomes 20% or less, and has a composition in which all the fractions of peak area appearing between the time which elapses eluting started after 3 minutes to the time that elapses 20 minutes is 30% or more, Enterobacteriaceae It is a mixture of lactic acid condensates characterized by having a growth promoting pharmacological action .
[0008]
[Conditions for high performance liquid chromatography]
(1) Column: An ODS column having an inner diameter of 4.6 mm and a length of 15 cm is used.
[0009]
(2) Eluent: A combination of distilled water (liquid A) and acetonitrile (liquid B) in which trifluoroacetic acid is dissolved at a ratio of 0.002% by weight is used.
[0010]
(3) Elution program: Elution solution is flowed at a fixed ratio of 75% by volume / 25% by volume from the start of elution (0 minutes) until 5 minutes have passed, and when 5 minutes have elapsed since the start of elution. 35 minutes after the elution, linear gradient elution is performed in which A liquid / B liquid = 75 vol% / 25 vol% changes to A liquid / B liquid = 0 vol% / 100 vol%. From the time when minutes elapse until the time when 40 minutes elapses, the eluent is allowed to flow at a constant ratio of liquid A / liquid B = 0 volume% / 100 volume%.
[0011]
(4) Flow rate of eluent: 1.0 ml / min
(5) Detection: Detection is carried out by an ultraviolet absorption method using an ultraviolet wavelength of 210 nm.
[0012]
The mixture of lactic acid condensates according to the present invention is a mixture containing a large amount of various lactic acid condensates having a relatively small molecular weight, and this can be applied to various routes (for example, oral, application, patching, insertion, embedding, etc.). When it is taken into a living body through), it specifically exhibits pharmacological effects such as promotion of intestinal bacterial growth, immunostimulation and immunoregulation, and exhibits little toxicity. The mixture of lactic acid condensates according to the present invention is a high-viscosity liquid or a low-hardness solid, but various physical components, materials or additives may be added depending on the target disease and application site to modify physical properties. The composition can be in various forms. For example, in order to improve the handleability, it is made into a powder of neutralized salt, diluted, or dosage form that can be administered orally, or a dosage form that can be applied, or a dosage form that can be applied to a non-woven fabric or the like. Or you may.
[0013]
In addition, the mixture of lactic acid condensates according to the present invention is used in the hope of improving, curing, or preventing endocrine abnormalities, metabolic abnormalities and immune abnormalities in the living body, so it is of course used as a pharmaceutical product. In addition, it may be used in the form of functional foods such as so-called health foods, cosmetics, quasi-drugs, medical supplies, hygiene products, and the like.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Next, embodiments of the present invention will be specifically described. The mixture of lactic acid condensates according to the present invention is obtained by heat condensation of lactic acid containing at least one of L-lactic acid, D-lactic acid or DL-lactic acid, and is subjected to high performance liquid chromatography under the following conditions. The peak area of lactic acid is 20% or less with respect to the total peak area, and the peak area of all fractions that appears between 3 minutes after the start of elution and 20 minutes has passed is 30% or more. It has the composition which becomes.
[0015]
[Conditions for high performance liquid chromatography]
(1) Column: An ODS column having an inner diameter of 4.6 mm and a length of 15 cm is used. As the ODS gel in the column, those having a pore diameter of 80 angstroms (Å) or more are usually used.
[0016]
(2) Eluent: A combination of distilled water (liquid A) and acetonitrile (liquid B) in which trifluoroacetic acid is dissolved at a ratio of 0.002% by weight is used.
[0017]
(3) Elution program: Elution solution is flowed at a fixed ratio of 75% by volume / 25% by volume from the start of elution (0 minutes) until 5 minutes have passed, and when 5 minutes have elapsed since the start of elution. 35 minutes after the elution, linear gradient elution is performed in which A liquid / B liquid = 75 vol% / 25 vol% changes to A liquid / B liquid = 0 vol% / 100 vol%. From the time when minutes elapse until the time when 40 minutes elapses, the eluent is allowed to flow at a constant ratio of liquid A / liquid B = 0 volume% / 100 volume%.
[0018]
(4) Flow rate of eluent: 1.0 ml / min
(5) Detection: Detection is carried out by an ultraviolet absorption method using an ultraviolet wavelength of 210 nm.
[0019]
In order to produce a mixture of lactic acid condensates that satisfy the above conditions, the reaction conditions must be controlled appropriately.
[0020]
As lactic acid used as a raw material, L-lactic acid, D-lactic acid, DL-lactic acid, or a mixture thereof is used. Lactic acid need not be reagent grade, and may be, for example, lactic acid for food addition. The concentration of lactic acid in the raw material is preferably a high concentration from the viewpoint of work efficiency, but may be a low concentration.
[0021]
The heating temperature at the time of dehydrating and condensing lactic acid is usually 100 to 180 ° C, preferably 120 to 150 ° C. When the heating temperature is lower than 100 ° C., dehydration condensation may not be performed sufficiently. On the other hand, when the heating temperature is higher than 180 ° C., the target relatively low-molecular lactic acid condensate decreases.
[0022]
The pressure during dehydration condensation may be normal pressure in order to obtain the desired condensate, but from the viewpoint of efficiency, reducing the pressure can shorten the reaction time. When reducing the pressure, it is usually 30 to 1 mmHg, preferably 10 to 1 mmHg. If this pressure is higher than 30 mmHg, the dehydration-condensation reaction does not proceed easily and takes time. The reaction time is usually 1 hour or longer, preferably 2 to 8 hours, although it depends on the decompression conditions. When performing dehydration condensation, you may ventilate inert gas, such as nitrogen gas, as needed.
[0023]
The specific operation for obtaining the mixture of the lactic acid condensates of the present invention may be performed, for example, by the following procedure. First, lactic acid, the original course, is prepared. As lactic acid, L-form, D-form or DL-form is used. These may be used alone or in combination of two or more. The lactic acid concentration is preferably high from the viewpoint of work efficiency. Then, the lactic acid is reduced under reduced pressure for 1-2 hours while changing the degree of reduced pressure stepwise from 140 ° C./760 mmHg to 140 ° C./300 mmHg for 1 hour or longer under conditions of a temperature of 100 ° C. or higher and a pressure of 760 mmHg to 300 mmHg. Water is removed by heating. Thereafter, a condensation reaction is carried out under conditions of a temperature of 100 ° C. or higher and a pressure of 10 to 1 mmHg for 1 hour or longer, for example, 140 ° C./10 mmHg for 1 to 4 hours to obtain a reaction solution.
[0024]
When the mixture of lactic acid condensates according to the present invention is analyzed under the above conditions by high performance liquid chromatography, the peak area of all fractions appearing between 3 minutes after elution start and 20 minutes have elapsed. The total reaches 30% or more of the total peak area and contains a large amount of a relatively low-molecular lactic acid condensate. Conventionally, as a mixture of lactic acid condensates obtained by heat-dehydrating lactic acid, those having a large number of low molecular fractions to those having a large number of high molecular fractions are known. This mixture contains an extremely large amount of a low molecular fraction as compared with a conventionally known mixture. However, it is unclear what kind of lactic acid condensate is contained in the mixture of lactic acid condensates according to the present invention.
[0025]
The mixture of lactic acid condensates according to the present invention exhibits pharmacological effects such as promotion of intestinal bacterial growth, immunostimulation and immunoregulation specifically for the living body, and exhibits little toxicity. More specifically, for example, suppression of side effects of cancer drugs, rheumatism, prostate diseases, diabetes, hypertension, viral hepatitis, autoimmune diseases, allergic diseases, neoplasms, autonomic dysfunction etc. Pharmacological effects such as improvement and healing, preoperative and postoperative wound recovery and physical strength, improvement and healing of gynecological diseases such as menopause or menstrual pain, or improvement and healing of other adult diseases are observed. In addition, by applying directly to the affected area by application, sticking, insertion, embedding, etc., it is also effective in improving and healing atopic dermatitis, burns, redheads, eyelids, acne, warts, fish eyes, octopus, etc. It is.
[0026]
Therefore, by applying the mixture of lactic acid condensates according to the present invention to a living body through various routes, an effect of improving, curing or preventing endocrine abnormalities, metabolic abnormalities and immune abnormalities in the living body can be expected. The mixture of lactic acid condensates according to the present invention is used in expectation of the pharmacological effects as described above, so that it can be used as a pharmaceutical product. It can be used in the form of various functional foods, cosmetics, quasi drugs, medical supplies, hygiene products, and the like.
[0027]
When the mixture of lactic acid condensates according to the present invention is produced, it is necessary to appropriately adjust the heating temperature, pressure, reaction time, etc. for the condensation reaction. It is not necessary to add components other than the raw materials. Therefore, the reaction liquid or reaction product obtained by the heat dehydration reaction can be used as it is as a mixture of the lactic acid condensate according to the present invention. However, since the mixture of lactic acid condensates obtained by the heat dehydration reaction is a liquid having a high viscosity or a solid having a low hardness, it is often difficult to use as it is. Therefore, various components, materials, or additives are added to the mixture of the lactic acid condensate according to the present invention depending on the target disease and application site to modify the physical properties or make the composition into various forms. Can do.
[0028]
For example, a mixture of lactic acid condensates may be used by dissolving in a solvent such as glycerin or propylene glycol. If necessary, add an organic solvent such as water or ethanol to the reaction solution obtained after completion of the heat dehydration reaction, and then add a metal salt such as calcium carbonate or sodium bicarbonate to neutralize it to the desired pH. You can also. When neutralized, drying is performed by various drying methods such as freeze drying, drying under reduced pressure, and spray drying. An appropriate method is selected from various drying methods in consideration of the purpose of use of the mixture of lactic acid condensates, but the lyophilization method is the most effective if it is powdered.
[0029]
The mixture of lactic acid condensates may be subjected to preliminary preparations such as dilution, neutralization, and pulverization, and then further processed to make a composition suitable for the intended use. For example, in order to facilitate ingestion and absorption in the living body, excipients and food additives are added to make functional foods (eg health foods), and other excipients and stabilizers are added. It can be used as a raw material for drugs (for example, oral preparations, transdermal absorption agents, etc.), or a mixture of the lactic acid condensate of the present invention can be applied to a support such as a nonwoven fabric to form a dosage form that can be applied.
Next, examples of the present invention will be given to describe the present invention more specifically. Among the examples shown below, Examples 1 to 3 are production examples of the mixture of lactic acid condensates according to the present invention, and Examples 4 and 5 clarify the properties involved in immunity of the mixture of lactic acid condensates. Examples are experimental examples, Examples 6 and 7 are experimental examples for clarifying the intestinal bacterial growth promoting action of a mixture of lactic acid condensates, and Examples 8-35 are application examples of a mixture of lactic acid condensates.
[0030]
(Example 1)
500 ml of L-lactic acid was heated for 12 hours under a nitrogen stream at 120 ° C./760 mmHg to obtain about 400 g of a mixture of lactic acid condensates. Subsequently, the mixture of the obtained lactic acid condensate was analyzed by performing a high performance liquid chromatography (HPLC) on the said conditions. As a result, the peak area of lactic acid, which is a raw material, is 14% of the total peak area, and the peak area of all fractions that appeared between the time when 3 minutes have passed from the start of elution and the time when it reached 20 minutes. Was 56%. Then, an appropriate amount of water was added to the mixture of the lactic acid condensate, and the mixture was neutralized by adding 68 g of calcium bicarbonate, and then freeze-dried to obtain a white powder.
[0031]
(Example 2)
By heating 500 ml of L monolactic acid stepwise in a nitrogen stream at 140 ° C./760 to 30 mmHg for 2 hours and further heating at 140 ° C./10 mmHg for 3 hours, about 350 g of the mixture of lactic acid condensates is obtained. Obtained. Subsequently, the mixture of the obtained lactic acid condensate was analyzed by performing a high performance liquid chromatography (HPLC) on the said conditions. As a result, the peak area of lactic acid, which is a raw material, is 18% of the total peak area, and the peak area of all fractions that appeared between 3 minutes after the start of elution and 20 minutes have elapsed. Was 56%. Then, an appropriate amount of water was added to the mixture of the lactic acid condensate, and the mixture was neutralized by adding 60 g of calcium bicarbonate, and then freeze-dried to obtain a white powder.
[0032]
(Example 3)
About 400 g of a mixture of lactic acid condensates was obtained by heating 500 ml of DL-lactic acid under a nitrogen stream at 140 ° C./760 mmHg for 3 hours and further heating at 140 ° C./150 mmHg for 2 hours. Subsequently, the mixture of the obtained lactic acid condensate was analyzed by performing a high performance liquid chromatography (HPLC) on the said conditions. As a result, the peak area of lactic acid, which is a raw material, is 12% of the total peak area, and the peak area of all fractions that appeared between 3 minutes after the elution start and 20 minutes have passed. Was 62%. Then, an appropriate amount of water was added to the mixture of the lactic acid condensate, and the mixture was neutralized by adding 68 g of calcium bicarbonate, and then freeze-dried to obtain a white powder.
[0033]
(Example 4)
The mixture of the lactic acid condensate obtained in Example 2 was used as a test substance and orally administered to SD rats at 4 mg / kg / day for 4 weeks. After the administration, flow paraffin was administered into the peritoneal cavity of each rat, and peritoneal exudate cells were collected 3 days later. With respect to the macrophages prepared from the peritoneal exudate cells, the migration ability test was performed by the glass capillary method. After 24 hours, the migration area of macrophages was measured, and the area ratio with the Control group that did not receive the mixture of lactic acid condensates was calculated. The results are shown in Table 1.
[0034]
[Table 1]

From the above results, the mixture of lactic acid condensates improves the macrophage migration ability of rats in an in vivo test.
[0035]
(Example 5)
Liquid paraffin was administered into the peritoneal cavity of untreated SD rats, and peritoneal exudate cells were collected 3 days later. A medium containing a mixture of lactic acid condensates was added to macrophages prepared from the peritoneal exudate cells and allowed to stand for 24 hours, and then the migration ability test was performed by a glass capillary method. The lactic acid condensate mixture obtained in Example 2 was used as a test substance, and 0.4 mg of the lactic acid condensate mixture was dissolved per 1 ml of the medium. The migration area of macrophages was measured, and the area ratio with the Control group using a medium not containing a mixture of lactic acid condensates was calculated. The results are shown in Table 2.
[0036]
[Table 2]

From the above results, the mixture of lactic acid condensates improves the macrophage migration ability of rats even in vitro.
[0037]
(Example 6)
The mixture of the lactic acid condensate obtained in Example 2 was used as a test substance and orally administered to SD rats at 4 mg / kg / day for 4 weeks. After the administration was completed, the intestinal contents of each rat were collected, diluted at a constant magnification, and then inoculated on an MRS agar medium, and the number of intestinal lactic acid bacteria was examined. The results are shown in Table 3. Table 3 shows the ratio when the number of intestinal lactic acid bacteria in the Control group to which the mixture of lactic acid condensates was not administered is 1.
[0038]
[Table 3]

From the above results, the mixture of lactic acid condensates allowed the growth of rat intestinal lactic acid bacteria in an in vivo test.
[0039]
(Example 7)
The mixture of the lactic acid condensate obtained in Example 2 was added to the culture solution containing Lactobacillus casei at a concentration of 0.125 mg mixture / 5 ml solution, cultured for 48 hours, diluted at a constant magnification, and then MRS. The agar medium was inoculated and the number of Lactobacillus casei was examined. The results are shown in Table 4. Table 4 shows the ratio when the number of Lactobacillus casei bacteria in the Control group to which the culture solution not containing the mixture of lactic acid condensates was added is 1.
[0040]
[Table 4]

From the above results, the mixture of the lactic acid condensate has grown lactic acid bacteria also in the in vitro test.
[0041]
(Example 8)
When a bone marrow cancer patient (65 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / Day, the physical condition improved in about one week. In about 2 months, the tumor that had metastasized to the lung after surgery was reduced.
[0042]
Example 9
The mixture of lactic acid condensate obtained in Example 2 was taken daily by the oral route at 1 g / day by a patient with renal cancer and bladder cancer (65 years old, male). After about 2 to 3 months, no abnormalities were observed in tests such as blood tests and CT tests.
[0043]
(Example 10)
When a patient with brain tumor (54 years old, male) took the mixture of lactic acid condensates obtained in Example 2 daily by the oral route at 2 g / day, the decrease in leukocytes due to radiotherapy and chemotherapy was suppressed. It was. Moreover, hair loss due to side effects recovered within a short period of time.
[0044]
(Example 11)
When the lactic acid condensate mixture obtained in Example 2 was taken daily by an oral route at 1 g / day by a critically ill patient (89 years old, female), the physical condition improved in about one week, In about one to two months, it became almost the same as a healthy person.
[0045]
(Example 12)
When a patient with polyp (66 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, it could not be removed by surgery three years ago. Despite the presence of a polyp in the sigmoid colon, no abnormalities due to X-ray examination were observed and disappeared within 2 to 3 weeks from the start of administration.
[0046]
(Example 13)
When the patient with hepatitis C (51 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 at 2 g / Day by the oral route every day, the subjective symptoms (yellow) After that, GOT and γ-one GPT values also decreased in blood tests.
[0047]
(Example 14)
When a patient with prostatic hypertrophy (52 years old, male) took the mixture of lactic acid condensates obtained in Example 2 daily by the oral route at 1 g / day, he was treated for 3 years and was not cured. The pain disappeared in 2 days, and the frequency of frequent urination and residual urine disappeared in about 2 weeks.
[0048]
(Example 15)
When a diabetic patient (60 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, subjective symptoms (numbness of limbs, frequent numbness in about one month) Urine, feeling of fatigue, etc.) improved, and the blood sugar level was 200-220, but it dropped to 93.
[0049]
(Example 16)
When the patient with hypertension (59 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / Day, subjective symptoms (tinnitus, fatigue, Joint pain, etc.) improved.
[0050]
(Example 17)
When a rheumatic patient (53 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, it did not improve even after a 7-year visit. The body was able to move in about 3-4 days, and improved so that I could go out in about 2 weeks.
[0051]
(Example 18)
When a rheumatic patient (70 years old, female) took the mixture of lactic acid condensates obtained in Example 2 daily by the oral route at 1 g / day, the pain disappeared in 3-4 days and the movement of the limbs Became easier. The progress was good even after one month, and improved so that he could walk.
[0052]
(Example 19)
The patient with arthralgia (67 years old, female) who took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 0.5 g / day was bedridden for 7 years until then. Things improved so that I could walk in 3-4 days.
[0053]
(Example 20)
When a patient with collagen disease (50 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, the pain was reduced in 2 to 3 days. After about a week, my pain disappeared and no other drugs needed to be used.
[0054]
(Example 21)
When a patient with atopic dermatitis (50 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily by oral route at 0.5 g / day, it took about 3-4 days. Reduced. Symptoms recurred after discontinuation of the drug, and the symptoms subsided when the drug was taken again. The patient also had mild climacteric disturbances, but her symptoms were cured by taking a mixture of lactic acid condensates.
[0055]
(Example 22)
When the patient with UV sensitivity (8 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily at 0.5 g / day by the oral route, the symptoms alleviated in about 10 days. .
[0056]
(Example 23)
When a patient with hay fever (50 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 0.5 g / day, the runny nose decreased in about 5 days. After one month, the situation was improved to the extent that it was not necessary to wear the protective glasses and masks that were required before.
[0057]
(Example 24)
When a patient with empyema (54 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, the symptoms were improved in about 10 days.
[0058]
(Example 25)
A mixture of the lactic acid condensate obtained in Example 2 was taken by a cataract patient (65 years old, female) daily by oral route at 0.5 g / day, and was said to not be cured by a doctor. Improved in about a month, and no longer needed to go to the hospital.
[0059]
(Example 26)
When a patient with hormonal secretion abnormality (33 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 0.5 g / day, about once every three months. The menstruation was back to normal.
[0060]
(Example 27)
The mixture of lactic acid condensates obtained in Example 2 was taken daily by an oral route at 0.5 g / day by an irregular patient (26 years old female), and returned to normal in about one month.
[0061]
(Example 28)
When a patient with autonomic dysfunction (42 years old, female) took the mixture of lactic acid condensates obtained in Example 2 daily by the oral route at 1 g / day, 23 years after 4 to 5 days had elapsed Subjective symptoms that were not cured (fatigue, headache, hypotension, weak constitution, dizziness, etc.) improved.
[0062]
(Example 29)
When the patient with Parkinson's disease (50 years old, female) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, he had been bedridden for 3 years until then. It improved so that I could live a normal life in about a month.
[0063]
(Example 30)
When a patient with alcohol rejection (53 years old, male) took the mixture of the lactic acid condensate obtained in Example 2 daily by the oral route at 1 g / day, it rejected the alcohol in about one month. I'm not waking up.
[0064]
(Example 31)
When a patient with low back pain (65 years old, female) took the mixture of lactic acid condensates obtained in Example 2 daily by the oral route at 1 g / day, the subjective symptoms improved in about 2 to 3 days. It also improved constipation that had been there before.
[0065]
(Example 32)
The mixture of the lactic acid condensate obtained in Example 2 was taken every day by the oral route at 1 g / day by a patient with whiplash (45 years old, female). My neck started to turn.
[0066]
(Example 33)
When a hemorrhoid patient (66 years old, male) dissolved an appropriate amount of the lactic acid condensate mixture obtained in Example 2 in water and applied it to the affected area, the affected area was painful in about 1-2 days. .
[0067]
(Example 34)
A patient (34 years old, female) with severe fish eyes dissolved an appropriate amount of the lactic acid condensate mixture obtained in Example 2 in a commercially available ointment and applied it to the affected area. The symptoms were relieved in 2-3 weeks.
[0068]
(Example 35)
When a patient (58 years old, female) with severe cracks and tears dissolved an appropriate amount of the mixture of the lactic acid condensate obtained in Example 2 in 5-6 ml of water and applied to the affected area, it took 1-3 days. Symptoms improved.
[0069]
【The invention's effect】
As described in detail above, the mixture of lactic acid condensates of the present invention exerts pharmacological effects such as promotion of intestinal bacterial growth, immunostimulation and immunoregulation specifically for the living body, and exhibits little toxicity. It is possible to improve, cure or prevent diseases such as endocrine abnormalities, metabolic abnormalities and immune abnormalities or symptoms thereof by ingesting them by various routes.
[0070]
And, for example, suppression of side effects of anticancer drugs, oral rheumatism, prostate disease, diabetes, hypertension, viral hepatitis, autoimmune diseases, allergic diseases, neoplasms, autonomic dysfunction etc., preoperative surgery It is extremely effective for the later recovery and healing of wounds, improvement and cure of gynecological diseases such as menopause or menstrual pain, or other adult diseases. In addition, it is extremely effective for the improvement and healing of atopic dermatitis, burns, bruises, wrinkles, acne, warts, fish eyes, octopus, etc. by application, patching, insertion and embedding to the affected area.
[0071]
The mixture of lactic acid condensates of the present invention is also effective for prevention and treatment of diseases of animals other than humans.

Claims

It is obtained by heat condensation of lactic acid, and when performing high performance liquid chromatography under the following conditions, the peak area of lactic acid is 20% or less with respect to the total peak area, and 20 minutes after 3 minutes from the start of elution. A mixture of lactic acid condensates, which has a composition in which the peak area of all fractions appearing until the point of time elapses is 30% or more and has a pharmacological action for promoting intestinal bacterial growth .
[Conditions for high performance liquid chromatography]
(1) Column: An ODS column having an inner diameter of 4.6 mm and a length of 15 cm is used.
(2) Eluent: A combination of distilled water (liquid A) and acetonitrile (liquid B) in which trifluoroacetic acid is dissolved at a ratio of 0.002% by weight is used.
(3) Elution program: Elution solution is flowed at a fixed ratio of 75% by volume / 25% by volume from the start of elution (0 minutes) until 5 minutes have passed, and when 5 minutes have elapsed since the start of elution. 35 minutes after the elution, linear gradient elution is performed in which A liquid / B liquid = 75 vol% / 25 vol% changes to A liquid / B liquid = 0 vol% / 100 vol%. From the time when minutes elapse until the time when 40 minutes elapses, the eluent is allowed to flow at a constant ratio of liquid A / liquid B = 0 volume% / 100 volume%.
(4) Flow rate of eluent: 1.0 ml / min
(5) Detection: Detection is carried out by an ultraviolet absorption method using an ultraviolet wavelength of 210 nm.

The mixture of lactic acid condensates according to claim 1 in the form of a neutralized salt.

It is obtained by heat condensation of lactic acid, and when performing high performance liquid chromatography under the following conditions, the peak area of lactic acid is 20% or less with respect to the total peak area, and 20 minutes after 3 minutes from the start of elution. A mixture of lactic acid condensates or a neutralization salt thereof having a composition in which the peak area of all fractions appearing up to the point of time elapses is 30% or more and having a pharmacological action for promoting intestinal bacterial growth A composition characterized by the above.
[Conditions for high performance liquid chromatography]
(1) Column: An ODS column having an inner diameter of 4.6 mm and a length of 15 cm is used.
(2) Eluent: A combination of distilled water (liquid A) and acetonitrile (liquid B) in which trifluoroacetic acid is dissolved at a ratio of 0.002% by weight is used.
(3) Elution program: Elution solution is flowed at a fixed ratio of 75% by volume / 25% by volume from the start of elution (0 minutes) until 5 minutes have passed, and when 5 minutes have elapsed since the start of elution. 35 minutes after the elution, linear gradient elution is performed in which A liquid / B liquid = 75 vol% / 25 vol% changes to A liquid / B liquid = 0 vol% / 100 vol%. From the time when minutes elapse until the time when 40 minutes elapses, the eluent is allowed to flow at a constant ratio of liquid A / liquid B = 0 volume% / 100 volume%.
(4) Flow rate of eluent: 1.0 ml / min
(5) Detection: Detection is carried out by an ultraviolet absorption method using an ultraviolet wavelength of 210 nm.

The composition according to claim 3, which is used as a cosmetic, quasi drug, medical product, hygiene product, pharmaceutical product or functional food.

The composition according to claim 4, which is applied to a living body through any of the following routes: oral ingestion, application or sticking to the surface of a living body, insertion into a living body, or embedding.